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2,332,100 | Hyperaemic response to cigarette smoking in healthy gingiva. | Cigarette smoking is currently considered as a risk factor for periodontal disease. Controversy exists as to whether the vasoconstrictive property of nicotine is one of the pathogenic mechanisms. To this end we tested the hypothesis that cigarette smoking is causing vasoconstriction in the healthy human gingiva.</AbstractText>Gingival blood flow was continuously measured with laser Doppler flowmetry in healthy (n=13) casual consumers of tobacco. Simultaneously, recordings were made of skin blood flow in the forehead and the thumb as well as heart rate (HR) and blood pressure (BP). In another session infraorbital nerve block anaesthesia (INB) with 1.0 ml of Carbocain without vasoconstrictive additives was used to identify nervously mediated vascular responses to cigarette smoking (n=8).</AbstractText>Cigarette smoking induced a modest hyperaemic response in the gingiva that was lower than the relative increases in BP and HR, and the calculated gingival vascular conductance decreased. In the forehead, flow responses were similar to those in the gingiva, while in the thumb a powerful vasoconstriction was observed. During the later part of the 10-min recovery period, BP and HR tended to decrease while blood flow in the gingiva and forehead remained high. INB potentiated the hyperaemic response to cigarette smoking in gingiva.</AbstractText>The present results help to shed some light on the understanding of the vasoactive mechanisms induced by cigarette smoking, and to support the hypothesis that cigarette smoking causes nervously mediated vasoconstriction in the healthy human gingiva. However, the degree of vasoconstriction was far less than in the thumb skin, and in our subjects was overcome by the evoked rise in arterial perfusion pressure. As a consequence, gingival blood flow increased during smoking. It is speculated that small repeated vasoconstrictive attacks due to cigarette smoking may in the long run contribute to gingival vascular dysfunction and periodontal disease.</AbstractText> |
2,332,101 | The use of sulfonylamido pyrimidines incorporating an unsaturated side chain as endothelin receptor antagonists. | A series of compounds structurally related to bosentan 1 featuring an unsaturated side chain at position 6 of the core pyrimidine have been studied for their potential to block the ET(A) and ET(B) receptor. Incorporation of a 2-butyne-1,4-diol linker bearing a pyridyl carbamoyl moiety led to in vitro highly potent endothelin receptor antagonists (e.g., 70 and 75). The propargyl derivative 26 significantly reduced blood pressure in in vivo model studies with hypertensive salt-sensitive Dahl rats. |
2,332,102 | [Molecular chaperone inducers in medicine and diseases]. | In response to stresses, mammalian cells induce heat shock proteins (HSP). Overproduction of a stress-inducible 70-kDa protein (Hsp70) results in the acquisition of tolerance against various types of stresses. An acyclic isoprenoid, geranylgeranylacetone (GGA), was introduced for the first time as a non-toxic Hsp 70 inducer, which selectively and safely induced Hsp70 in cultured guinea pig gastric mucosal cells and rat gastric mucosa. GGA also primed other types of cells for enhanced induction of Hsp70, when exposed to stress. Pretreatment of rats with GGA markedly suppressed ischemia-reperfusion injury of the liver, small intestine, or heart, and improved survival after 95% hepatectomy as well as liver transplantation. GGA can block insult-induced apoptosis at multiple levels; it inhibited activation of c-Jun N-terminal kinases, decline of mitochondrial membrane potential, and formation of apoptosome by binding with Apaf-1. Recently, GGA has been shown to induce thioredoxin and anti-viral genes, suggesting that GGA may exhibit protective actions independently of Hsp70 induction. HSP are members of molecular chaperones that are essential for the quality control of intracellular proteins. New compounds specifically targeting molecular chaperones that function to prevent the accumulation of misfolded proteins may be useful for the treatment of neurodegenerative disorders in the near future. |
2,332,103 | Cardiac memory mimicking myocardial ischaemia.<Pagination><StartPage>131</StartPage><EndPage>132</EndPage><MedlinePgn>131-2</MedlinePgn></Pagination><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Gautschi</LastName><ForeName>O</ForeName><Initials>O</Initials><AffiliationInfo><Affiliation>Department of Internal Medicine, University Hospital, Bern, Switzerland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Naegeli</LastName><ForeName>B</ForeName><Initials>B</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D002363">Case Reports</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>J R Soc Med</MedlineTA><NlmUniqueID>7802879</NlmUniqueID><ISSNLinking>0141-0768</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000368" MajorTopicYN="N">Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000369" MajorTopicYN="N">Aged, 80 and over</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002304" MajorTopicYN="N">Cardiac Pacing, Artificial</DescriptorName><QualifierName UI="Q000009" MajorTopicYN="Y">adverse effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D003937" MajorTopicYN="N">Diagnosis, Differential</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004562" MajorTopicYN="Y">Electrocardiography</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006329" MajorTopicYN="N">Heart Conduction System</DescriptorName><QualifierName UI="Q000503" MajorTopicYN="Y">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D017202" MajorTopicYN="N">Myocardial Ischemia</DescriptorName><QualifierName UI="Q000175" MajorTopicYN="Y">diagnosis</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D012804" MajorTopicYN="N">Sick Sinus Syndrome</DescriptorName><QualifierName UI="Q000628" MajorTopicYN="N">therapy</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2003</Year><Month>3</Month><Day>4</Day><Hour>4</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2003</Year><Month>4</Month><Day>11</Day><Hour>5</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2003</Year><Month>3</Month><Day>4</Day><Hour>4</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">12612116</ArticleId><ArticleId IdType="pmc">PMC539422</ArticleId><ArticleId IdType="doi">10.1258/jrsm.96.3.131</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Chatterjee K, Harris A, Davies G, Leatham A. 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Repolarization abnormalities after catheter ablation of accessory atrioventricular connections with radiofrequency current. J Am Coll Cardiol 1991;18: 1761-6</Citation><ArticleIdList><ArticleId IdType="pubmed">1960327</ArticleId></ArticleIdList></Reference><Reference><Citation>Kernohan RJ. Post-paroxysmal tachycardia syndrome. Br Heart J 1969;31: 803-6</Citation><ArticleIdList><ArticleId IdType="pmc">PMC487596</ArticleId><ArticleId IdType="pubmed">5358184</ArticleId></ArticleIdList></Reference><Reference><Citation>Patberg KW, Plotnikow A, Giannulin R, et al. Cardiac memory is associated with alterations in the cAMP responsive element binding protein and its phosphorylation form. PACE 2001;24: 645</Citation></Reference></ReferenceList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">12611296</PMID><DateCompleted><Year>2003</Year><Month>07</Month><Day>28</Day></DateCompleted><DateRevised><Year>2018</Year><Month>11</Month><Day>30</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0201-7563</ISSN><JournalIssue CitedMedium="Print"><Issue>5</Issue><PubDate><Year>2002</Year><Season>Sep-Oct</Season></PubDate></JournalIssue><Title>Anesteziologiia i reanimatologiia</Title><ISOAbbreviation>Anesteziol Reanimatol</ISOAbbreviation></Journal>[Modern nondepolarizing myorelaxants in cardiac surgery].<Pagination><StartPage>24</StartPage><EndPage>29</EndPage><MedlinePgn>24-9</MedlinePgn></Pagination><Abstract><AbstractText>The electromyographic and hemodynamic profile and side effects of the new nondepolarizing myorelaxants Mivacurium chloride (Mivacron), Cisathracurium besilate (Nimbex), Rocuronium bromide (Esmerone) were studied in 117 adult patients. All the test myorelaxants as bolus or infusion in a dose of 3.ED95 were found to be effective in creating adequate conditions for tracheal intubation and neuromuscular block (NMB) maintenance during operations on the coronary arteries and cardiac vales under extracorporeal circulation. In terms of the onset rate of NMB, Esmerone is the drug of choice for tracheal intubation. Esmerone and Nimbex in a dose of 3.ED95 did not produce a noticeable hemodynamic effect. The former was found to have a slight vagolytic effect. When rapidly injected as bolus, Mivacron caused a significant decrease in blood pressure and heart rate by 10-12%. Based on a comprehensive study, the authors have scientifically substantiated principles in the choice of nondepolarizing myorelaxants in cardiac surgical patients in relation to the baseline hemodynamic values, the stage of an operation, and the duration of artificial pulmonary ventilation.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Vanina</LastName><ForeName>S V</ForeName><Initials>SV</Initials></Author><Author ValidYN="Y"><LastName>Trekova</LastName><ForeName>N A</ForeName><Initials>NA</Initials></Author><Author ValidYN="Y"><LastName>Flerov</LastName><ForeName>E V</ForeName><Initials>EV</Initials></Author><Author ValidYN="Y"><LastName>Iavorovskiĭ</LastName><ForeName>A G</ForeName><Initials>AG</Initials></Author><Author ValidYN="Y"><LastName>Shmyrin</LastName><ForeName>M M</ForeName><Initials>MM</Initials></Author><Author ValidYN="Y"><LastName>Buniatian</LastName><ForeName>A A</ForeName><Initials>AA</Initials></Author></AuthorList><Language>rus</Language><PublicationTypeList><PublicationType UI="D003160">Comparative Study</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><VernacularTitle>Sovremennye nedepoliarizuiushchie miorelaksanty v kardiokhirurgii.</VernacularTitle></Article><MedlineJournalInfo><Country>Russia (Federation)</Country><MedlineTA>Anesteziol Reanimatol</MedlineTA><NlmUniqueID>7705399</NlmUniqueID><ISSNLinking>0201-7563</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000732">Androstanols</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D007546">Isoquinolines</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D003473">Neuromuscular Nondepolarizing Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>2GQ1IRY63P</RegistryNumber><NameOfSubstance UI="D001279">Atracurium</NameOfSubstance></Chemical><Chemical><RegistryNumber>77D66S9Q93</RegistryNumber><NameOfSubstance UI="D000077590">Mivacurium</NameOfSubstance></Chemical><Chemical><RegistryNumber>QX62KLI41N</RegistryNumber><NameOfSubstance UI="C101584">cisatracurium</NameOfSubstance></Chemical><Chemical><RegistryNumber>WRE554RFEZ</RegistryNumber><NameOfSubstance UI="D000077123">Rocuronium</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000328" MajorTopicYN="N">Adult</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000368" MajorTopicYN="N">Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000732" MajorTopicYN="N">Androstanols</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName><QualifierName UI="Q000009" MajorTopicYN="N">adverse effects</QualifierName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000768" MajorTopicYN="Y">Anesthesia, General</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001279" MajorTopicYN="N">Atracurium</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName><QualifierName UI="Q000009" MajorTopicYN="N">adverse effects</QualifierName><QualifierName UI="Q000031" MajorTopicYN="Y">analogs & derivatives</QualifierName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006348" MajorTopicYN="N">Cardiac Surgical Procedures</DescriptorName><QualifierName UI="Q000379" MajorTopicYN="Y">methods</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006439" MajorTopicYN="N">Hemodynamics</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007275" MajorTopicYN="N">Injections, Intravenous</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007442" MajorTopicYN="N">Intubation, Intratracheal</DescriptorName><QualifierName UI="Q000379" MajorTopicYN="Y">methods</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D007546" MajorTopicYN="N">Isoquinolines</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName><QualifierName UI="Q000009" MajorTopicYN="N">adverse effects</QualifierName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000077590" MajorTopicYN="N">Mivacurium</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016343" MajorTopicYN="N">Monitoring, Intraoperative</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009126" MajorTopicYN="N">Muscle Relaxation</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D009469" MajorTopicYN="N">Neuromuscular Junction</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D003473" MajorTopicYN="N">Neuromuscular Nondepolarizing Agents</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="Y">administration & dosage</QualifierName><QualifierName UI="Q000009" MajorTopicYN="N">adverse effects</QualifierName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000077123" MajorTopicYN="N">Rocuronium</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2003</Year><Month>3</Month><Day>4</Day><Hour>4</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2003</Year><Month>7</Month><Day>29</Day><Hour>5</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2003</Year><Month>3</Month><Day>4</Day><Hour>4</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">12611296</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">12611293</PMID><DateCompleted><Year>2003</Year><Month>07</Month><Day>28</Day></DateCompleted><DateRevised><Year>2007</Year><Month>11</Month><Day>15</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0201-7563</ISSN><JournalIssue CitedMedium="Print"><Issue>5</Issue><PubDate><Year>2002</Year><Season>Sep-Oct</Season></PubDate></JournalIssue><Title>Anesteziologiia i reanimatologiia</Title><ISOAbbreviation>Anesteziol Reanimatol</ISOAbbreviation></Journal>[Anesthesiological aspects of early activation of patients after aortocoronary bypass surgery]. | The electromyographic and hemodynamic profile and side effects of the new nondepolarizing myorelaxants Mivacurium chloride (Mivacron), Cisathracurium besilate (Nimbex), Rocuronium bromide (Esmerone) were studied in 117 adult patients. All the test myorelaxants as bolus or infusion in a dose of 3.ED95 were found to be effective in creating adequate conditions for tracheal intubation and neuromuscular block (NMB) maintenance during operations on the coronary arteries and cardiac vales under extracorporeal circulation. In terms of the onset rate of NMB, Esmerone is the drug of choice for tracheal intubation. Esmerone and Nimbex in a dose of 3.ED95 did not produce a noticeable hemodynamic effect. The former was found to have a slight vagolytic effect. When rapidly injected as bolus, Mivacron caused a significant decrease in blood pressure and heart rate by 10-12%. Based on a comprehensive study, the authors have scientifically substantiated principles in the choice of nondepolarizing myorelaxants in cardiac surgical patients in relation to the baseline hemodynamic values, the stage of an operation, and the duration of artificial pulmonary ventilation.</Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Vanina</LastName><ForeName>S V</ForeName><Initials>SV</Initials></Author><Author ValidYN="Y"><LastName>Trekova</LastName><ForeName>N A</ForeName><Initials>NA</Initials></Author><Author ValidYN="Y"><LastName>Flerov</LastName><ForeName>E V</ForeName><Initials>EV</Initials></Author><Author ValidYN="Y"><LastName>Iavorovskiĭ</LastName><ForeName>A G</ForeName><Initials>AG</Initials></Author><Author ValidYN="Y"><LastName>Shmyrin</LastName><ForeName>M M</ForeName><Initials>MM</Initials></Author><Author ValidYN="Y"><LastName>Buniatian</LastName><ForeName>A A</ForeName><Initials>AA</Initials></Author></AuthorList><Language>rus</Language><PublicationTypeList><PublicationType UI="D003160">Comparative Study</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><VernacularTitle>Sovremennye nedepoliarizuiushchie miorelaksanty v kardiokhirurgii.</VernacularTitle></Article><MedlineJournalInfo><Country>Russia (Federation)</Country><MedlineTA>Anesteziol Reanimatol</MedlineTA><NlmUniqueID>7705399</NlmUniqueID><ISSNLinking>0201-7563</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000732">Androstanols</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D007546">Isoquinolines</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D003473">Neuromuscular Nondepolarizing Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>2GQ1IRY63P</RegistryNumber><NameOfSubstance UI="D001279">Atracurium</NameOfSubstance></Chemical><Chemical><RegistryNumber>77D66S9Q93</RegistryNumber><NameOfSubstance UI="D000077590">Mivacurium</NameOfSubstance></Chemical><Chemical><RegistryNumber>QX62KLI41N</RegistryNumber><NameOfSubstance UI="C101584">cisatracurium</NameOfSubstance></Chemical><Chemical><RegistryNumber>WRE554RFEZ</RegistryNumber><NameOfSubstance UI="D000077123">Rocuronium</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000328" MajorTopicYN="N">Adult</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000368" MajorTopicYN="N">Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000732" MajorTopicYN="N">Androstanols</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName><QualifierName UI="Q000009" MajorTopicYN="N">adverse effects</QualifierName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000768" MajorTopicYN="Y">Anesthesia, General</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001279" MajorTopicYN="N">Atracurium</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName><QualifierName UI="Q000009" MajorTopicYN="N">adverse effects</QualifierName><QualifierName UI="Q000031" MajorTopicYN="Y">analogs & derivatives</QualifierName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006348" MajorTopicYN="N">Cardiac Surgical Procedures</DescriptorName><QualifierName UI="Q000379" MajorTopicYN="Y">methods</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006439" MajorTopicYN="N">Hemodynamics</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007275" MajorTopicYN="N">Injections, Intravenous</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007442" MajorTopicYN="N">Intubation, Intratracheal</DescriptorName><QualifierName UI="Q000379" MajorTopicYN="Y">methods</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D007546" MajorTopicYN="N">Isoquinolines</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName><QualifierName UI="Q000009" MajorTopicYN="N">adverse effects</QualifierName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000077590" MajorTopicYN="N">Mivacurium</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016343" MajorTopicYN="N">Monitoring, Intraoperative</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009126" MajorTopicYN="N">Muscle Relaxation</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D009469" MajorTopicYN="N">Neuromuscular Junction</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D003473" MajorTopicYN="N">Neuromuscular Nondepolarizing Agents</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="Y">administration & dosage</QualifierName><QualifierName UI="Q000009" MajorTopicYN="N">adverse effects</QualifierName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000077123" MajorTopicYN="N">Rocuronium</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2003</Year><Month>3</Month><Day>4</Day><Hour>4</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2003</Year><Month>7</Month><Day>29</Day><Hour>5</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2003</Year><Month>3</Month><Day>4</Day><Hour>4</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">12611296</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">12611293</PMID><DateCompleted><Year>2003</Year><Month>07</Month><Day>28</Day></DateCompleted><DateRevised><Year>2007</Year><Month>11</Month><Day>15</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0201-7563</ISSN><JournalIssue CitedMedium="Print"><Issue>5</Issue><PubDate><Year>2002</Year><Season>Sep-Oct</Season></PubDate></JournalIssue><Title>Anesteziologiia i reanimatologiia</Title><ISOAbbreviation>Anesteziol Reanimatol</ISOAbbreviation></Journal><ArticleTitle>[Anesthesiological aspects of early activation of patients after aortocoronary bypass surgery].</ArticleTitle><Pagination><StartPage>13</StartPage><EndPage>17</EndPage><MedlinePgn>13-7</MedlinePgn></Pagination><Abstract>The specific features of the course of anesthesia and the time of extubation were studied in 142 patients suffering from coronary heart disease who had undergone myocardial revascularization. All the patients were divided into 3 groups in accordance with the type of anesthesia. Group 1 patients (n = 48) received routine anesthesia with ketamine, benzodiazepines, and large-dose fentanyl. Group 2 (n = 45) had combined anesthesia with inhalational and intravenous anesthetics having their better pharmacodynamics (such as isoflurane, diprivan, tracrium). In Group 3 (n = 49), the authors employed another developed modality of anesthesia using high thoracic (TII-TIV) epidural anesthesia as a basic component of anesthesiological maintenance. The two developed modalities of anesthesia almost halved the use of total dose opioids, which promoted patients' early postoperative recovery of consciousness and respiration. The time before extubation was 9.9 +/- 2.1, 4.5 +/- 1.1, and 1.5 +/- 1.2 hours in Groups 1, 2, and 3, respectively (p < 0.05). The developed anesthesia procedure using isoflurane, midazolam, propofol, and small-dose fentanyl ensures safe and early (up to 6-hour) extubation in 73% of the patients undergone aortocoronary bypass surgery. The developed anesthesiological protocol based on thoracic epidural anesthesia enables extubation to be carried out on the operating table within an hour in 75% of patients after aortocoronary bypass surgery. A comparative intraoperative analysis of hemodynamics, the incidence of myocardial ischemia, arrhythmias, glucose levels has indicated that the anesthesia techniques aimed at a patient's early activation are not inferior in the degree of protection to routine anesthesia using large doses of opioids, ketamine, and diazepam. When used in combination with thoracic epidural block, the methods are superior to the latter. |
2,332,104 | Progressive skeletal myopathy, a phenotypic variant of desmin myopathy associated with desmin mutations. | Desmin myopathy is a familial or sporadic disorder characterized by the presence of desmin mutations that cause skeletal muscle weakness associated with cardiac conduction block, arrhythmia and heart failure. Distinctive histopathologic features include intracytoplasmic accumulation of desmin-reactive deposits and electron-dense granular aggregates in skeletal and cardiac muscle cells. We describe two families with features of adult-onset slowly progressive skeletal myopathy without cardiomyopathy. N342D point mutation was present in the desmin helical rod domain in patients of family 1, and I451M mutation was found in the non-helical tail domain in patients of family 2. Of interest, the same I451M mutation has previously been reported in patients with cardiomyopathy and no signs of skeletal myopathy. Some carriers of the I451M mutation did not develop any disease, suggesting incomplete penetrance. Expression studies demonstrated inability of the N342D mutant desmin to form cellular filamentous network, confirming the pathogenic role of this mutation, but the network was not affected by the tail-domain I451M mutation. Progressive skeletal myopathy is a rare phenotypic variant of desmin myopathy allelic to the more frequent cardio-skeletal form. |
2,332,105 | Inactivation of mitochondrial succinate dehydrogenase by adriamycin activated by horseradish peroxidase and hydrogen peroxide. | Although human cancers are widely treated with anthracycline drugs, these drugs have limited use because they are cardiotoxic. To clarify the cardiotoxic action of the anthracycline drug adriamycin (ADM), the inhibitory effect on succinate dehydrogenase (SDH) by ADM and other anthracyclines was examined by using pig heart submitochondrial particles. ADM rapidly inactivated mitochondrial SDH during its interaction with horseradish peroxidase (HRP) in the presence of H(2)O(2) (HRP-H(2)O(2)). Butylated hydroxytoluene, iron-chelators, superoxide dismutase, mannitol and dimethylsulfoxide did not block the inactivation of SDH, indicating that lipid-derived radicals, iron-oxygen complexes, superoxide and hydroxyl radicals do not participate in SDH inactivation. Reduced glutathione was extremely efficient in blocking the enzyme inactivation, suggesting that the SH group in enzyme is very sensible to ADM activated by HRP-H(2)O(2). Under anaerobic conditions, ADM with HRP-H(2)O(2) caused inactivation of SDH, indicating that oxidized ADM directly attack the enzyme, which loses its activity. Other mitochondrial enzymes, including NADH dehydrogenase, NADH oxidase and cytochrome c oxidase, were little sensitive to ADM with HRP-H(2)O(2). SDH was also sensitive to other anthracycline drugs except for aclarubicin. Mitochondrial creatine kinase (CK), which is attached to the outer face of the inner membrane of muscle mitochondria, was more sensitive to anthracyclines than SDH. SDH and CK were inactivated with loss of red color of anthracycline, indicating that oxidative activation of the B ring of anthracycline has a crucial role in inactivation of enzymes. Presumably, oxidative semiquinone or quinone produced from anthracyclines participates in the enzyme inactivation. |
2,332,106 | Nucleotide excision repair rates in rat tissues. | We have determined and compared nucleotide excision repair capability of several rat tissues by a method based on restoration of the transformation activity of UV-irradiated pBlueScript by incubation in repair-competent protein extracts. After 3 h of incubation, plasmid DNA was isolated and used to transform competent Escherichia coli cells. Damaged plasmids showed low transformation efficiency prior to incubation in repair-competent extracts. After incubation the transformation efficiency was restored to different extents permitting calculation of the repair capacity of the extracts. Our results showed that rapidly proliferating tissues such as liver, kidney and testis showed higher nucleotide excision repair capacity than slowly proliferating tissues such as heart, muscle, lung and spleen. When liver and splenocytes were stimulated to proliferation by partial hepatectomy and mitogen stimulation, their repair capability increased in parallel with the respective proliferative rates. |
2,332,107 | Common molecular determinants of flecainide and lidocaine block of heart Na+ channels: evidence from experiments with neutral and quaternary flecainide analogues. | Flecainide (pKa 9.3, 99% charged at pH 7.4) and lidocaine (pKa 7.6-8.0, approximately 50% neutral at pH 7.4) have similar structures but markedly different effects on Na(+) channel activity. Both drugs cause well-characterized use-dependent block (UDB) of Na(+) channels due to stabilization of the inactivated state, but flecainide requires that channels first open before block develops, whereas lidocaine is believed to bind directly to the inactivated state. To test whether the charge on flecainide might determine its state specificity of Na(+) channel blockade, we developed two flecainide analogues, NU-FL (pKa 6.4), that is 90% neutral at pH 7.4, and a quaternary flecainide analogue, QX-FL, that is fully charged at physiological pH. We examined the effects of flecainide, NU-FL, QX-FL, and lidocaine on human cardiac Na(+) channels expressed in human embryonic kidney (HEK) 293 cells. At physiological pH, NU-FL, like lidocaine but not flecainide, interacts preferentially with inactivated channels without prerequisite channel opening, and causes minimal UDB. We find that UDB develops predominantly by the charged form of flecainide as evidenced by investigation of QX-FL at physiological pH and NU-FL investigated over a more acidic pH range where its charged fraction is increased. QX-FL is a potent blocker of channels when applied from inside the cell, but acts very weakly with external application. UDB by QX-FL, like flecainide, develops only after channels open. Once blocked, channels recover very slowly from QX-FL block, apparently without requisite channel opening. Our data strongly suggest that it is the difference in degree of ionization (pKa) between lidocaine and flecainide, rather than gross structural features, that determines distinction in block of cardiac Na(+) channels. The data also suggest that the two drugs share a common receptor but, consistent with the modulated receptor hypothesis, reach this receptor by distinct routes dictated by the degree of ionization of the drug molecules. |
2,332,108 | Blocking of responses to endotoxin by E5564 in healthy volunteers with experimental endotoxemia. | E5564 is a second-generation synthetic analogue of the lipid A component of endotoxin (lipopolysaccharide [LPS]). The ability of E5564 to block the toxic activity of LPS was assessed in a double-blind, placebo-controlled study. A bolus infusion of endotoxin (4 ng/kg) was administered to healthy subjects to induce a mild transient syndrome similar to clinical sepsis. Single E5564 doses of 50-250 microg ameliorated or blocked all of the effects of LPS in a dose-dependent manner. All E5564 dose groups had statistically significant reductions in elevated temperature, heart rate, C-reactive protein levels, white blood cell count, and cytokine levels (tumor necrosis factor-alpha and interleukin-6), compared with placebo (P<.01). In doses of > or = 100 microg, E5564 acted as an LPS antagonist and completely eliminated these signs. E5564 also blocked or ameliorated LPS-induced fever, chills, headache, myalgia, and tachycardia (P<.01). These results demonstrate that E5564 blocks the effects of LPS in a human model of clinical sepsis and indicate its potential in the treatment and/or prevention of clinical sepsis. |
2,332,109 | Haploinsufficiency in combination with aging causes SCN5A-linked hereditary Lenègre disease. | The goal of this study was to investigate the genotype-to-phenotype relationship between SCN5A gene mutation and progressive cardiac conduction defect in order to gain insights into the pathophysiologic mechanisms of the disease.</AbstractText>Progressive cardiac conduction defect is a frequent disease commonly attributed to degeneration and fibrosis of the His bundle and its branches. In a French family, we have identified a splicing mutation in the SCN5A gene leading to hereditary progressive cardiac conduction defect.</AbstractText>We have extended the size of the pedigree and phenotyped and genotyped all family members, and also investigated in vitro the functional consequences of the mutation.</AbstractText>Among 65 potentially affected members, 25 individuals were carriers of the IVS.22+2 T-->C SCN5A mutation. In relation to aging, gene carriers exhibit various types of conduction defects. P-wave, PR, and QRS duration increased progressively with age in gene carriers and in noncarriers. Whatever the age, conduction parameters were longer in gene carriers. The widening in the QRS complex with aging was more pronounced in gene carriers older than 40 years. Functional studies show that the IVS.22+2 T-->C SCN5A mutation lead to exon 22 skipping and to a complete loss of function of the affected allele, but to a normal trafficking of the mutated gene product.</AbstractText>Our findings demonstrate that hereditary Lenègre disease is caused by a haploinsufficiency mechanism, which in combination with aging leads to progressive alteration in conduction velocity.</AbstractText> |
2,332,110 | Spironolactone and its main metabolite, canrenoic acid, block human ether-a-go-go-related gene channels. | It has been demonstrated that spironolactone (SP) decreases the QT dispersion in chronic heart failure. In this study, the effects of SP and its metabolite, canrenoic acid (CA), on human ether-a-go-go-related gene (HERG) currents were analyzed.</AbstractText>HERG currents elicited in stably transfected Chinese hamster ovary cells were measured with the whole-cell patch-clamp technique. SP decreased HERG currents in a concentration-dependent manner (IC50=23.0+/-1.5 micromol/L) and shifted the midpoint of the activation curve to more negative potentials (Vh=-13.1+/-3.4 versus -18.9+/-3.6 mV, P<0.05) without modifying the activation and deactivation kinetics. SP-induced block (1 micromol/L) appeared at the range of membrane potentials coinciding with that of channel activation, and thereafter, it remained constant, reaching 24.7+/-3.8% at +60 mV (n=6, P<0.05). CA (0.01 nmol/L to 500 micromol/L) blocked HERG channels in a voltage- and frequency-independent manner. CA at 1 nmol/L shifted the midpoint of the activation curve to -19.9+/-1.8 mV and accelerated the time course of channel activation (tau=1064+/-125 versus 820+/-93 ms, n=11, P<0.01). The envelope of the tail test demonstrated that at the very beginning of the pulses to +40 mV (25 ms), a certain amount of block was apparent (31.3+/-9.9%). CA did not modify the voltage-dependence of HERG channel inactivation (Vh=-60.8+/-5.6 versus -62.9+/-3.1 mV, n=6, P>0.05) or the kinetics of the reactivation process at any potential tested. CA and aldosterone also blocked the native I(Kr) in guinea-pig ventricular myocytes.</AbstractText>At concentrations reached after administration of therapeutic doses of SP, CA blocked the HERG channels by binding to both the closed and open states of the channel.</AbstractText> |
2,332,111 | Could n-3 polyunsaturated fatty acids reduce pathological pain by direct actions on the nervous system? | The intake of n-3 polyunsaturated fatty acids (PUFAs) in many industrialized countries is relatively low and its increased consumption has protective and modifying effects on such diverse conditions as atherosclerosis, ventricular arrhythmias, multiple sclerosis, major depression and inflammatory and autoimmune diseases. In addition, n-3 PUFAs have been shown to alleviate pain in patients with rheumatoid arthritis, inflammatory bowel disease and in a number of other painful conditions. This has been attributed to the inhibition of pro-inflammatory eicosanoid and cytokine production by peripheral tissues. n-3 PUFAs have also been shown to inhibit eicosanoid production in glial cells, block voltage-gated sodium channels (VGSCs), inhibit neuronal protein kinases and modulate gene expression. They also appear to have mood-stabilizing and sympatholytic effects. The present article explores the possibility that, based on what is known about their neural and non-neural effects, n-3 PUFAs directly attenuate the neuronal and glial processes that underlie neuropathic and inflammatory pain. |
2,332,112 | Neonatal monitoring after maternal fentanyl analgesia in labor. | To characterize different methods of monitoring neonatal effects associated with maternal opioid analgesia. Special focus was on the static-charge-sensitive bed (SCSB), which could potentially serve as a non-invasive neonatal monitor.</AbstractText>12 healthy, term newborns from normal pregnancies were included in this prospective, randomized, controlled study. Maternal labor analgesia was either intravenous fentanyl (n = 5) or paracervical bupivacaine blockade (n = 7). Neonatal recording from delivery to the age of 12 hours included continuous SCSB monitoring with ECG and oximeter for sleep states, respiration, oxygenation, heart rate, and body movements. In addition, umbilical blood pH, Apgar, Amiel-Tison's Neurologic and Adaptive Capacity Scoring (NACS), skin cyanosis scoring, blood pressure, rectal and skin temperatures, and skin blood flow measurements were performed.</AbstractText>The study was interrupted, because one baby in the fentanyl group had a significant decrease in oxyhemoglobin saturation (SpO2) to 59%. This was considcred to be residual effect of fentanyl and was treated with naloxone. SpO2 was generally lower in the fentanyl group. Epochs with SpO2 < 90% were more frequent in the fentanyl group, especially during active sleep (mean +/- SD 11.9 +/- 10.7% vs. 2.0 +/- 1.7% of epochs, p = 0.034). Mean heart rate values were lower in the fentanyl group (121.1 +/- 6.4 vs. 132.6 +/- 6.8 beats per minute, p = 0.02), and this difference was seen during wake and all sleep states. Maximum heart rate values were lower in the fentanyl group, too. The opiate group had less quiet sleep than controls (9.6 +/- 2.8% vs. 18.3 +/- 8.3%, p = 0.05). NACS after birth was lower in the fentanyl group (median [range] 15 [13-26] vs. 22 [20-25], p = 0.004).</AbstractText>Several differences were seen between the fentanyl and the control group babies. The SCSB method proved sensitive enough to find neonatal effects of maternal analgesia. Together with ECG and SpO2 monitoring, SCSB gives plentiful information on neonatal well-being in a non-invasive way. Results of this study emphasize the importance of neonatal monitoring after maternal opiate use in labor.</AbstractText> |
2,332,113 | [Effect of KB-R7943 on Na(+)-Ca2+ exchange current in guinea pig ventricular myocytes]. | To study whether KB-R7943 has selective inhibitory effect on the inward and outward Na(+)-Ca2+ exchange current (INa-Ca) in guinea pig ventricular myocytes.</AbstractText>Through setting up the model of intracellular Na(+)-overload during myocardial ischemia and reperfusion, the current-voltage relationship of INa-Ca was recorded using whole-cell patch clamp technique under bi-directional ionic conditions.</AbstractText>Currents were elicited by a declining ramp pulse depolarized immediately from holding potential of -40 mV to +60 mV, then repolarized to -100 mV at a speed of 80 mV.s-1 and returned to the holding potential under bi-directional ionic conditions, while the [Na+] was 25 mmol.L-1 in the pipette solution. The currents increased time-dependently and voltage-dependently which reached from (2.51 +/- 0.15) pA.pF-1 to (5.94 +/- 0.13) pA.pF-1 at mV and from (-1.92 +/- 0.13) pA.pF-1 to (-3.17 +/- 0.16) pA.pF-1 at -80 mV (n = 12) after 3 min and there is no significant run-down of the current. KB-R7943 10(-6) mol.L-1 was found to decrease the current to (4.62 +/- 0.05) pA.pF-1 by 29.4% at mV and to (-2.30 +/- 0.18) pA.pF-1 by 22.1% at -80 mV (n = 5) after 5 min. While 10(-5) mol.L-1 KB-R7943 was shown to decrease the current to (3.13 +/- 0.03) pA.pF-1 by 61.7% at mV and to (-1.62 +/- 0.03) pA.pF-1 by 56.9% at -80 mV (n = 7).</AbstractText>KB-R7943 can block INa-Ca in guinea pig ventricular myocytes. But, it did not show selective inhibition effect on inward and outward currents.</AbstractText> |
2,332,114 | Effectiveness of oxygenation and suction in cataract surgery: is suction of CO2-enriched air under the drape during cataract surgery necessary? | To investigate the effectiveness of aspiration of expired air by a suction system on peripheral oxygen saturation (SpO(2)) and end tidal carbon dioxide (EtCO(2)) during cataract surgery.</AbstractText>In total, 160 pre-medicated patients aged between 40 and 70 years (ASA I-III, classification of patients according to the American Society of Anesthesiologists) scheduled for cataract surgery under retrobulbar or peribulbar block were examined in a randomised, single-blind manner. The patients were sedated with 3 mg midazolam i.v. 15 min before operation and were monitored with an anaesthesia monitor. Heart rate (HR), non-invasive mean arterial pressure (MAP), SpO(2) and EtCO(2) were continuously measured using a standardised monitor. The first group (non-suction group, n = 80) received 4 L min(-1) O(2) with nasal cannule while the second group (suction group, n = 80) received 4 L min(-1) O(2) with nasal cannule, and the expired air was aspired with a Y-piece suction system. EtCO(2) was measured with the line of the sampling tube in the anaesthesia monitor. Respiratory rate (RR) was counted for a period of 1 min at each measurement time with thoracic excursions. The results were evaluated by unpaired t-test and analysis of variance.</AbstractText>Severe reduction of SpO(2) and raising of EtCO(2) were observed significantly in the first group during the operation. RR, HR and MAP increased due to hypoxaemia. In the second group, SpO(2) was stabilised at high levels and EtCO(2) did not increase. RR, HR and MAP levels remained within the normal limits. Differences between the two groups were statistically significant (P < 0.05).</AbstractText>During cataract surgery with local anaesthesia, SpO(2) decreases and RR, HR and MAP increase because of reinspiration of expired air under the drape. Insufflation of O(2) and aspiration of expired air with a suction system have prevented severe reduction of SpO(2) and raising of EtCO(2). It was suggested that O(2) delivery and use of an aspiration system decreased the risk of hypoxaemia significantly in the patients undergoing the cataract surgery.</AbstractText> |
2,332,115 | Activity-dependent role of NMDA receptors in transmission of cardiac mechanoreceptor input to the NTS. | Evidence suggests that transmission of barosensitive input from arterial baroreceptors and cardiac mechanoreceptors at nucleus tractus solitarius (NTS) neurons involves non-N-methyl-d-aspartate (NMDA) glutamate receptors, but there is a possibility that the contribution of NMDA receptors might increase during periods of increased afferent input, when enhanced neuronal depolarization could increase the activation of NMDA receptors by removal of a Mg(2+) block. Thus the effects of NMDA on cardiac mechanoreceptor-modulated NTS neuronal discharges were examined at different levels of arterial pressure used to change cardiac mechanoreceptor afferent input. To determine whether the response was specific to NMDA, (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA) was also administered at different levels of neuronal discharge. In anesthetized dogs, neuronal activity was recorded from the NTS while NMDA or AMPA was picoejected at high versus low arterial stimulating pressures. NMDA, but not AMPA, produced a significantly greater discharge of mechanoreceptor-driven NTS neurons at higher versus lower levels of stimulating pressure. These data suggest that the role played by NMDA receptors is greater during periods of enhanced neuronal depolarization, which could be produced by increases in afferent barosensitive input. |
2,332,116 | Cutaneous vasoconstrictor response to whole body skin cooling is altered by time of day. | To test for a diurnal difference in the vasoconstrictor control of the cutaneous circulation, we performed whole body skin cooling (water-perfused suits) at 0600 (AM) and 1600 (PM). After whole body skin temperature (T(sk)) was controlled at 35 degrees C for 10 min, it was progressively lowered to 32 degrees C over 18-20 min. Skin blood flow (SkBF) was monitored by laser-Doppler flowmetry at three control sites and at a site that had been pretreated with bretylium by iontophoresis to block noradrenergic vasoconstriction. After whole body skin cooling, maximal cutaneous vascular conductance (CVC) was measured by locally warming the sites of SkBF measurement to 42 degrees C for 30 min. Before whole body skin cooling, sublingual temperature (T(or)) in the PM was significantly higher than that in the AM (P < 0.05), but CVC, expressed as a percentage of maximal CVC (%CVC(max)), was not statistically different between AM and PM. During whole body skin cooling, %CVC(max) levels at bretylium-treated sites in AM or PM were not significantly reduced from baseline. In the PM, %CVC(max) at control sites fell significantly at T(sk) of 34.3 +/- 0.01 degrees C and lower (P < 0.05). In contrast, in the AM %CVC(max) at control sites was not significantly reduced from baseline until T(sk) reached 32.3 +/- 0.01 degrees C and lower (P < 0.05). Furthermore, the decrease in %CVC(max) in the PM was significantly greater than that in AM at T(sk) of 33.3 +/- 0.01 degrees C and lower (P < 0.05). Integrative analysis of the CVC response with respect to both T(or) and T(sk) showed that the cutaneous vasoconstrictor response was shifted to higher internal temperatures in the PM. These findings suggest that during whole body skin cooling the reflex control of the cutaneous vasoconstrictor system is shifted to a higher internal temperature in the PM. Furthermore, the slope of the relationship between CVC and T(sk) is steeper in the PM compared with that in the AM. |
2,332,117 | Molecular action of lidocaine on the voltage sensors of sodium channels. | Block of sodium ionic current by lidocaine is associated with alteration of the gating charge-voltage (Q-V) relationship characterized by a 38% reduction in maximal gating charge (Q(max)) and by the appearance of additional gating charge at negative test potentials. We investigated the molecular basis of the lidocaine-induced reduction in cardiac Na channel-gating charge by sequentially neutralizing basic residues in each of the voltage sensors (S4 segments) in the four domains of the human heart Na channel (hH1a). By determining the relative reduction in the Q(max) of each mutant channel modified by lidocaine we identified those S4 segments that contributed to a reduction in gating charge. No interaction of lidocaine was found with the voltage sensors in domains I or II. The largest inhibition of charge movement was found for the S4 of domain III consistent with lidocaine completely inhibiting its movement. Protection experiments with intracellular MTSET (a charged sulfhydryl reagent) in a Na channel with the fourth outermost arginine in the S4 of domain III mutated to a cysteine demonstrated that lidocaine stabilized the S4 in domain III in a depolarized configuration. Lidocaine also partially inhibited movement of the S4 in domain IV, but lidocaine's most dramatic effect was to alter the voltage-dependent charge movement of the S4 in domain IV such that it accounted for the appearance of additional gating charge at potentials near -100 mV. These findings suggest that lidocaine's actions on Na channel gating charge result from allosteric coupling of the binding site(s) of lidocaine to the voltage sensors formed by the S4 segments in domains III and IV. |
2,332,118 | Presentation of nitric oxide regulates monocyte survival through effects on caspase-9 and caspase-3 activation. | In the absence of survival factors, blood monocytes undergo spontaneous apoptosis, which involves the activation of caspase-3. Although nitric oxide can block caspase-3 activation and promote cell survival, it can also induce apoptosis. We hypothesized that nitrosothiols that promote protein S-nitrosylation would reduce caspase-3 activation and cell survival, whereas nitric oxide donors (such as 1-propamine 3-(2-hydroxy-2-nitroso-1-propylhydrazine (PAPA) NONOate and diethylamine (DEA) NONOate) that do not target thiol residues would not. Using human monocytes as a model, we observed that nitrosothiol donors S-nitrosoglutathione and S-nitroso-N-acetylpenicillamine suppressed caspase-9 and caspase-3 activity and DNA fragmentation. In contrast, PAPA or DEA NONOate did not promote monocyte survival events and appeared to inhibit monocyte survival induced by macrophage colony-stimulating factor. The caspase-3-selective inhibitor DEVD-fluoromethyl ketone reversed DNA fragmentation events, and the caspase-9 inhibitor LEHD-fluoromethyl ketone reversed caspase-3 activity in monocytes treated with PAPA or DEA NONOate in the presence of macrophage colony-stimulating factor. These results were not caused by differences in glutathione levels or the kinetics of nitric oxide release. Moreover, S-nitrosoglutathione and S-nitroso-N-acetylpenicillamine directly blocked the activity of recombinant caspase-3, which was reversed by the reducing agent dithiothreitol, whereas PAPA or DEA NONOate did not block the enzymatic activity of caspase-3. These data support the hypothesis that nitrosylation of protein thiol residues by nitric oxide is critical for promoting the survival of human monocytes. |
2,332,119 | Monotherapy with mastic does not eradicate Helicobacter pylori infection from mice. | To determine the ability of mastic monotherapy to eradicate Helicobacter pylori infection from mice.</AbstractText>The susceptibility of H. pylori SS1 to mastic was assessed by broth dilution determination of the MIC and MBC. Mice were inoculated intragastrically with either a suspension of H. pylori SS1 (n = 70) or brain-heart infusion broth alone (n = 10). Mice were given antimicrobial chemotherapy 4 weeks after infection and were administered the mouse equivalent of either 2 g of mastic twice daily for 7 days or a triple therapy regimen containing the mouse equivalent of 400 mg of metronidazole, 250 mg of clarithromycin and 20 mg of omeprazole twice daily for 7 days. Mice were killed either immediately or 1 month after the completion of treatment, and their stomachs cultured for H. pylori.</AbstractText>The mastic MIC and MBC of H. pylori SS1 were 7.80 and 31.25 mg/L, respectively. The triple therapy regimen eradicated infection from 19 of 20 SS1-infected mice. Mastic failed to eradicate infection from any of the 18 SS1-infected mice (P < 0.001) and there was no signifi- cant reduction in gastric bacterial load in mice treated with this regimen.</AbstractText>Despite reported beneficial effects in ulcer patients and the good in vitro activity of mastic against H. pylori, this compound is unable to eradicate H. pylori infection from mice.</AbstractText> |
2,332,120 | Comparison of fentanyl-bupivacaine or midazolam-bupivacaine mixtures with plain bupivacaine for caudal anaesthesia in children. | The aim of this study was to evaluate the intensity and effectiveness of 0.75 ml.kg-1 bupivacaine 0.25% with the addition of fentanyl or midazolam for caudal block in children undergoing inguinal herniorrhaphy.</AbstractText>Seventy-five children were allocated randomly to three groups to receive a caudal block with either 0.25% bupivacaine with fentanyl 1 microg.kg(-1) (group BF) or with midazolam 50 microg.kg(-1) (group BM) or bupivacaine alone (group B) after induction of anaesthesia. Haemodynamic parameters, degree of pain, additional analgesic requirements and side-effects were evaluated.</AbstractText>The mean systolic arterial pressure at 10, 20, 30 min after caudal block was higher in group B compared with groups BF and BM. Mean intraoperative heart rate was lower in group BF than the other groups. Adequate analgesia was obtained in all patients (100%) in group BF, 23 patients (92%) in group BM and 21 patients (84%) in group B (P > 0.05). The time to recovery to an Aldrete score of 10 was significantly shorter in group B than group BM (P < 0.05). Although not significant, it was also shorter in group B than group BF. There was no difference in additional analgesic requirements between the groups in the first 24 h. Sedation score was higher in the midazolam group at 60 and 90 min postoperatively than the other groups.</AbstractText>Caudal block with 0.75 ml.kg(-1) 0.25% bupivacaine and 50 microg.kg(-1) midazolam or 1 microg.kg(-1) fentanyl provides no further analgesic advantages to bupivacaine alone when administered immediately after induction of anaesthesia in children undergoing unilateral inguinal herniorrhaphy.</AbstractText> |
2,332,121 | [Priming versus bolus: a comparative study with different cisatracurium doses.]. | The priming technique is an alternative to shorten nondepolarizing neuromuscular blockers onset time. This study aimed at evaluating maximum neuromuscular block onset, tracheal intubation conditions and cardiocirculatory changes determined by different cisatracurium single or fractional doses.</AbstractText>Participated in this study 80 patients physical status ASA I and II, who were distributed into two groups according to cisatracurium doses: Group I (0.1 mg.kg-1) and Group II (0.2 mg.kg-1). Subgroups were constituted according to the curarization technique employed: subgroups P1 and P2 (priming-dose) - 0.02 mg.kg-1 or 0.04 mg.kg-1cisatracurium, respectively, followed one minute later, by 0.08 mg.kg-1 or 0.16 mg.kg-1 of the same neuromuscular blocker, respectively; subgroups U1 and U2 - total bolus injection of 0.1 mg.kg-1 or 0.2 mg.kg-1 cisatracurium, respectively. Anesthesia was induced with etomidate, preceded by alfentanil. Train of Four (TOF) stimulation was applied at 12-second intervals to monitor neuromuscular function. Maximum neuromuscular blockade onset time, tracheal intubation conditions and changes in hemodynamic parameters (arterial mean blood pressure and heart rate) were evaluated.</AbstractText>Mean times for maximum neuromuscular block onset were: Group I (3.90 +/- 0.60 min and 3.88 +/- 0.74 min, for subgroups P1 and U1, respectively) and Group II (1.40 +/- 0.40 min and 2 +/- 0.30 min, for subgroups P2 and U2, respectively) with no significant differences. Comparison between subgroups P1 and P2 and between subgroups U1 and U2, has shown statistically significant differences. Tracheal intubation conditions were acceptable in all patients and there were no cardiovascular changes.</AbstractText>Fractional cisatracurium doses have not shortened maximum neuromuscular block onset as compared to bolus injections. They have however produced acceptable tracheal intubation conditions without cardiovascular changes.</AbstractText> |
2,332,122 | Insulin revisited. | Injury and critical illness are characterised by hyperglycaemia, high free fatty acids and high net protein catabolism, due partly to suppression of insulin secretion in the shock phase and insulin resistance in the flow phase of injury, accompanied by high levels of cytokines and the catabolic hormones cortisol, glucagon and catecholamines. Pre-operative carbohydrate loading reduces post-operative insulin resistance and its consequences. Insulin has been shown to reduce the catabolic response as well as controlling hyperglycaemia. In contrast to its sodium retaining properties in normal, obese and diabetic subjects, insulin-glucose-potassium therapy may induce a sodium diuresis in catabolic patients with salt and water overload and in patients with congestive heart failure in whom haemodynamic improvement has also been observed. Diabetic patients with myocardial infarction and cardiac surgery also benefit from insulin treatment. Recent studies have described positive effects on clinical outcome in critical illness. Whether this is due simply to maintenance of euglycaemia or to the other effects of insulin remains to be determined. |
2,332,123 | Anaesthetic and haemodynamic effects of continuous spinal versus continuous epidural anaesthesia with prilocaine. | To compare, using prilocaine, the effects of continuous spinal anaesthesia (CSA) and continuous epidural anaesthesia (CEA) on haemodynamic stability as well as the quality of anaesthesia and recovery in patients undergoing transurethral resection of the prostate gland.</AbstractText>Thirty patients (>60 yr) were randomized into two groups. Prilocaine, 2% 40 mg, was given to patients in the CSA group, and prilocaine 1% 150mg was given to patients in the CEA group. Incremental doses were given if the level of sensory block was lower than T10 or if needed during surgery.</AbstractText>There was a significant decrease in mean arterial pressure in Group CEA compared with Group CSA (P < 0.01). The decrease in heart rate in Group CSA occurred 10 min after the first local anaesthetic administration and continued through the operation (P < 0.05). The level of sensory anaesthesia was similar in both groups. The times to reach the level of T10 and the upper level of sensory blockade (Tmax) were 18.0 +/- 4.7 and 25.3 +/- 7.0 min in Groups CSA and CEA, respectively, and were significantly longer in Group CEA. The duration of anaesthesia was 76.8 +/- 4min and was shorter in Group CSA (P < 0.01).</AbstractText>Spinal or epidural anaesthesia administered continuously was reliable in elderly patients undergoing transurethral resection of the prostate. Continuous spinal anaesthesia had a more rapid onset of action, produced more effective sensory and motor blockade and had a shorter recovery period. Prilocaine appeared to be a safe local anaesthetic for use with either continuous spinal anaesthesia or continuous epidural anaesthesia.</AbstractText> |
2,332,124 | Neutralizing intraspinal nerve growth factor with a trkA-IgG fusion protein blocks the development of autonomic dysreflexia in a clip-compression model of spinal cord injury. | Increased intraspinal nerve growth factor (NGF) after spinal cord injury (SCI) is detrimental to the autonomic nervous system. Autonomic dysreflexia is a debilitating condition characterized by episodic hypertension, intense headache, and sweating. Experimentally, it is associated with aberrant primary afferent sprouting in the dorsal horn that is nerve growth factor (NGF)-dependent. Therapeutic strategies that neutralize NGF may ameliorate initial apoptotic cellular responses to the injury and aberrant afferent plasticity that occurs weeks after the injury. Subsequently, the development of autonomic disorders may be suppressed. We constructed a protein including the extracellular portion of trkA fused to the Fc portion of human IgG and expressed it using a baculovirus system. Binding of our trkA-IgG fusion protein was specific for NGF with a K(d) = 4.26 x 10(-11) M and blocked NGF-dependent neuritogenesis in PC-12 cells. We hypothesized that binding of NGF in the injured cord by our trkA-IgG fusion protein would diminish autonomic dysreflexia. Severe, high thoracic SCI was induced with clip compression and the rats were treated with intrathecal infusions (4 microg/day) of trkA-IgG or control IgG. At 14 days post-SCI, the magnitude of autonomic dysreflexia was assessed. Colon distension increased mean arterial pressure (MAP) in control rats by 46 +/- 2 from 96 +/- 5 mmHg. In contrast, MAP of rats treated with trkA-IgG increased by only 30 +/- 2 mmHg. Likewise, the MAP response to cutaneous stimulation was also reduced in rats treated with trkA-IgG (20 +/- 1 vs. 29 +/- 2). In contrast, trkA-IgG treatment had no effect on heart rate responses during colon distension or cutaneous stimulation. These results indicate that treatment with trkA-IgG to block NGF suppresses the development of autonomic dysreflexia after a clinically relevant spinal cord injury. |
2,332,125 | Neonatal lupus erythematosus with recurrent pancytopenia: a case report. | Neonatal lupus erythematosus is an immune-mediated disease associated with the transplacental passage of maternal autoantibodies, primarily anti-Ro (SS-A) and anti-La (SS-B). The major clinical manifestations are isolated congenital heart block and cutaneous lupus lesions. Other symptoms include hematologic and hepatic abnormalities. We report a male neonate, born to a mother with Sjögren's syndrome, who experienced cutaneous lupus lesions and 2 episodes of pancytopenia. Both anti-Ro and anti-La antibodies were positive in infant and mother. |
2,332,126 | Statistical and heuristic image noise extraction (SHINE): a new method for processing Poisson noise in scintigraphic images. | Poisson noise is one of the factors degrading scintigraphic images, especially at low count level, due to the statistical nature of photon detection. We have developed an original procedure, named statistical and heuristic image noise extraction (SHINE), to reduce the Poisson noise contained in the scintigraphic images, preserving the resolution, the contrast and the texture. The SHINE procedure consists in dividing the image into 4 x 4 blocks and performing a correspondence analysis on these blocks. Each block is then reconstructed using its own significant factors which are selected using an original statistical variance test. The SHINE procedure has been validated using a line numerical phantom and a hot spots and cold spots real phantom. The reference images are the noise-free simulated images for the numerical phantom and an extremely high counts image for the real phantom. The SHINE procedure has then been applied to the Jaszczak phantom and clinical data including planar bone scintigraphy, planar Sestamibi scintigraphy and Tl-201 myocardial SPECT. The SHINE procedure reduces the mean normalized error between the noisy images and the corresponding reference images. This reduction is constant and does not change with the count level. The SNR in a SHINE processed image is close to that of the corresponding raw image with twice the number of counts. The visual results with the Jaszczak phantom SPECT have shown that SHINE preserves the contrast and the resolution of the slices well. Clinical examples have shown no visual difference between the SHINE images and the corresponding raw images obtained with twice the acquisition duration. SHINE is an entirely automatic procedure which enables halving the acquisition time or the injected dose in scintigraphic acquisitions. It can be applied to all scintigraphic images, including PET data, and to all low-count photon images. |
2,332,127 | The effectiveness and safety of spinal anaesthesia in the pyloromyotomy procedure. | Hypertrophic pyloric stenosis is a relatively common disorder of the gastrointestinal tract in infancy, causing projectile vomiting and metabolic abnormalities. Surgical management in the form of pyloromyotomy under general anaesthesia has been reported as safe for relieving the obstructed bowel. A number of studies have demonstrated the advantages of spinal anaesthesia over general anaesthesia in high risk infants undergoing minor infraumbilical surgery. The purpose of this study was to evaluate spinal anaesthesia as an alternative option to general anaesthesia in infants undergoing pyloromyotomy.</AbstractText>Twenty-five infants undergoing pyloromyotomy under spinal anaesthesia were studied. Haemodynamic and respiratory parameters were noted before performing the spinal block, 5 min after the spinal block, and every 10 min after performing the spinal block; for a total period of 30 min. The spinal block was performed using spinal isobaric bupivacaine 0.5%, 0.8 mg.kg-1. Blood pressure, heart rate, respiratory rate and oxygen saturation values were recorded.</AbstractText>The sensory levels achieved ranged between T3-T5 thoracic segments within 6-8 min and were sufficient to perform surgery in 23 cases. There were no statistically significant differences in the oxygen saturation, systolic blood pressure and respiratory rate compared with before the spinal block and after 5, 10, 20 and 30 min.</AbstractText>This study proposes that spinal anaesthesia is an alternative option to general anaesthesia in infants undergoing pyloromyotomy, and should be considered in infants undergoing pyloromyotomy.</AbstractText> |
2,332,128 | Cerebrovascular carbon dioxide reactivity in children anaesthetized with propofol. | Propofol, by virtue of its favourable pharmacokinetic profile, is suitable for maintenance of anaesthesia by continuous infusion during neurosurgical procedures in adults. It is gaining popularity for use in paediatric patients. To determine the effects of propofol on carbon dioxide cerebrovascular reactivity in children, middle cerebral artery blood flow velocity was measured at different levels of endtidal (PECO2) by transcranial Doppler sonography.</AbstractText>Ten ASA I or II children, aged 1-6 years undergoing elective urological surgery were enrolled. Anaesthesia comprized propofol aimed at producing an estimated steady-state serum concentration of 3 microg x ml-1 and a caudal epidural block. PECO2 was adjusted randomly in an increasing or decreasing fashion between 3.3, 5.2 and 7.2 kPa (25, 40 and 55 mmHg) with an exogenous source of CO2 while maintaining ventilation parameters constant.</AbstractText>Cerebral blood flow velocity increased as PECO2 increased from 3.3 to 5.2 kPa (25-40 mmHg) (P < 0.001) and from 5.2 to 7.2 kPa (40-55 mmHg) (P < 0.001). Mean heart rate and blood pressure did not change significantly.</AbstractText>This study demonstrates that cerebrovascular CO2 reactivity is maintained over PECO2 values of 3.3, 5.2 and 7.2 kPa (25, 40 and 55 mmHg) in healthy children anaesthetized with propofol.</AbstractText> |
2,332,129 | Antagonism of glutamatergic metabotropic receptors in the NTS of awake rats does not affect the gain of the baroreflex. | There is evidence suggesting that metabotropic receptors may play a role in the neurotransmission of the baroreflex in the nucleus tractus solitarius (NTS) of rats. In a recent study from our laboratory, we verified that microinjection of a metabotropic receptor agonist, trans-1-amino-1,3-cyclopentanediocarboxylic acid, into the NTS of awake and anesthetized rats produced baroreflex-like responses (hypotension and bradycardia). In the present study, we evaluated the possible role of L-glutamate metabotropic receptors of the NTS in the neuromodulation of the parasympathetic component of baroreflex activation in awake rats. Bilateral microinjection (50 nl) of a metabotropic receptor antagonist (alpha-methyl-4-carboxyphenylglycine, MCPG, 100 mM) into the rostral commissural NTS produced no change in the gain of the baroreflex bradycardia. In addition, microinjection of MCPG into the NTS produced no changes in baseline mean arterial pressure (MAP) or heart rate (HR), indicating that metabotropic receptors play no tonic role in the neurotransmission of the baroreflex. The dose of MCPG used to block the metabotropic receptors was effective in reducing the bradycardic and hypotensive responses to microinjection (50 nl) of trans-1-amino-1,3-cyclopentanediocarboxylic acid (5 mM) into the NTS. The data show that metabotropic glutamate receptors play no major role in the neuromodulation of the parasympathetic component of the baroreflex at the NTS level. |
2,332,130 | The novel serine protease PreR-Co promotes endothelium-independent vasorelaxation in rabbit aortic rings. | The effect of a novel enzyme (PreR-Co) that activates renal prorenin was studied on rabbit aortas with and without endothelium. It was tested 1) in the basal tone of nonstimulated or ANG II-sensitized rings or rings precontracted with norepinephrine (NE), PGF(2alpha), high KCl concentration, and 2) in rings pretreated with enalaprilat, losartan, PD-123319, N(omega)-nitro-l-arginine methyl ester, HOE-140, indomethacin, or serine protease inhibitors (PMSF, aprotinin, or soybean trypsin inhibitor); kallilkrein and bradykinin were also tested in ANG II-sensitized rings. PreR-Co produced a vasorelaxant effect in the basal tone and in the precontracted rabbit aorta. The effect was endothelium independent, potentiated by endothelium removal or nitric oxide (NO) synthase inhibition, and abolished by boiling the enzyme. In addition, the effect improved when basal tone was increased in ANG II-sensitized aortic rings or in precontracted vessels. No activation of the ANG II, bradykinin, prostaglandin, or NO pathway mediating the PreR-Co response could be obtained, suggesting a direct action of the enzyme. This action seems to be dependent on esterasic activity because serine protease inhibitors like PMSF and aprotinin were able to block the vasorelaxant effect of PreR-Co. |
2,332,131 | CYP4A metabolites of arachidonic acid and VEGF are mediators of skeletal muscle angiogenesis. | Vascular endothelial growth factor (VEGF) has been implicated in angiogenesis induced by electrical stimulation in skeletal muscle. Less is known about the role of arachidonic acid metabolites in the control of growth of blood vessels in vivo. The present study examined the role of 20-hydroxyeicosatetraenoic acid (20-HETE) on the angiogenesis induced by electrical stimulation in skeletal muscle. The tibialis anterior and extensor digitorum longus muscles of rats were stimulated for 7 days. Electrical stimulation significantly increased the 20-HETE formation and angiogenesis in the muscles, which was blocked by chronic treatment with N-hydroxy-N'-(4-butyl-2-methylphenol)formamidine (HET0016) or 1-aminobenzotriazole (ABT). Chronic treatment with either HET0016 or ABT did not block the increases in VEGF protein expression in both muscles. To analyze the role of VEGF on 20-HETE formation, additional rats were treated with VEGF-neutralizing antibody (VEGF Ab). VEGF Ab blocked the increases of 20-HETE formation induced by stimulation. These results place 20-HETE in the downstream signaling pathway for angiogenesis and show that both VEGF and 20-HETE are involved in the angiogenesis induced by electrical stimulation in skeletal muscle. |
2,332,132 | Effects of inhibition of neuronal nitric oxide synthase on NMDA-induced changes in cerebral blood flow and oxygen consumption. | This study was performed to determine whether neuronal nitric oxide synthase (nNOS) is involved in altering regional cerebral blood flow (rCBF) and oxygen consumption during N-methyl- D-aspartate (NMDA) receptor stimulation. A craniotomy was performed in rats, under isoflurane anesthesia, to expose the cerebral cortex. For the control group (n=7), an NMDA patch (10(-3) M) was applied to the exposed cortex (ipsilateral cortex, IC) for 10 min before determining rCBF and O(2) consumption. The patch was changed every 5 min. To block nNOS, 7-nitroindazole (7-NI, 25 mg/kg i.p.) was administered 30 min before NMDA application (7-NI group, n=7). The autoradiographic technique was used to determine rCBF and regional O(2) consumption was measured using cryomicrospectrophotometry. Blood pressure, heart rate, blood gases, and hemoglobin were similar between the two groups. In the control group, rCBF (108+/-32 ml/100 g per min) and O(2) consumption (4.8+/-0.8 ml O(2)/100 g per min) of the IC where NMDA was applied were higher than those of the contralateral cortex (CC) (78+/-16 ml/100 g per min and 3.1+/-0.4 ml O(2)/100 g per min, respectively). Neither rCBF nor O(2) consumption of the IC of the 7-NI group was statistically different from that of the CC. However, O(2) consumption of the IC of the 7-NI group was lower (3.9+/-1.0 ml O(2)/100 g per min) than that of the IC of the control group. Our data demonstrated that a direct cortical application of NMDA increased O(2) consumption and rCBF, and that pretreatment with 7-NI not only attenuated the effects of NMDA on rCBF but also decreased the O(2) consumption during NMDA receptor stimulation. |
2,332,133 | New ECG criteria for high-risk Brugada syndrome.<Pagination><StartPage>8</StartPage><EndPage>10</EndPage><MedlinePgn>8-10</MedlinePgn></Pagination><Abstract><AbstractText>To identify high-risk patients with Brugada syndrome, the present study reviewed 60 standard 12-lead electrocardiograms from 60 patients collected by the Japanese Brugada syndrome registry. Under blinded conditions, the S wave of lead V(1) was measured from the tip of r to r', and the amplitude of the ST segment in lead V(2) was measured at 0.08 s from the J point. In patients with ventricular fibrillation (n=17), the S wave was significantly longer in V(1) (0.085+/-0.007 s vs 0.075+/-0.011 s, p=0.001), and ST segment elevation in V(2) was significantly greater (0.323+/-0.133 mV vs 0.236+/-0.129 mV, p=0.012) than in patients without fibrillation. An S wave width of 0.08 s or more in V(1) had a positive predictive value of 40.5% and negative predictive value of 100% for ventricular fibrillation, with 100% sensitivity. ST elevation of 0.18 mV or more in V(2) had a positive predictive value of 37.8% and a negative predictive value of 100% for ventricular fibrillation, with 100% sensitivity. Both an S wave width > or =0.08 s in V(1) and ST elevation > or =0.18 mV in V(2) were highly specific indicators of ventricular fibrillation and are proposed as new criteria for high-risk Brugada syndrome.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Atarashi</LastName><ForeName>Hirotsugu</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Department of Internal Medicine, Nippon Medical School Tama-Nagayama Hospital, Tokyo, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ogawa</LastName><ForeName>Satoshi</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><CollectiveName>Idiopathic Ventricular Fibrillation Investigators</CollectiveName></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D023362">Evaluation Study</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>Japan</Country><MedlineTA>Circ J</MedlineTA><NlmUniqueID>101137683</NlmUniqueID><ISSNLinking>1346-9843</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000328" MajorTopicYN="N">Adult</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002037" MajorTopicYN="N">Bundle-Branch Block</DescriptorName><QualifierName UI="Q000175" MajorTopicYN="Y">diagnosis</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004562" MajorTopicYN="Y">Electrocardiography</DescriptorName><QualifierName UI="Q000592" MajorTopicYN="N">standards</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011237" MajorTopicYN="N">Predictive Value of Tests</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012042" MajorTopicYN="N">Registries</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012189" MajorTopicYN="N">Retrospective Studies</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012307" MajorTopicYN="N">Risk Factors</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012680" MajorTopicYN="N">Sensitivity and Specificity</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016037" MajorTopicYN="N">Single-Blind Method</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2003</Year><Month>1</Month><Day>10</Day><Hour>4</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2003</Year><Month>6</Month><Day>14</Day><Hour>5</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2003</Year><Month>1</Month><Day>10</Day><Hour>4</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">12520143</ArticleId><ArticleId IdType="doi">10.1253/circj.67.8</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">12519582</PMID><DateCompleted><Year>2003</Year><Month>02</Month><Day>21</Day></DateCompleted><DateRevised><Year>2020</Year><Month>05</Month><Day>11</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1469-493X</ISSN><JournalIssue CitedMedium="Internet"><Issue>4</Issue><PubDate><Year>2002</Year></PubDate></JournalIssue><Title>The Cochrane database of systematic reviews</Title><ISOAbbreviation>Cochrane Database Syst Rev</ISOAbbreviation></Journal>Cardioselective beta-blockers for reversible airway disease. | To identify high-risk patients with Brugada syndrome, the present study reviewed 60 standard 12-lead electrocardiograms from 60 patients collected by the Japanese Brugada syndrome registry. Under blinded conditions, the S wave of lead V(1) was measured from the tip of r to r', and the amplitude of the ST segment in lead V(2) was measured at 0.08 s from the J point. In patients with ventricular fibrillation (n=17), the S wave was significantly longer in V(1) (0.085+/-0.007 s vs 0.075+/-0.011 s, p=0.001), and ST segment elevation in V(2) was significantly greater (0.323+/-0.133 mV vs 0.236+/-0.129 mV, p=0.012) than in patients without fibrillation. An S wave width of 0.08 s or more in V(1) had a positive predictive value of 40.5% and negative predictive value of 100% for ventricular fibrillation, with 100% sensitivity. ST elevation of 0.18 mV or more in V(2) had a positive predictive value of 37.8% and a negative predictive value of 100% for ventricular fibrillation, with 100% sensitivity. Both an S wave width > or =0.08 s in V(1) and ST elevation > or =0.18 mV in V(2) were highly specific indicators of ventricular fibrillation and are proposed as new criteria for high-risk Brugada syndrome.</Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Atarashi</LastName><ForeName>Hirotsugu</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Department of Internal Medicine, Nippon Medical School Tama-Nagayama Hospital, Tokyo, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ogawa</LastName><ForeName>Satoshi</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><CollectiveName>Idiopathic Ventricular Fibrillation Investigators</CollectiveName></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D023362">Evaluation Study</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>Japan</Country><MedlineTA>Circ J</MedlineTA><NlmUniqueID>101137683</NlmUniqueID><ISSNLinking>1346-9843</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000328" MajorTopicYN="N">Adult</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002037" MajorTopicYN="N">Bundle-Branch Block</DescriptorName><QualifierName UI="Q000175" MajorTopicYN="Y">diagnosis</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004562" MajorTopicYN="Y">Electrocardiography</DescriptorName><QualifierName UI="Q000592" MajorTopicYN="N">standards</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011237" MajorTopicYN="N">Predictive Value of Tests</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012042" MajorTopicYN="N">Registries</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012189" MajorTopicYN="N">Retrospective Studies</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012307" MajorTopicYN="N">Risk Factors</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012680" MajorTopicYN="N">Sensitivity and Specificity</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016037" MajorTopicYN="N">Single-Blind Method</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2003</Year><Month>1</Month><Day>10</Day><Hour>4</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2003</Year><Month>6</Month><Day>14</Day><Hour>5</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2003</Year><Month>1</Month><Day>10</Day><Hour>4</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">12520143</ArticleId><ArticleId IdType="doi">10.1253/circj.67.8</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">12519582</PMID><DateCompleted><Year>2003</Year><Month>02</Month><Day>21</Day></DateCompleted><DateRevised><Year>2020</Year><Month>05</Month><Day>11</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1469-493X</ISSN><JournalIssue CitedMedium="Internet"><Issue>4</Issue><PubDate><Year>2002</Year></PubDate></JournalIssue><Title>The Cochrane database of systematic reviews</Title><ISOAbbreviation>Cochrane Database Syst Rev</ISOAbbreviation></Journal><ArticleTitle>Cardioselective beta-blockers for reversible airway disease.</ArticleTitle><Pagination><StartPage>CD002992</StartPage><MedlinePgn>CD002992</MedlinePgn></Pagination><Abstract><AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">Beta-blocker therapy has mortality benefit in patients with hypertension, heart failure and coronary artery disease, as well as during the perioperative period. These drugs have traditionally been considered contraindicated in patients with reversible airway disease.<AbstractText Label="OBJECTIVES" NlmCategory="OBJECTIVE">To assess the effect of cardioselective beta-blockers in patients with asthma or COPD.<AbstractText Label="SEARCH STRATEGY" NlmCategory="METHODS">A search of EMBASE, MEDLINE and CINAHL was performed up to May 2002 using the terms: asthma*, bronchial hyperreactivity*, respiratory sounds*, wheez*, obstructive lung disease* or obstructive airway disease*, and adrenergic antagonist*, sympatholytic* or adrenergic receptor block*.<AbstractText Label="SELECTION CRITERIA" NlmCategory="METHODS">Randomized, blinded, placebo-controlled trials of single dose or continued treatment of the effects of cardioselective beta-blockers in patients with reversible airway disease.<AbstractText Label="DATA COLLECTION AND ANALYSIS" NlmCategory="METHODS">Two independent reviewers extracted data from the selected articles, reconciling differences by consensus. Beta1-blockers were divided into those with or without intrinsic sympathomimetic activity (ISA). Interventions were: administration of single or continued beta1-blocker, and response to beta2-agonist given after the study drug.<AbstractText Label="MAIN RESULTS" NlmCategory="RESULTS">Nineteen studies on single-dose treatment and 10 studies on continued treatment met the inclusion criteria. Single dose cardioselective beta-blocker produced a 7.46% (95% CI 5.59, 9.32) reduction in FEV1, but with a 4.63% (95% CI 2.47, 6.78) increase in FEV1 with beta2-agonist, compared to placebo. Treatment lasting 3 - 28 days produced no change in FEV1 (-0.42%; 95% CI -3.74, 2.91), symptoms or inhaler use, whilst maintaining a 8.74% (95% CI 1.96, 15.52) response to beta2-agonist. There was no significant change in FEV1 treatment effect for those patients with COPD: single doses -5.28% (95% CI -10.03, -0.54%), continued treatment 1.07% (CI -3.3, 5.44. With continued treatment there was no significant difference in FEV1 response for beta1-blockers without ISA compared to those with IS: -3.22% (96%CI -7.79, 1.36) compared to 2.72% (95% CI -2.12, 7.59). Those without ISA produced a 12.0% increase in FEV1 after beta2-agonist administration compared to placebo (95%CI 4.12,19.87) while beta1-blockers with ISA produced no change compared to placebo (-0.60% [95%CI -13.93, 12.73). These results were obtained in a small number od studies of few patients. The difference was not significant.<AbstractText Label="REVIEWER'S CONCLUSIONS" NlmCategory="CONCLUSIONS">Cardioselective beta-blockers given in mild - moderate reversible airway disease or COPD, do not produce adverse respiratory effects in the short term. Given their demonstrated benefit in conditions such as heart failure, cardiac arrhythmias and hypertension, these agents should not be withheld from such patients, but long term safety (especially their impact during an acute exacerbation) still needs to be established. |
2,332,134 | Comparison of microsphere-equivalent blood flow (15O-water PET) and relative perfusion (99mTc-tetrofosmin SPECT) in myocardium showing metabolism-perfusion mismatch. | Myocardial perfusion imaging with (99m)Tc-tetrofosmin is based on the assumption of a linear correlation between myocardial blood flow (MBF) and tracer uptake. However, it is known that (99m)Tc-tetrofosmin uptake is directly related to energy-dependent transport processes, such as Na(+)/H(+) ion channel activity, as well as cellular and mitochondrial membrane potentials. Therefore, cellular alterations that affect these energy-dependent transport processes ought to influence (99m)Tc-tetrofosmin uptake independently of blood flow. Because metabolism ((18)F-FDG)-perfusion ((99m)Tc-tetrofosmin) mismatch myocardium (MPMM) reflects impaired but viable myocardium showing cellular alterations, MPMM was chosen to quantify the blood flow-independent effect of cellular alterations on (99m)Tc-tetrofosmin uptake. Therefore, we compared microsphere-equivalent MBF (MBF_micr; (15)O-water PET) and (99m)Tc-tetrofosmin uptake in MPMM and in "normal" myocardium.</AbstractText>Forty-two patients with severe coronary artery disease, referred for myocardial viability diagnostics, were examined using (18)F-FDG PET and (99m)Tc-tetrofosmin perfusion SPECT. Relative (18)F-FDG and (99m)Tc-tetrofosmin uptake values were calculated using 18 segments per patient. Normal myocardium and MPMM myocardium were classified using a previously validated (99m)Tc-tetrofosmin SPECT/(18)F-FDG PET score. In addition, (15)O-water PET was performed to assess kinetic-modeled MBF (MBF_kin), the water-perfusable tissue fraction (PTF), and the resulting MBF_micr (MBF_kin x PTF), which is comparable to tracer uptake values. (99m)Tc-tetrofosmin uptake and MBF_micr values were calculated for all normal and MPMM segments and averaged within their respective classifications.</AbstractText>Mean relative (99m)Tc-tetrofosmin uptake was 86% +/- 1% in normal myocardium and 56% +/- 1% in MPMM, showing a significant difference (P < 0.001), as was expected from the classification. Contrary to these findings, mean MBF_micr in MPMM myocardium was 0.60 +/- 0.03 mL x min(-1) x mL(-1), which did not significantly differ from normal myocardium (0.64 +/- 0.01 mL x min(-1) x mL(-1)). All values are given as mean +/- SEM.</AbstractText>Differences between reduced (99m)Tc-tetrofosmin uptake and the unchanged MBF_micr in MPMM myocardium suggest that the pathophysiologic basis of MPMM is not a blood flow reduction but cellular alterations that affect uptake and retention of (99m)Tc-tetrofosmin independently of blood flow. Therefore, it seems that perfusion deficits in MPMM myocardium are greatly overestimated by (99m)Tc-tetrofosmin and that it tends to give false-positive findings.</AbstractText> |
2,332,135 | Hyperhomocysteinemia: An emerging risk factor for cardiovascular disease. | There is considerable epidemiological evidence, which confirms the importance of plasma homocysteine as a powerful predictor of future risk of coronary heart disease and other complications of atherosclerosis. Treatment of hyperhomocysteinemia varies with the underlying cause. However, an inexpensive vitamin supplementation with folic acid, vitamin B12 and vitamin B 6 is generally effective in reducing homocysteine concentrations. Several randomised, controlled trials evaluating the effects of folic acid based supplements on homocysteine concentrations have been conducted over the last decade. In most patients, folic acid alone, and in combination of vitamin B12 and B6, has been shown to reduce homocysteine concentrations within four to six weeks after the initiation of therapy (34).However, no study has yet demonstrated that lowering of homocysteine by vitamin supplementation decreases the cardiovascular morbidity or mortality. Avoidance of excessive meat intake and increased consumption of fresh vegetables and fruits is a dietary measure, which has many health benefits, including a potential to reduce elevated homocysteine levels. The other reasonable approach is to determine levels of fasting homocysteine in high risk patients and it may be advisable to increase their intake of vitamin fortified foods and/or to suggest the daily use of supplemental vitamins. Several large scale randomised trials like Heart Outcomes Prevention Evaluation (HOPE-2) Study, Mcmaster University, Canada, Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SERCH), Clinical Trial Service Unit, Oxford, U.K, Cambridge Heart Antioxidant Study (CHAOS-2) University of Cambridge, U.K, Bergen Vitamin Study, University of Bergen Norway, Women's Antioxidant and Cardiovascular Disease Study (WACS) Harvard Medical School, U.S.A, Prevention with a combined inhibitor and folate in Coronary Heart Disease (PACIFIC) study, University of Sydney, Australia, and many others are ongoing to assess the effect of homocysteine-lowering by vitamin supplementation on risk of vascular disease. |
2,332,136 | Structural basis of inward rectification: cytoplasmic pore of the G protein-gated inward rectifier GIRK1 at 1.8 A resolution. | Inward rectifier K(+) channels govern the resting membrane voltage in many cells. Regulation of these ion channels via G protein-coupled receptor signaling underlies the control of heart rate and the actions of neurotransmitters in the central nervous system. We have determined the protein structure formed by the intracellular N- and C termini of the G protein-gated inward rectifier K(+) channel GIRK1 at 1.8 A resolution. A cytoplasmic pore, conserved among inward rectifier K(+) channels, extends the ion pathway to 60 A, nearly twice the length of a canonical transmembrane K(+) channel. The cytoplasmic pore is lined by acidic and hydrophobic amino acids, creating a favorable environment for polyamines, which block the pore. These results explain in structural and chemical terms the basis of inward rectification, and they also have implications for G protein regulation of GIRK channels. |
2,332,137 | Innate immune sensing of microbial infection: the mechanism and the therapeutic challenge. | Studies of sepsis conducted over the century have led to an understanding of many of the molecular events that take place during a severe infection. But what are the first events? Very recent genetic analyses have provided an answer to this question. Genetic studies have disclosed that bacterial endotoxin is sensed through a solitary biochemical pathway. At the heart of this pathway is the Toll-like receptor 4 (TLR4): one member of an ancient receptor family dedicated to the detection of infectious organisms. Most and perhaps all of the untoward effects of infection are initiated by the TLRs, ten of which are represented in humans. At the same time, it is known that TLRs are required to sense infection at its earliest stages, and thereby defeat it. The means to block TLR signal transduction is now at hand. Will this do good or harm? |
2,332,138 | Effect of agmatine on intracellular free calcium concentration in isolated rat ventricular myocytes. | The present study was to investigate the effects of agmatine (Agm) on free intracellular calcium concentration ([Ca(2+)]( i )) of isolated rat ventricular myocytes. [Ca(2+)]( i ) was measured by confocal microscopy in single rat ventricular myocytes which were dissociated by enzymatic dissociation method and loaded with Fluo 3-AM. The changes in [Ca(2+)]( i ) were represented by fluorescence intensity (FI) or relative fluorescence intensity (F/F(0)%). The results showed that the control level of FI value of single rat ventricular myocytes was 128.8+/-13.8 and 119.6+/-13.6 in the presence of normal Tyrode's solution containing Ca(2+) 1.0 mmol/L and Ca(2+)-free Tyrode's solution, respectively. There was no difference between these two groups (P>0.05). Agm 0.1, 1, and 10 mmol/L significantly reduced the [Ca(2+)]( i ) in both extracellular solutions in a concentration-dependent manner. The similar effect of Agm on [Ca(2+)]( i ) was also observed in the presence of EGTA 3 mmol/L. KCl 60 mmol/L, PE 30 micromol/L, and Bay-K-8644 10 micromol/L, all these substances induced [Ca(2+)]( i ) elevations in ventricular myocytes. Agm (0.1, 1, and 10 mmol/L) markedly inhibited the increase in [Ca(2+)]( i ) induced by KCl, phenylephrine (PE), and Bay-K-8644. When Ca(2+) waves were produced by increasing extracellular Ca(2+) concentration from 1 to 10 mmol/L, 1 mmol/L Agm could block the propagating waves of elevated [Ca(2+)]( i ), and reduce the velocity and duration of propagating waves. These results suggest that Agm possesses an inhibitory effects on [Ca(2+)]( i ) via blocking voltage-dependent Ca(2+) channel, and possibly by alleviating calcium release from SR in single isolated rat ventricular myocytes. |
2,332,139 | Ketamine differentially blocks sensory afferent synaptic transmission in medial nucleus tractus solitarius (mNTS). | Ketamine increases blood pressure and heart rate by unknown mechanisms, but studies suggest that an intact central nervous system and arterial baroreceptors are required. In the brain stem, medial nucleus tractus solitarius receives afferents from nodose neurons that initiate cardiovascular autonomic reflexes. Here, the authors assessed ketamine actions on afferent medial nucleus tractus solitarius synaptic transmission.</AbstractText>Ketamine was applied to horizontally sliced brain stems. Solitary tract (ST) stimulation evoked excitatory postsynaptic currents (eEPSCs) in medial nucleus tractus solitarius neurons. Capsaicin (200 nm) block of ST eEPSCs sorted neurons into sensitive (n = 19) and resistant (n = 23). In nodose ganglion slices, shocks to the peripheral vagal trunk activated afferent action potentials in sensory neurons classified by conduction velocities and capsaicin.</AbstractText>Ketamine potently (10-100 mciro m) blocked small, ST-evoked -methyl-d-aspartate synaptic currents found only in a subset of capsaicin-resistant neurons (6 of 12). Surprisingly, ketamine reversibly inhibited ST eEPSC amplitudes and induced synaptic failure at lower concentrations in capsaicin-sensitive than in capsaicin-resistant neurons (P < 0.005; n = 11 and 11). Spontaneous EPSCs using non- -methyl-d-aspartate receptors were insensitive even to 1-3 mm ketamine, suggesting that ST responses were blocked presynaptically. Similarly, ketamine blocked C-type action potential conduction at lower concentrations than A-type nodose sensory neurons.</AbstractText>The authors conclude that ketamine inhibits postsynaptic -methyl-d-aspartate receptors and presynaptic afferent processes in medial nucleus tractus solitarius. Unexpectedly, capsaicin-sensitive (C-type), unmyelinated afferents are significantly more susceptible to block than capsaicin-resistant (A-type), myelinated afferents. This differentiation may be related to tetrodotoxin-resistant sodium currents. Since C-type afferents mediate powerful arterial baroreflexes effects, these differential actions may contribute to ketamine-induced cardiovascular dysfunction.</AbstractText> |
2,332,140 | Comparison of lidocaine and compression for velvet antler analgesia in wapiti. | This research compared ring block lidocaine anesthesia (L) and compression (C) for velvet antler removal in elk. Thirty-two wapiti were given 1 mg/kg body weight of zuclopenthixol acetate. The next day, they were restrained in a hydraulic chute and given either a compression device or a lidocaine ring block on the antler pedicle. Behavioral and physiological responses to treatment application and antler removal were recorded, and blood was collected for cortisol analysis. During application of L and C, increases in mean heart rate and systolic arterial blood pressure were greater in the C treatment group (P < 0.05, and P = 0.05, respectively). When antler was removed, more behavioral responses occurred in the C treatment group (P = 0.02) and its median behavior score was higher (P = 0.03). Mean heart rates increased for both treatment groups when antlers were removed (P < 0.01). It was concluded that application of C may be painful, and that C was not as effective as L for analgesia for velvet antler removal. |
2,332,141 | Down-regulation of voltage-gated Ca2+ channels by neuronal calcium sensor-1 is beta subunit-specific. | Neuronal Ca(2+) sensor protein-1 (NCS-1) is a member of the Ca(2+) binding protein family, with three functional Ca(2+) binding EF-hands and an N-terminal myristoylation site. NCS-1 is expressed in brain and heart during embryonic and postnatal development. In neurons, NCS-1 facilitates neurotransmitter release, but both inhibition and facilitation of the Ca(2+) current amplitude have been reported. In heart, NCS-1 co-immunoprecipitates with K(+) channels and modulates their activity, but the potential effects of NCS-1 on cardiac Ca(2+) channels have not been investigated. To directly assess the effect of NCS-1 on the various types of Ca(2+) channels we have co-expressed NCS-1 in Xenopus oocytes, with Ca(V)1.2, Ca(V)2.1, and Ca(V)2.2 Ca(2+) channels, using various subunit combinations. The major effect of NCS-1 was to decrease Ca(2+) current amplitude, recorded with the three different types of alpha(1) subunit. When expressed with Ca(V)2.1, the depression of Ca(2+) current amplitude induced by NCS-1 was dependent upon the identity of the beta subunit expressed, with no block recorded without beta subunit or with the beta(3) subunit. Current-voltage and inactivation curves were also slightly modified and displayed a different specificity toward the beta subunits. Taken together, these data suggest that NCS-1 is able to modulate cardiac and neuronal voltage-gated Ca(2+) channels in a beta subunit specific manner. |
2,332,142 | Comparison of epidural, continuous femoral block and intraarticular analgesia after anterior cruciate ligament reconstruction. | The purpose of this study was to compare three locoregional techniques of pain management after arthroscopic anterior cruciate ligament reconstruction (ACLR).</AbstractText>Sixty ASA I-II subjects were enrolled after obtaining written informed consent. Patients were randomly allocated to three groups of 20 subjects. The first group (EPI) received epidural ropivacaine 0.2% plus sufentanil 0.2 micro g ml-1, at 5 ml h-1. Patients in the second group (CFB) were given a continuous infusion of the same analgesic mixture through a femoral catheter. The third group (IA) received a continuous intraarticular infusion of ropivacaine 0.2% plus sufentanil 0.2 micro g ml-1, at 5 ml h-1. All subjects were allowed PCA boluses of 5 ml of local anesthetic. Analgesia was assessed for 36 h after the end of surgery by means of a visual analog scale (VAS) and a verbal scale (VS), as well as the number of PCA boluses administered and the amount of supplementary i.v. ketorolac, if given.</AbstractText>The VAS and VS scores were significantly higher in group IA during the 24 h following surgery. Ketorolac requirement was higher in group IA throughout the postoperative observation. Adverse effects were similar in all groups except for urinary retention, which was significantly more frequent in group EPI.</AbstractText>We conclude that either epidural or continuous femoral nerve block provide adequate pain relief in patients who undergo ACLR, whereas intraarticular analgesia seems unable to cope satisfactorily with the analgesic requirements of this surgical procedure.</AbstractText> |
2,332,143 | The effect of nitrous oxide on cerebral blood flow velocity in children anaesthetised with desflurane. | The aim of this study was to determine the effect of nitrous oxide on cerebral blood flow velocity in children anaesthetised with desflurane. Eighteen healthy children scheduled for elective surgery were enrolled into the study. Anaesthesia was induced using sevoflurane, and a caudal block was performed following tracheal intubation. Anaesthesia was maintained with 1 age-adjusted MAC desflurane. A transcranial Doppler probe was used to measure middle cerebral artery blood flow velocity. Each patient was randomised to receive a sequence of either air/nitrous oxide/air or nitrous oxide/air/nitrous oxide in 30% oxygen. Fifteen minutes after each change in the nitrous oxide concentration, three measurements of cerebral blood flow velocity, blood pressure and heart rate were recorded. Neither the addition nor removal of nitrous oxide caused any significant changes in middle cerebral artery blood flow velocity, heart rate or blood pressure. This may be due to a more potent cerebral vasodilatory effect of desflurane in children. |
2,332,144 | [Functional analysis of Na+/Ca2+ exchanger using novel drugs and genetically engineered mice]. | The Na+/Ca2+ exchanger (NCX) is an ion transporter that exchanges Na+ and Ca2+ in either Ca2+ efflux or Ca2+ influx mode, depending on the ion gradients across the plasma membrane and the membrane potential. In heart, smooth muscle cells, neurons, and nephron cells, this exchanger is thought to play an important role in the regulation of intracellular Ca2+ concentration. We aim at clarifying the function and pathologic state of the exchanger by developing NCX inhibitors and NCX-engineered mice as experimental tools, and finally establishing a novel therapeutic method using the exchanger as a molecular target. First, we present the pharmacological profiles and the molecular mechanism of NCX inhibitors (KB-R7943, SEA0400, SN-6) recently developed. Our results suggest that these NCX inhibitors preferentially block the Ca2+ influx mode rather than the Ca2+ efflux mode. Further mutational analysis reveals that these NCX inhibitors have different interaction domains in the exchanger molecule. Secondly, we present that heterozygous NCX1-knockout mice are useful as a low NCX1-expressing animal model. From comparative experiments with heterozygous and wild-type mice and pharmacological experiments of the NCX inhibitors, we provided an evidence that NCX1 functionally contributes to maintaining the vascular tension. |
2,332,145 | Interaction between naltrexone and oral THC in heavy marijuana smokers. | Studies in non-human animals suggest that opioid antagonists block the reinforcing effects of cannabinoids.</AbstractText>The present studies in humans investigated how naltrexone modulates (1) the subjective and physiological effects of oral THC in comparison to methadone, (2) the reinforcing effects of oral THC, and (3) plasma levels of oral THC.</AbstractText>In study 1, marijuana smokers (n=9) received naltrexone (0, 50 mg) followed 30 min later by THC (0, 15, 30 mg) or methadone (5, 10 mg). Subjective effects, task performance, pupillary diameter, and cardiovascular parameters were measured repeatedly. In study 2a, marijuana smokers (n=23) were randomly assigned to one THC dose condition (0, 15 or 30 mg). One set of color-coded capsules containing THC and active naltrexone (50 mg) was given in one session, while another set of color-coded capsules containing THC and placebo naltrexone was given in another session. In the final three sessions, participants chose which color capsules they would receive. In study 2b, a subset of participants from study 2a (n=7) received naltrexone (0, 50 mg) 30 min prior to oral THC (30 mg) administration, and blood was drawn repeatedly.</AbstractText>Pretreatment with naltrexone significantly increased many of the "positive" subjective effects of oral THC (30 mg) e.g. ratings of Good Drug Effect and Capsule Liking. Naltrexone tended to increase the reinforcing effects of oral THC (30 mg), as indicated by performance in a drug choice test. Naltrexone did not alter plasma THC levels.</AbstractText>These studies demonstrate that naltrexone increases the subjective effects of oral THC. Thus, oral THC's effects are enhanced rather than antagonized by opioid receptor blockade in heavy marijuana smokers.</AbstractText> |
2,332,146 | Short-term variability of respiration and sleep during unattended nonlaboratory polysomnography--the Sleep Heart Health Study. [corrected]. | To determine the short-term variability of indices of disturbed respiration and sleep during 2 nights of unattended nonlaboratory polysomnography conducted several months apart.</AbstractText>Participants were randomly selected using a block design with stratification on preliminary estimates of 2 criteria: respiratory disturbance index [RDI3% (apnea or hypopnea events associated with > or = 3% O2 desaturation): < 15/hour total sleep time, > or = 15/hour total sleep time] and sleep efficiency (SEff: < 85% and > or = 85%). The RDI and sleep data from initial and repeated polysomnography were compared.</AbstractText>NA.</AbstractText>A subset of 99 participants in the Sleep Heart Health Study who agreed to have a repeat polysomnogram within 4 months of their original study.</AbstractText>NA.</AbstractText>Acceptable repeat polysomnograms were obtained in 91 subjects (mean study interval: 77 +/- 18 [sd] days; range: 31-112 days). There was no significant bias in RDI between study nights using several different RDI definitions including RDI3% and RDI4% (apnea or hypopnea events associated with > or = 4% O2 desaturation). Variability between studies estimated using intraclass correlations (ICC) ranged from 0.77 to 0.81. For subjects with a RDI3% < 15, variability increased as a function of increasing RDI, but for those with a RDI3% > or = 15, variability was constant. Body mass index, SEff, gender, or age did not directly predict RDI variability. Using RDI4% cutpoints of < or = 5, < or = 10 and < or = 15 events per hour of sleep demonstrated that 79.1%, 85.7%, and 87.9% of subjects, respectively, had the same classification of SDB status on both nights of study. There also was no significant bias in sleep staging, sleep efficiency, or arousal index between studies. However, variability was greater with ICC values ranging from 0.37 (% time in REM) to 0.76 (arousal index).</AbstractText>In the Sleep Heart Health Study, accurate estimates of the severity of sleep-disordered breathing and the quality of sleep were obtained from a single night of unattended nonlaboratory polysomnography. These findings may be applicable to other large epidemiologic studies provided that similar recording techniques and quality-assurance procedures are followed.</AbstractText> |
2,332,147 | Bursting in leech heart interneurons: cell-autonomous and network-based mechanisms. | Rhythmic activity within the heartbeat pattern generator of the medicinal leech is based on the alternating bursting of mutually inhibitory pairs of oscillator heart interneurons (half-center oscillators). Bicuculline methiodide has been shown to block mutual inhibition between these interneurons and to cause them to spike tonically while recorded intracellularly (Schmidt and Calabrese, 1992). Using extracellular recording techniques, we show here that oscillator and premotor heart interneurons continue to burst when pharmacologically isolated with bicuculline, although the bursting is not robust in some preparations. We propose that a nonspecific leak current introduced by the intracellular microelectrode suppresses endogenous bursting activity to account for the discrepancy with results using intracellular recording. A two-parameter bifurcation diagram (E(leak) vs g(leak)) of a mathematical model of a single heart interneuron shows a narrow stripe of parameter values where bursting occurs, separating large zones of tonic spiking and silence. A similar analysis performed for a half-center oscillator model outlined a much larger area of bursting. Bursting in the half-center oscillator model is also less sensitive to variation in the maximal conductances of voltage-gated currents than in the single-neuron model. Thus, in addition to ensuring appropriate bursting characteristics such as period, phase, and duty cycles, the half-center configuration enhances oscillation robustness, making them less susceptible to random or imposed changes in membrane parameters. Endogenous bursting, in turn, ensures appropriate bursting if the strength of mutual inhibition is weakened and limits the minimum period of the half-center oscillator to a period near that of the single neuron. |
2,332,148 | [Sympathetic block in dogs by a local anesthetic with addition of clonidine]. | The aim of this study is to examine the duration and magnitude of vasodilating effect induced by sympathetic block with the addition of different concentrations of clonidine to mepivacaine.</AbstractText>In dogs, mean arterial pressure (MAP), heart rate (HR), and right as well as left brachial artery blood flow (BABF) were measured before and after stellate ganglion block (SGB) used as sympathetic block. The experimental protocol was designed as follows: 1) Group 1: left SGB using 0.5% mepivacaine 1 ml (n = 6), 2) Group 2: left SGB using the addition of clonidine 0.5 microgram to 0.5% mepivacaine 1 ml (n = 6), 3) Group 3: left SGB using the addition of clonidine 5 micrograms to 0.5% mepivacaine 1 ml (n = 6).</AbstractText>MAP showed no significant change throughout the study in the groups 1 and 2. In the group 3, MAP was lower than that of the group 1. HR showed no significant change throughout the study in the three groups. Left BABF increased significantly after left SGB in the three groups. The duration of increased BABF in the group 2 was the longest, and that in the group 3 was the shortest among them. Right BABF after left SGB decreased significantly throughout the study in the three groups, and the magnitude of the decrease in BABF in the group 3 was the highest among them.</AbstractText>Sympathetic block with the addition of clonidine to local anesthetics increases both duration and magnitude of its vasodilating effect. However, sympathetic block with the addition of higher doses of clonidine to local anesthetics may induce shorter duration and lower magnitude of vasodilating effect compared with local anesthetics alone.</AbstractText> |
2,332,149 | Localization of sodium channels in intercalated disks modulates cardiac conduction. | It is well known that the sodium current (I(Na)) and the degree of gap-junctional electrical coupling are the key determinants of action potential (AP) conduction in cardiac tissue. Immunohistochemical studies have shown that sodium channels (NaChs) are preferentially located in intercalated disks (IDs). Using dual immunocytochemical staining, we confirmed the colocalization of NaChs with connexin43 in cultures of neonatal rat ventricular myocytes. In mathematical simulations of conduction using the Luo-Rudy dynamic model of the ventricular AP, we assessed the hypothesis that conduction could be modulated by the preferential localization of NaChs in IDs. Localization of I(Na) at the ID caused a large negative potential in the intercellular cleft, which influenced conduction in two opposing ways, depending on the degree of electrical coupling: (1) for normal and moderately reduced coupling, the negative cleft potential led to a large overshoot of the transmembrane potential resulting in a decreased driving force for I(Na) itself (self-attenuation), which slowed conduction; (2) for greatly reduced coupling (<10%), the negative cleft potential induced by I(Na) in the prejunctional membrane led to suprathreshold depolarization of the postjunctional membrane, which facilitated and accelerated conduction. When cleft potential effects were not incorporated, conduction was not significantly affected by the ID localization of I(Na). By enhancing conduction through the establishment of cleft potentials, the localization of NaChs in IDs might protect the myocardium from conduction block, very slow conduction, and microreentry under conditions of greatly reduced coupling. Conversely, by supporting moderately slow conduction, this mechanism could also promote arrhythmias. |
2,332,150 | Embryonal cardiotoxicity of the Helicobacter pylori lipopolysaccharide. | Helicobacter (H.) pylori is the causative agent of the peptic ulcer disease and a co-factor in the development of gastric malignancies. Recently, it has been maintained that chronic H. pylori infections in adults are linked to a higher risk of coronary heart diseases. In this respect, the acute toxic effects of the H. pylori lipopolysaccharide (LPS) on embryonal cardiomyocytes at different developmental stages was evaluated. White Leghorn chick embryos and smooth (S)--form NCTC 11637 strain H. pylori organisms were used. Both whole heath-killed H. pylori suspensions (3.10(6) bacteria/egg) and isolated S-LPS (500 ng/egg) or S-Lipid A (500 ng/egg) were non-lethal to 4-day embryos, becoming moderately lethal (5% to 30%) to 6- and 8-day embryos and highly lethal (> 90%) to 10- to 17-day embryos. The contractile activity of isolated atrial fragments from 10-day embryos was completely inhibited, within 5 min, following treatments with heath-killed H. pylori (3 x 10(6)/ml), or S-LPS (500 ng/ml), or S-Lipid A (500 ng/ml); the block determined by S-LPS and S-Lipid A was irreversible, while the block by bacterial suspensions was completely reversible upon withdrawal. Following a 24-hour treatment with S-LPS or S-Lipid A of single-cell cultures of cardiomyocytes (isolated from 10-day embryos) a dose-dependent cell loss was observed, as assessed by total protein dosage and direct counting of adherent cells. Propidium Iodide/Annexin V FACS-analysis confirmed the occurrence of cellular necrosis, but did not show any evidence of apoptotic processes. The release of superoxide anion radicals by cultured cardiomyocytes was as follows: S-Lipid A (25 micrograms/ml) > S-LPS (25 micrograms/ml) > heath killed H. pylori suspensions (3 x 10(6)/ml); control cultures did not release detectable amounts of superoxide anion radicals. Furthermore, cultured cardiomyocytes produced increased amounts of NO (N-monomethylarginine-inhibitable) following stimulation with S-LPS (25 micrograms/ml) or S-Lipid A (25 micrograms/ml) (but not heath killed H. pylori 3 x 10(6)/ml suspensions). Under all the above experimental conditions S-polysaccharide proved to be non-toxic. Concluding, H. pylori LPS is relatively non-toxic to the less differentiated cardiomyocytes; cardiomyocytes which are more advanced in their biochemical differentiation become highly sensitive to LPS and produce ROS and NO. ROS are probably responsible for the early toxic actions, while both ROS and NO are likely to be involved in the later degenerative/necrotic effects. |
2,332,151 | Pregnancy outcome in 100 women with autoimmune diseases and anti-Ro/SSA antibodies: a prospective controlled study. | Anti-Ro/SSA antibodies are associated with neonatal lupus but are also considered a possible cause for unexplained pregnancy loss and adverse pregnancy outcome. In a large multicentres cohort study we have prospectively followed 100 anti-Ro/SSA positive women (53 systemic lupus erythematosus (SLE)) during their 122 pregnancies and 107 anti-Ro/SSA negative women (58 SLE) (140 pregnancies). Anti-Ro/SSA antibodies were tested by immunoblot and counterimunoelectrophoresis. Mean gestational age at delivery (38 vs 37.9 weeks), prevalence of pregnancy loss (9.9 vs 18.6%), preterm birth (21.3 vs 13.9%), cesarean sections (49.2 vs 53.4%), premature rupture of membranes (4.9 vs 8.1%), preeclampsia (6.6 vs 8%), intrauterine growth retardation (0 vs 2.3%)and newborns small for gestational age (11.5 vs 5.8%) were similar in anti-Ro/SSA positive and negative SLE mothers; findings were similar in non-SLE women. Two cases of congenital heart block were observed out of 100 anti-Ro/SSA positive women. In conclusion, anti-Ro/SSA antibodies are responsible for congenital heart block but do not affect other pregnancy outcomes, both in SLE and in non-SLE women. The general outcome of these pregnancies is now very good, ifprospectively followed by multidisciplinary teams with ample experience in this field. |
2,332,152 | Multigrid block preconditioning for a coupled system of partial differential equations modeling the electrical activity in the heart. | The electrical activity of the heart may be modeled with a system of partial differential equations (PDEs) known as the bidomain model. Computer simulations based on these equations may become a helpful tool to understand the relationship between changes in the electrical field and various heart diseases. Because of the rapid variations in the electrical field, sufficiently accurate simulations require a fine-scale discretization of the equations. For realistic geometries this leads to a large number of grid points and consequently large linear systems to be solved for each time step. In this paper, we present a fully coupled discretization of the bidomain model, leading to a block structured linear system. We take advantage of the block structure to construct an efficient preconditioner for the linear system, by combining multigrid with an operator splitting technique. |
2,332,153 | Effects of the venom of a Mygalomorph spider (Lasiodora sp.) on the isolated rat heart. | We studied the effect of the venom of the Brazilian spider, Lasiodora sp. (Mygalomorphae, Theraphosidae), on force generation and electrical activity in the isolated rat heart. Previous work showed that this venom is excitotoxic to excitable cells due to Na(+) channel gating modifier activity [Toxicon 39 (2001) 991]. In the isolated heart, the venom (10-100 microg bolus administration) caused a dose-dependent bradycardia, with transient cardiac arrest and rhythm disturbances. The electrocardiogram showed that the reduction of heart rate was due to sinus bradycardia, sinus arrest and partial or complete A-V block. All of the effects were reversible upon washout of the venom. The effect of the venom was potentiated by the anticholinesterase neostigmine (3.3 microM), suppressed by the muscarinic acetylcholine receptor antagonist atropine (1.4 microM), and inhibited by the vesicular acetylcholine transporter inhibitor (-)-vesamicol (10 microM). Tetrodotoxin (200 nM) did not inhibit the effect of the venom. Together, these data suggest that this Lasiodora venom evokes vesicular release of acetylcholine from parasympathetic nerve terminals by activating tetrodotoxin-resistant Na(+) channels. |
2,332,154 | Involvement of the parabrachial nucleus in the pressor response to chemoreflex activation in awake rats. | Activation of the chemoreflex with potassium cyanide (KCN, 40 microg/rat, i.v.) in awake rats produces pressor and bradycardic responses as well as a tachypneic response. In the present study, we evaluated the involvement of the periaqueductal gray matter (PAG) and the parabrachial nucleus (PBN) in the neural pathways of the cardiovascular responses to chemoreflex activation. The cardiovascular responses to chemoreflex activation were evaluated before and after bilateral microinjection of 2% lidocaine, a local anesthetic, into the PBN or PAG in order to block in a reversible manner the neuronal activity and axonal conduction of fibers of passage in these areas. The data show that the pressor response to chemoreflex activation 3 min after bilateral microinjection of lidocaine into the dorsolateral aspect of the PBN was significantly reduced in comparison to the control response (32 +/- 5 vs. 48 +/- 4 mm Hg, n = 7), with no significant changes in the bradycardic responses. The effect of lidocaine was reversible since the pressor response was back to control levels 15 min after microinjection of this anesthetic. Bilateral microinjections of lidocaine into the dorsolateral (n = 11) or lateral (n = 8) columns of the PAG in distinct groups of rats produced no significant changes in the pressor or bradycardic responses of the chemoreflex. These data indicate that the PBN is part of the neuronal pathways involved in the sympathoexcitatory component of the chemoreflex while the PAG is not. |
2,332,155 | Electrophysiological effects of morphine in an in vitro model of the 'border zone' between normal and ischaemic-reperfused guinea-pig myocardium. | Morphine is commonly used in clinical practice in pain management. Although morphine has been shown to precondition the myocardium, its effects on action potential parameters and ischaemia-reperfusion-induced arrhythmias and conduction blocks remain unknown.</AbstractText>In a double-chamber bath, guinea-pig right ventricular muscle strips were subjected partly to normal conditions and partly to 30 min of simulated ischaemia (hypoxia, hyperkalaemia, acidosis, and lack of nutritional substrate) followed by 30 min of reperfusion. Action potential parameters were recorded continuously in the normal zone and in the ischaemic- reperfused zone. Spontaneous arrhythmias and conduction blocks were noted. The electro physiological effects of morphine were studied at 0.01 and 0.1 micro M.</AbstractText>In control conditions, morphine did not modify action potential parameters of resting membrane potential, maximal upstroke velocity (V(max)), action potential amplitude (APA) and action potential duration at 50 and 90% of repolarization. Morphine reduced ischaemia-induced depolarization and lessened the ischaemia-induced decrease in APA and V(max). Morphine significantly decreased the occurrence of conduction block during simulated ischaemia (20% at 0.01 and 0.1 micro M vs 67% in the control group, P<0.05) and reperfusion-induced arrhythmias (40% at 0.01 micro M and 30% at 0.1 micro M vs 92% in the control group, P<0.05).</AbstractText>In ischaemic-reperfused guinea-pig myocardium, morphine at clinically relevant concentrations decreased ischaemia-induced conduction blocks and reperfusion-induced ventricular arrhythmias.</AbstractText> |
2,332,156 | Simultaneous and rapid analysis of cyclosporin A and creatinine in finger prick blood samples using liquid chromatography tandem mass spectrometry and its application in C2 monitoring. | A simple and rapid liquid chromatography tandem mass spectrometry (LC-MS/MS) method for the simultaneous analysis of cyclosporin A (CsA) and creatinine using capillary blood has been developed. Venous and capillary blood samples were taken predose and at C2 from 65 heart and lung transplant recipients (65 x 4 samples). For comparisons, serum creatinine and blood CsA concentrations were measured by the Jaffe and EMIT methods, respectively, using an Olympus AU600 analyzer. For the LC-MS/MS assay, samples were prepared in a 96 x 700-microL well block by adding 10 microL of blood (or serum) to 40 microL of 0.1 mol/L zinc sulphate solution containing deuterated creatinine internal standard. Proteins were precipitated by adding 100 microL acetonitrile containing ascomycin internal standard. After vigorous mixing and centrifugation, 5 microL of the supernatant was injected into the LC-MS/MS system. A Waters 2795 high-performance liquid chromatography (HPLC) system was used to elute a C18 cartridge (3 mm x 4 mm) at 0.6 mL/min with a step gradient of 50-100% methanol containing 2 mmol/L ammonium acetate and 0.1% (v/v) formic acid. The column was maintained at 55 degrees C, and the retention times were creatinine, 0.4 minutes; ascomycin, 0.98 minutes; and CsA, 1.2 minutes. Cycle time was 2.5 minutes, injection to injection. The analytes were monitored using a Quattro microtandem mass spectrometer operated in multiple reaction monitoring mode using the following transitions: creatinine, m/z 114>44; d3-creatinine (IS), m/z 117>47; ascomycin (IS), m/z 809>756; and CsA, m/z 1,220>1,203. Assay characteristics were CsA intraassay CV, 3.6-3.0% (33-1,500 microg/L); CsA interassay CV, 6.7-2.5% (10-5,000 microg/L); LC-MS/MS capillary [CsA] = 0.99 x LC-MS/MS venous [CsA] - 4.2, R = 0.98; and LC-MS/MS venous [CsA] = 0.93 x EMIT venous [CsA] + 2.9, R = 0.98. Creatinine intraassay CV, 6.6-2.5% (20-720 micromol/L); interassay CV, 5.7-3.3% (80-590 micromol/L); LC-MS/MS capillary [creatinine] = 0.99 Jaffe plasma [creatinine] -42.6, R = 0.87. Total time for the preparation and analysis of 30 samples was approximately 2 hours. This assay will provide a flexible, robust, and cost-effective solution for the monitoring of CsA and creatinine in transplant recipients with potential applications in pediatric medicine and pharmacokinetic studies, in which frequent sampling is required. |
2,332,157 | Programmed death-1 targeting can promote allograft survival. | The recently identified CD28 homolog and costimulatory molecule programmed death-1 (PD-1) and its ligands, PD-L1 and PD-L2, which are homologs of B7, constitute an inhibitory regulatory pathway of potential therapeutic use in immune-mediated diseases. We examined the expression and functions of PD-1 and its ligands in experimental cardiac allograft rejection. In initial studies, we found that most normal tissues and cardiac isografts had minimal expression of PD-1, PD-L1, or PD-L2, but intragraft induction of all three molecules occurred during development of cardiac allograft rejection. Intragraft expression of all three genes was maintained despite therapy with cyclosporin A or rapamycin, but was prevented in the early posttransplant period by costimulation blockade using CD154 or anti-inducible costimulator mAb. We prepared PD-L1.Ig and PD-L2.Ig fusion proteins and showed that each bound to activated PD-1(+) T cells and inhibited T cell functions in vitro, thereby allowing us to test the effects of PD-1 targeting on allograft survival in vivo. Neither agent alone modulated allograft rejection in wild-type recipients. However, use of PD-L1.Ig administration in CD28(-/-) recipients, or in conjunction with immunosuppression in fully MHC-disparate combinations, markedly prolonged cardiac allograft survival, in some cases causing permanent engraftment, and was accompanied by reduced intragraft expression of IFN-gamma and IFN-gamma-induced chemokines. PD-L1.Ig use also prevented development of transplant arteriosclerosis post-CD154 mAb therapy. These data show that when combined with limited immunosuppression, or in the context of submaximal TCR or costimulatory signals, targeting of PD-1 can block allograft rejection and modulate T and B cell-dependent pathologic immune responses in vivo. |
2,332,158 | Conduction block in one-dimensional heart fibers. | We present a nonlinear dynamical systems analysis of the transition to conduction block in one-dimensional cardiac fibers. We study a simple model of wave propagation in heart tissue that depends only on the recovery of action potential duration and conduction velocity. If the recovery function has slope >or=1 and the velocity recovery function is nonconstant, rapid activation causes dynamical heterogeneity and finally conduction block away from the activation site. This dynamical mechanism may play a role in the initiation and breakup of spiral waves in excitable media. |
2,332,159 | Spinal anaesthesia for inguinal herniotomy in preterm infants sedated with nitrous oxide: a comparison of lumbar puncture in the lateral or sitting position. | This study compares spinal anaesthesia for inguinal herniotomy in preterm infants in the lateral or sitting position. Thirty patients were randomly divided into two equal groups. One hour before spinal anaesthesia, a eutetic mixture of local anaesthetic cream was applied to the lower lumbar spine. Sedation with nitrous oxide 50% in oxygen was given to all patients before and during induction of spinal anaesthesia, and throughout surgery. Lumbar punctures were performed at the L4-5 interspace using a 2.5 cm 22 G needle. Isobaric bupivacaine 0.5% with epinephrine 1 : 200 000 at a bupivacaine dose of 1 mg.kg-1 was injected in the lateral or sitting position. Measurements included heart rate, blood pressure, oxygen saturation, maximum sensory block height and duration of motor block and analgesia. There were no statistically significant differences between the groups in any measured parameters. Median [range] maximum block height was T5[T4-T7] in the lateral group and T5[T4-T5] in the sitting group. The median [range] duration of motor blockade was 67 [50-85] min in the lateral group and 63 [50-80] min in the sitting group. Our results indicate that in preterm infants sedated with nitrous oxide, spinal anaesthesia for inguinal herniotomy performed with isobaric bupivacaine 0.5% at a dose 1.0 mg.kg-1 in the lateral or sitting position is equally effective and is associated with minimal side effects. |
2,332,160 | F11-receptor (F11R/JAM) mediates platelet adhesion to endothelial cells: role in inflammatory thrombosis. | The F11 receptor (F11R) is a cell adhesion molecule (CAM), member of the immunoglobulin superfamily found on the surface of human platelets, and determined to play a role in platelet aggregation, secretion, adhesion and spreading. The same molecule is present also at tight junctions of endothelial cells (EC) where it is known as JAM and acts as a CAM through homophilic interactions. The role of F11R/JAM in the interaction of platelets with endothelial cells was investigated in the current studies. We report here that washed human platelets adhere specifically to a matrix made of immobilized, recombinant sF11R. Furthermore, platelets adhere to cytokine- (TNF-alpha, INF-gamma) stimulated human umbilical vein endothelial cells (HUVEC), and approximately 40-60% of the adhesive force is exerted by homophilic interactions between the F11R of platelets and EC. This is evidenced by the inhibition of platelet adhesion to endothelial cells by recombinant soluble form of the F11R, and by two F11R peptides with amino acid sequences of the N-terminal region, and in the 1(st) Ig fold of the F11R, respectively. This study suggests a role for F11R in the adhesion of platelets to cytokine-inflamed endothelial cells and thus in thrombosis and atherosclerosis induced in non-denuded blood vessels by inflammatory processes. Agents that block the F11R-mediated adhesion of platelets to EC may be of therapeutic value in controlling thrombosis and preventing heart attacks and stroke. |
2,332,161 | The involvement of nervous and some inflammatory response mechanisms in the acute snuff-induced gingival hyperaemia in humans. | Tobacco users and especially cigarette smokers are at higher risk than non-smokers for periodontal disease. The pathogenic mechanism has been proposed to be the vasoconstrictive properties of nicotine, with reduced gingival blood flow (GBF) as a contributing factor in the development of periodontal disease. However, in a previous study in humans, we found GBF to increase in response to acute exposure to snuff. The present study was designed to investigate whether the tobacco-induced acute GBF increase is dependent on intact nervous conduction. We further investigated the effect of piroxicam (NSAID) and dexchlorpheniramin (DCPA) (antihistamine) on the snuff-induced responses in the gingiva, to see if chemical mediators of inflammation also influenced the response.</AbstractText>Laser Doppler flowmetry (LDF) was used to measure gingival blood flow bilaterally in the buccal maxillary gingiva, in the forehead skin and in the thumb. Also arterial blood pressure (BP) and heart rate (HR) were monitored. Infraorbital nerve block anaesthesia (INB), superficial mucosal anaesthesia, 20 mg piroxicam or 2 mg DCPA were used in combination with snuff to study the vascular responses to 500 mg snuff (1% nicotine).</AbstractText>Snuff induced a rapid increase in GBF that was higher than the increase in BP, indicating an active vasodilatation. The snuff-induced vasodilatation was partly blocked by INB and more so by superficial mucosal anaesthesia. Piroxicam and DCPA exerted diverse effects on vascular homeostasis but had no effect on the snuff-induced vasodilatation in the gingiva.</AbstractText>The results of this study confirm that snuff induces local gingival vasodilatation, and imply that this vasodilatation most likely is a summation of responses due to both autonomic and antidromic reflex mechanisms. We further discuss the possible involvement of the nervously mediated effects of tobacco and nicotine on vascular homeostasis and in tobacco-associated periodontitis.</AbstractText> |
2,332,162 | Just the beginning: novel functions for angiotensin-converting enzymes. | Cardiovascular disease is predicted to be the commonest cause of death worldwide by the year 2020. Diabetes, smoking and hypertension are the main risk factors. The renin-angiotensin system plays a key role in regulating blood pressure and fluid and electrolyte homeostasis in mammals. The discovery of specific drugs that block either the key enzyme of the renin-angiotensin system, angiotensin-converting enzyme (ACE), or the receptor for its main effector angiotensin II, was a major step forward in the treatment of hypertension and heart failure. In recent years, however, the renin-angiotensin system has been shown to be a far more complex system than initially thought. It has become clear that additional peptide mediators are involved. Furthermore, a new ACE, angiotensin-converting enzyme 2 (ACE2), has been discovered which appears to negatively regulate the renin-angiotensin system. In the heart, ACE2 deficiency results in severe impairment of cardiac contractility and upregulation of hypoxia-induced genes. We shall discuss the interplay of the various effector peptides generated by angiotensin-converting enzymes ACE and ACE2, highlighting the role of ACE2 as a negative regulator of the renin-angiotensin system. |
2,332,163 | Major complications of regional anesthesia in France: The SOS Regional Anesthesia Hotline Service. | Several previous surveys have estimated the rate of major complications that occur after regional anesthesia. However, because of the increase in the use of regional anesthesia in recent years and because of the introduction of new techniques, reappraisal of the incidence and the characteristics of major complications is useful.</AbstractText>All French anesthesiologists were invited to participate in this 10-month prospective survey based on (1) voluntary reporting of major complications related to regional anesthesia occurring during the study period using a telephone hotline service available 24 h a day and managed by three experts, and (2) voluntary reporting of the number and type of regional anesthesia procedures performed using pocket booklets. The service was free of charge for participants.</AbstractText>The participants (n = 487) reported 56 major complications in 158,083 regional anesthesia procedures performed (3.5/10,000). Four deaths were reported. Cardiac arrest occurred after spinal anesthesia (n = 10; 2.7/10,000) and posterior lumbar plexus block (n = 1; 80/10,000). Systemic local anesthetic toxicity consisted of seizures only, without cardiac toxicity. Lidocaine spinal anesthesia was associated with more neurologic complications than bupivacaine spinal anesthesia (14.4/10,000 vs. 2.2/10,000). Most neurologic complications were transient. Among 12 that occurred after peripheral nerve blocks, 9 occurred in patients in whom a nerve stimulator had been used.</AbstractText>This prospective survey based on a free hotline permanent telephone service allowed us to estimate the incidence of major complications related to regional anesthesia and to provide a detailed analysis of these complications.</AbstractText> |
2,332,164 | Remifentanil requirements during sevoflurane administration to block somatic and cardiovascular responses to skin incision in children and adults. | The authors found no studies comparing intraoperative requirements of opioids between children and adults, so they determined the infusion rate of remifentanil to block somatic (IR50) and autonomic response (IRBAR50) to skin incision in children and adults.</AbstractText>Forty-one adults (aged 20-60 yr) and 24 children (aged 2-10 yr) undergoing lower abdominal surgery were studied. In adults, anesthesia induction was with sevoflurane during remifentanil infusion, whereas in children remifentanil administration was started after induction with sevoflurane. After intubation, sevoflurane was administered in 100% O2 and was adjusted to an ET% of 1 MAC-awake corrected for age at least 15 min before surgery. Patients were randomized to receive remifentanil at a rate ranging from 0.05 to 0.35 microg x kg(-1) x min(-1) for at least 20 min before surgery. At the beginning of surgery, only the skin incision was performed, and the somatic and autonomic responses were observed. The somatic response was defined as positive with any gross movement of extremity, and the autonomic response was deemed positive with any increase in heart rate mean arterial pressure equal to or more than 10% of preincision values. Using logistic regression, the IR50 and IRBAR50 were determined in both groups of patients and compared with unpaired Student t test. A P value less than 0.05 was considered significant.</AbstractText>The IR50 +/- SD was 0.10 +/- 0.02 microg x kg(-1) x min(-1) in adults and 0.22 +/- 0.03 microg x kg(-1) x min(-1) in children (P < 0.001). The IRBAR50 +/- SD was 0.11 +/- 0.02 microg x kg(-1) x min(-1) in adults and 0.27 +/- 0.06 microg x kg(-1) x min(-1) in children (P < 0.001).</AbstractText>To block somatic and autonomic responses to surgery, children require a remifentanil infusion rate at least twofold higher than adults.</AbstractText> |
2,332,165 | Intravenous regional anesthesia using prilocaine and neostigmine. | Neostigmine has been added to local anesthetics for central and peripheral nerve blocks resulting in prolonged, increased anesthesia and improved analgesia. We conducted this study to evaluate the effects of neostigmine when added to prilocaine for IV regional anesthesia (IVRA). Thirty patients undergoing hand surgery were randomly assigned to two groups to receive IVRA. The control group received 1 mL of saline plus 3 mg/kg of prilocaine diluted with saline to a total dose of 40 mL; the study group received 0.5 mg of neostigmine plus 3 mg/kg of prilocaine diluted with saline to a total dose of 40 mL. Sensory and motor block onset and recovery, anesthesia quality determined by an anesthesiologist, anesthesia quality determined by a surgeon, and dryness of the operative field were noted. Heart rate, mean arterial blood pressure, and oxygen saturation values were noted at 1, 5, 10, 20, and 40 min before surgery and after tourniquet release. Time to first analgesic requirement was also noted. Shortened sensory and motor block onset times, prolonged sensory and motor block recovery times, improved quality of anesthesia, and prolonged time to first analgesic requirement were found in the neostigmine group. We conclude that neostigmine as an adjunct to prilocaine improves quality of anesthesia and is beneficial in IVRA.</AbstractText>Neostigmine has been added to local anesthetics for central and peripheral nerve blocks. This study was conducted to evaluate the effects of neostigmine when added to prilocaine for IV regional anesthesia (IVRA). Neostigmine as an adjunct to prilocaine improves quality of anesthesia and is beneficial in IVRA.</AbstractText> |
2,332,166 | A randomized, double-blinded comparison of thoracic epidural ropivacaine, ropivacaine/fentanyl, or bupivacaine/fentanyl for postthoracotomy analgesia. | Epidural ropivacaine has not been compared with bupivacaine for postthoracotomy analgesia. Eighty patients undergoing elective lung surgery were randomized in a double-blinded manner to receive one of three solutions for high thoracic epidural analgesia. A continuous epidural infusion of 0.1 mL. kg(-1). h(-1) of either 0.2% ropivacaine, 0.15% ropivacaine/fentanyl 5 micro g/mL, or 0.1% bupivacaine/fentanyl 5 micro g/mL was started at admission to the intensive care unit. We assessed pain scores (rest and spirometry), IV morphine consumption, spirometry, hand grip strength, PaCO(2), heart rate, blood pressure, respiratory rate, and side effects (sedation, nausea, vomiting, and pruritus) for 48 h. Thoracic epidural ropivacaine/fentanyl provided adequate pain relief similar to bupivacaine/fentanyl during the first 2 postoperative days after posterolateral thoracotomy. The use of plain 0.2% ropivacaine was associated with worse pain control during spirometry, larger consumption of IV morphine, and increased incidence of postoperative nausea and vomiting. Morphine requirements were larger in the ropivacaine group, with no differences between bupivacaine/fentanyl and ropivacaine/fentanyl groups. Patients in the ropivacaine group experienced more pain and performed worse in spirometry than patients who received epidural fentanyl. There was no significant difference in motor block. We conclude that epidural ropivacaine/fentanyl offers no clinical advantage compared with bupivacaine/fentanyl for postthoracotomy analgesia.</AbstractText>Thoracic epidural ropivacaine/fentanyl provided adequate pain relief and similar analgesia to bupivacaine/fentanyl during the first 2 postoperative days after posterolateral thoracotomy. Plain 0.2% ropivacaine was associated with worse pain control and an increased incidence of postoperative nausea and vomiting. We conclude that epidural ropivacaine/fentanyl offers no clinical advantage compared with bupivacaine/fentanyl for postthoracotomy analgesia.</AbstractText> |
2,332,167 | Intermittent left anterior hemiblock. A rare case report. | The Authors report a rare case of intermittent left anterior hemiblock in a 86-year-old man admitted to Department of Emergency Medicine for progressive impoverishment of intellectual functions and episodes of chest pain. They present this rare case of intermittent left anterior hemiblock where the intermittence was not linked to heart rate variations preceding the beginning of the hemiblock being present on the same ECG two different QRS complexes with no modification in frequency or A-V conduction: this finding suggesting a vascular origin of the disturbance. They also stress the importance of a prompt diagnosis in a Department of Emergency Medicine. |
2,332,168 | A nonionic amphiphile agent promotes gene delivery in vivo to skeletal and cardiac muscles. | Direct injection of naked DNA into skeletal or cardiac muscle induces detectable gene expression. Although this provides a practical system for transgene expression, the reported efficacy is too low to confer a therapeutic benefit. By following a rational strategy based on the supramolecular structures adopted by active complexes, we have discovered a novel nonionic amphiphile synthetic agent [poly(ethyleneoxide)(13)-poly(propyleneoxide)(30)-poly(ethyleneoxide)(13) block copolymer; PE6400] that enables gene expression in up to 35% of muscle fibers from mouse tibial cranial muscle. PE6400 abolishes the ceiling effect on transgene expression of increasing amounts of naked DNA and permits long-term expression of the beta-galactosidase reporter gene in immunologically tolerant transgenic rats. This improvement in gene expression over naked DNA was observed irrespective of the reporter gene, ranging from 0.7 to 3.4 kb, and of the animal model used. In skeletal muscle, the PE6400 formulation led to a level of transfection efficiency similar to that obtained by electrotransfer. PE6400 also promotes high transgene expression in cardiac muscle. In contrast, PE6400-DNA formulations were inefficient in vitro in established cell lines and in isolated cardiomyocytes. When microinjected into the cell cytoplasm, PE6400 promotes DNA trafficking into the nucleus and induces gene expression. PE6400 provides a simple gene delivery system for skeletal and myocardial gene transfer. We propose that the PE6400 formulation could serve for the treatment of diseases primarily affecting muscle or for the expression of therapeutic proteins for local or systemic benefit. |
2,332,169 | A carbamate-type cholinesterase inhibitor 2-sec-butylphenyl N-methylcarbamate insecticide blocks L-type Ca2+ channel in guinea pig ventricular myocytes. | 2-sec-Butylphenyl N-methylcarbamate (BPMC) is a carbamate-type cholinesterase (ChE) inhibitor with unique toxicological properties such as noncholinergic cardiovascular collapse. Effects of BPMC on L-type Ca2+ channel currents (ICa(L)) were studied in isolated guinea pig ventricular myocytes using the whole-cell patch-clamp technique, since the examination of cardiovascular responses indicated its Ca2+ antagonistic action. BPMC induced bradycardic and hypotensive responses in vivo and inhibited contraction of isolated papillary muscles (IC50 = 1.3 x 10(-4) M) in guinea pigs. BPMC produced reversible block of ICa(L) in the concentration range of 10(-4) - 10(-3) M. At test potentials between -30 mV and +20 mV, BPMC at 3 x 10(-4) M caused marked acceleration of decay rate of ICa(L) with moderate reduction of peak ICa(L) amplitude. BPMC (3 x 10(-4) M) shifted the steady-state inactivation curve to the hyperpolarizing direction by 12.7 mV. Decay rate of Ba2+ currents (IBa(L)) was also accelerated by BPMC. Fitting analysis of inactivation kinetics of IBa(L) with a two-exponential equation revealed that BPMC accelerates the slow inactivation component. At concentrations for blocking peak IBa(L) by ca. 30%, the inactivation kinetics of IBa(L) were significantly accelerated by BPMC, but merely slightly accelerated by Ca2+ channel antagonists such as diltiazem, nifedipine, or verapamil. These results indicate that BPMC, in addition to the inhibition of ChE, blocks L-type Ca2+ channels by accelerating voltage-dependent inactivation. |
2,332,170 | Cytokine modulators as novel therapies for airway disease. | Cytokines play a critical role in orchestrating and perpetuating inflammation in asthma and chronic obstructive pulmonary disease (COPD), and several specific cytokine and chemokine inhibitors are now in development for the future therapy of these diseases. Anti-interleukin (IL)-5 is very effective at reducing peripheral blood and airway eosinophil numbers, but does not appear to be effective against symptomatic asthma. Inhibition of IL4 with soluble IL4 receptors has shown promising early results in asthma. Inhibitory cytokines, such as IL-10, interferons and IL-12 are less promising, as systemic delivery causes side-effects. Inhibition of tumour necrosis factor-alpha may be useful in severe asthma and for treating severe COPD with systemic features. Many chemokines are involved in the inflammatory response of asthma and COPD and several low-molecular-weight inhibitors of chemokine receptors are in development. CCR3 antagonists (which block eosinophil chemotaxis) and CXCR2 antagonists (which block neutrophil and monocyte chemotaxis) are in clinical development for the treatment of asthma and COPD respectively. Because so many cytokines are involved in asthma, drugs that inhibit the synthesis of multiple cytokines may prove to be more useful; several such classes of drug are now in clinical development and any risk of side-effects with these nonspecific inhibitors may be reduced by the use of inhalational route of delivery. |
2,332,171 | [Effects of intraperitoneal CO2 insufflation on hemodynamics and oxygen consumption during intravenous propofol anesthesia combined with epidural block]. | To investigate the effects of intraperitoneal CO2 insufflation on the hemodynamics, oxygen consumption (VO2) and carbon dioxide production (VCO2) during intravenous anesthesia with propofol in combination with epidural block.</AbstractText>Intratracheal intubation was performed after rapid induction of anesthesia and mechanical ventilation was given. Maintenance of anesthesia was achieved using continuous intravenous propofol infusion (2 mg/kg/h) ?N2O inhalation and intermittent epidural administration. Indices of hemodynamics and respiratory function were collected 5 min before induction, 1 min before CO2 insufflation, and 5, 10, 20, 30, 40, 50, 60 min after the start of insufflation and 5 min after the termination of insufflation.</AbstractText>The mean arterial pressure (MAP), heart rate (HR), end-tidal PCO2 (P(ET)CO2), VO2 and VCO2 1 min before insufflation were markedly reduced(P<0.01), compared with those recorded before induction. MAP and HR did not undergo any conspicuous changes during CO2 insufflation and 5 min after insufflation termination. Compared with that 1 min before insufflation, PETCO2 was significantly increased 20 min after the start of insufflation (P<0.01), and subsequently carried on the increase though of a lesser scale. VO2 and VCO2 gradually rose after the start of insufflation, and VO2 presented a significantly elevation (P<0.01) 10 min after the insufflation while VCO2 did not show this marked increase(P<0.05) till 20 min after the insufflation in comparison with the levels before insufflation. Subsequently, VO2 continued to rise and VCO2 also retained the increase but of smaller magnitude.</AbstractText>Intravenous propofol anesthesia combined with epidural block assisted by well-managed excessive ventilation before insufflation can alleviate the adverse effects of CO2 insufflation on respiratory and circulatory systems.</AbstractText> |
2,332,172 | Symptomatic orthostasis with extended-release nifedipine and protease inhibitors. | Human immunodeficiency virus (HIV) protease inhibitors are prone to drug interactions with other agents. As individuals with HIV infection live longer, the clinical significance of many interactions is becoming recognized. A 51-year-old man with HIV infection who was receiving extended-release nifedipine developed symptomatic orthostasis and heart block after starting antiretroviral therapy that included nelfinavir. He experienced dizziness, fatigue, and hypotension and developed complete heart block with a junctional escape rhythm. Electrocardiogram abnormalities abated within 24 hours of discontinuing antiretroviral therapy. The patient developed orthostatic symptoms after restarting nelfinavir. He was switched successfully to an efavirenz-based regimen. Subsequent administration of antiretroviral therapy containing ritonavir and indinavir with extended-release nifedipine resulted in recurrence of his orthostatic symptoms. Discontinuation of atenolol, and nifedipine dosage reduction by 50% were effective in managing his orthostatic changes. Careful monitoring by clinicians is necessary when concomitant administration of HIV protease inhibitors are prescribed with other agents that are metabolized through the cytochrome P450 system. |
2,332,173 | VEGF increases endothelial permeability by separate signaling pathways involving ERK-1/2 and nitric oxide. | We tested the hypothesis that VEGF regulates endothelial hyperpermeability to macromolecules by activating the ERK-1/2 MAPK pathway. We also tested whether PKC and nitric oxide (NO) mediate VEGF-induced increases in permeability via the ERK-1/2 pathway. FITC-Dextran 70 flux across human umbilical vein endothelial cell monolayers served as an index of permeability, whereas Western blots assessed the phosphorylation of ERK-1/2. VEGF-induced hyperpermeability was inhibited by antisense DNA oligonucleotides directed against ERK-1/2 and by blockade of MEK and Raf-1 activities (20 microM PD-98059 and 5 microM GW-5074). These blocking agents also reduced ERK-1/2 phosphorylation. The PKC inhibitor bisindolylmaleimide I (10 microM) blocked both VEGF-induced ERK-1/2 activation and hyperpermeability. The NO synthase (NOS) inhibitor N(G)-nitro-l-arginine methyl ester (200 microM) and the NO scavenger 2-phenyl-4,4,5,5-tetramethylimidiazoline-1-oxyl-3-oxide (100 microM) abolished VEGF-induced hyperpermeability but did not block ERK-1/2 phosphorylation. These observations demonstrate VEGF-induced hyperpermeability involves activation of PKC and NOS as well as Raf-1, MEK, and ERK-1/2. Furthermore, our data suggest that ERK-1/2 and NOS are elements of different signaling pathways in VEGF-induced hyperpermeability. |
2,332,174 | COX-2-derived prostacyclin mediates opioid-induced late phase of preconditioning in isolated rat hearts. | Opioids confer biphasic (early and late) cardioprotection against myocardial infarction by opening mitochondrial ATP-sensitive K(+) channels. It is unknown whether cyclooxygenase-2 (COX-2), which mediates ischemia-induced late preconditioning, also mediates opioid-induced cardioprotection. Isolated perfused rat hearts were subjected to 20 min of global ischemia followed by 20 min of reperfusion. BW-373U86 (BW), a delta-opioid receptor agonist, was administered 1, 12, or 24 h before death. Recovery of left ventricular developed pressure (LVDP) after ischemia-reperfusion improved when BW was administered 1 or 24 h before ischemia (control: 57 +/- 8, BW 1 h: 75 +/- 5, BW 24 h: 85 +/- 6%) but not when it was administered 12 h before (60 +/- 5%). Levels of 6-keto-PGF(1alpha) (a stable metabolite of PGI(2)) in coronary effluent after 20 min of reperfusion were higher with 24-h BW pretreatment than in controls (1,053 +/- 92 vs. 724 +/- 81 pg/ml), whereas 6-keto-PGF(1alpha) levels at baseline did not differ. Administration of a selective COX-2 inhibitor, NS-398, abolished the late phase of cardioprotection (recovery of LVDP, 53 +/- 8%) and attenuated the increase in PGI(2) (706 +/- 138 pg/ml) but did not block the early phase of cardioprotection. The selective COX-1 inhibitor SC-560 did not affect either phase of protection. Western immunoblotting revealed upregulation of PGI(2) synthase protein 24 h after BW administration without changes in COX-1 and COX-2 protein levels. In conclusion, the late (but not the early) phase of delta-opioid receptor-induced preconditioning is mediated by COX-2. A functional coupling between COX-2 and upregulated PGI(2) synthase appears to underlie this cardioprotective phenomenon in the rat. |
2,332,175 | ACh and adenosine activate PI3-kinase in rabbit hearts through transactivation of receptor tyrosine kinases. | Adenosine and acetylcholine (ACh) trigger preconditioning through different signaling pathways. We tested whether either could activate myocardial phosphatidylinositol 3-kinase (PI3-kinase), a putative signaling protein in ischemic preconditioning. We used phosphorylation of Akt, a downstream target of PI3-kinase, as a reporter. Exposure of isolated rabbit hearts to ACh increased Akt phosphorylation 2.62 +/- 0.33 fold (P = 0.001), whereas adenosine caused a significantly smaller increase (1.52 +/- 0.08 fold). ACh-induced activation of Akt was abolished by the tyrosine kinase blocker genistein indicating at least one tyrosine kinase between the muscarinic receptor and Akt. ACh-induced Akt activation was blocked by the Src tyrosine kinase inhibitor 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP2) and by 4-(3-chloroanilino)-6,7-dimethoxyquinazoline (AG-1478), an epidermal growth factor receptor (EGFR) inhibitor, suggesting phosphorylation of a receptor tyrosine kinase in an Src tyrosine kinase-dependent manner. ACh caused tyrosine phosphorylation of the EGFR, which could be blocked by PP2, thus supporting this receptor hypothesis. AG-1478 failed to block the cardioprotection of ACh, however, suggesting that other receptor tyrosine kinases might be involved. Therefore, G(i) protein-coupled receptors can activate PI3-kinase/Akt through transactivation of receptor tyrosine kinases in an Src tyrosine kinase-dependent manner. |
2,332,176 | Use of an adenosine triphosphate-based 'cocktail' early in reperfusion substantially improves brain protein synthesis after global ischemia in rats. | Neurological damage is a serious problem after cardiac arrest and resuscitation. We used a rat cardiac arrest model to test the ability of a post-ischemic infusion of adenosine triphosphate-magnesium chloride (ATP-MgCl(2)) to sustain cortical protein synthesis after 7 min global ischemia. We used norepinephrine (NE) to block the vasodilatory action of ATP, and a trace of vanadate to simulate the equine-derived ATP Chaudry used to protect against ischemia or hemorrhage in other organs. Our ATP 'cocktail' (3 ml of 4 mg/ml ATP-MgCl(2), 18 microg/ml NE, 2.4 microg/ml vanadate, infused intravenously over 18 min) tripled post-ischemic protein synthesis. ATP without vanadate, and vanadate without ATP, both had lesser but still significant effects. This ATP 'cocktail' may be useful as a neuroprotectant after cardiac arrest and resuscitation. |
2,332,177 | Nerve blocks in stereotactic neurosurgery. | The advantage of performing preoperative nerve blocks of the supraorbital and occipital nerves facilitates frame fixation and the perioperative management of patients in stereotactic neurosurgery, resulting in better patient handling with reduced intraoperative medication and less monitoring by anesthesia personnel. |
2,332,178 | Pulmonary oedema fluid induces non-alpha-ENaC-dependent Na(+) transport and fluid absorption in the distal lung. | To determine if pulmonary oedema fluid (EF) alters ion and fluid transport of distal lung epithelium (DLE), EF was collected from rats in acute heart failure. EF, but not plasma, increased amiloride-insensitive short circuit current (I(sc)) and Na(+)-K(+) ATPase protein content and pump activity of DLE grown in primary culture. Inhibitors of Cl(-) transport or cGMP-gated cation channels had a significant (P < 0.05), but limited ability to block the increased I(sc). EF increased amiloride-insensitive, but not amiloride-sensitive, DLE apical membrane Na(+) conductance. The level of mRNA encoding epithelial sodium channel (ENaC) subunits was unchanged (alpha, beta), or decreased (gamma, P < 0.05) in EF-exposed DLE. EF also induced an amiloride-insensitive increase in the potential difference across murine tracheal cysts. Distal lung explants from late gestation wild-type and alpha-ENaC-deficient fetal mice, which normally expand due to liquid secretion, decreased in size due to liquid absorption when exposed to EF. Trypsin digestion or heat treatment of EF abrogated the ability of EF to increase amiloride-insensitive I(sc) in DLE and liquid absorption by distal lung explants. Thus proteins or protein-dependent factors within cardiogenic EF induce an alpha-ENaC-independent and amiloride-insensitive apical membrane Na(+) conductance and liquid absorption in the distal lung. |
2,332,179 | Cumulative effect of preceding pacing cycle length on ventricular repolarization after a pause.<Pagination><StartPage>1324</StartPage><EndPage>1327</EndPage><MedlinePgn>1324-7</MedlinePgn></Pagination><Abstract><AbstractText>This study was designed to investigate if the components of the QT interval after a pause are influenced by the preceding pacing cycle length. Ten patients (seven women and three men; age 79 +/- 9 years, means +/- SD) with complete atrioventricular block or sick sinus syndrome whose own heart rate was < 40 beats/min were examined. All patients had already undergone implantation of a permanent pacemaker. Ventricular pacing protocol was performed with simultaneous recording of a 12-lead electrocardiogram. One set of regular stimuli for 30 seconds (S1) with a variable cycle length (1,000, 700, and 400 ms) was followed by a single stimulus (S2) with a fixed coupling interval of 1,500 ms. QT intervals in response to the last S1 (S1-QT) and S2 (S2-QT) were measured. The QT interval was divided into two components, the interval from start of Q wave to the peak of T wave (QaT) and that from the peak to end of T wave (Tae). The S2-QT and S1-QT interval shortened in association with a decrease in the S1S1 interval. The abbreviation of S2-QT interval was not associated with a significant change in the Tae interval. The results demonstrated that the QT interval after a pause shortened by reducing the preceding pacing cycle length. This shortening is probably due to a homogenous abbreviation of action potential duration across the ventricular wall.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Kira</LastName><ForeName>Tetsuya</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Department of Internal Medicine I, School of Medicine, Oita Medical University, Hasama, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Takahashi</LastName><ForeName>Naohiko</ForeName><Initials>N</Initials></Author><Author ValidYN="Y"><LastName>Sato</LastName><ForeName>Yasukazu</ForeName><Initials>Y</Initials></Author><Author ValidYN="Y"><LastName>Takakura</LastName><ForeName>Takeshi</ForeName><Initials>T</Initials></Author><Author ValidYN="Y"><LastName>Hara</LastName><ForeName>Masahide</ForeName><Initials>M</Initials></Author><Author ValidYN="Y"><LastName>Saikawa</LastName><ForeName>Tetsunori</ForeName><Initials>T</Initials></Author><Author ValidYN="Y"><LastName>Sakata</LastName><ForeName>Toshiie</ForeName><Initials>T</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Pacing Clin Electrophysiol</MedlineTA><NlmUniqueID>7803944</NlmUniqueID><ISSNLinking>0147-8389</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D002121">Calcium Channel Blockers</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000368" MajorTopicYN="N">Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002121" MajorTopicYN="N">Calcium Channel Blockers</DescriptorName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002304" MajorTopicYN="N">Cardiac Pacing, Artificial</DescriptorName><QualifierName UI="Q000379" MajorTopicYN="Y">methods</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004562" MajorTopicYN="N">Electrocardiography</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006327" MajorTopicYN="N">Heart Block</DescriptorName><QualifierName UI="Q000628" MajorTopicYN="Y">therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010138" MajorTopicYN="Y">Pacemaker, Artificial</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012804" MajorTopicYN="N">Sick Sinus Syndrome</DescriptorName><QualifierName UI="Q000628" MajorTopicYN="Y">therapy</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2002</Year><Month>10</Month><Day>17</Day><Hour>4</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2003</Year><Month>2</Month><Day>7</Day><Hour>4</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2002</Year><Month>10</Month><Day>17</Day><Hour>4</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">12380767</ArticleId><ArticleId IdType="doi">10.1046/j.1460-9592.2002.01324.x</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">12380520</PMID><DateCompleted><Year>2002</Year><Month>12</Month><Day>13</Day></DateCompleted><DateRevised><Year>2013</Year><Month>11</Month><Day>21</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0042-8787</ISSN><JournalIssue CitedMedium="Print"><Issue>4</Issue><PubDate><Year>2002</Year><Season>Jul-Aug</Season></PubDate></JournalIssue><Title>Voprosy kurortologii, fizioterapii, i lechebnoi fizicheskoi kultury</Title><ISOAbbreviation>Vopr Kurortol Fizioter Lech Fiz Kult</ISOAbbreviation></Journal>[Effects of the combination of nitrogen baths and physical training on physical performance and extrasystole in patients with coronary heart disease with intraventricular blocks]. | This study was designed to investigate if the components of the QT interval after a pause are influenced by the preceding pacing cycle length. Ten patients (seven women and three men; age 79 +/- 9 years, means +/- SD) with complete atrioventricular block or sick sinus syndrome whose own heart rate was < 40 beats/min were examined. All patients had already undergone implantation of a permanent pacemaker. Ventricular pacing protocol was performed with simultaneous recording of a 12-lead electrocardiogram. One set of regular stimuli for 30 seconds (S1) with a variable cycle length (1,000, 700, and 400 ms) was followed by a single stimulus (S2) with a fixed coupling interval of 1,500 ms. QT intervals in response to the last S1 (S1-QT) and S2 (S2-QT) were measured. The QT interval was divided into two components, the interval from start of Q wave to the peak of T wave (QaT) and that from the peak to end of T wave (Tae). The S2-QT and S1-QT interval shortened in association with a decrease in the S1S1 interval. The abbreviation of S2-QT interval was not associated with a significant change in the Tae interval. The results demonstrated that the QT interval after a pause shortened by reducing the preceding pacing cycle length. This shortening is probably due to a homogenous abbreviation of action potential duration across the ventricular wall.</Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Kira</LastName><ForeName>Tetsuya</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Department of Internal Medicine I, School of Medicine, Oita Medical University, Hasama, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Takahashi</LastName><ForeName>Naohiko</ForeName><Initials>N</Initials></Author><Author ValidYN="Y"><LastName>Sato</LastName><ForeName>Yasukazu</ForeName><Initials>Y</Initials></Author><Author ValidYN="Y"><LastName>Takakura</LastName><ForeName>Takeshi</ForeName><Initials>T</Initials></Author><Author ValidYN="Y"><LastName>Hara</LastName><ForeName>Masahide</ForeName><Initials>M</Initials></Author><Author ValidYN="Y"><LastName>Saikawa</LastName><ForeName>Tetsunori</ForeName><Initials>T</Initials></Author><Author ValidYN="Y"><LastName>Sakata</LastName><ForeName>Toshiie</ForeName><Initials>T</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Pacing Clin Electrophysiol</MedlineTA><NlmUniqueID>7803944</NlmUniqueID><ISSNLinking>0147-8389</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D002121">Calcium Channel Blockers</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000368" MajorTopicYN="N">Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002121" MajorTopicYN="N">Calcium Channel Blockers</DescriptorName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002304" MajorTopicYN="N">Cardiac Pacing, Artificial</DescriptorName><QualifierName UI="Q000379" MajorTopicYN="Y">methods</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004562" MajorTopicYN="N">Electrocardiography</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006327" MajorTopicYN="N">Heart Block</DescriptorName><QualifierName UI="Q000628" MajorTopicYN="Y">therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010138" MajorTopicYN="Y">Pacemaker, Artificial</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012804" MajorTopicYN="N">Sick Sinus Syndrome</DescriptorName><QualifierName UI="Q000628" MajorTopicYN="Y">therapy</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2002</Year><Month>10</Month><Day>17</Day><Hour>4</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2003</Year><Month>2</Month><Day>7</Day><Hour>4</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2002</Year><Month>10</Month><Day>17</Day><Hour>4</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">12380767</ArticleId><ArticleId IdType="doi">10.1046/j.1460-9592.2002.01324.x</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">12380520</PMID><DateCompleted><Year>2002</Year><Month>12</Month><Day>13</Day></DateCompleted><DateRevised><Year>2013</Year><Month>11</Month><Day>21</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0042-8787</ISSN><JournalIssue CitedMedium="Print"><Issue>4</Issue><PubDate><Year>2002</Year><Season>Jul-Aug</Season></PubDate></JournalIssue><Title>Voprosy kurortologii, fizioterapii, i lechebnoi fizicheskoi kultury</Title><ISOAbbreviation>Vopr Kurortol Fizioter Lech Fiz Kult</ISOAbbreviation></Journal><ArticleTitle>[Effects of the combination of nitrogen baths and physical training on physical performance and extrasystole in patients with coronary heart disease with intraventricular blocks].</ArticleTitle><Pagination><StartPage>3</StartPage><EndPage>5</EndPage><MedlinePgn>3-5</MedlinePgn></Pagination><Abstract>99 patients with coronary heart disease (CHD), stable angina pectoris (functional class I-II), intraventricular blocks (IVB) took a course of general artificial nitrogen baths. Of them, 31 patients took the baths alone; 35 patients, in addition, exercised on veloergometer; 33 patients took baths and continued physical training up to 6 months. The results of the treatment were assessed with spiroveloergometry, ambulatory Holter ECG monitoring. Those who took baths and exercised for 6 months benefited from the treatment most as their muscular performance and coronary heart reserve increased; mean daily number of ventricular extrasystoles reduced by 73.3%, supraventricular extrasystoles--by 72.2%; intraventricular conduction was not damaged. |
2,332,180 | [Neonatal cutaneous lupus. Necessary interdisciplinary collaboration]. | Neonatal lupus erythematosus is a rare syndrome (affecting 5% of the children born of mothers with lupus), characterized essentially by cutaneous lesions and/or congenital auricular-ventricular heart block. It is due to the transplacental passage of maternal antibodies (anti-SSA or anti-SSB, or occasionally anti-U1RNP antibodies) into the fetal circulation.</AbstractText>We report a case of neonatal lupus erythematosus, having appeared 4 weeks after birth. The 26 years old mother exhibited systemic lupus erythematosus concomitant to Gougerot-Sjögren's syndrome, with positive antinuclear factors (1/2560), native anti-DNA, anti-SSA and anti-SSB antibodies and anticardiolipin antibodies. During pregnancy, the mother had been treated with aspirin at the dose of 100 mg/day, followed by subcutaneous enoxaparin 0.4 ml/day, and combined with prednisone 10 mg/d and hydroxychloroquine 400 mg/day. Early and regular cardiac monitoring of the foetus was performed. The clinical examination and the electrocardiogram at birth were normal. Four weeks later, the infant presented with erythematous cutaneous lesions with atrophic center. No systemic treatment was initiated and the lesions partially regressed.</AbstractText>Cutaneous lesions can also appear after the 4th week of life. It is important that the pediatricians clinically monitor all the children born to mothers exhibiting anti-SSA or anti-SSB antibodies, at least during the first 7 months of life.</AbstractText> |
2,332,181 | Propofol decreases cerebral blood flow velocity in anesthetized children. | Propofol, by virtue of its favourable pharmacokinetic profile, is suitable for maintenance of anesthesia by continuous infusion during neurosurgical procedures in adults. It is gaining popularity for use in pediatric patients. To determine the effects of propofol on cerebral blood flow in children, middle cerebral artery blood flow velocity (Vmca) was measured at different levels of propofol administration by transcranial Doppler (TCD) sonography.</AbstractText>Twelve ASA I or II children, aged one to six years undergoing elective urological surgery were randomized to receive one of two propofol dosing regimens. Half of the patients received propofol in an escalating fashion, initially targeting an estimated steady-state serum concentration of 3 microg x mL-1, which was then doubled. The other half received propofol designed initially to target the high concentration followed by the lower one. In each child anesthesia was induced and maintained with propofol according to the protocol, rocuronium was given to facilitate tracheal intubation, and a caudal epidural block was performed. A TCD probe was placed appropriately to measure Vmca. Cerebral blood flow velocity (CBFV), mean arterial pressure (MAP) and heart rate (HR) were recorded simultaneously at both levels of propofol administration.</AbstractText>Twelve patients were studied. At the higher estimated target serum propofol concentration there were significant decreases in Vmca (17%, P < 0.001), MAP (6%, P < 0.002) and HR (8%, P < 0.05) when compared to the lower targeted concentration.</AbstractText>This study shows that a higher rate of propofol infusion is associated with lower CBFV and MAP values in children. Propofol's cerebral vasoconstrictive properties may be responsible for this finding.</AbstractText> |
2,332,182 | Total spinal anesthesia provides transient relief of intractable pain. | Intentional total spinal anesthesia (TSA) has been used for intractable pain treatment. However, the long-term effect of pain-relief is controversial. We investigate the short- and long-term effects of pain-relief by TSA.</AbstractText>Twelve patients with intractable pain participated in a crossover study. All participants received two different treatments in random order at a 30-day interval: i.v. infusion with 300 mg of lidocaine (i.v.-Lido), and TSA with 20 mL of 1.5% lidocaine (TSA-Lido). Pain level at rest was scored with the visual analogue scale (VAS: 0-100), and blood pressure and heart rate were measured before and at two hours, 24 hr, seven days, and 30 days after treatment. Plasma lidocaine concentrations were measured at 0.5, one, and two hours.</AbstractText>Heart rate and mean arterial pressure during or after TSA-Lido were similar to those before TSA-Lido. Plasma lidocaine concentrations were similar between the two treatments. No significant difference in any value occurred in the i.v.-Lido treatment. VAS were similar before both treatments (87 +/- 6 for TSA-Lido; 86 +/- 7 for i.v.-Lido). After TSA-Lido, VAS decreased significantly until day seven (two hours, 17 +/- 22, P < 0.01; 24 hr, 43 +/- 20, P < 0.01; seven days, 66 +/- 16, P < 0.01). However, VAS returned to the pre-block values 30 days after TSA-Lido.</AbstractText>Intractable pain was decreased significantly for several days after TSA, but pain-relief was not sustained.</AbstractText> |
2,332,183 | Sodium transporter abundance profiling in kidney: effect of spironolactone. | Renal tubule profiling studies were carried out to investigate the long-term effects of administration of spironolactone, a mineralocorticoid receptor antagonist, on abundances of the major Na transporter and Na channel proteins along the rat renal tubule. Oral administration of spironolactone for 7 days to NaCl-restricted rats did not significantly alter abundances of Na transporters expressed proximal to the macula densa, while substantially decreasing the abundances of the thiazide-sensitive Na-Cl cotransporter (NCC), the alpha-subunit of the amiloride-sensitive epithelial Na channel (ENaC), and the 70-kDa form of the gamma-subunit of ENaC. A dependency of NCC expression on aldosterone was confirmed by showing increased NCC expression in response to aldosterone infusion in adrenalectomized rats. Immunoperoxidase labeling of ENaC in renal cortex confirmed that dietary NaCl restriction causes a redistribution of ENaC to the apical domain of connecting tubule cells and showed that high-dose spironolactone administration does not block this apical redistribution. In contrast, spironolactone completely blocked the increase in alpha-ENaC abundance in response to dietary NaCl restriction. We conclude that the protein abundances of NCC, alpha-ENaC, and the 70-kDa form of gamma-ENaC are regulated via the classical mineralocorticoid receptor, but the subcellular redistribution of ENaC in response to dietary NaCl restriction is not prevented by blockade of the mineralocorticoid receptor. |
2,332,184 | Desmosomes and disease: an update. | Desmosomes play a critical role in the maintenance of normal tissue architecture. Skin blistering can occur when desmosomal adhesion is compromised by antibodies in autoimmune diseases such as pemphigus. Inherited mutations in genes encoding desmosomal constituents can adversely affect the skin, and result in heart abnormalities. Desmosomes may have a tumour suppressor function: expression of desmosomal components is reduced in some human cancers, and desmosomal cadherins have the capacity to suppress the invasiveness of cells in culture. Transgenic animal research has provided important insights into the role of these junctions in normal epithelial morphogenesis and disease. |
2,332,185 | Cardiac 5-HT(4) serotoninergic receptors, 52kD SSA/Ro and autoimmune-associated congenital heart block. | It was recently reported that sera from patients with systemic lupus erythematosus contain antibodies reactive with the second extracellular loop of the serotoninergic 5-HT(4) receptor expressed in the human heart. This antibody response was associated with antibodies to 52kD SSA/Ro, a reactivity prevalent in mothers of children with congenital heart block (CHB). The current study was undertaken to determine whether the 5-HT(4) receptor is a target of the immune response in these mothers. Initial experiments demonstrated mRNA expression of the 5-HT(4) receptor in the human foetal atrium. Electrophysiologic studies established that human foetal atrial cells express functional 5-HT(4) receptors. Sera from 116 mothers enrolled in the Research Registry for Neonatal Lupus, whose children have CHB, were evaluated. Ninety-nine (85%) of these maternal sera contained antibodies to SSA/Ro, 84% of which were reactive with the 52kD SSA/Ro component by immunoblot. None of the 116 sera were reactive with the peptide spanning aa165-185 of the serotoninergic receptor. Rabbit antisera which recognized this peptide did not react with 52kD SSA/Ro or peptide aa365-382 in the C terminus. Although 5-HT(4) receptors are present and functional in the human foetal heart, maternal antibodies to the 5-HT(4) receptor are not associated with the development of CHB. |
2,332,186 | Heart block associated with spinocerebellar ataxia type 2. | A 20-year-old man was discharged from the U.S. Army because of increasing gait abnormalities. One year later, he developed episodes of syncope secondary to high-degree atrial/ventricular block with periods of complete heart block and ventricular asystole. A permanent dual-chamber, rate-responsive cardiac pacemaker was implanted. At age 29 years, an abnormal expansion of the CAG trinucleotide repeat in the ataxin-2 gene on chromosome 12 was identified. This case suggests that cardiac conduction abnormalities should be included as part of the recognized clinical heterogeneity of spinocerebellar ataxia type 2. |
2,332,187 | Fenamate-induced enhancement of heterologously expressed HERG currents in Xenopus oocytes. | The human ether-a-go-go related gene (HERG) product encodes for the pore-forming subunit of the rapid component of the delayed rectifier K(+) channel that mediates repolarization of cardiac action potential. HERG channels are also potential targets of a large variety of pharmacological agents most of which tend to block HERG currents. In this study, we examined the effects of the non-steroidal anti-inflammatory agents, flufenamic acid and niflumic acid, on heterologously expressed HERG channels in oocytes. The cRNA of HERG (30 ng) was injected into Xenopus oocytes and currents were recorded using two-electrode voltage clamp technique in a low Cl(-) solution. Flufenamic and niflumic acids (10(-4)-5 x 10 (-4) M) enhanced the amplitude of outward currents evoked by depolarizing pulses. At potentials positive to 0 mV, an initial transient component was also evident in the presence of fenamates. Fenamates accelerated the activation rate of HERG channels and decelerated their deactivation. Flufenamic acid (5 x 10 (-4) M) shifted the I(tail)-V relationship from -26.7+/-0.1 to -31.4+/-0.2 mV. Neither flufenamic acid or niflumic acid affected the kinetics of HERG channel inactivation. Using a voltage protocol that mimicked the cardiac action potential, both fenamates increased the outward current during the plateau and during the phase 3 repolarization of action potential. The effects of the fenamates were blocked by the HERG channel blocker, E-4031 and were also not observed in water-injected oocytes. Our data suggest that fenamates enhance HERG currents and affect the action potential duration in the heart. |
2,332,188 | The pre-emptive effect of epidural ketamine on wound sensitivity in horses tested by using von Frey filaments. | To evaluate the pre-emptive analgesic effect of pre-incisional epidural ketamine.</AbstractText>A blinded, randomized experimental study.</AbstractText>Sixteen mixed breed mares, 7.6 ± 2.8 years old, weighing 352 ± 32 kg.</AbstractText>In a pilot study, an incision was made on one lateral thigh using a lidocaine block and no further analgesics, and it was verified that the nociceptive threshold was lower on the incised side than nonincised side (p ≤ 0.05), and that von Frey filaments evoked a pain response. The 16 animals were divided into group A (ketamine, n = 9) and B (saline, n = 7). An epidural catheter was inserted 24 hours before the trials. The thigh was shaved bilaterally, and the right side was blocked (incised side) using lidocaine. Twenty-five minutes later, ketamine (A) or saline (B) was administered epidurally. Five minutes later, a 10-cm skin incision was made on the right side, and then sutured. Nociceptive threshold was determined with von Frey filaments at 1, 3, and 5 cm around the incision at 15-minute intervals for 2 hours, then at 4, 6, and 8 hours. Behavioral alterations, heart and respiratory rates were recorded. Nociceptive thresholds from these points were averaged to obtain mean values at each time, converted to a logarithmic scale, and submitted to a nonparametric analysis (Mann-Whitney and one-way repeated measures anova test, p ≤ 0.05).</AbstractText>After 8 hours, the global range score revealed reduced hyperalgesia (p < 0.01) around the incision in 92% (4.65-4.27) of evaluated intervals in group A (ketamine). There were no significant changes in behavior, heart and respiratory rates.</AbstractText>It was concluded that pre-emptive epidural ketamine reduced post-incisional pain in the horse, and that von Frey filaments were able to quantify cutaneous sensitivity after tissue damage.</AbstractText>Epidural ketamine injection can reduce post-incisional sensitivity in the horse.</AbstractText>Copyright © 2002 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.</CopyrightInformation> |
2,332,189 | Long-term renal function in kidneys from non-heart-beating donors: A single-center experience. | Cadaveric kidneys from brain-stem-dead donors continue to be limited because the number of donors has reached a plateau. Wide recruitment of non-heart-beating donors (NHBD) could significantly increase the donor pool. NHBD renal transplants are underused because of the concern of poor quality graft function from such donors. In response to this perception, we reviewed 46 NHBD renal transplants performed in our center since 1998.</AbstractText>All NHBD kidneys were machine-perfused using the Newcastle continuous-hypothermic pulsatile preservation system before transplantation. A control heart-beating-donor (HBD) group was taken as the next consecutive HBD renal transplant to the NHBD transplant. The outcome and quality of function of the groups of renal transplants were analyzed for short-term and long-term performance.</AbstractText>The renal transplant patients were matched for donor and recipient factors. Survival rates for allografts and patients were similar for 1 to 3 years. There was an increased incidence of delayed graft function in the NHBD renal transplants in the perioperative period. The creatinine clearance was 22.8+/-2.3 mL/minute for NHBD patients and 44.4+/-2.9 mL/minute for HBD patients at the time of discharge from hospital. This difference equalized after 3 months and the creatinine clearance for NHBD was 44.2+/-2.4 mL/minute and for HBD 49.2+/-3.4 mL/minute.</AbstractText>Our results for NHBD renal transplants confirm that such grafts suffer primary warm ischemic injury, shown by the increased incidence of acute tubular necrosis and consequent delayed graft function. This produced poor renal function at the time of hospital discharge. After 3 months, the renal function of NHBD cases improved to the level seen in HBD patients.</AbstractText> |
2,332,190 | Differential neuroprotection by cyclosporin A and FK506 following ischemia corresponds with differing abilities to inhibit calcineurin and the mitochondrial permeability transition. | Transient global or forebrain ischemia leads to severe brain damage following delayed neuronal cell death. We previously reported that cyclosporin A (CsA) provides near total suppression of brain damage in rat forebrain ischemia when allowed to pass the blood brain barrier, whereas Tacrolimus (FK506) is considerably less effective. We demonstrate herein that when administered prior to ischemic insult, both immunosuppressants equally block calcineurin, a type 2B Ser/Thr phosphatase, and efficiently inhibit dephosphorylation of pro-apoptotic protein Bad. CsA demonstrates more potent anti-ischemic effects than FK506, partially attributable to amelioration of mitochondrial damage as assayed in vivo and in vitro. These results suggest that pathways including calcineurin and cyclophilins, particularly mitochondrial cyclophilin D, play pivotal roles in ischemic brain damage. Since previous results have shown that CsA is efficacious also when administered after focal ischemia, the present findings give hints to clinical applications for new drugs for the treatment of ischemic damage in the brain as well as in the heart and liver. |
2,332,191 | Epidural morphine injection after combined spinal and epidural anaesthesia. | Although combined spinal and epidural anaesthesia is efficient and easy to perform, the technique can be a double-edged sword having the potential risk that an increased flux of drugs across the meninges through the hole made in it may lead to severe adverse effects. The aim was to compare the incidence of adverse events when an epidural injection of morphine was given after combined spinal and epidural anaesthesia or after epidural anaesthesia.</AbstractText>Fifteen patients had an epidural catheter inserted at the L2-3 interspace, and then a spinal block administered via the L3-4 interspace. Another 15 patients only had an epidural catheter inserted. After the onset of spinal or epidural anaesthesia had been confirmed, morphine 2 mg was injected into the epidural space, and a continuous epidural infusion of morphine was started. At the end of the operation and at 4, 8 and 12 h after the administration of epidural morphine and on the next day, the following variables were examined: blood pressure, heart rate, respiratory rate, arterial blood-gas analysis, visual analogue scale pain scores, nausea/vomiting scores, and pruritus scores.</AbstractText>In the study population, the epidural injection of morphine was not associated with a significantly higher incidence of adverse events when given after spinal anaesthesia than after epidural anaesthesia.</AbstractText>The adverse effects associated with epidural morphine given after spinal anaesthesia did not increase significantly when a 27-G Whitacre needle was used. Thus, the morphine flux through the meningeal hole into the cerebrospinal fluid was trivial.</AbstractText> |
2,332,192 | Postoperative pain management in orthopaedic patients: no differences in pain score, but improved stress control by epidural anaesthesia. | To investigate the interactions of postoperative pain and endocrine stress response, three groups of 21 patients each with total knee arthroplasty were compared in a randomized, prospective design. For postoperative pain management, a three-in-one block, an epidural catheter analgesia or an intravenous patient-controlled analgesia was used.</AbstractText>After standardized balanced anaesthesia, the pain intensity was measured by a visual analogue scale (VAS). For detection of epinephrine, norepinephrine, antidiuretic hormone, adrenocorticotropic hormone and cortisol in the plasma, blood samples were taken at six time points before and up to 180 min after the start of pain therapy. In addition, systolic arterial pressure, heart rate, partial arterial oxygen saturation, nausea, vomiting and satisfaction of the patients were recorded.</AbstractText>Within 15 min after the start of pain therapy, VAS in all groups was similarly reduced from >40 mm to a range <10 mm (P < 0.001). Initially, all endocrine stress variables exceeded the normal range. Epidural anaesthesia led to a significant decrease of epinephrine and norepinephrine concentrations, while an increase was observed in the group with patient-controlled analgesia, and the decrease in patients with the three-in-one block was less than in patients receiving epidural anaesthesia (P = 0.001). Differences in antidiuretic hormone, adrenocorticotropic hormone and cortisol were less pronounced. Systolic arterial pressure decreased significantly in all groups, particularly in patients with epidural anaesthesia. Partial arterial oxygen saturation and the incidence of nausea and vomiting were comparable. All patients were satisfied with the methods used.</AbstractText>All methods of pain management led to sufficient analgesia, but they were not accompanied by an adequate reduction in endocrine stress response. Thus, postoperative pain is only a secondary stressor and sufficient analgesia with subjective well-being does not prove a stress-free state. With regard to the reduction of sympathoadrenergic stress response, epidural anaesthesia is superior to the three-in-one block and patient-controlled analgesia. Epidural anaesthesia is recommended particularly for high-risk patients with hypertension, coronary heart disease and diabetes mellitus. In these patients, the reduction of a 'hidden' endocrine stress response in addition to prevention of pain is of special interest.</AbstractText> |
2,332,193 | Precocious expression of cardiac troponin T in early chick embryos is independent of bone morphogenetic protein signaling. | Cardiac troponin T (cTNT) is a component of the troponin complex, which confers calcium sensitivity to contraction in skeletal and cardiac muscle. Although it is thought that most components of the contractile myofibril are expressed exclusively in differentiated muscle cells, we observed that mRNAs coding for cTNT were detectable in explanted late gastrula mesoderm at least 12 hr before cardiac myocyte differentiation. We therefore conducted a detailed analysis of cTNT gene expression in the early chick embryo. Whole-mount in situ hybridization studies showed that by Hamburger and Hamilton stage 5, cTNT mRNAs are detectable in lateral mesoderm and, by stage 6, are observed throughout the lateral embryonic and extraembryonic mesoderm in a distribution that is much broader than the recognized heart field. As myocardial cell differentiation commences, cTNT transcripts become progressively localized to the forming heart and, by stage 14, are completely restricted to heart muscle cells. Western blot analyses demonstrated that cTNT protein expression is under translational control, as cTNT protein is not detectable until stage 9, concomitant with myocardial cell differentiation. Removal of endoderm at stage 5 had no effect on cTNT mRNA levels, and the bone morphogenetic protein (BMP) inhibitor noggin failed to block cTNT expression, even in the heart-forming region and in cases where heart formation was inhibited. Implantation of noggin-expressing CHO cells at the anterior midline of stage 7 embryos resulted in cardia bifida. These findings demonstrate the precocious, BMP-independent expression of a gene coding for a myofibrillar protein and suggest that an additional regulatory pathway exists for activation of some cardiogenic genes. |
2,332,194 | Interaction of different potassium channels in cardiac repolarization in dog ventricular preparations: role of repolarization reserve. | 1 The aim of this study was to investigate the possible role of the interaction of different potassium channels in dog ventricular muscle, by applying the conventional microelectrode and whole cell patch-clamp techniques at 37 degrees C. 2 Complete block of I(Kr) by 1 micro M dofetilide lengthened action potential duration (APD) by 45.6+/-3.6% at 0.2 Hz (n=13). Chromanol 293B applied alone at 10 micro M (a concentration which selectively blocks I(Ks)) did not markedly lengthen APD (<7%), but when repolarization had already been prolonged by complete I(Kr) block with 1 micro M dofetilide, inhibition of I(Ks) with 10 micro M chromanol 293B substantially delayed repolarization by 38.5+/-8.2% at 0.2 Hz (n=6). 3 BaCl(2), at a concentration of 10 micro M which blocks I(Kl) without affecting other currents, lengthened APD by 33.0+/-3.1% (n=11), but when I(Kr) was blocked with 1 micro M dofetilide, 10 micro M BaCl(2) produced a more excessive rate dependent lengthening in APD, frequently (in three out of seven preparations) initiating early afterdepolarizations. 4 These findings indicate that if only one type of potassium channels is inhibited in dog ventricular muscle, excessive APD lengthening is not likely to occur. Dog ventricular myocytes seem to repolarize with a strong safety margin ('repolarization reserve'). However, when this normal 'repolarization reserve' is attenuated, otherwise minimal or moderate potassium current inhibition can result in excessive and potentially proarrhythmic prolongation of the ventricular APD. Therefore, application of drugs which are able to block more than one type of potassium channel is probably more hazardous than the use of a specific inhibitor of one given sort of potassium channel, and when simultaneous blockade of several kinds of potassium channel may be presumed, a detailed study is needed to define the determinants of 'repolarization reserve'. |
2,332,195 | Differential effects of linoleic Acid metabolites on cardiac sodium current. | 9,10-Epoxy-12-octadecenoic acid (EOA), a metabolite of linoleic acid, causes cardiac arrest in dogs. Other metabolites of linoleic acid also have toxic effects. This study investigates the mechanism of action of four of these compounds on cardiac Na(+) current (I(Na)). The whole-cell patch-clamp technique was used to investigate the effects of EOA, 9,10-dihydroxy-12-octadecenoic acid (DHOA), and their corresponding methyl esters (9,10-epoxy-12-octadecenoic methyl ester, EOM; and 9,10-dihydroxy-12-octadecenoic methyl ester, DHOM) on I(Na) in isolated adult rat ventricular myocytes. Extracellular application of each compound elicited a concentration-dependent inhibition of I(Na). The dose-response curve yielded 50% inhibition concentrations of 301 +/- 117 microM for DHOA, 41 +/- 6 microM for DHOM, 34 +/- 5 microM for EOA, and 160 +/- 41 microM for EOM. Although there was no effect on activation, 50 microM DHOM, EOA, and EOM significantly hyperpolarized the steady-state inactivation curve by approximately -6 mV. Furthermore, EOM significantly increased the slope of the steady-state inactivation curve. These compounds also seemed to stabilize the inactivated state because the time for recovery from inactivation was significantly slowed from a control value of 12.9 +/- 0.5 ms to 30.5 +/- 3.3, 31.4 +/- 1.4, and 20.5 +/- 1.0 ms by 50 microM DHOM, EOA, and EOM, respectively. These compounds have multiple actions on Na(+) channels and that despite their structural similarities their actions differ from each other. The steady-state block of I(Na) suggests that either the pore is being blocked or the channels are prevented from gating to the open state. In addition, these compounds stabilize the inactivated state and promote increased population of a slower inactivated state. |
2,332,196 | Inhibitory effects of the antiestrogen agent clomiphene on cardiac sarcolemmal anionic and cationic currents. | The aim of this study was to determine the effects of the antiestrogen agent clomiphene on cardiac anionic and cationic sarcolemmal ion channels. Whole-cell recordings were made from rat and guinea pig ventricular myocytes. Clomiphene inhibited the volume-regulated chloride current [I(Cl,vol), activated by cell swelling after hypotonic shock (approximately 145 mOsM)] with an IC(50) value of approximately 9.4 microM. In contrast, at concentrations up to 100 microM, clomiphene failed to inhibit both the chloride current activated by cyclic AMP (I(Cl,cAMP)) and the anionic background current (I(AB)). At 10 microM, clomiphene blocked the voltage-gated fast sodium current and the L-type calcium current (I(Ca,L)) in both species. The voltage-independent fractional block of I(Ca,L) induced by clomiphene (10 microM) was approximately 82%, this concentration also inhibited the inwardly rectifying K(+) current with a fractional current block of approximately 26% at -90 mV. Fractional block of outward current at +70 mV in rat was approximately 25%, implying that delayed rectifying K(+) channels were also affected by clomiphene. We conclude that clomiphene shows selectivity for I(Cl,vol) over I(Cl,cAMP) and I(AB) and therefore represents a useful tool for studying chloride conductances in isolated ventricular myocytes with interfering currents blocked. However, due to its effects on cation conductances it would be of little value in this regard for other types of in vitro or in vivo experiments. |
2,332,197 | TLR4 inactivation and rBPI(21) block burn-induced myocardial contractile dysfunction. | Both large burns and severe gram-negative sepsis are associated with acute myocardial contractile dysfunction. Because others have reported that burn injury may be followed by transient endotoxemia, we hypothesized that bacterial endotoxin induces contractile impairment after burn trauma. We tested this hypothesis in two rodent models. In each model, postburn myocardial contractility was assessed using Langendorff preparations of excised hearts. In the first model, mice expressing either a mutant form of or no Toll-like receptor 4 (TLR4), a critical element of the mammalian endotoxin receptor, were resistant to postburn myocardial contractile dysfunction. In the second model, starting 30 min or 4 h after burn injury, rats were infused with recombinant bactericidal/permeability-increasing protein (rBPI(21)), a protein that binds and neutralizes endotoxin. Hearts from rBPI(21)-treated animals were completely protected from postburn contractile impairment. Because burn-induced contractile dysfunction can be prevented either by blocking signaling through the endotoxin receptor or by neutralizing circulating LPS, bacterial endotoxin may contribute to impaired myocardial contractility after burn injury. |
2,332,198 | Functional evidence for intracellular acid extruders in human ventricular myocardium. | Intracellular pH (pH(i)) is a major homeostatic system within the cell. Changes in pH(i) exert great influence on cardiac contractility and rhythm. Both the housekeeping Na+ - H+ exchanger (NHE) and the Na+ - HCO3- symporter (NHS) have been confirmed as major transporters for the active acid extrusion mechanism in animal cardiomyocytes. However, whether the NHE and NHS functionally coexist in human ventricular cardiomyocytes remains unclear. We therefore examined the mechanism of pH(i) recovery following an NH4Cl-induced intracellular acidosis in the human ventricular myocardium. The pH(i) was monitored by microspectrofluorimetry by the use of intracellular 2',7'-bis(2-carboxyethyl)-5(6)-carboxy-fluorescein (BCECF)-fluorescence. HOE 694 (30 microM), a specific NHE inhibitor could block pH(i) recovery from induced intracellular acidosis completely in nominally HCO3- -free HEPES Tyrode solution, but it only partially inhibited the pH(i) recovery in 5% CO2/HCO3- Tyrode solution. In 5% CO2/HCO3- Tyrode solution, the addition of HOE 694 together with DIDS (an NHS inhibitor) or the removal of [Na+](o) could entirely inhibit the acid extrusion. We conclude for the first time that two different acid extruders, HCO3- -independent and -dependent, were most likely the NHE and NHS, respectively, that functionally coexisted in the human ventricular cardiomyocytes. |
2,332,199 | [Pretreatment with lidocaine accelerates onset of vecuronium-induced neuromuscular blockade]. | The purpose of this study was to investigate the effect of pre-treatment with lidocaine on the onset of vecuronium-induced neuromuscular block in a randomized, double-blinded trial. Thirty-one patients were randomly allocated to one of two groups according to the agents administrated 3 min prior to vecuronium injection; Group C, normal saline 0.75 ml.kg-1 and Group L, 2% lidocaine 1.5 mg.kg-1. Anesthesia was induced with propofol 1.5 mg.kg-1 followed by continuous infusion at 8 mg.kg-1.hr-1. Neuromuscular blockade was evaluated with accelerometry, which measured a train-of-four (TOF) pattern of abductor policies muscle. The disappearance of the first response in TOF was regarded as onset of neuromuscular block. Changes in systolic and diastolic arterial pressure (SBP, DBP) and heart rate (HR) were measured before and after tracheal intubation. Times to onset of neuromuscular blockade induced by vecuronium in Group L and Group C were 115 +/- 20 sec and 174 +/- 45 sec, respectively. After tracheal intubation, SBP, DBP and HR in both groups increased compared with those before tracheal intubation, but the changes were not significant. Changes in SBP, DBP and HR did not differ between Group L and Group C. The mechanisms by which lidocaine reduced the time to onset of neuromuscular block caused by vecuronium could not be clarified from our study, but this may be related to pre- and post-junctional effects of lidocaine at neuromuscular junction. In conclusion, administration of lidocaine prior to tracheal intubation reduces the time to onset of neuromuscular block caused by vecuronium, but does not attenuate changes in blood pressure and heart rate caused by tracheal intubation. |
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