title stringlengths 0 1.13k | abstract stringlengths 1 15.7k | PMID int64 22 36.5M |
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Epigallocatechin-3-gallate diminishes CCL2 expression in human osteoblastic cells via up-regulation of phosphatidylinositol 3-Kinase/Akt/Raf-1 interaction: a potential therapeutic benefit for arthritis. | To assess the effects of epigallocatechin-3-gallate (EGCG) on oncostatin M (OSM)-induced CCL2 synthesis and the associated signaling pathways in human osteoblastic cells. The therapeutic effect of EGCG on collagen-induced arthritis (CIA) in rats was also studied. CCL2 and c-Fos messenger RNA expression was analyzed by Northern blotting. The modulating effects of EGCG on the activation of Raf-1, Akt, and phosphatidylinositol 3-kinase (PI 3-kinase) were examined by coimmunoprecipitation, Western blotting, and PI 3-kinase activity assay. Interactions between c-Fos and CCL2 promoter were evaluated by electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assay. The effect of EGCG on CIA in rats was examined clinically and immunohistochemically. EGCG inhibited OSM-stimulated CCL2 expression in primary human osteoblasts and MG-63 cells. In MG-63 cells, EGCG alleviated the OSM-induced phosphorylation of Raf-1 at Ser338 but restored the dephosphorylation of Raf-1 at Ser259. EGCG increased the activity of PI 3-kinase, the level of phosphorylated Akt (Ser473), and binding between Raf-1 and active Akt. EMSA and ChIP assay revealed that EGCG attenuated activator protein 1 (AP-1)-CCL2 promoter interaction, possibly by reducing c-Fos synthesis. Codistribution of CD68+ macrophages and CCL2+ osteoblasts in osteolytic areas was obvious in the CIA model. Administration of EGCG markedly diminished the severity of CIA, macrophage infiltration, and the amount of CCL2-synthesizing osteoblasts. By stimulating PI 3-kinase activity, EGCG promoted Akt/Raf-1 crosstalk, resulting in decreased AP-1 binding to CCL2 promoter, and finally reduced CCL2 production in osteoblasts. EGCG alleviated the severity of CIA, probably by suppressing CCL2 synthesis in osteoblasts to diminish macrophage infiltration. Our data support the therapeutic potential of EGCG on arthritis. | 18,821,707 |
Nimesulide associated fulminant hepatic failure. | It is controversial whether the non-steroidal inflammatory drug nimesulide is associated with severe hepatotoxicity. Our objective was to determine whether nimesulide is associated with fulminant hepatic failure. Retrospective cohort study in the Irish national liver transplant unit. All patients who received a liver transplant for fulminant hepatic failure of unknown cause, between January 1994 and March 2007, were evaluated. New medications started within 6 months prior to transplant were identified. Likelihood of association assessed using the Naranjo and Roussel UCLAF Causality Assessment Method (RUCAM) scoring systems. Thirty-two patients with sero-negative, non-paracetamol fulminant hepatic failure, who received an emergency liver transplant, were identified. Nimesulide had been started within 6 months in 6 patients. Five of the six were middle aged females. Nimesulide was assessed as probably associated with liver injury in all six cases. Nimesulide was associated with fulminant hepatic failure requiring liver transplant in 6/32 cases of unknown origin. This association requires further investigation. | 18,821,716 |
Characteristic negative ion fragmentations of deprotonated peptides containing post-translational modifications: mono-phosphorylated Ser, Thr and Tyr. A joint experimental and theoretical study. | Peptides and proteins may contain post-translationally modified phosphorylated amino acid residues, in particular phosphorylated serine (pSer), threonine (pThr) and tyrosine (pTyr). Following earlier work by Lehmann et al., the [M-H]- anions of peptides containing pSer and pThr functionality show loss of the elements of H3PO4. This process, illustrated for Ser (and using a model system), is CH3CONH-C(CH2OPO3H2)CONHCH(3) --> [CH3CONHC(==CH2)CONHCH3 (-OPO3H2)] (a) --> [CH3CONHC(==CH2)CONHCH3-H]- + H3PO4, a process endothermic by 83 kJ mol(-1) at the MP2/6-31++G(d,p)//HF/6-31++G(d,p) level of theory. In addition, intermediate (a) may decompose to yield CH3CONHC(==CH2)CONHCH3 + H2PO4 - in a process exothermic by 3 kJ mol(-1). The barrier to the transition state for these two processes is 49 kJ mol(-1). Characteristic cleavages of pSer and pThr are more energetically favourable than the negative ion backbone cleavages of peptides described previously. In contrast, loss of HPO3 from [M-H]- is characteristic of pTyr. The cleavage [NH2CH(CH2-C6H4-OPO3H-)CO2H] --> [NH2C(CH2-C6H4-O-)CO2H (HPO3)] (b) --> NH2CH(CH2-C6H4-O-)CO2H + HPO3 is endothermic by 318 kJ mol(-1) at the HF/6-31+G(d)//AM1 level of theory. In addition, intermediate (b) also yields NH2CH(CH2-C6H4-OH)CO2H + PO3 - (reaction endothermic by 137 kJ mol(-1)). The two negative ion cleavages of pTyr have a barrier to the transition state of 198 kJ mol(-1) (at the HF/6-31+G(d)//AM1 level of theory) comparable with those already reported for negative ion backbone cleavages. | 18,821,730 |
Characteristics and comparison of different radiofrequency-only multipole cooling cells. | Various multipole cooling cells are widely used in mass spectrometry for their outstanding performance with regard to transmission and cooling effects. Among these, radiofrequency (RF)-only quadrupoles, hexapoles, and octopoles are routinely used in practical instrumentation. A study of their performance has been carried out using a house-built electrospray time-of-flight mass spectrometer equipped with three different multipole devices. In addition, a user-written program was developed using SIMION 7.0 to simulate ion transmission characteristics for the different devices utilized. Systematic experiments and simulations were performed with an RF-only quadrupole, hexapole, and octopole to study their theoretical and practical characteristics. | 18,821,731 |
Interpretation of the electronic spectra of four disilanes. | Time-dependent density functional theory (TD-DFT/B3LYP(AC)/cc-pVTZ/cc-pVTZ/6-311G//MP2/cc-pVTZ/cc-pVTZ/6-31G**) has been used to compute vertical excitation energies and oscillator strengths of the six low-lying excited states of four peralkylated disilanes, hexamethyldisilane (1), hexa-tert-butyldisilane (2), 1,6-disila[4.4.4]propellane (3), and 1,7-disila[5.5.5]propellane (4). The results provide an accurate interpretation of the reported UV absorption spectra of 1-4 in solution, and for 1 also in the gas phase up to 62,000 cm(-1). The excellent agreement of the calculated with the available experimental energies and oscillator strengths, and with magnetic circular (MCD) and linear (LD) dichroism, gives us confidence that the method will be useful for dependable interpretation of the electronic spectra of longer oligosilanes. Although the disilane chromophore finds itself in quite different environments in 1-4, its fundamental characteristics remain the same, with one important exception. In all four compounds, the first valence excited state is due to an electron promotion from the sigma(1) HOMO to the pi(1)* orbital, and the second valence excited state to a promotion from the sigma(1) HOMO to the sigma(1)* orbital. Surprisingly, however, it is only in 2, which has an extraordinarily long SiSi bond, that the terminating sigma(1)* orbital is the sigma*(SiSi) antibond, as anticipated, and the sigma sigma* transition has the expected very high oscillator strength. In 1, 3, and 4, the sigma*(SiSi) antibonding orbital is high in energy and does not play any role in low-energy excitations. Instead, the terminating orbital of the sigma(1)sigma(1)* excitation is represented by Si-alkyl antibonds, combined symmetrically with respect to rotation around the SiSi axis and antisymmetrically with respect to operations that interchange the two Si atoms. The common assumption that the characteristic intense sigma sigma* transitions of longer peralkylated oligosilanes extrapolate to the lowest sigma sigma* transition in common peralkylated disilanes is incorrect, and only the weak sigma pi* transitions extrapolate simply. | 18,821,735 |
Realization of SOMO-HOMO level conversion for a TEMPO-dithiolate ligand by coordination to platinum(II). | We developed a TEMPO-bound dithiolate ligand (= tempodt) and its Pt(diimine)(dithiolate) complex to realize a unique electronic structure with the potential for unprecedented functionalities. The physical properties and electronic structures of tempodt, (tempodt)Pt, and their related compounds were investigated by cyclic voltammetry, UV-visible spectroscopy, electron spin resonance (ESR) spectroscopy, and other techniques. It was revealed that (tempodt)Pt showed an unusual electronic structure in which the HOMO level (= pi-conjugated dithiolate-based orbital) was located above the SOMO level attributed to the TEMPO moiety, and that this situation was achieved via a drastic electronic structure change of SOMO-HOMO level conversion through complex formation. These findings were further supported by an investigation into a one-electron oxidized (tempodt)Pt and related complexes. | 18,821,762 |
Highly diastereoselective addition of lithio vinyl sulfoxides to N-sulfinimines: an entry to enantiopure 3-sulfinyl-2,5-cis-dihydropyrroles. | The addition of enantiopure alpha-metalated vinyl and dienyl sulfoxides to enantiomerically pure N-sulfinimines takes place with high diastereoselectivity primarily directed by the N-sulfinimine sulfur. The resulting allylic amines have been further transformed into highly functionalized 3-sulfinyl and 3-sulfonyl 2,5- cis-dihydropyrroles by reaction with electrophiles. | 18,821,766 |
Total synthesis of (+)-lepadin F. | An enantioselective total synthesis of (+)-lepadin F is described. The synthetic sequence features an intermolecular aza-[3 + 3] annulation, homologation of a vinylogous amide via Eschenmoser's episulfide contraction, and a highly stereoselective hydrogenation essential for achieving the 1,3-anti relative stereochemistry at C2 and C8a. | 18,821,767 |
Identification of adducts formed in the reactions of 5'-acetoxy-N'-nitrosonornicotine with deoxyadenosine, thymidine, and DNA. | N'-Nitrosonornicotine (NNN) is the most prevalent of the carcinogenic tobacco-specific nitrosamines found in all tobacco products. Previous studies have demonstrated that cytochrome P450-mediated 5'-hydroxylation of NNN is a major metabolic pathway leading to mutagenic products, but to date, DNA adducts formed by this pathway have been only partially characterized, and there have been no studies reported on adducts formed with bases other than dGuo. Because adducts with dAdo and dThd have been identified in the DNA of the livers of rats treated with the structurally related carcinogen N-nitrosopyrrolidine, we investigated dAdo and dThd adduct formation from 5'-acetoxyNNN (3), a stable precursor to 5'-hydroxyNNN (2). Reaction of 3 with dAdo gave diastereomeric products, which were identified by their spectral properties and LC-ESI-MS/MS-SRM analysis as N(6)-[5-(3-pyridyl)tetrahydrofuran-2-yl]dAdo (9). This adduct was further characterized by NaBH(3)CN reduction to N(6)-[4-hydroxy-4-(3-pyridyl)but-1-yl]dAdo (17). A second dAdo adduct was identified, after NaBH(3)CN treatment, as 6-[2-(3-pyridyl)pyrrolidin-1-yl]purine-2'-deoxyriboside (18). Reaction of 3 with dThd, followed by NaBH(3)CN reduction, gave O(2)-[4-(3-pyridyl)-4-hydroxybut-1-yl]thymidine (11). Adducts 9, 11, 17, and 18 were all identified by LC-ESI-MS/MS-SRM comparison to synthetic standards. The reaction of 3 with calf thymus DNA was then investigated. The DNA was enzymatically hydrolyzed to deoxyribonucleosides, and the resulting mixture was treated with NaBH(3)CN and analyzed by LC-ESI-MS/MS-SRM. Adducts 11, 17, and 18, as well as the previously identified dGuo adducts, were identified. The results of this study provide a more comprehensive picture of DNA adduct formation by the quantitatively important 5'-hydroxylation pathway of NNN and will facilitate investigation of the presence of these adducts in laboratory animals treated with NNN or in people who use tobacco products. | 18,821,782 |
Ag4V2O6F2 (SVOF): a high silver density phase and potential new cathode material for implantable cardioverter defibrillators. | The electrochemical reactivity of the cathode material Ag 4V 2O 6F 2 (SVOF) versus lithium, with a particular emphasis on the lithium insertion mechanism, was studied by means of the complementary techniques in situ X-ray diffraction, electron paramagnetic resonance, and high-resolution transmisssion electron microscopy. This study confirms the initial reports of a high capacity for SVOF of 148 mAh/g above 3 V and that the reduction of silver above 3 V (vs Li (+)/Li (0)) leads to a loss of SVOF crystallinity until it becomes completely amorphous between the third and fourth lithiums inserted. Next, vanadium is reduced between 2.5 and 1.5 V (vs Li (+)/Li (0)) for the fifth and sixth lithiums inserted. In addition, the polarization within the cathode is significantly lower for the vanadium reduction than for the silver reduction. The silver metal morphologies consisted of nanoparticles ( approximately 5 nm diameter) and dendrites and were both seen in samples of lithiated SVOF. | 18,821,813 |
Status of trivalent copper and charge-transfer excitons in high-TC cuprates. | A chemical bonding approach based on tight-binding cluster and band calculations, taking into account on-site Coulomb repulsion (Hubbard U parameter) to differentiate doubly and singly occupied states, was applied to high- T C superconducting cuprates and related compounds. This work provides rational insight and explanations for issues such as (i) the actual oxidation number Cu (I+) for formally trivalent copper in oxides such as La 2Li 1/2Cu 1/2O 4, (ii) the dominant oxygen character of the doping holes in (CuO 2) ( n- ) planes, (iii) the Mott-Hubbard character of the insulator-to-metal transition triggered by hole doping, leading to an oxygen-to-copper charge transfer of avalanche type, (iv) the occurrence of an excitonic phase with anisotropic Frenkel-type excitons, (v) the role of Coulomb interactions between excitons and between doping holes and their exciton surroundings, and (vi) the on-time pairing of doping holes by means of an "excitonic glue". | 18,821,815 |
Structures and properties of functional metal selenites and tellurites. | Metal selenites and tellurites are a class of very important compounds. In this paper, the structures and properties of metal selenites or tellurites combining with transition-metal (TM) ions with the d (0) electronic configuration or tetrahedral MO 4 building blocks of post-transition main-group elements were reviewed. Most compounds in the alkali or alkaline-earth-d (0) TM-Se (IV) (or Te (IV))-O systems exhibit extended anionic architectures composed of distorted octahedra of (d (0)) TM cations and tellurite or selenite groups. The distortion of the octahedron is always away from the lone-pair cation, and some of them exhibit excellent second-order nonlinear optical properties due to the adductive effects of two types of bond polarizations. Because of the high coordination number of Ln (III) ions, most of compounds in the Ln-d (0) TM-Se (IV) (or Te (IV))-O systems are not second-harmonic-generation active; however, they are able to emit strong luminescence in the visible or near-IR region; also in most cases, the d (0) TM cations are in tetrahedral geometry and are well separated from selenite or tellurite groups. It is also interesting to note that the selenite group is normally "isolated", whereas the TeO x ( x = 3-5) can be polymerized into a variety of discrete polynuclear anionic clusters or extended architectures via Te-O-Te bridges. | 18,821,816 |
A-site-ordered perovskites with intriguing physical properties. | Recent findings on intriguing physical properties of new A-site-ordered perovskite structure oxides are reviewed. High-pressure and high-temperature conditions stabilize the square-coordinated Jahn-Teller Cu (2+) ions in the original 12-fold-coordinated positions of the perovskite structure. The special-ordered arrangement of the square-coordinated A'O 4 units that align perpendicularly to each other sets a characteristic structural framework, and the presence of Cu (2+) ions at the A' site and A'-B interactions play crucial roles for the diverse and intriguing physical properties. | 18,821,822 |
Using mechanistic models to understand synchrony in forest insect populations: the North American gypsy moth as a case study. | In many forest insects, subpopulations fluctuate concurrently across large geographical areas, a phenomenon known as population synchrony. Because of the large spatial scales involved, empirical tests to identify the causes of synchrony are often impractical. Simple models are, therefore, a useful aid to understanding, but data often seem to contradict model predictions. For instance, chaotic population dynamics and limited dispersal are not uncommon among synchronous forest defoliators, yet both make it difficult to achieve synchrony in simple models. To test whether this discrepancy can be explained by more realistic models, we introduced dispersal and spatially correlated stochasticity into a mechanistic population model for the North American gypsy moth Lymantria dispar. The resulting model shows both chaotic dynamics and spatial synchrony, suggesting that chaos and synchrony can be reconciled by the incorporation of realistic dynamics and spatial structure. By relating alterations in model structure to changes in synchrony levels, we show that the synchrony is due to a combination of spatial covariance in environmental stochasticity and the origins of chaos in our multispecies model. | 18,821,838 |
Optimization of amniotic membrane (AM) denuding for tissue engineering. | Amniotic membrane (AM) has gained increasing popularity as a useful carrier for ex vivo-expanded cells for tissue engineering, particularly in ocular surface reconstruction. However, current methods employed for denuding AM are highly variable, and the consequent effects on the structural and molecular composition of the AM basement membrane (BM) are ambiguous. We compare the effects of the main denuding procedures, and propose a highly effective standardized alternative. AMs preserved for transplantation were denuded using published ethylenediaminetetraacetic acid (EDTA)- and dispase-based methodologies and our novel thermolysin-based procedure. Scanning and transmission electron microscopy and immunohistochemistry, for BM components (collagens IV and VII, laminin 5, and integrins alpha6 and beta4), were used to assess effectiveness of denuding epithelium, whilst maintaining the integrity of the BM. EDTA- and dispase-based denuding techniques resulted in the disaggregation and even destruction of the BM structure and molecular composition. Employing thermolysin effectively denuded epithelium whilst maintaining BM structural and molecular integrity. Current procedures for preparing AM are variable and often ineffective, resulting in nonstandard membranes. Our novel thermolysin-based technique effectively denudes the AM whilst preserving an essentially intact and consistent BM. Therefore, we propose that this novel thermolysin procedure may potentially improve overall generation of tissue-engineered constructs using AM. | 18,821,842 |
Hyperbaric oxygen activates discoidin domain receptor 2 via tumour necrosis factor-alpha and the p38 MAPK pathway to increase vascular smooth muscle cell migration through matrix metalloproteinase 2. | DDR2 (discoidin domain receptor 2) regulates collagen turnover mediated by SMCs (smooth muscle cells) in atherosclerosis. HBO (hyperbaric oxygen) has been used in medical practice; however, the molecular mechanism of the beneficial effects of HBO is poorly understood. Furthermore, the effect of HBO on DDR2 has not been reported previously. In the present study, we investigated the cellular and molecular mechanisms of DDR2 regulation by HBO in VSMCs (vascular SMCs). Cells were exposed to 2.5 ATA (atmosphere absolute) of oxygen in a hyperbaric chamber. DDR2 protein (3.63-fold) and mRNA (2.34-fold) expression were significantly increased after exposure to 2.5 ATA HBO for 1 h. Addition of SB203580 and p38 MAPK (mitogen-activated protein kinase) siRNA (small interfering RNA) 30 min before HBO inhibited the induction of DDR2 protein. HBO also significantly increased DNA-protein binding activity of Myc/Max. Addition of SB203580 and an anti-TNF-alpha (tumour necrosis factor-alpha) monoclonal antibody 30 min before HBO abolished the DNA-protein binding activity induced by HBO. HBO significantly increased the secretion of TNF-alpha from cultured VSMCs. Exogenous addition of TNF-alpha significantly increased DDR2 protein expression, whereas anti-TNF-alpha and anti-(TNF-alpha receptor) antibodies blocked the induction of DDR2 protein expression. HBO significantly increased VSMC migration and proliferation, whereas DDR2 siRNA inhibited the migration induced by HBO. HBO increased activated MMP2 (matrix metalloproteinase 2) protein expression, and DDR2 siRNA abolished the induction of activated MMP2 expression induced by HBO. In conclusion, HBO activates DDR2 expression in cultured rat VSMCs. HBO-induced DDR2 is mediated by TNF-alpha and at least in part through the p38 MAPK and Myc pathways. | 18,821,853 |
Redox control of renal function and hypertension. | Loss of redox homeostasis and formation of excessive free radicals play an important role in the pathogenesis of kidney disease and hypertension. Free radicals such as reactive oxygen species (ROS) are necessary in physiologic processes. However, loss of redox homeostasis contributes to proinflammatory and profibrotic pathways in the kidney, which in turn lead to reduced vascular compliance and proteinuria. The kidney is susceptible to the influence of various extracellular and intracellular cues, including the renin-angiotensin-aldosterone system (RAAS), hyperglycemia, lipid peroxidation, inflammatory cytokines, and growth factors. Redox control of kidney function is a dynamic process with reversible pro- and anti-free radical processes. The imbalance of redox homeostasis within the kidney is integral in hypertension and the progression of kidney disease. An emerging paradigm exists for renal redox contribution to hypertension. | 18,821,850 |
Tandem measurement of D-dimer and myeloperoxidase or C-reactive protein to effectively screen for pulmonary embolism in the emergency department. | The hypothesis was that the tandem measurement of D-dimer and myeloperoxidase (MPO) or C-reactive protein (CRP) could significantly decrease unnecessary pulmonary vascular imaging in emergency department (ED) patients evaluated for pulmonary embolism (PE) compared to D-dimer alone. The authors measured the sequential combinations of D-dimer and MPO and D-dimer and CRP in a prospective sample of ED patients evaluated for PE at two centers. Patients were followed for 90 days for venous thromboembolism (VTE, either PE or deep venous thrombosis [DVT]), which required the consensus of two of three blinded physician reviewers. The authors enrolled 304 patients, 22 with VTE (7%; 95% confidence interval [CI] = 5% to 10%). The sensitivity and specificity of a D-dimer alone (cutoff > or = 500 ng/mL) were 100% (95% CI = 85% to 100%) and 59% (95% CI = 53% to 65%), respectively, and was followed by pulmonary vascular imaging negative for PE in 38% (115/304; 95% CI = 32% to 44%). The combination of either a negative D-dimer, or MPO < 22 mg/dL, had a sensitivity of 100% and specificity of 73% (95% CI = 67% to 78%). Thus, tandem measurement of D-dimer and MPO would have decreased the frequency of subsequent negative pulmonary vascular imaging from 38% to 25% (95% CI of the difference of -13% = -5% to -20%). The combination of CRP and D-dimer would not have significantly improved the rate of negative imaging. The tandem measurement of D-dimer and MPO would have significantly decreased negative pulmonary vascular imaging compared with D-dimer alone and should be validated prospectively. | 18,821,859 |
Genetic and environmental contributions to the diversity of substances used in adolescent twins: a longitudinal study of age and sex effects. | To determine how genetic and environmental contributions affecting the number of psychoactive substances used varies with age and gender over the course of adolescence. Estimates of genetic, shared environmental and non-shared environmental contributions to total variance in diversity of substances used at ages 11, 14 and 17 years were obtained by fitting a multivariate behavior genetic (Cholesky) model. A total of 711 male and 675 female twins. Participants reported whether they had used each of 11 substances. The average diversity of substances used increased over time for both males and females, and males generally reported a wider diversity of substances used than females. Influences of genetic factors increased with age and were greater for males than for females at ages 14 and 17 years. Genetic factors remained consistent (i.e. highly correlated) across ages for both males and females, as did shared environmental influences for males. Non-shared environmental factors for both sexes and females' shared environmental factors were age-specific. Regardless of sex, the proportion of variance in substances used attributable to genetic factors increases during adolescence, although it is greater for males than females at later ages. These findings indicate that prevention interventions may be most effective if they target early adolescence when environmental factors account for the majority of variance in substance use. The high correlation of genetic factors across ages suggests that early use may sometimes signal an early expression of a developmentally stable genetic predisposition. | 18,821,880 |
Nipple-sparing mastectomy: lessons from ex vivo procedures. | Moderate size series have reported successful nipple-sparing mastectomy using a variety of surgical techniques. This study aimed to understand which aspects of these techniques are safe, necessary, and successful. Eight skin-sacrificing mastectomy specimens were used as ex vivo models of nipple-sparing mastectomy. After inking the resection margins of the specimen, the skin ellipse was elevated in the subcutaneous plane using a scalpel. The retroareolar breast tissue was taken as a margin specimen. The nipple was inverted and the nipple core removed. The hollowed-out nipple remnant (which would have remained with the patient in a true nipple-sparing mastectomy) was submitted for confirmatory histopathologic analysis. Precise identification of the duct margin directly beneath the nipple proved difficult once the duct bundle had been divided. Successful retroareolar margin identification was achieved by grasping the duct bundle with atraumatic forceps as soon as it became exposed. A cut made below and above the forceps resulted in a full cross-section of the duct bundle. Nipple core tissue was difficult to excise in one piece and cannot be oriented, thus complete evaluation of the specimen required examination of multiple levels. Histologic artifacts caused by freezing may be present in frozen sections of nipple core and retroareolar margin specimens; the impact of such changes must be considered when developing institutional protocols for this procedure. Evaluation of the hollowed-out nipple revealed that the inverted nipple must be substantially thinned to remove all ducts. Modification of technique resulted in more complete excision of duct tissue. This series of ex vivo procedures provides information that can be used to modify surgical and pathologic techniques for nipple-sparing mastectomy. When performing nipple-sparing mastectomy for breast cancer, these measures may be advisable as complements to careful patient selection. | 18,821,932 |
Higher constitutive IL15R alpha expression and lower IL-15 response threshold in coeliac disease patients. | The IL-15 triggering effect of gliadin is not exclusive to coeliac disease (CD) patients, whereas the secondary response is CD specific. We have studied the expression of the IL-15 receptor, and the IL-15 response upon stimulation, in non-CD and CD patients, and the possible existence of a lower immunological threshold in the latter. Forty-two CD patients (20 on a gluten-containing diet, GCD, and 22 on gluten-free diet, GFD) and 24 non-CD healthy individuals were studied. IL15R alpha mRNA expression, and tissue characterization, were assayed in the duodenum. Biopsies from six CD patients on GFD and 10 non-CD individuals were studied in vitro using organ culture in basal conditions, as well as after IL-15 stimulation discarding basal IL-15 production. Secretion of immune mediators was measured in the culture supernatants. IL15R alpha mRNA expression was increased in CD patients, as compared with non-CD controls (on GFD P = 0.0334, on GCD P = 0.0062, respectively), and confirmed also by immunofluorescence. No differences were found between CD patients on GFD and on GCD. After in vitro IL-15 stimulation, IL15R alpha expression was only triggered in non-CD controls (P = 0.0313), though it remained increased in CD patients. Moreover, IL-15 induced a more intense immunological response in CD patients after triggering the production of both nitrites and IFN gamma (P = 0.0313, P = 0.0313, respectively). Gliadin-induced IL15 has a lower response threshold in CD patients, leading to the production of other immune mediators and the development of the intestinal lesion, and thus magnifying its effects within the CD intestine. | 18,821,940 |
Regulatory T cells in human immunodeficiency virus-infected patients are elevated and independent of immunological and virological status, as well as initiation of highly active anti-retroviral therapy. | Infection with human immunodeficiency virus (HIV) causes a dysregulation of the immune system. This is caused by HIV-specific as well as non-specific mechanisms and has not been explained fully. In particular, knowledge is lacking about the potential role of host-mediated immunosuppressive mechanisms. During recent years it has become evident that a subpopulation of T cells [T regulatory (T(regs))] play a major role in sustaining tolerance to self-antigens. To investigate the influence of initiation of highly active anti-retroviral therapy (HAART) on the T(reg) level in HIV-infected patients we have conducted a prospective study enrolling treatment-naive HIV-infected patients just prior to starting treatment with HAART, measuring levels of T(regs) by flow cytometry and mRNA expression of forkhead box P3 (FoxP3) at weeks 0, 4, 12 and 24 of treatment. In this prospective study neither the percentage of CD4(+)CD25(high+) nor the expression of FoxP3 changed significantly during 24 weeks of HAART. Furthermore, HIV patients have higher T(regs) measured as percentages of CD4(+)CD25(high+) cells paralleled by higher levels of FoxP3 compared with healthy controls. The elevated level of T(regs) was found to be independent of both immunological and virological status, indicating that initiation of HAART has minor effects on the T(reg) level in HIV-infected patients. | 18,821,942 |
pH changes after manual or ultrasonic instrumentation and smear layer removal with EDTA or ultrasonic. | The purpose of the present study was to evaluate the influence of instrumentation techniques associated with the smear layer removal, in the pH changes of the root surface. Thirty mandibular humans premolars were divided into three groups: Group I - instrumentation by Ohio technique and final cleaning with EDTA (3 minutes); Group II - instrumentation by Ohio technique and final cleaning with ultrasonic (1 minute); Group III - instrumentation by the ultrasonic technique and final cleaning with ultrasonic (1 minute). The pH was measured in the cavities prepared in the cervical, middle and apical thirds of the lateral wall of each root. The teeth were evaluated at the initiation of the experiment, and 3, 7, 14, 21, 30 days after of the intracanal dressing of the calcium hydroxide with camphorated p-monochlorophenol (Calen/PMCC). All the groups presented increasing pH values; group III presented the highest average pH, followed by groups II and I; the values for the apical third were lower than those of the middle and cervical thirds (anova and Tukey test). The results showed that the biomechanical preparation by the ultrasonic technique and smear layer removal with ultrasonic showing the highest diffusion of the calcium and hydroxyl ions from the intracanal dressing (P < 0.05). | 18,821,959 |
An unusual lateral luxation of an upper incisor owing to long-term boxing without protection. | This case report describes a lateral luxation of an upper incisor in a 19-year-old non-professional boxer. The tooth displacement gradually worsened over several months because the boxer received repeated blows to the head without using a mouthguard. Being a chronic dental trauma, rather than an acute lateral luxation, this case had several unique features: the labial plate of the alveolar bone was penetrated, the root apex was free in the vestibulum, the tooth was mobile (second degree) and radiographs revealed bone resorption. This case emphasized the need for a mouthguard to be used even with amateur boxing. The dental practitioner should educate his sportsmen-patients of the risk of sport-related dental trauma and the benefit of a mouthguard. | 18,821,961 |
Partial replacement of the dentin-pulp complex by periodontal supporting tissues in a traumatically intruded primary maxillary incisor. | This paper describes a case of a 9-year-old patient who presented a completely intruded primary maxillary incisor because of a traumatic injury sustained at the age of 3 years. After tooth extraction, histological analysis revealed that the dentin-pulp complex was partially replaced by cementum, periodontal ligament and alveolar bone. No signs of ankylosis were noticed. It is suggested that the lack of spontaneous re-eruption of the traumatized primary tooth after 6 years could be due to the development of functional periodontal supporting tissues in the pulp chamber secondary to the traumatism. | 18,821,962 |
External multiple invasive cervical resorption with subsequent arrest of the resorption. | A rare, the uncommon, case of multiple invasive cervical resorption (MICR) with subsequent arrest of the resorption involving eight teeth of the mandible (tooth 46 to tooth 32) is presented. This case is noteworthy because of the characteristics of its clinical evolution. There have only been a few cases in the literature were found presenting involvement of such a large number of teeth. Furthermore, no reports on cases of MICR with arrest of the resorption, as described in this report, were found. | 18,821,963 |
Taste deficits after middle ear surgery for otosclerosis: taste somatosensory interactions. | The aim of this study was to evaluate the postoperative consequences of chorda tympani reclining during middle ear surgery for otosclerosis. Electrogustometric taste thresholds were measured at 11 loci on the tongue and the soft palate in 14 patients before surgery, and 8 d, 1 month and (in some cases) 6 months after surgery. A significant increase in thresholds was observed on the ipsilateral side of the tongue after surgery. The extent of the deficit and the recovery time course depended on tongue locus. The tip of the tongue displayed a limited deficit, suggesting bilateral chorda tympani innervation. The edge of the tongue was less impaired than the dorsal or the lateral tip loci; it may be dually innervated by both chorda tympani and glossopharyngeal nerves in humans, as already shown in rats. Likewise for the fungiform papillae located just anterior to the circumvallate papillae. Somatosensory early complaints suggest a derepression of chorda tympani on lingual nerve signals. In a second stage, relief of complaints before electrogustometric threshold recovery suggested trigeminal compensation of the chorda tympani deficit. Relief of complaints seems to involve central integrative processes, whereas the evolution of electrogustometric threshold represents the actual recovery time course of chorda tympani peripheral sensitivity. | 18,821,980 |
Mutations in the EDA gene are responsible for X-linked hypohidrotic ectodermal dysplasia and hypodontia in Chinese kindreds. | X-linked hypohidrotic ectodermal dysplasia (XLHED, OMIM 305100) is a rare congenital disorder that results in the defective development of teeth, hair, nails, and eccrine sweat glands. Previous studies found that mutations in the ectodysplasin A (EDA) gene are associated with XLHED. In the present study, we investigated four Chinese families suffering from classical XLHED and investigated two additional families segregating hypodontia in an X-linked recessive manner. Mutations were characterized respectively in the EDA gene in all families, and five of these mutations were found to be novel. Among these mutations, five were missense (c.200A>T, c.463C>T, c.758T>C, c.926T>G, and c.491A>C) and located in the functional domain of EDA, and one was a splice donor site mutation in intron 5 (c.IVS5 + 1G>A), which may result in an alternative transcript derived from a new cryptic splice site. Our data further confirm that EDA mutations could cause both XLHED and isolated hypodontia and provide evidence that EDA is a strong candidate gene for tooth genesis. | 18,821,982 |
Myelin basic protein is temporospatially expressed in developing rat molars. | Tooth development occurs through a complex and intricate set of gene-expression cascades. Although its early events have been examined extensively, there are fewer reports on the late events, such as dental hard-tissue formation. This study searched for genes involved in the late stages of tooth development. Differential display-polymerase chain reaction revealed myelin basic protein (MBP) mRNA to be expressed differentially in the second molar root stage germs compared with the third molar cap/early bell stage germs. The MBP expressed during hard tissue formation was confirmed to be a 21.5 kDa molecule by Western blotting. Immunoreactivity of MBP in the third molar (cap/early bell stage) germs was barely detectable in the dental papilla and inner enamel epithelia, whereas strong reactivity was noted in the differentiating and differentiated ameloblasts and odontoblasts in a temporospatial pattern. However, after complete formation of the full-thickness enamel, no reactivity was observed in the maturation-stage and protection stage ameloblasts. Myelin basic protein immunoreactive nerve fibers were also observed near the developing molar germs. This is the first report showing the presence of MBP in dental hard tissue cells, and its functional implications should be studied further. | 18,821,983 |
Reducing psychotropic medications in elderly rehabilitation inpatients with a fall-related admission: how often is it happening? | To assess the frequency of psychotropic medication withdrawal in an inpatient geriatric rehabilitation population with a fall-related admission diagnosis. A retrospective medical record audit. The medical records department randomly selected 100 patients admitted between October 2006 and April 2007 to the geriatric rehabilitation ward of Casey Hospital with a fall-related admission diagnosis. The population was predominantly female (71%) and elderly (average age, 80 years) with the vast majority of patients living at home (88%) prior to admission. Twenty-six of 49 (53%) of patients admitted on psychotropic medication were on a reduced regime by discharge (reduced dose or number of psychotropic medications). Just 7 of 100 patients had an increased psychotropic medication regime by discharge. Benzodiazepines were far more likely to be reduced (20/24, 83%) than other psychotropic medications. This audit does suggest an acceptable awareness in this geriatric rehabilitation setting of the fall risk posed by psychotropic medication. It needs to be further explored why benzodiazepines are so much more likely to be reduced in this population than other psychotropic medications, despite those other types also posing a significant fall risk. | 18,821,996 |
Simultaneous determination of 21 preservatives in cosmetics by ultra performance liquid chromatography. | An ultra performance liquid chromatography (UPLC) method has been developed for the simultaneous determination of 21 preservatives: 2-methyl-4-isothiazoline-3-ketone, bronopol, 5-chloro-2-methyl-4-isothiazoline-3-ketone, benzyl alcohol, 2-phenoxyethanol, methyl-p-hydroxy benzoate, ethyl-p-hydroxy benzoate, methyl benzoate, 4-hydroxybenzoic acid iso-propyl ester, propyl-p-hydroxy benzoate, 4-chloro-3-methylphenol, ethyl benzoate, 2-phenylphenol, 4-hydroxybenzoic acid iso-butyl ester, butyl-p-hydroxy benzoate, 4-chloro-3,5-dimethylphenol, phenyl benzoate, 2,4-dichloro-3,5-dimethylphenol, 2-benzyl-4-chlorophenol, triclocarban and triclosan in cosmetics. A Waters ACQUITY UPLC BEH C(18) column was used with 0.1% formic acid solution as the mobile phase under the condition of gradient elution. Preservatives were extracted with methanol by ultrasonicator, and then they were analysed by UPLC-PDA detector. All these preservatives were baseline separated in 8.5 min. The pre-treatment method of samples and the chromatographic condition of analysis were critically examined in this study. The recoveries ranged from 90.5 to 97.8%, with RSD values below 3.2%, and all correlation coefficients (r) were no less than 0.9997. Thus, this method could be used for analysing the preservatives in cosmetic products. | 18,822,043 |
Comparison of apomorphine and levodopa infusions in four patients with Parkinson's disease with symptom fluctuations. | Motor fluctuations in patients with advanced Parkinson's disease may be successfully treated with subcutaneous apomorphine infusion or intraduodenal levodopa/carbidopa infusion. No comparative trials of these two alternatives were performed. We present a subanalysis from a randomized crossover clinical trial where levodopa infusion as monotherapy was compared with any other combination of pharmacotherapy in fluctuating patients. Four patients used apomorphine infusion and oral levodopa in the comparator arm. The results of these four patients are presented in detail. The duration of the trial was 3 + 3 weeks. Patients were video-recorded half-hourly on two non-consecutive days of both treatment arms. Blinded video ratings were used. Patient self-assessments of motor function and quality-of-life (QoL) parameters were captured using an electronic diary. Ratings in moderate to severe "off" state ranged 0-44% on apomorphine infusion and 0-6% on levodopa infusion. Moderate to severe dyskinesias were not recorded in any of the treatments. QoL was reported to be improved in all patients on duodenal levodopa infusion. Monotherapy with duodenal infusion of levodopa was more efficacious and brought greater QoL than combination therapy with apomorphine infusion in these fluctuating patients. | 18,822,087 |
A GYS1 gene mutation is highly associated with polysaccharide storage myopathy in Cob Normand draught horses. | Glycogen storage diseases or glycogenoses are inherited diseases caused by abnormalities of enzymes that regulate the synthesis or degradation of glycogen. Deleterious mutations in many genes of the glyco(geno)lytic or the glycogenesis pathways can potentially cause a glycogenosis, and currently mutations in fourteen different genes are known to cause animal or human glycogenoses, resulting in myopathies and/or hepatic disorders. The genetic bases of two forms of glycogenosis are currently known in horses. A fatal neonatal polysystemic type IV glycogenosis, inherited recessively in affected Quarter Horse foals, is due to a mutation in the glycogen branching enzyme gene (GBE1). A second type of glycogenosis, termed polysaccharide storage myopathy (PSSM), is observed in adult Quarter Horses and other breeds. A severe form of PSSM also occurs in draught horses. A mutation in the skeletal muscle glycogen synthase gene (GYS1) was recently reported to be highly associated with PSSM in Quarter Horses and Belgian draught horses. This GYS1 point mutation appears to cause a gain-of-function of the enzyme and to result in the accumulation of a glycogen-like, less-branched polysaccharide in skeletal muscle. It is inherited as a dominant trait. The aim of this work was to test for possible associations between genetic polymorphisms in four candidate genes of the glycogen pathway or the GYS1 mutation in Cob Normand draught horses diagnosed with PSSM by muscle biopsy. | 18,822,097 |
Differential invasion of Trypanosoma brucei brucei and lymphocytes into the brain of C57BL/6 and 129Sv/Ev mice. | Trypanosoma brucei subspecies invade the brain parenchyma at late stages of human and experimental rodent infections. In this study, we compared the outcome of infection with T. b. brucei in MHC-matched (H-2b) C57BL/6 (B6) and 129Sv/Ev (Sv-129). Sv-129 showed higher parasitaemia and lower specific IgM (but not IgG) antibody levels than B6 mice. The number of trypanosomes, CD4+ and CD8+ T cells in the brain parenchyma was higher in B6 mice. B6 mice lost weight and showed higher cumulative mortality when compared with Sv-129 mice. Higher levels of IL-1beta, IL-6, IL-10, TNF-alpha, IFN-gamma, ICAM-1 and E-selectin, but low levels of TGF-beta mRNA were present in brains of B6 when compared with Sv-129-infected mice. Thus, host genetics differentially determine the invasion of T. b. brucei into the brain parenchyma, which is paralleled by the severity of inflammation in the brain and course of the disease, but not by parasitaemia nor by antibody titres. | 18,822,108 |
Mining tissue specificity, gene connectivity and disease association to reveal a set of genes that modify the action of disease causing genes. | The tissue specificity of gene expression has been linked to a number of significant outcomes including level of expression, and differential rates of polymorphism, evolution and disease association. Recent studies have also shown the importance of exploring differential gene connectivity and sequence conservation in the identification of disease-associated genes. However, no study relates gene interactions with tissue specificity and disease association. We adopted an a priori approach making as few assumptions as possible to analyse the interplay among gene-gene interactions with tissue specificity and its subsequent likelihood of association with disease. We mined three large datasets comprising expression data drawn from massively parallel signature sequencing across 32 tissues, describing a set of 55,606 true positive interactions for 7,197 genes, and microarray expression results generated during the profiling of systemic inflammation, from which 126,543 interactions among 7,090 genes were reported. Amongst the myriad of complex relationships identified between expression, disease, connectivity and tissue specificity, some interesting patterns emerged. These include elevated rates of expression and network connectivity in housekeeping and disease-associated tissue-specific genes. We found that disease-associated genes are more likely to show tissue specific expression and most frequently interact with other disease genes. Using the thresholds defined in these observations, we develop a guilt-by-association algorithm and discover a group of 112 non-disease annotated genes that predominantly interact with disease-associated genes, impacting on disease outcomes. We conclude that parameters such as tissue specificity and network connectivity can be used in combination to identify a group of genes, not previously confirmed as disease causing, that are involved in interactions with disease causing genes. Our guilt-by-association algorithm should be useful for the discovery of additional modifiers of genetic diseases, and more generally, for the ability to associate genes of unknown function to clusters of genes with defined functions allowing for novel biological inference that can be subsequently validated. | 18,822,114 |
Ultrasound evaluation of the abductor hallucis muscle: Reliability study. | The Abductor hallucis muscle (AbdH) plays an integral role during gait and is often affected in pathological foot conditions. The aim of this study was to evaluate the within and between-session intra-tester reliability using diagnostic ultrasound of the dorso-plantar thickness, medio-lateral width and cross-sectional area, of the AbdH in asymptomatic adults. The AbdH muscles of thirty asymptomatic subjects were imaged and then measured using a Philips HD11 Ultrasound machine. Interclass correlation coefficients (ICC) with 95% confidence intervals (CI) were used to calculate both within and between session intra-tester reliability. The within-session reliability results demonstrated for dorso-plantar thickness an ICC of 0.97 (95% CI: 0.99-0.99); medio-lateral width an ICC: of 0.97 (95% CI: 0.92-0.97) and cross-sectional area an ICC of 0.98 (95% CI: 0.98-0.99). Between-session reliability results demonstrated for dorso-plantar thickness an ICC of 0.97 (95% CI: 0.95 to 0.98); medio-lateral width an ICC of 0.94 (95% CI 0.90 to 0.96) and for cross-sectional area an ICC of 0.79 (95% CI 0.65 to 0.88). Diagnostic ultrasound has the potential to be a reliable tool for evaluating the AbdH muscle in asymptomatic subjects. Subsequent studies may be conducted to provide a better understanding of the AbdH function in foot and ankle pathologies. | 18,822,116 |
Menopause, postmenopausal hormone use and serum uric acid levels in US women--the Third National Health and Nutrition Examination Survey. | Despite the substantial prevalence of gout in the ageing female population, female hormonal influence has not been comprehensively examined. We evaluated and quantified the potential independent association between menopause, postmenopausal hormone use and serum uric acid levels in a nationally representative sample of women. Using data from 7662 women aged 20 years and older in the Third National Health and Nutrition Examination Survey (1988 to 1994), we examined the relation between menopause, postmenopausal hormone use and serum uric acid levels. We used multivariate linear regression to adjust for other risk factors for hyperuricaemia such as dietary factors, age, adiposity, alcohol use, renal function, hypertension and diuretic use. Menopause was associated with higher serum uric acid levels. After adjusting for covariates, serum uric acid levels among women with natural menopause and surgical menopause were greater than premenopausal women by 0.34 mg/dl (95% confidence interval [CI], 0.19 to 0.49) and 0.36 mg/dl (95% CI, 0.14 to 0.57), respectively. Current postmenopausal hormone use was associated with a lower serum uric acid level among postmenopausal women (multivariate difference, 0.24 mg/dl [95% CI, 0.11 to 0.36]). The serum uric acid levels increased with increasing age categories (crude difference between 20 to 29 years and 70 years and over = 1.03 mg/dl, p for trend < 0.001), but this increase was not present after adjusting for other covariates (p for trend = 0.66). These findings from a nationally representative sample of US women indicate that menopause is independently associated with higher serum uric acid levels, whereas postmenopausal hormone use is associated with lower uric acid levels among postmenopausal women. The age-associated increase in serum uric acid levels in women may be explained by menopause and other age-related factors. | 18,822,120 |
The KBG syndrome: Case report. | The KBG syndrome is a rare autosomal dominant condition, first described by Hermann et al. in 1975. Fundamental findings are: mild development delay, short stature, craniofacial dysmorphism and skeletal anomalies. A 32 years old woman, Caucasian race, weight 57 Kg, affected by KBG syndrome was sent to our clinics for preoperative anaesthesia evaluation. She was schedules for left ossicular reconstruction under general anaesthesia for bilateral hearing loss. A psycho-motor retardation was associated to morphological anomalies such as short neck, hyperlordosis without neck extension imparirment, craniofacial anomalies and dento-skeletal abnormalities. An echocardiography showed the presence of interatrial defect with left-to-right shunt. The patient was sent to a cardiac surgery centre. Perioperative evaluation of patients affected by KBG syndrome must take into consideration the management of difficult airways, due to the associated craniofacial dysmorphism. The possible presence of cardiac anomalies in the KBG syndrome is currently being evalueted. In this report the finding of cardiomegaly and congestion of the pulmonary circulation was attributed to presence of an interatrial defect with left-to-right shunt. The risk of cardiopulmonary failure led us to ask for a cardiac surgery consult. Perioperative management of these patients should be extremely accurate, even in the case of minor surgery, and should include also chest X-rays and echocardiography evaluation. | 18,822,138 |
Role of Smac/DIABLO in cancer progression. | Second mitochondria-derived activator of caspase/direct inhibitor of apoptosis-binding protein with low pI (Smac/DIABLO) is a proapoptogenic mitochondrial protein that is released to the cytosol in response to diverse apoptotic stimuli, including commonly used chemotherapeutic drugs. In the cytosol, Smac/DIABLO interacts and antagonizes inhibitors of apoptosis proteins (IAPs), thus allowing the activation of caspases and apoptosis. This activity has prompted the synthesis of peptidomimetics that could potentially be used in cancer therapy. For these reasons, several authors have analyzed the expression levels of Smac/DIABLO in samples of patients from different tumors. Although dissimilar results have been found, a tissue-specific role of this protein emerges from the data. The objective of this review is to present the current knowledge of the Smac/DIABLO role in cancer and its possible use as a marker or therapeutic target for drug design. | 18,822,137 |
Kikuchi-Fujimoto Disease: A case report and review of the literature. | Kikuchi-Fujimoto Disease is a rare benign, condition of necrotising histiocytic lymphadenitis. A case of a 55 year old gentleman is described here. He presented with fevers, weight loss and tender cervical lymph nodes. Kikuchi-Fujimoto disease was diagnosed after cervical lymph node biopsy. Symptomatic treatment was provided and an uneventful full recovery was made. Of significant note, this patient's daughter had Kikuchi-Fujimoto disease almost a decade earlier. Although Kikuchi-Fujimoto disease has been reported widely, we believe this is the first familial report in the literature of a case of Kikuchi-Fujimoto disease occurring in a parent and child. | 18,822,141 |
Uncovering mechanisms of transcriptional regulations by systematic mining of cis regulatory elements with gene expression profiles. | Contrary to the traditional biology approach, where the expression patterns of a handful of genes are studied at a time, microarray experiments enable biologists to study the expression patterns of many genes simultaneously from gene expression profile data and decipher the underlying hidden biological mechanism from the observed gene expression changes. While the statistical significance of the gene expression data can be deduced by various methods, the biological interpretation of the data presents a challenge. A method, called CisTransMine, is proposed to help infer the underlying biological mechanisms for the observed gene expression changes in microarray experiments. Specifically, this method will predict potential cis-regulatory elements in promoter regions which could regulate gene expression changes. This approach builds on the MotifADE method published in 2004 and extends it with two modifications: up-regulated genes and down-regulated genes are tested separately and in addition, tests have been implemented to identify combinations of transcription factors that work synergistically. The method has been applied to a genome wide expression dataset intended to study myogenesis in a mouse C2C12 cell differentiation model. The results shown here both confirm the prior biological knowledge and facilitate the discovery of new biological insights. The results validate that the CisTransMine approach is a robust method to uncover the hidden transcriptional regulatory mechanisms that can facilitate the discovery of mechanisms of transcriptional regulation. | 18,822,150 |
Growing pains: contemporary knowledge and recommended practice. | Leg pain in children, described as growing pains, is a frequent clinical presentation seen by an array of health care professionals. Described since 1823, growing pains continues to puzzle practitioners, yet diagnostic criteria and evidence based treatment is available. The medical literature has been searched exhaustively to access all articles (English language) pertaining to leg pains in children which are ascribed to being 'growing pains'. The literature, whilst plentiful in quantity and spanning two centuries, is generally replete with reiterated opinion and anecdote and lacking in scientific rigour. The author searched 45 articles for relevance, determined according to title, abstract and full text, resulting in a yield of 22 original studies and 23 review articles. From the original studies, one small (non-blinded) randomised controlled trial that focused on GP treatment with leg muscle stretching was found. Nine prevalence studies were found revealing disparate estimates. Ten cohort (some case-controlled) studies, which investigated pain attribute differences in affected versus unaffected groups, were found. One series of single case experiment designs and one animal model study were found. Growing pains is prevalent in young children, presents frequently in the health care setting where it is poorly managed and is continuing to be researched. A common childhood complaint, growing pains needs to be acknowledged and better managed in the contemporary medical setting. | 18,822,152 |
Designing a tobacco counter-marketing campaign for African American youth. | The objectives of this qualitative study were to: a) identify common marketing themes and tactics used by the tobacco industry to entice African Americans (AA's) and youth to initiate and maintain smoking behavior, especially smoking mentholated brands of cigarettes, and b) determine AA youths' knowledge, attitudes, intentions, and beliefs about smoking and the tobacco industry. Together, these activities could aid in the development of effective tobacco counter-marketing campaigns for AA youth. Using publicly available tobacco industry documents, computerized searches using standardized keywords were run and results were cataloged and analyzed thematically. Subsequently, 5 focus groups were conducted with n = 28 AA middle school-aged youth. Results suggest that the tobacco industry consistently recruited new AA smokers through a variety of means, including social and behavioral marketing studies and targeted media and promotional campaigns in predominantly AA, urban, and low income areas. AA youth interviewed in this study were largely unaware of these tactics, and reacted negatively against the industry upon learning of them. Youth tended to externalize control over tobacco, especially within the AA community. In designing a counter-marketing campaign for this population, partnering knowledge of tobacco industry practices with youth needs and community resources will likely increase their effectiveness. | 18,822,164 |
Acral lentiginous melanoma of the foot and ankle: A case series and review of the literature. | Acral lentiginous melanoma (ALM) is an uncommon, cutaneous malignant tumour which may arise on the foot. Its relative rarity, atypical appearance and late presentation frequently serve as poor prognostic indicators. At a tertiary skin tumour centre, a retrospective review was undertaken of all patients diagnosed with the tumour at the level of ankle or below. Over a six year period, 27 cases (20 female, 7 male) were identified with positive histology confirming the disease. The age ranged from 35-96 years of age (mean 62.7 years). The majority of the cohort were white (59%) with plantar lesions (62%). 33% of patients were initially were diagnosed incorrectly. The average time taken from the point of recognition, by the patient, to the lesion being correctly diagnosed was around 13.5 months. Earlier diagnosis of ALM requires education at both a patient and practitioner level. | 18,822,168 |
Prevalence of abnormal glucose metabolism in atrial fibrillation: a case control study in 75-year old subjects. | The prevalence of atrial fibrillation (AF) is increasing world wide and amongst factors that aggravate the risk is diabetes mellitus (DM), also in epidemic development.However, although DM is a potentially modifiable risk factor for AF, few, if any, studies have explored the prevalence of undiagnosed dysglycaemia among subjects with AF or if duration of AF are related to parameters of glycaemia or dysglycaemia prevalence. In this case control study, amongst 75-year old subjects with and without AF, the prevalence of dysglycaemia, i.e., impaired fasting glycaemia, impaired glucose tolerance or DM, according to World Health Organisation criteria was assessed by a 75-g oral glucose tolerance test (OGTT). Prevalence of undiagnosed DM among the 108 subjects (male/female 73/35, BMI 25.4 +/- 3.2) without and the 46 (male/female 34/12, BMI 25.3 +/- 3.7) with AF (median AF duration five years) where 3.7% and 13.0%, respectively (p = 0.031, Odds ratio (OR) 3.86 (95% Confidence interval [CI]: 1.01, 16.25)) whereas the overall prevalence of dysglycaemia (prediabetes and DM) where similar (respectively 43.5% and 39.1%, p = 0.46, OR 0.83 [95% CI: 0.41, 1.69]). Patients with AF duration >or= 5 years had however a higher dysglycaemia prevalence (61.1% [DM 22.2%, prediabetes 38.9%]) as compared to AF duration < 5 years (25% [DM 7.1%, prediabetes 17.9%], p = 0.0014, OR 4.7 [95% CI: 1.30, 16.90]) or no AF (p = 0.17, OR 2.04 [95% CI: 0.73, 5.66]). There was also a significant correlation between the duration of AF and HbA1c (r = 0.408, p = 0.005) and fasting glucose levels (r = 0.353, p = 0.016). AF is associated with chronic hyperglycaemia amongst 75-year old subjects. Prediabetes and DM should be pro-actively assessed if AF duration >or= 5 years. | 18,822,173 |
Leaders, leadership and future primary care clinical research. | A strong and self confident primary care workforce can deliver the highest quality care and outcomes equitably and cost effectively. To meet the increasing demands being made of it, primary care needs its own thriving research culture and knowledge base. Review of recent developments supporting primary care clinical research. Primary care research has benefited from a small group of passionate leaders and significant investment in recent decades in some countries. Emerging from this has been innovation in research design and focus, although less is known of the effect on research output. Primary care research is now well placed to lead a broad re-vitalisation of academic medicine, answering questions of relevance to practitioners, patients, communities and Government. Key areas for future primary care research leaders to focus on include exposing undergraduates early to primary care research, integrating this early exposure with doctoral and postdoctoral research career support, further expanding cross disciplinary approaches, and developing useful measures of output for future primary care research investment. | 18,822,178 |
[Effects of over-expressed Smac gene coupling with cisplatin on proliferation and apoptosis of hepatocarcinoma cells]. | To investigate the effects of over-expressed Smac gene combined with cisplatin (CDDP) on proliferation and apoptosis of hepatic carcinoma cells. The recombinant plasmid pcDNA3.1+-hSmac was introduced into the human hepatic carcinoma SMMC-7721 cells using a liposome-mediated method. The expression of Smac protein was detected by Western blot and flow cytometry. The cells were treated with three different doses of CDDP, 5, 15 and 25microg/ml, for 24 hours after the transfection. MTT colorimetry was used to detect the cellular growth-inhibitory effects; acridine orange-ethidium bromide fluorescent staining (AO/EB) and flow cytometry with annexin V-PI double staining were used to detect the changes of cell apoptosis. Western blot and flow cytometry results demonstrated that the Smac protein level in SMMC-7721 cells was significantly increased after the transfection (P less than 0.01). Compared with that of the control group, the over-expressed Smac gene inhibited the cell growth and induced cell apoptosis (P less than 0.01). After being treated with CDDP, the inhibitory rates were increased significantly with increasing concentrations of CDDP compared with that of the control group, and the inhibitory rate of the CDDP-treated plus Smac group was significantly higher than that of the CDDP-treated group (P less than 0.01). The results detected by AO/EB and flow cytometry demonstrated that the apoptotic rates of CDDP-treated plus Smac group were higher than those of the CDDP-treated group (P less than 0.01). The results demonstrated that the Smac over-expression enhanced the effects of cell growth inhibition and apoptotic promotion induced by CDDP. The pro-apoptotic Smac gene could be over-expressed in hepatocarcinoma SMMC-7721 cells and inhibit cell growth and induce apoptosis. Moreover the over-expressed Smac could enhance the chemotherapeutic sensitivity of SMMC-7721 to cisplatin. This experimental work may help in further study on the regulatory mechanism of Smac in apoptosis and improve the chemotherapeutic effect on hepatoma. | 18,822,208 |
[Exogenous surfactant therapy: new synthetic surfactants]. | There are numerous pulmonary conditions in which qualitative or quantitative anomalies of the surfactant system have been demonstrated. In premature newborns with immature lungs, a functional deficit in surfactant is the main physiopathologic mechanism of the neonatal respiratory distress syndrome (RDS). Since the landmark pilot study of Fujiwara, published more than 20 years ago, the efficacy of exogenous surfactant for the treatment of neonatal RDS has been established by numerous controlled studies and meta-analyses. Enlightened by a growing insight into both the structure and function of the different surfactant components, a new generation of synthetic surfactants has been developed. Various complementary approaches have confirmed the fundamental role of the two hydrophobic proteins, SP-B and SP-C, in the surfactant system, thus opening the way to the design of analogues, either by chemical synthesis or expression in a prokaryotic system. An example of these peptide-containing synthetic surfactant preparations, lucinactant (Surfaxin), has been recently tested in comparison to a synthetic surfactant that does not contain protein as well as to animal derived surfactant preparations. Major clinical outcomes between lucinactant and animal-derived surfactant preparations were fund similar in two randomized controlled trials, opening the way to a new generation of synthetic surfactants in the near future. | 18,822,258 |
The E163K DJ-1 mutant shows specific antioxidant deficiency. | Recent discoveries of genetic mutations linked to familial forms of Parkinson's disease (PD), including mutations in DJ-1, have provided insights into the pathogenesis of sporadic PD. Recently, a novel homozygous missense mutation in the gene encoding human DJ-1 protein resulting in the E163K amino acid substitution has been reported. This mutation is associated with early-onset and clinical presentations that include parkinsonism, cognitive decline, and amyotrophic lateral sclerosis. The specific effect of this mutation on the function of DJ-1 protein as it relates to disease pathogenesis is currently unknown. Herein we show that the E163K pathogenic mutant retains similar properties to wild-type DJ-1 protein as it relates to protein stability, solubility, and dimerization. However, we show that the E163K mutant loses the ability to protect against oxidative stress while demonstrating a reduced redistribution towards mitochondria, but retains the ability to mitigate toxicity due to mitochondrial stress and proteasomal impairment. These findings suggest that DJ-1 influences several neuroprotective pathways and that the E163K mutation impairs the mechanism that is more specific to oxidative stress. | 18,822,273 |
Direct effect of light on 24-h variation of aqueous humor protein concentration in Sprague-Dawley rats. | Sprague-Dawley rats 10-12 weeks of age were entrained to a standard light-dark cycle with lights turned on at 6 am and off at 6 pm. Variations of 24-h aqueous humor protein concentration were determined. Samples were taken every 4h (N=10-14) under the standard light-dark condition at 8 pm, midnight, 4 am, 8 am, noon, and 4 pm. Under an acute constant dark condition, when lights were not turned on at 6 am, samples were collected at 8 am, noon, 4 pm, and 8 pm. Aqueous humor protein concentrations under the standard light-dark condition were found in the range of 0.305+/-0.115 mg/ml (mean+/-SD, N=10) at midnight to 1.505+/-0.342 mg/ml (N=14) at noon. The 3 light-phase protein concentrations were each higher than the 3 dark-phase concentrations. Aqueous humor protein concentrations at 8 am, noon, and 4 pm under the acute constant dark condition were each higher than the concentrations at 8 pm (after both 2h and 26 h in the dark), midnight, and 4 am, demonstrating an endogenously driven 24-h pattern. At 8 am, noon, and 4 pm, protein concentrations were 56-147% higher when exposed to light. Intraocular pressure (IOP) was monitored using telemetry in separate groups of light-dark entrained rats under the standard light-dark condition and the acute constant dark condition. The 24-h IOP pattern was inverse to the 24-h pattern of aqueous humor protein concentration under the standard light-dark condition, and this IOP pattern was not altered by the acute constant dark condition. In conclusion, an endogenously driven 24-h variation of aqueous humor protein concentration occurred in Sprague-Dawley rats with higher concentrations during the light-phase than the dark-phase. This endogenous pattern of protein concentration was accentuated by a direct effect of light, which was unrelated to the 24-h pattern of IOP. | 18,822,284 |
Regenerating cellulose from ionic liquids for an accelerated enzymatic hydrolysis. | The efficient conversion of lignocellulosic materials into fuel ethanol has become a research priority in producing affordable and renewable energy. The pretreatment of lignocelluloses is known to be key to the fast enzymatic hydrolysis of cellulose. Recently, certain ionic liquids (ILs) were found capable of dissolving more than 10wt% cellulose. Preliminary investigations [Dadi, A.P., Varanasi, S., Schall, C.A., 2006. Enhancement of cellulose saccharification kinetics using an ionic liquid pretreatment step. Biotechnol. Bioeng. 95, 904-910; Liu, L., Chen, H., 2006. Enzymatic hydrolysis of cellulose materials treated with ionic liquid [BMIM]Cl. Chin. Sci. Bull. 51, 2432-2436; Dadi, A.P., Schall, C.A., Varanasi, S., 2007. Mitigation of cellulose recalcitrance to enzymatic hydrolysis by ionic liquid pretreatment. Appl. Biochem. Biotechnol. 137-140, 407-421] suggest that celluloses regenerated from IL solutions are subject to faster saccharification than untreated substrates. These encouraging results offer the possibility of using ILs as alternative and non-volatile solvents for cellulose pretreatment. However, these studies are limited to two chloride-based ILs: (a) 1-butyl-3-methylimidazolium chloride ([BMIM]Cl), which is a corrosive, toxic and extremely hygroscopic solid (m.p. approximately 70 degrees C), and (b) 1-allyl-3-methylimidazolium chloride ([AMIM]Cl), which is viscous and has a reactive side-chain. Therefore, more in-depth research involving other ILs is much needed to explore this promising pretreatment route. For this reason, we studied a number of chloride- and acetate-based ILs for cellulose regeneration, including several ILs newly developed in our laboratory. This will enable us to select inexpensive, efficient and environmentally benign solvents for processing cellulosic biomass. Our data confirm that all regenerated celluloses are less crystalline (58-75% lower) and more accessible to cellulase (>2 times) than untreated substrates. As a result, regenerated Avicel((R)) cellulose, filter paper and cotton were hydrolyzed 2-10 times faster than the respective untreated celluloses. A complete hydrolysis of Avicel((R)) cellulose could be achieved in 6h given the Trichoderma reesei cellulase/substrate ratio (w/w) of 3:20 at 50 degrees C. In addition, we observed that cellulase is more thermally stable (up to 60 degrees C) in the presence of regenerated cellulose. Furthermore, our systematic studies suggest that the presence of various ILs during the hydrolysis induced different degrees of cellulase inactivation. Therefore, a thorough removal of IL residues after cellulose regeneration is highly recommended, and a systematic investigation on this subject is much needed. | 18,822,323 |
Alloantigen-induced regulatory CD8+CD103+ T cells. | Regulatory T cells (Tregs) appear of great importance in the balance between alloreactivity and tolerance and subsets of both CD4(+) and CD8(+) T cells have been recognized to function as regulatory T cells after allogenic transplantation. Among the CD8(+) T-cell subsets, the CD103(+) cells were most recently identified as regulatory. In this review, we describe their phenotypical and functional properties, as well as their relevance for the alloimmune response in vivo. These CD8(+)CD103(+) Tregs are generated within mixed lymphocyte cultures (MLCs) and are elevated by additional transforming growth factor-beta. Interestingly, myeloid dendritic cells are the responsible cell type for induction of CD103(+) Tregs. Allostimulated CD8(+)CD103(+) Tregs display an antigen-experienced effector phenotype with limited effector functions such as cytotoxicity and interferon-gamma production and show a reduced proliferation capacity after restimulation. Beside this anergic phenotype, CD8(+)CD103(+) Tregs are able to suppress alloreactive effector T cells. Through intracellular cytokine staining and transwell assays, we showed that the mechanism of suppression is cytokine independent, but close cell-cell contact is required for suppression. | 18,822,329 |
Enantioselective cytotoxicity of the insecticide bifenthrin on a human amnion epithelial (FL) cell line. | Synthetic pyrethroids (SPs) are used in preference to organochlorines and organophosphates due to their high efficiency, low toxicity to mammals, and ready biodegradability. Previous studies reported that enantioselective toxicity of SPs occurs in aquatic toxicity. Several studies have indicated that SPs could lead to oxidative damage in humans or animals which was associated with their toxic effects. Little is known about the differences in the effects of chronic toxicity induced by individual stereoisomers of chiral SPs. The present study was therefore undertaken to evaluate the enantioselectivity in cytotoxicity, genotoxicity caused by bifenthrin (BF) on human amnion epithelial (FL) cell lines and pesticidal activity on target organism. The cell proliferation and cytoflow analysis indicated that 1S-cis-BF presented more toxic effects than 1R-cis-BF above the concentration of 7.5 mg L(-1) (p>0.05). FL cells incubated with 1S-cis-BF exhibited a dose-dependent accumulation of intracellular reactive oxygen species (ROS). In the comet assay, the number of cells with damaged DNA incubated with 1S-cis-BF was more than that with 1R-cis-BF (p<0.01). While the LC(50) values of enantiomer to the target pest on Pieris rapae L. show that 1R-cis-BF was 300 times more active than 1S-cis-BF. These results indicate that the enantioselective toxicity and activity of BF between non-target organism and target organism was reversal. These implications together suggest that assessment of the environmental safety and new pesticides development with chiral centers should consider enantioselectivity. | 18,822,338 |
Evolution of carrying capacity in evolution experiments focusing on a single locus on the Escherichia coli chromosome. | We performed a series of evolution experiments, the results of which illustrated the relationship between mutations and increased carrying capacity (K). Performing an evolution experiment with repeated cycles of mutation by PCR and selection makes it possible to obtain results over shorter culture durations than in methods reported previously relying on spontaneous mutation and selection. We constructed random mutant populations of Escherichia coli in which members differed only in part of the genomic copy of the glutamine synthetase gene and performed daily serial transfer culture where the populations were in K-selected environments. The value of K in this system was increased by 10(5)- to 10(8)-fold relative to the parent clone, which was achieved by four randomly introduced mutations. This method can be applied to any gene and will be useful for analyzing a number of important issues in evolutionary biology. | 18,822,342 |
Evidence that TRPC1 is involved in hippocampal glutamate-induced cell death. | Massive neuronal activation by glutamate can result in an excessive rise in cytoplasmic calcium, a process ultimately leading to neuronal death. We have investigated the role of the transient receptor potential channel 1 (TRPC1) in mediating glutamate-induced neuron death. We show that 2-APB (a blocker of store-operated Ca2+ entry) dramatically reduces glutamate-induced cell death in hippocampal organotypic slice cultures and that glutamate-induced toxicity is accompanied by an increase in TRPC1 expression. RNAi mediated knock-down ofTRPC1 in slice cultures prevented glutamate-induced cell death, indicating that TRPC1 plays a prominent role in calcium entry following exposure to glutamate. Thus, TRPC1 may represent a promising target for pharmacological interventions to prevent or reduce glutamate-induced neuronal damage. | 18,822,346 |
When they see, they see it almost right: normal subjective experience of detected stimuli in spatial neglect. | Unilateral spatial neglect (USN) patients show reduced contrast sensitivity on their contralesional side and often miss their non-salient stimuli. What their subjective experience is when successfully reporting a stimulus remains unclear. Here, we report that despite large contrast sensitivity differences between the sides, the relative attenuation in perceived contrast measured in a contrast-matching task was small. This was true even at threshold levels where the patients missed up to 40% of the contralesional target patches, in contrast to a 100% detection rate on their ipsilesional side. When the misses were counted as zero perceived contrast events, the attenuation in perceived contrast was less than half of the sensitivity loss. When the misses were ignored, there was almost no attenuation in perceived contrast, implying that whenever the patients detected a target, they perceived it with the correct contrast. These findings suggest that contrast sensitivity reduction in USN is not due to attenuation occurring at a peripheral low-level processing stage. More likely it reflects a high-threshold added at a higher level of processing, which prevents sensory events from reaching conscious awareness. Hence, patients may often miss contralesional stimuli but see them in full contrast once they clear the high-level hurdle. | 18,822,347 |
Identification of aquaporin-5 and lipid rafts in human resting saliva and their release into cevimeline-stimulated saliva. | It is unknown whether AQP5 and lipid rafts are released into human unstimulated (resting) saliva and saliva in response to secretagogues. In order to quantitate the salivary concentration of AQP5, we produced a polyclonal antibody for human AQP5 and developed an enzyme-like immunosorbent assay (ELISA). AQP5 and lipid rafts were identified in human resting saliva. The amount of AQP5 in resting saliva showed a diurnal variation with high levels during waking hours, and an age-related decrease in AQP5 was coincident with the volume of resting saliva. Cevimeline, a muscarinic acetylcholine receptor (mAChR) agonist, induced the release of AQP5 with lipid rafts, amylase, mucin, and lysozyme. Changes in saliva AQP5 levels after cevimeline administration occurred simultaneously with changes in saliva flow rates. Confocal microscopy revealed that AQP5 was located in the apical plasma membrane and showed a diffuse pattern in parotid glands under resting conditions. Following cevimeline administration, AQP5 was predominantly associated with the APM and was localized in the lumen. AQP5 and lipid rafts were released with salivary proteins from human salivary glands by the stimulation of M3 mAChRs, and that changes in saliva AQP5 levels can be used as an indicator of salivary flow rate and also as a useful index of M3 mAChR agonist's action on human salivary glands. | 18,822,351 |
Anticonvulsant activity of Carissa edulis (Vahl) (Apocynaceae) root bark extract. | To investigate the anticonvulsant activity of root bark extract of Carissa edulis. The median lethal dose (LD(50)) of Carissa edulis extract was determined using Lork's method (1983). The anticonvulsant activity of the extract was assessed in pentylenetetrazole (PTZ)-induced convulsion in mice and maximal electroshock test (MEST) in chicks, with benzodiazepine and phenytoin as standard drugs, respectively. While mechanistic studies were conducted using both flumazenil, a GABA(A)-benzodiazepine receptor complex site antagonist and naloxone a non-specific opioid receptor antagonist. The median lethal dose (LD(50)) of Carissa edulis was 282.8mg/kg and over 5000mg/kg following intraperitoneal and oral administration, respectively. Carissa edulis produced 40% and 20% protection against convulsion at 5 and 20mg/kg, respectively, compared with 100% protection with benzodiazepine. The mean onset and percentage protection against convulsion in Carissa edulis extract-treated mice were reduced by flumazenil and naloxone. Carissa edulis exhibited dose-dependent inhibition of the convulsion induced by MEST with 20mg/kg providing 90% protection while phenytoin (20mg/kg) produced 100% protection. These results suggest that Carissa edulis possesses biologically active constituent(s) that have anticonvulsant activity which supports the ethnomedicinal claims of the use of the plant in the management of epilepsy. | 18,822,365 |
Glycosyltransferases, glycoside hydrolases: surprise, surprise! | Several in the field-and many outside-consider that solving the three-dimensional structures of more glycoside hydrolases (GHs) and glycosyltransferases (GTs) confines to stamp collection and some even think that there is no main revelation to expect in this area. It is wrong! The past year has come as a refreshing wake-up call with major surprises for both GHs and GTs. | 18,822,375 |
Apolipophorin III from Hyphantria cunea shows different anti-oxidant ability against LDL oxidation in the lipid-free and lipid-bound state. | Insect apolipophorin III (apoLp-III) and human apolipoprotein A-I (apoA-I) are major protein constituents of the lipoprotein system that share various properties. In order to compare the anti-oxidant ability of apoLp-III and apoA-I in the lipid-free and lipid-bound state, both proteins were purified and synthesized individually as a palmitoyloleoyl phosphatidylcholine (POPC)-reconstituted high-density lipoprotein (rHDL) using the same molar ratio. In the lipid-bound state, apoLp-III and apoA-I showed good anti-oxidant activities against copper-mediated LDL oxidation. Furthermore, apoLp-III and apoA-I, in the lipid-bound state, exhibited potent activities in ferric ion-reducing ability (FRA). However, lipid-free apoLp-III lost the anti-oxidant activity and FRA ability in contrast to lipid-free apoA-I. Lipid-free apoA-I treatment prevented the cellular uptake of oxLDL in macrophages, as visualized by oil-red O staining and detection assays for malondialdehyde (MDA) and lipid hydroperoxide (LPO) in the culture media. However, lipid-free apoLp-III did not prevent the uptake of oxLDL. These results indicate that the putative conformational change of apoLp-III during lipid association is critical for the maintenance of anti-oxidant activity and that the physiologic role of apoLp-III may differ when it is in the lipid-free state and the lipid-bound state. | 18,822,383 |
Low hanging fruit in infectious disease drug development. | Cost estimates for developing new molecular entities (NME) are reaching non-sustainable levels and coupled with increasing regulatory requirements and oversight have led many pharmaceutical sponsors to divest their anti-microbial development portfolios [Projan SJ: Why is big Pharma getting out of anti-bacterial drug discovery?Curr Opin Microbiol 2003, 6:427-430] [Spellberg B, Powers JH, Brass EP, Miller LG, Edwards JE, Jr: Trends in antimicrobial drug development: implications for the future.Clin Infect Dis 2004, 38:1279-1286]. Operational issues such as study planning and execution are significant contributors to the overall cost of drug development that can benefit from the leveraging of pre-randomization data in an evidence-based approach to protocol development, site selection and patient recruitment. For non-NME products there is even greater benefit from available data resources since these data may permit smaller and shorter study programs. There are now many available open source intelligence (OSINT) resources that are being integrated into drug development programs, permitting an evidence-based or 'operational epidemiology' approach to study planning and execution. | 18,822,387 |
Population genomics: diversity and virulence in the Neisseria. | Advances in high-throughput nucleotide sequencing and bioinformatics make the study of genomes at the population level feasible. Preliminary population genomic studies have explored the relationships among three closely related bacteria, Neisseria meningitidis, Neisseria gonorrhoeae and Neisseria lactamica, which exhibit very different phenotypes with respect to human colonisation. The data obtained have been especially valuable in the establishing of the role of horizontal genetic exchange in bacterial speciation and shaping population structure. In the meningococcus, they have been used to define invasive genetic types, search for virulence factors and potential vaccine components and investigate the effects of vaccines on population structure. These are generic approaches and their application to the Neisseria provides a foretaste for their application to the wider bacterial world. | 18,822,386 |
Development of the Gateway system for cloning and expressing genes in Entamoeba histolytica. | The early branching eukaryote Entamoeba histolytica is a human parasite that is the etiologic agent of amebic dysentery and liver abscess. The sequencing of the E. histolytica genome combined with the development of an E. histolytica microarray has resulted in the identification of several distinct gene expression profiles associated with virulence. The function of many modulated transcripts is unknown and their role in pathogenicity is unclear. They however represent a pool of potential virulence factors that could be targets for the development of novel therapeutics. Efficient tools and methods to characterize these novel virulence-associated genes and proteins would be beneficial. Here we report the use of the Gateway((R)) cloning system to generate the E. histolytica expression vector pAH-DEST. To test the usefulness of this system, the vector was used to construct a plasmid containing a recombinant version of the locus EHI_144490, which encoded a protein of unknown function. The recombinant gene was expressed and the recombinant protein, which was strep-myc-tagged, showed a cytoplasmic localization in transfected trophozoites. This expression vector with the Gateway((R)) system should facilitate investigation into the functions of novel proteins in E. histolytica. | 18,822,389 |
Induction of late airway response was involved in serum antigen-specific immunoglobulin G in rats. | The antigen-induced immediate airway response (IAR) has been considered a form of bronchoconstriction mainly provoked by histamine and leukotriene C4/D4/E4, which are released by stimulation by antigen-specific IgE. However, the pathophysiological features of the antigen-induced late airway response (LAR) are not yet fully understood. In the present study, sensitized rats were repeatedly exposed to ovalbumin (OVA) to induce IAR and LAR, and the immunological profiles of IAR and LAR were examined. The first antigen inhalation induced only IAR but not LAR. However, the second antigen inhalation 7 days after IAR induced LAR but not IAR. Tumor necrosis factor (TNF)-alpha level in BALF in LAR was significantly higher than that in IAR, although there were no differences in histamine, leukotriene C4/D4/E4, interleukin (IL)-1beta, or IL-13 levels between IAR and LAR. Serum antigen-specific IgE titer was high in both IAR and LAR, but serum antigen-specific IgG, IgG1, and IgG2a titers were dramatically high in LAR but not IAR. There were significant correlations between antigen-specific IgG, IgG1, and IgG2a titers and LAR. Interestingly, LAR could be induced in normal rats by transfer of serum from LAR rats, which exhibited high antigen-specific IgG, IgG1, and IgG2a titers. In conclusion, these findings suggest that repeated antigen inhalation converts IAR to LAR, and that LAR is a reaction triggered by antigen-specific IgG and involving TNF-alpha. This is the first study to directly suggest the involvement of antigen-specific IgG in the induction of LAR. | 18,822,391 |
A thixotropic hydrogel from chemically cross-linked guar gum: synthesis, characterization and rheological behaviour. | Polysaccharide guar gum (GG) was cross-linked in an alkaline solution with polyethylene glycol diglycidyl ether (PEGDGE) to create a new hydrogel. The GG hydrogel was examined by FT-IR spectroscopy, AFM analysis and SEM analysis. The water uptake of the GG hydrogel was measured at different pHs, and rheological studies were performed to verify the thixotropic nature of the material. Rheological studies revealed the pseudoplastic behaviour of the GG hydrogel and its thixotropic nature. AFM analysis on a sample which was subjected to shear stress showed the presence of nanoparticles in the hydrogel. When the sample was left to settle, the gel surface returned to its original homogenous morphology. The thixotropic and injectable nature of the GG hydrogel suggest its possible use in biomedical applications. | 18,822,410 |
Effects of oral niacin on endothelial dysfunction in patients with coronary artery disease: results of the randomized, double-blind, placebo-controlled INEF study. | High-density-lipoproteins-cholesterol (HDL-C) is invertedly related to the incidence of cardiovascular events. Recent studies suggest that HDL-C directly improves endothelial function. Nicotinic acid (niacin) effectively raises serum HDL-C. We therefore hypothesized that treatment with niacin improves endothelial dysfunction in patients with coronary artery disease (CAD). One hundred seven patients with CAD were randomly assigned to double-blinded treatment for 12 weeks with extended-release (ER)-niacin 1000 mg/day (N) or placebo (C), respectively. Flow-mediated dilation (FMD) of the brachial artery, nitroglycerin-mediated endothelium-independent dilation (NMD) and serum lipid concentrations were measured before and after treatment. Triglycerides (P=0.013), low-density-lipoprotein-cholesterol (LDL-C) (P=0.013) and HDL-C (P<0.0001) were altered by N compared to C. Niacin treatment was without effect on FMD or NMD, respectively, compared to placebo. However, post-hoc subgroup analysis revealed an improvement in FMD in patients with low HDL-C at baseline (absolute change in FMD (mean+/-S.D.) N: +3.25+/-3.88%, C: +1.03+/-2.71% in low tertile HDL-C <or=45 mg/dl. P=0.047). The present findings indicate that ER-niacin treatment improves endothelial dysfunction in patients with CAD and low HDL-C, but not with normal HDL-C. | 18,822,413 |
Randomized trial of milrinone versus placebo for prevention of low systemic blood flow in very preterm infants. | To assess the effectiveness of early prophylactic milrinone versus placebo for prevention of low systemic blood flow in high-risk preterm infants. Double-blind randomized placebo controlled trial of milrinone (loading dose 0.75 microg/kg/min for 3 hours then maintenance 0.2 microg/kg/min until 18 hours after birth) versus placebo. Infants born <30 weeks gestational age and <6 hours of age were eligible and were monitored with serial echocardiography, head ultrasound scanning, and continuous invasive blood pressure. Primary outcome was maintenance of superior vena cava (SVC) flow > or =45 mL/kg/min through the first 24 hours. The exit criterion was hypotension unresponsive to volume and inotropes. Ninety infants were enrolled, equal proportions maintained SVC flow > or =45 mL/kg/min after treatment commenced. No significant difference was observed in SVC flow, right ventricular output, and blood pressure during the first 24 hours; or grades 3 to 4 periventricular/intraventricular hemorrhage and death. Heart rate was higher and constriction of the ductus was slower in the infants randomized to milrinone. Milrinone did not prevent low systemic blood flow during the first 24 hours in very preterm infants, and no adverse effects were attributable to milrinone. Use of a preventative treatment with rescue model allowed comparison of an inotrope with placebo in this high-risk group of infants. | 18,822,428 |
The implications of immunogenicity for protein-based multiple sclerosis therapies. | Administered proteins are inherently immunogenic, which may influence their efficacy or safety when used therapeutically. A review of the published literature was performed to compare and evaluate the development and consequences of antibodies against therapeutic protein agents for the treatment of multiple sclerosis (MS). Interferon beta (IFNbeta), glatiramer acetate (GA), and natalizumab are all protein-based therapeutic agents approved to treat MS and are associated with the development of antibodies. Both binding antibodies and neutralizing antibodies (NAbs) develop to varying degrees in patients treated with any of the formulations of IFNbeta. Comparison between studies is complicated by differences in methods, assays, criteria for determining NAb positivity, treatment duration, and fluctuation of NAb status. Despite these confounding factors, current data indicate that high-titer persistent NAbs may be relevant in terms of their effect on IFNbeta bioavailability and bioefficacy. GA-reactive antibodies developed in a high proportion of GA-treated patients, but the clinical relevance of these antibodies remains to be established. Immunogenicity against natalizumab was associated with reduced efficacy and increased incidence of infusion reactions. Other emerging monoclonal antibody therapeutics have also been associated with the development of antibodies. Experience with generic biosimilars of other protein therapeutics suggests that the immunogenicity of generic biosimilar agents cannot be assumed and must be established for each formulation. | 18,822,434 |
Toxoplasma gondii infection in pregnant women in China. | Infection with Toxoplasma gondii is common and usually asymptomatic, but it can have serious consequences in pregnant women if passed to the developing fetus. The aims of this study were to determine the prevalence of toxoplasmosis in pregnant women and to identify the possible risk factors associated with T. gondii infection in China. Of a sample of 235 pregnant women in Changchun, China, 25 (10.6%) were found by ELISA to be positive for IgG and none (0%) for IgM. Major risk factors were found by bivariate and multivariate analysis to include eating raw or undercooked meat, unwashed raw vegetables or fruit, contact with cats, living in rural areas, and low educational standards. In order to lower congenital infection, pregnant women need to be informed about the risk factors for toxoplasmosis. | 18,822,439 |
Toward understanding the mechanism of improving the production of volatile fatty acids from activated sludge at pH 10.0. | A well-defined fractionation approach for sludge flocs was applied to a better understanding of the underlying mechanism of improving the production of volatile fatty acids (VFA) in the hydrolysis and acidification processes at pH 10.0. Specifically, sludge flocs were fractionated through centrifugation and ultrasound into four fractions: (1) slime, (2) loosely bound extracellular polymeric substances (LB-EPS), (3) tightly bound EPS (TB-EPS) and (4) pellet. Result showed that during 20 days of fermentation, the total VFA production at pH 10.0 was higher, from 2 to 34 times, than that at pH 5.5. At pH 10.0, however, the enzyme activities (i.e. protease, alpha-amylase, alkaline phosphatase and acid phosphatase) in all fractions of sludge flocs were all lower than pH 5.5, which strongly suggests that the biotic effect was not the leading cause of the VFA improvement. Further investigation suggests that pH 10.0 could significantly improve the VFA production through the break of sludge matrix which is usually hydrolyzed by the extracellular enzymes embedded in itself, increase the effective contact between extracellular organic matters and enzymes, and create a favorable environment for microbes to accumulate VFA. Hydrolysis and acidification at pH 10.0 can be considered as part of an appropriate solution for tertiary treatment and contribute to the headway toward the goal of sustainable water treatment technologies. | 18,822,441 |
Polychlorinated dibenzo-p-dioxins and dibenzofurans in soils and sediments from Daliao River Basin, China. | Polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/F) were analyzed in surface sediments and top soils collected from 30 sites in Daliao River Basin. The concentrations of PCDD/F ranged from 0.28 to 29.01 ng TEQ kg(-1) dw (mean value, 7.45 ng TEQ kg(-1)dw) in sediments, and from 0.31 to 53.05 ng TEQ kg(-1)dw (mean value, 7.00 ng TEQ kg(-1)dw) in soils. PCDD/F pollution in sediments from the mid- and downstream sections of Hun River was found to be relatively heavy, and the levels of PCDD/F contamination in paddy soils were generally higher than those of upland soils. Using multivariate statistical analysis, the PCDD/F homologue and congener profiles of all soil and sediment samples were compared with those of suspected PCDD/F sources. The results showed that, PCDD/F contamination in most sediments of Hun River should mainly originated from the production of organochlorine chemicals, while metal smelting was the important potential source of PCDD/F in the drainage area of Taizi River. PCDD/F contamination in paddy soils should be simultaneously attributed to the polluted water irrigation and the organochlorine pesticide application. | 18,822,443 |
Minimal effect of cold ischemia time on progression to late-stage chronic kidney disease observed long term after partial nephrectomy. | To assess the influence of cold ischemia on postoperative renal function and the new onset of late-stage chronic kidney disease during long-term follow-up after partial nephrectomy. A total of 131 patients with renal tumors who underwent partial nephrectomy and were followed up for >or=12 months were included in the present study. Renal function was analyzed using the estimated glomerular filtration rate (e-GFR). We classified the subjects into 3 groups according to the length of cold ischemia time: group 1, 1-30 minutes; group 2, 31-60 minutes; and group 3, >60 minutes. Although the postoperative e-GFR was lower in group 3 than in groups 1 and 2, no significant difference was found among the 3 groups during long-term follow-up when preoperative CKD was absent. A cold ischemia time of >or=44 minutes significantly increased the probability of freedom from the new onset of an e-GFR of <45 mL/min/1.73 m(2), but this difference was minimal. Multivariate analysis showed that the preoperative e-GFR and the relative decrease of e-GFR at 1 year after surgery were the significant factors determining postoperative renal function. A cold ischemia time of >44 minutes appears to be a threshold influencing the new onset of late-stage CKD; however, it was not a significant factor on multivariate analysis. Thus, renal hypothermia appears to prevent the deterioration of renal function long term after surgery for patients undergoing a longer ischemia time. | 18,822,449 |
The newer the better? Comparison of the 1997 and 2001 partin tables for pathologic stage prediction of prostate cancer in China. | The use of the Partin tables for pathologic stage prediction of prostate cancer in China has 2 problems. First, the validity of such U.S.-derived predictive tools has not been tested in China. Second, because an updated version of the Partin tables created using a more contemporary cohort was introduced in 2001, it is important to determine whether this renewed version (2001 Partin tables) is superior to the old version (1997 Partin tables). To investigate these problems, we compared these 2 predictive tools for their ability to predict the pathologic stage in Chinese patients. From June 2001 to May 2007, 271 consecutive patients who met the inclusion criteria for Partin table prediction and underwent radical prostatectomy for clinically localized prostate cancer at a single center were evaluated. The predictive accuracy of the 1997 Partin tables and 2001 Partin tables were assessed using receiver operating characteristics analysis. For the 1997 Partin tables, the area under the receiver operating characteristics curve for the prediction of organ-confined disease, established capsular penetration, seminal vesicle involvement, and lymph node involvement was 0.723, 0.674, 0.749, and 0.781, respectively. The corresponding values for the 2001 Partin tables were consistently low at 0.604, 0.539, 0.654, and 0.631. The results of our study have confirmed good predictive accuracy for the 1997 Partin tables for Chinese patients, but not for their updated 2001 version. | 18,822,453 |
Clinical manifestations of hyperuricemia and gout. | Biologically significant hyperuricemia occurs when serum urate levels exceed urate solubility, ie, at approximately 6.8 mg/dL. At serum urate levels above this threshold, manifestations of chronic crystal deposition, including gouty arthritis, may occur, although asymptomatic hyperuricemia often persists for many years without progression. Intercritical asymptomatic periods follow the resolution of acute gout flares, but crystals remain in the joint during these intervals and further deposition may continue silently. Ultimately this may lead to persistent attacks, chronic pain, and, in some patients, joint damage. | 18,822,469 |
[Anopheles mosquitoes (Diptera, Culicidae) of the Tien Shan: morphological, cytogenetic, and molecular genetic analysis]. | Morphological, cytogenetic, and molecular genetic studies of the Anopheles fauna in the valley and foothills of the Tien Shan identified 5 species of malaria mosquitoes: An. artemievi Gordeev et al., An. messeae Fall, An. claviger Meigen, An. hyrcanus Pallas, An. pulcherrimus Theobald, and superpictus Grassi. An. claviger, An. hyrcanus, and An. messeae were prevalent in the Northern Tien-Shan. An. artemievi, An. claviger, An. hyrcanus, An. messeae, and An. superpictus were detected in the Western Tien Shan. An. artemievi was first recorded in Kazakhstan. An. artemievi, An. claviger, and An. superpictus were noted in the Inferior Tien Shan. An. messeae was first observed in the Issyk Kul hollow. An. artemievi, An. claviger, and An. superpictus were habitants of the foothills of the South-Western Tien Shan. An. artemievi, An. hyrcanus, An. superpictus, and An. pulcherrimus were in the plain. An. pulcherrimus and An. superpicts mosquitoes are regarded as important vectors in the new malaria foci of the Fergana regions. The role of An. artemievi in the transmission of malaria is to be specified. | 18,822,504 |
Response to a combined treatment program with clomipramine, behavioral, and environmental management of compulsive tail chasing in a German Shepherd. | A 15-month-old female German Shepherd dog showing compulsive tail chasing was treated with a treatment protocol of pharmacological therapy (using clomipramine) in conjunction with behavioral and environmental management. The responses to the treatment protocol were assessed once a week for 7 weeks in respects to behavioral conditions and the frequency of bouts and its duration. The behavior history including mother, father, and her littermates were also evaluated for the apparent diagnosis. The compulsive tail chasing of the patient dog was improved on the aspect of behavioral condition and gradually decreased in the frequency and duration of bouts. However, in the mid of treatment, the animal showed an aggressive behavior as a concurrent sign associated with compulsive tail chasing. | 18,822,603 |
[Estimation of genetic parameters for radiographic signs of hip dysplasia in Labrador Retrievers]. | The aim of this study was the analysis of environmental factors and estimation of genetic parameters for hip dysplasia in Labrador Retrievers. We analysed hip dysplasia scores of 2970 dogs from the official screening programme of the Labrador Club Deutschland (LCD) according to the FCI protocols. Traits evaluated were HD-Mit (average value of HD scores), HD-Max (higher score of both hip joints), HD-LI and HD-RE (HD score of the left or right hip joint). A linear animal model was employed to estimate heritabilities, additive genetic and residual correlations using Residual Maximum Likelihood (REML). Only inbreeding was significant after testing all non-genetic effects. Higher inbreeding coefficients were associated with higher HD scores. Heritability estimates and their standard errors were 0.38 +/- 0.04 for HD-Mit, 0.40 +/- 0.04 for HD-Max, 0.33 +/- 0.03 for HD-LI and 0.38 +/- 0.04 for HD-RE. The additive genetic correlation between HD-LI and HD-RE was 1. Heritability for female dogs was 0.31 and 0.30 for male dogs. The analysis of HD scores of Labrador Retrievers showed that the highest HD score of the hips should be used in breeding programmes, that heritabilities are not different among females and males, and that genetic components are much more important than environmental factors. | 18,822,607 |
Fatal cerebral abscess caused by Cladophialophora bantiana. | Primary cerebral phaeohyphomycosis is caused by pigmented fungi that exhibit distinct neurotropism often in immunocompetent individuals. A 20-yr-old male presented with multiple brain abscess which was subsequently proven microbiologically to be due to Cladophialophora Bantiana. In spite of near total excision and appropriate antifungal agents succumbed to his illness. We report this case to highlight its rarity and high mortality in an immunocompetent host. There is no initial clinical or laboratory feature that makes a preoperative diagnosis possible and relies on microbiological confirmation. | 18,822,631 |
Is ascending urethrogram mandatory for all urethral strictures? | To determine the role of ascending urethrogram in decision making for patients with suspected urethral strictures. Medical Records were reviewed of male patients presenting with lower urinary tract symptoms who were subjected to ascending urethrogram and selected cases for cystourethroscopy from January 2001 to December 2002. Cystourethroscopy was performed on those patients who complied with treatment for urethral stricture or who had persistent low flow of urine despite ascending urethrogram reporting no urethral stricture. Data was analyzed on SPSS 10.0. Sensitivity, specificity, positive and negative predictive values were calculated for ascending urethrogram as a measure to evaluate urethral stricture. Ascending urethrogram was done on 92 patients. Of whom 55 were reported to have urethral stricture. The mean age of patients was 42.8 +/- 13.2 years. Of the 92 patients who had ascending urethrogram, 62 were subjected to cystourethroscopy proceed optical internal urethrotomy (OIU) in cases of stricture. It was that out of 45 reported urethral strictures on ascending urethrogram, 5 did not have stricture on cystourethroscopy (P = 0.001). Likewise in the same group of 62 patients, 17 patients were reported to have no stricture on ascending urethrogram, whereas subsequent cystourethroscopy revealed stricture in 4 patients. The calculated sensitivity of ascending urethrogram was 91% and specificity 72%. The calculated positive and negative predictive values were 89% and 76% respectively. The study concluded that Ascending Urethrogram does not completely rule out urethral stricture (Negative Predictive Value 76%). It was also observed that urethral stricture may be non-existent even though suggested in Ascending Urethrogram (Positive Predictive Value 89%). With a sensitivity of 91% and a low specificity of 72% of the ascending urethrogram for diagnosing urethral stricture, it would be advisable to subject the patient to cystourethroscopy proceed Optical Internal Urethrotomy in cases of urethral stricture. This will save cost, avoid infection reduce risk of radiation and contrast related hypersensitivity reaction. | 18,822,639 |
Primary drug resistance to antituberculous drugs in NWFP Pakistan. | To assess the prevalence of Primary drug resistance to Antituberculous drugs in NWFP METHOD: A cross-sectional prevalence study was undertaken to evaluate the prevalence of drug resistance among new TB patients, using a non-probability convenience sampling methodology. Sample size was calculated according to the population and WHO's estimated incidence of smear positive tuberculosis in the province/country. Sputum samples were obtained from 122 newly diagnosed patients of pulmonary tuberculosis from centres in Peshawar and Abbotabad in NWFP. Sensitivities were performed by proportion method which showed the following resistance values in 118 eligible patients: 15 (12.7%) samples showed primary resistance to one or more drugs. 8 (6.4%) isolates were resistant to a single drug, 2 (1.6%) were resistant to 2 drugs, 4 (3.2%) to 3 drugs, 1 (0.8%) to 4 drugs while none to all 5 first line agents. Resistance to Streptomycin (10 microg/ml) was seen in 7 (5.9%), Isoniazid (1 microg/ml) in 10 (8.4%), Rifampicin (5 microg/ml) in 3 (2.5%), Ethambutol (10 microg/ml) in 2 (1.6%) and Pyrazinamide in 6 (5.0%) samples. Primary Multidrug resistance was 2.5%. This study suggests that prevalence of MDR amongst untreated patients in NWFP is 2.5%, which is a cause of concern and should be addressed through effective TB control programmes with DOTS strategy. | 18,822,641 |
Awareness of bird flu amongst young college students. | To assess the awareness among students about the disease, their attitude during the outbreak, along with their perceptions about treatment, and severity of disease. A cross sectional study was conducted among 220 intermediate students. The data was collected through a self filled questionnaire after taking verbal consent. The variables included in this study were age, gender and department (medical/non-medical). A total of 220 students participated with mean age of 17 +/- 1 year. There were 132 (61%) males and 84 (39%) females. The students were divided into pre-medical 110 (50%) and non-premedical 110 (50%). About 211 (96%) students said that they had heard about bird flu but only 86 (39%) correctly identified it as a disease of birds and humans both. One hundred and fifty-four (70%) participants said that virus causes it and the most common source of knowledge was media (T.V) by 153 (70%) followed by newspaper 113 (51%) respondents. Flu like symptoms were identified by 77 (35%) and 160 (73%) considered birds to human as the most likely route of transmission. Regarding vaccine, 133 (70%) replied that it is not available and 80 (41%) said that there is a treatment for the disease. About 143 (73%) thought that it is life-threatening. According to 105 (48%) the suitable preventive measure taken by the government would be to kill susceptible chickens. The awareness regarding bird flu was quite low among students. As bird flu is a world wide public health problem therefore increasing awareness would be a solution to avoid its spread and complications. | 18,822,652 |
On microRNA and the need for exploratory experimentation in post-genomic molecular biology. | This paper is devoted to an examination of the discovery, characterization, and analysis of the functions of microRNAs, which also serves as a vehicle for demonstrating the importance of exploratory experimentation in current (post-genomic) molecular biology. The material on microRNAs is important in its own right: it provides important insight into the extreme complexity of regulatory networks involving components made of DNA, RNA, and protein. These networks play a central role in regulating development of multicellular organisms and illustrate the importance of epigenetic as well as genetic systems in evolution and development. The examination of these matters yields principled arguments for the historicity of the functions of key biological molecules and for the indispensability of exploratory experimentation in contemporary molecular biology as well as some insight into the complex interplay between exploratory experimentation and hypothesis-driven science. This latter result is not only important for philosophy of science, but also of practical importance for the evaluation of grant proposals, although the elaboration of this latter claim must be left for another occasion. | 18,822,659 |
Clinical update on palonosetron in the management of chemotherapy-induced nausea and vomiting. | The need to control chemotherapy-induced nausea and vomiting is continuously stimulating research to find better options for the optimal antiemetic care. Palonosetron is different from conventional serotonin receptor antagonists not only by the fact of having a longer half-life but also by higher binding affinity for serotonin receptors. It is the first agent in the class which is approved for preventing both delayed and acute emesis induced by moderately emetogenic chemotherapy. Recent studies using palonosetron-based antiemetic regimens, as well as in the clinical setting of multiple-day chemotherapy, have been reported. Palonosetron plus dexamethasone given as a pre-treatment infusion was effective for preventing acute and delayed emesis after moderately emetogenic chemotherapy. Palonosetron in combination with dexamethasone and aprepitant was highly effective in preventing emesis in the days following administration of moderately emetogenic chemotherapy. Treatment was well tolerated, with no unexpected adverse events. Multiple-day dosing of palonosetron plus dexamethasone was safe and effective for prevention of emesis induced by 5-day cisplatin-based chemotherapy. There was no evidence of cumulative toxicity when palonosetron was given three times over 5 days. Further evidence from ongoing clinical trials with palonosetron with or without dexamethasone will be available soon. Palonosetron represents an useful addition to the therapeutic armamentarium for the management of chemotherapy-induced nausea and vomiting. Further studies are needed to assess the effectiveness of palonosetron in combination with dexamethasone compared with that of older serotonin receptor antagonists combined with dexamethasone. However, palonosetron may offer advantages of convenience over the short-acting older antagonists due to its ability to be given as a single intravenous dose prior to chemotherapy. | 18,822,676 |
Stromal tumors of the stomach: a clinicopathological study of 15 cases and review of the literature. | Gastrointestinal stromal tumors are the most common mesenchymal tumors of the digestive tract, although their incidence is low. These tumors make up a unique entity based on their molecular pathogenesis, immunohistochemical staining and responsiveness to targeted therapy. Gastrointestinal stromal tumors vary in malignant potential ranging from small incidentally detected tumors with an excellent outcome to aggressive sarcomas. Their optimal diagnostic approach and treatment remain a matter of debate. We present our experience in this rapidly moving field. We present our experience on 15 patients presented during a 5-year period (June 2000-September 2005) with gastrointestinal stromal tumors located in the stomach. Upper gastrointestinal endoscopy and CT scan revealed the tumors in all cases. All patients underwent curative surgery. A definitive diagnosis was established after surgery. Although an inverse correlation between level of risk and survival of patients with gastrointestinal stromal tumors has been observed, 6 of our patients with an intermediate risk of recurrence had a favorable outcome. | 18,822,678 |
Retroperitoneal soft tissue sarcoma: prognostic factors and therapeutic approaches. | Retroperitoneal sarcomas are a rare group of malignant soft tissue tumors with a generally poor prognosis. The aim of the study was to assess clinical, pathological and treatment-related factors affecting prognosis in patients with retroperitoneal sarcomas. The hospital records of 73 patients who underwent surgical exploration at our unit for primary retroperitoneal sarcomas between 1984 and 2003 were reviewed. Factors influencing overall and disease-free survival were analyzed for all patients and for those who underwent complete surgical resection. The complete resectability rate was 69.8% (51/73). Operative mortality and morbidity rates were 2.7% and 21.9%, respectively. For patients who underwent complete resection, the 5-year survival rate was 58.3%, whereas it was 0% in cases of incomplete or no resection (P < 0.001). Local recurrence rate was 37.2%. Incomplete gross surgical resection and microscopic infiltration of margins were the most important independent predictors of a poor prognosis. The present study confirmed the importance of an aggressive surgical management for retroperitoneal sarcomas to offer these patients the best chance for long-term survival. | 18,822,685 |
Clinicopathological significance of overexpression of TSPAN1, Ki67 and CD34 in gastric carcinoma. | To investigate the expression of TSPAN1 (Gene ID: 10103), Ki67 and CD34 in gastric carcinomas and the clinicopathological significance, the expression of TSPAN1, Ki67 and CD34 was detected in 86 cases of gastric carcinoma, paraffin-embedded sections using an immunohistochemical method. The rates of overexpression of TSPAN1, Ki67 and CD34 in gastric carcinomas were 56.98%, 74.42%, and 62.79%, respectively. The overexpression of these markers was positively correlated with clinical stage and negatively correlated with survival rates (at 3 and 5 years). The overexpression of TSPAN1 and Ki67 was negatively correlated with carcinoma differentiation, and the overexpression of TSPAN1 and CD34 was positively correlated with infiltration and lymph node status of the tumor. Thus, overexpression of TSPAN1, Ki67 and CD34 in gastric cancer tissues is associated with development of the cancer. The detection of expression of TSPAN1, Ki67 and CD34 in gastric cancer may provide useful prognostic information for patients with the disease. | 18,822,690 |
[Experimental study on neural stem cell transplantation delaying denervated muscle atrophy]. | To observe the delaying effect of neural stem cell (NSC) transplantation on denervated muscle atrophy after peripheral nerve injury, and to investigate its mechanism. NSCs were separated from the spinal cords of green fluorescent protein (GFP) transgenic rats aged 12-14 days mechanically and were cultured and induced to differentiate in vitro. Thirty-two F344 rats, aged 2 months and weighed (180 +/- 20) g, were randomized into two groups (n=16 per group). The animal models of denervated musculus triceps surae were established by transecting right tibial nerve and common peroneal nerve 1.5 cm above the knee joints. In the experimental and the control group, 5 microL of GFP-NSC suspension and 5 microL of culture supernatant were injected into the distal stump of the tibial nerve, respectively. The general condition of rats after operation was observed. At 4 and 12 weeks postoperatively, the wet weight of right musculus triceps surae was measured, the HE staining, the Mallory trichrome staining and the postsynaptic membrane staining were adopted for the histological observation. Meanwhile, the section area of gastrocnemius fiber and the area of postsynaptic membrane were detected by image analysis software and statistical analysis. The wounds in both groups of animals healed by first intension, no ulcer occurred in the right hind limbs. At 4 and 12 weeks postoperatively, the wet weight of right musculus triceps surae was (0.849 +/- 0.064) g and (0.596 +/- 0.047) g in the experimental group, respectively, and was (0.651 +/- 0.040) g and (0.298 +/- 0.016) g in the control group, respectively, showing a significant difference (P < 0.05). The fiber section area of the gastrocnemius was 72.55% +/- 8.12% and 58.96% +/- 6.07% in the experimental group, respectively, and was 50.23% +/- 4.76% and 33.63% +/- 4.41% in the control group, respectively. There were significant differences between them (P < 0.05). Mallory trichrome staining of muscle notified that there was more collagen fiber hyperplasia of denervated gastrocnemius in the control group than that in the experimental group at 4 and 12 weeks postoperatively. After 12 weeks of operation, the area of postsynaptic membrane in the experimental group was (137.29 +/- 29.14) microm2, which doubled that in the control group as (61.03 +/- 11.38) microm2 and was closer to that in normal postsynaptic membrane as (198.63 +/- 23.11) microm2, showing significant differences (P < 0.05). The transplantation in vivo of allogenic embryonic spinal cord NSCs is capable of delaying denervated muscle atrophy and maintaining the normal appearance of postsynaptic membrane, providing a new approach to prevent and treat the denervated muscle atrophy clinically. | 18,822,726 |
[Study on treating residual cavity of body surface after abscess drainage by sodium hyaluronate hydrogel]. | To study the effect of sodium hyaluronate hydrogel in treating residual cavity on body surface after abscess drainage so as to provide new method to speed up the healing of residual cavity after body surface abscess drainage and reduce the frequency of dressing change and clinic nursing workload. From June 2007 to March 2008, 60 outpatients with body surface abscess drainage were randomly divided into hydrogel group (group A, 30 cases) and the control group (group B, 30 cases). In group A, there were 16 males and 14 females aged (49.5 +/- 6.1) years, the disease course was (3.8 +/- 0.6) days, and the volume of residual cavity was (4.19 +/- 1.31) mL. In group B, there were 18 males and 12 females aged (50.2 +/- 7.6) years, the disease course was (4.3 +/- 0.5) days, and the volume of residual cavity was (4.04 +/- 1.22) mL. There was no significant difference between two groups in gender, age, disease course and volume of residual cavity (P > 0.05). Residual cavity was smeared with 1 mL/cm2 sodium hyaluronate hydrogel in group A and drained by saline gauze in group B, the dressing was changed every two to three days. Residual cavity volume was recorded every four days, and the residual cavity volume, the frequency of out-patient dressing and the healing time residual of cavity were compared. The volume of residual cavity was (3.11 +/- 1.12), (1.75 +/- 0.95) and (0.55 +/- 0.56) mL in group A, and was (3.39 +/- 1.12), (2.64 +/- 0.99) and (1.81 +/- 0.81) mL in group B at 4, 8 and 12 days after treatment respectively, showing no significant differences at 4 days (P > 0. 05), but significant difference at 8 and 12 days (P < 0.01). Residual cavity healing time was (12.70 +/- 2.78) days in group A and (20.27 +/- 3.89) days in group B, and the frequency of dressing change was 5.53 +/- 1.33 in group A and 9.13 +/- 1.81 in group B, indicating significant differences between two groups (P < 0.01). Sodium hyaluronate hydrogel can promote residual cavity healing, reduce the frequency of dressing change of out-patient and decrease the clinic nursing care workload. | 18,822,733 |
[Investigation of new classification and repair methods for fingertip traverse amputation]. | To investigate new classification and repair methods for the traverse amputated fingertip. From March 2000 to October 2006, 20 cases of 20 fingers with traverse amputated fingertip, including 13 males and 7 females aged 17-47 years, were treated. Twenty patients (9 crush injuries, 5 cutting injuries and 6 sawing injuries) were classified into 4 types, namely type I (the distal one third of nail bed), type II (the middle of nail bed), type III (the proximal one third of nail bed), and type IV (the root of nail bed). There were 3 patients (2 index fingers and 1 little finger) of type I, 8 patients (2 thumbs, 3 index fingers and 3 middle fingers) of type II, 5 patients (3 index fingers, 1 ring finger and 1 little finger) of type III, and 4 patients (2 thumbs, 1 middle finger and 1 little finger) of type IV. The soft tissue defect ranged from 1.2 cm x 1.2 cm to 1.5 cm x 1.2 cm. The time from injury to surgery was 3-10 hours. Fingers of type I and type II were treated with forward flow axial flap and modified nail bed lengthening. Fingers of type III and type IV were treated with forward flow axial flap and partial nail bed replantation as well as modified nail bed lengthening. The flaps ranged in size from 1.5 cm x 1.2 cm to 2.0 cm x 1.4 cm. Twenty patients incisions healed by first intention and the flaps, nails and skin grafting survived. All donor sites healed by first intention. All patients were followed up for 2-6 months (4 months on average). The appearances of fingertips were good. The texture of the flap was soft, and the fingers had no tenderness and motor disturbance. The two-point discrimination was 4.5-6.5 mm. The finger nails of type I and type II extended 3-4 mm after operation, while the finger nails of type III and type IV extended 8-10 mm after operation. All finger nails were smooth and flat without pain. Hook nail happened in 1 case 6 months after operation. Classification of the injured fingers according to the condition of the amputation base is helpful in choosing repair methods, and is conducive to maximize the recovery of the function and shape of fingertips. | 18,822,735 |
[Microvascular decompression for cranial nerve hyperactive dysfunction]. | To assess the results of microvascular decompression (MVD) in treating cranial nerve hyperactive dysfunction. From October 2002 to January 2007, 106 patients with cranial never hyperactive dysfunction were treated with MVD. Among them, there were 47 males and 59 females with an average age of 62 years (42-85 years), including 56 cases of trigeminal neuralgia, 33 cases of hemifacial spasm and 17 cases of spasmodic torticollis. MRI showed obvious nerve root compression in 60 patients (56.6%), suspected nerve root compression in 33 patients (31.1%) and no nerve root compression in 13 patients (12.3%). The disease course was 2-300 months with median course of 54 months. The typical manifestations before operation were pain and myospasm in corresponding innervation region. The superior cerebellar artery was the most common offending vessel in trigeminal neuralgia (44.6%, 25/56), the anterior inferior cerebellar artery in hemifacial spasm (33.3%, 11/33), and the vertebra-basilar artery in spasmodic torticolis (82.4%, 14/17). Complications of facial paralysis, hypoacusia, facial numbness, dizziness, pain of neck and shoulder, muscles weakness of neck and subcutaneous dropsy occurred in 31 patients (29.2%). All patients were followed up for 6-42 months. The total response rate was 90.6%. The curative rate of MVD was 83.9% (47/56) in trigeminal neuralgia, 81.8% (27/33) in hemifacial spasm and 41.2% (7/17) in spasmodic torticolis, respectively. Five patients failed to response (4.7%), 2 of them were cured after re-operation and 3 abandoned further treatment. Five patients suffered recurrence 3-8 months after operation (4.7%), 2 of them recovered after re-operation, 1 got relief by Gamma-knife treatment, and 2 abandoned further treatment. MVD has a good therapeutic effect on the disease caused by vascular compression of cranial nerve. Comprehensive preoperative evaluation, skillful operational technique and intraoperative electrophysiological monitoring should be implemented to enhance the therapeutic effects of MVD and to prevent possible complications. | 18,822,736 |
[The relationship between the family member and the child with AIDS: understanding in the light of Martin Buber]. | This qualitative study with a phenomenological approach aimed at understanding what it means to be a family caregiver of a child living with the Acquired Immunodeficiency Syndrome (AIDS) in the light of Martin Buber's philosophy. The study was carried out at the Pediatric outpatient Unit of a teaching hospital of Porto Alegre, Rio Grande do Sul, Brazil with the participation of 7 family caregivers. Data was collected between September and October, 2006 using phenomenological interviews, and interpreted using Ricouer's hermeneutics. The ethical issues were considered. Being a family member of a child with AIDS is a complex existential phenomenon including changes, caring, dialogues, and concerns in search of the wellbeing of both children and caretaker in the world. Understanding the meaning of these phenomena the life of these families is essential to Nursing in order to plan and to develop a humanistic, ethical, esthetical, and solidary care. | 18,822,758 |
[Patient satisfaction in a laboratory test collection unit]. | This exploratory descriptive study aimed at identifying customer satisfaction attributes in the field of laboratory tests. Data were collected in 2006, using 104 interviews in a laboratorial unit inside a teaching hospital, using the critical incident technique, and submitted to content analysis. Three attribute categories were identified: time spent in waiting for care, interpersonal contact, and technical skills. These results subsidize the assessment of the current satisfaction survey tool, and point to its reformulation. They also allow the identification of improvement needs in customer attention, and provide elements to be taken into account in personnel selection, training programs, personnel performance assessment. | 18,822,760 |
[Pain similarities and differences in the chest syndromes: systematic literature review]. | Clinical conditions that present chest pain should be its causes quickly and precisely diagnosed. The objective of this study was to identify the existence of specific and common pain characteristics in acute myocardial infarction, angina, pericarditis, dissected thoracic aorta, and esophagus conditions. A systematic literature search was carried out using descriptors related to pain and chest syndromes. The following databases were searched for articles published between 1996 and November, 2005: Caribbean and Latin American in Health Sciences Literature (LILACS), Medical Literature and Retrieval System On Line (MEDLINE), Nursing Database (BDEnf), Pan-American Health Organization Database (PAHO), World Health Organization Library Database (WHOLIS), and Cochrane Library, between 1966 and November of 2005. No conclusive studies on the characterization of chest pain diagnosis were found. | 18,822,764 |
[Effect of growth conditions on the molecular weight of poly-3-hydroxybutyrate produced by Azotobacter chroococcum 7B]. | It has been shown that poly-3-hydroxybutyrate (PHB) of predetermined molecular weight can be obtained by varying the growth conditions of the producer strain, Azotobacter chroococcum 7B: pH, temperature, aeration, presence of sodium acetate as an additional carbon source, or growth on crude complex carbon sources (molasses, vinasse, or starch). High-molecular-weight polymer can be obtained at pH 7.0, optimal for the culture (1485 kDa), temperature 30-37 degrees C (1600-1450 kDa, respectively), and low aeration (2215 kDa). The following factors decrease PHB MW: pH deviation to the acidic (pH 6.0, 476 kDa) or alkaline (pH 8.0, 354 kDa) range or lower temperature (20 degrees C, 897 kDa). Introduction of additional carbon source (sodium acetate) at concentrations in the medium varying from 0 to 5 g/l provides an original method of production of PHB with predetermined MW in a wide range, from 270 to 1515 kDa, with high PHB content in the cell. | 18,822,772 |
[Posttranslation regulation of programmable cell events in unicellular eukaryotes]. | The review considers the up to date achievements about posttranslational regulation of programmable cell events: growth, development, and apoptosis in unicellular eukaryotes mediated by histone modifications and DNA metylation. Special attention is given to the evolution aspects of the problem. | 18,822,786 |
Orientation sensitive properties of visually driven neurons in extrastriate area 21a of cat cortex. | Orientation sensitive properties of extrastriate area 21a neurons were investigated. Special attention was paid to the qualitative characteristics of neuron responses to the different orientations of visual stimulus motion across neuron classical receptive fields (CRF). The results of experiments have shown that a group of neurons (31%) in area 21a with specialized responses to moving visual stimuli changed their direction selective (DS) characteristics depending on the orientation of the stimulus movement. Some neurons reveal an abrupt drop of the direction sensitivity index (DI) to certain orientation (58%), and some show significant increase of DI at one of applied orientations of stimulus motion (22%). Detailed investigation of response patterns of non-directional neurons to different orientations of stimulus motion have revealed clear-cut qualitative differences, such as different regularities in the distribution of inter-peak inhibitory intervals in the response pattern in dependence of the orientation of stimulus motion. The investigation of neuron CRF stationary functional organization did not reveal correlations between RF's spatial functional organization, and that of qualitative modulations of neuron response patterns. A suggestion was put forward, that visual information central processing of orientation discrimination is a complex integrative process that includes quantitative as well as qualitative transformations of neuron activity. | 18,822,799 |
Sealants fight back aginst bacteria. | Mike Moran, business development manager, Industrial Construction, at Bostik, explains how a range of new sealants increase protection in hospital bathrooms, shower rooms and kitchen facilities against healthcare-acquired infections. | 18,822,825 |
[Ultrastructural aspects of intercostal muscles in patients with COPD]. | The studies to the electron microscope have shown that external and internal intercostal muscles present characteristic changes of ultra structural organization in COPD. The diameter of muscle fibers become unequal, sarcolemma shows frequently deep invaginations, having in the near sarcoplasma concentrations of mitochondria and tubes of the system T. Here and there, myocytes appear divided or with sarcomere frequently being in contraction state. Ultra structural changes are more emphasized to the external intercostal muscles, more requested than those internal. In this way, the results show that the intercostal breathing muscle are affected by the chronic obstructive pulmonary disease. | 18,822,871 |
[Investigation of anti-R7V antibodies in HIV-infected patients under highly active antiretroviral therapy]. | R7V is a seven-aminoacid peptide epitope derived from cellular beta-2 microglobulin, present on human immunodeficiency virus (HIV) virion surface in patients with HIV infection. Antibodies against R7V peptide have the property of neutralizing all strains of HIV, unrelated to genotype, phenotype, or geographical origin of the virus, even in the presence of anti-retroviral drug resistance. Patients that mount an anti-R7V antibody response have been shown to be slow or non-progressors and this epitope has been considered for vaccine and/or therapeutic uses. In this study, HIV-infected patients under highly active anti-retroviral therapy (HAART) at Hacettepe University Faculty of Medicine, Department of Internal Medicine, Division of Infectious Diseases, were evaluated for the presence of anti-R7V antibodies. Thirty-three HIV positive patients and 10 healthy controls were enrolled to the study. For HIV-infected patients, determination of viral load and CD4+ T lymphocyte counts were performed by a commercial real-time PCR assay and flow cytometry, respectively. Anti-R7V antibodies were detected from serum samples by a commercial ELISA (Anti-R7V ELISA, Ivagen, France) test. Three HIV infected patients (3/33, 9.1%) displayed anti-R7V antibodies whereas the remaining 30 (90.9%) patients and all controls were interpreted as negative. No statistically significant difference was detected for HIV-RNA levels and CD4+ T lymphocyte counts between anti-R7V positive and negative patients (p= 0.871 and p= 0.287, respectively). These results indicate the presence of anti-R7V antibodies in our study population with HIV infection. No correlation with the presence of anti-R7V and disease progression were displayed in this study. Clinical impact of anti-R7V antibody assays for the management of HIV-infected patients will be revealed in the near future with the help of advanced studies. | 18,822,884 |
[Nosocomial meningitis with dual agents and treatment with intraventricular gentamicin]. | Nosocomial central nervous system infections constitute 0.4% of all nosocomial infections. The responsible pathogens of nosocomial meningitis are quite different from community-acquired meningitis with high rates of morbidity and mortality. The most important prognostic factor is the appropriate choice of pathogen-specific antibacterial therapy. In this report, a 64 years old woman with nosocomial meningitis caused by Klebsiella pneumoniae and Acinetobacter spp. after lumbar disc hernia operation, has been presented. The risk factors were detected as recent history of neurosurgical operation for three times and long term (29 days) use of external ventricular drainaige (EVD) catheter. Empirical meropenem (3 x 2 g, IV) and vancomycin (2 x 1 g, IV) therapy was initiated upon the diagnosis of nosocomial meningitis based on the clinical and laboratory findings on the postoperative fifth day. Extended-spectrum beta-lactamase (ESBL) producing K. pneumoniae (susceptible to amikacin, imipenem, meropenem, cefoxitine, ciprofloxacin, piperasillin-tazobactam and trimethoprim/sulfamethoxazole) was recovered from cerebrospinal fluid (CSF) and blood samples obtained on the same day. There was no change in the status of the patient on the eighth day of meropenem therapy, with high leukocyte number (1300/mm3) and presence of gram-negative bacilli in CSF, and ESBL positive K. pneumoniae (antibiotic susceptibility pattern same with the previous isolate) growth in CSF culture. Thereupon intravenous ciprofloxacin (3 x 400 mg) was added to the therapy and her EVD has been changed. However, ESBL positive K. pneumoniae (antibiotic susceptibility pattern same with the previous isolate) together with Acinetobacter spp. (susceptible to gentamycin, tobramycin, netilmicin, ciprofloxacin, levofloxacin and cefepime) were isolated from CSF and blood cultures obtained on the 13th day of meropenem and fifth day of ciprofloxacin therapy. Therefore intraventricular and intravenous gentamicin (15 mg/days and 3 x 120 mg, respectively) were added to the therapy. The patient recovered at the end of three weeks treatment without any additional sequela other than her primary illness. This case was the first case of nosocomial meningitis due to ESBL positive K. pneumoniae together with Acinetobacter spp. in the available literature. | 18,822,895 |
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