title
stringlengths 0
1.13k
| abstract
stringlengths 1
15.7k
| PMID
int64 22
36.5M
|
|---|---|---|
Determination of chemical warfare agents: Gas chromatographic analysis of ethylarsine dichloride by derivatization with dithiols (3rd Communication).
|
Ethylarsine dichloride was used during WW I as a chemical warfare agent. Residues of this chemical warfare agent and its metabolites are still present today and continue to contaminate soil and water. A gas Chromatographic method for the detection and determination of ethylarsine dichloride is shown. Six dithiols were tested as possible derivatization reagents for ethylarsine dichloride. With selection of the dithiol, matrix interferences can be eliminated because of the different retention times of the derivatives.
| 19,005,811
|
A study of BTEX-ratios in the urban area of Munich/Germany using rapid gas chromatography.
|
During October 1993 rapid in-situ quasi-continuous GC/FID measurements of aromatic compounds (BTEX) were carried out at two urban sites in Munich/Germany. A cycle time of 10 min allowed determination of shorttime BTEX emission variations and their impact on selected BTEX ratios. The ethylbenzene/ Sigmam/p-xylene ratio showed the smallest variations even in case of rapid changes in the BTEX-mixture. It appeared to be almost independent of the emission strength. Therefore this ratio is suggested to be primarily dependent on photochemical processes in urban environments. It provides an indicator for the impact of anthropogenically related hydrocarbon chemistry leading to the formation of secondary pollutants.
| 19,005,812
|
Phosphine by bio-corrosion of phosphide-rich iron.
|
Phosphine is a toxic agent and part of the phosphorus cycle. A hitherto unknown formation mechanism for phosphine in the environment was investigated. When iron samples containing iron phosphide were incubated in corrosive aquatic media affected by microbial metabolites, phosphine was liberated and measured by gas chromatography. Iron liberates phosphine especially in anoxic aquatic media under the influence of sulfide and an acidic pH. A phosphine-forming mechanism is suggested: Phosphate, an impurity of iron containing minerals, is reduced abioticly to iron phosphide. When iron is exposed to the environment (e.g. as outdoor equipment, scrap, contamination in iron milled food or as iron meteorites) and corrodes, the iron phosphide present in the iron is suspended in the medium and can hydrolyze to phosphine. Phosphine can accumulate to measurable quantities in anoxic microbial media, accelerating corrosion and preserving the phosphine formed from oxidation.
| 19,005,813
|
Ecological recovery of vegetation at a former industrial sludge basin and its implications to phytoremediation.
|
Examination of a former industrial sludge basin containing organic pollutants showed that the basin had undergone substantial ecological recovery through natural forces following the removal of surface water in 1982. Conventional phases of ecological recovery (plant invasion and succession) have occurred, but the structure of the biodiverse plant community (51 species and 22 families) was different from that at a recovering non-polluted disturbed site. Three plant species (Bermuda grass, mulberry, and sunflower) believed to be early invaders of the basin still persist in large numbers indicating that these species are well suited to cope with normal environmental stresses at this area (i.e. seasonal drought and flood) as well as organic pollutants. There was an indication that early invaders of the site fostered disappearance of contaminants thereby creating more favorable conditions for a broader spectrum of plants to grow. Vegetation analyses of naturally vegetated hazardous waste sites hold promise as a screening device for identifying plant species and management practices worthy of further phytoremediation investigations.
| 19,005,834
|
Efavirenz Mannich bases: synthesis, anti-HIV and antitubercular activities.
|
A series of efavirenz Mannich bases has been synthesized by reacting efavirenz, formaldehyde, and various aryl substituted piperazines using microwave irradiation (yield 35-88%). The synthesized compounds were evaluated for in-vitro anti-HIV and antimycobacterial activities. The in-vitro antiretroviral activities indicated that compound 7-(4-((6-chloro-4-(2-cyclopropylethynyl)-4-(trifluoromethyl)-2-oxo-2H-benzo[d] [1,3]oxazin-1 (4H)-yl)methyl)-3-methylpiperazin-l -yl)-1-cyclopropyl-6-fluoro-l,4-dihydro-8-methoxy-4-oxoquinoline-3-carboxylic acid (4i) was equipotent to efavirenz with EC(50) of 2.4 nM. Compound 4i also inhibited M. tuberculosis with minimum inhibitory concentration of 0.2 microg/mL.
| 19,005,871
|
From psychosurgery to neuromodulation: deep brain stimulation for intractable Tourette syndrome.
|
Tourette syndrome is a neuropsychiatric disorder characterized by motor and vocal tics. It is often associated with depression, obsessive-compulsive symptoms, self-injurious behaviour and attention deficit-hyperactivity disorder (ADHD). In intractable patients, neuromodulation using deep brain stimulation (DBS) has widely replaced psychosurgery. Three different key structures are defined for DBS, the medial portion of the thalamus, the globus pallidus internus and the anterior limb of the internal capsule/nucleus accumbens. This is a comprehensive overview on the effect of DBS on motor and non-motor symptoms using different case series and two larger studies.
| 19,005,877
|
Long-term mortality trends in functionally-dependent adults following severe traumatic-brain injury.
|
To investigate mortality trends in functionally dependent adults following traumatic brain injury (TBI). Data for 966 consecutive admissions to a specialist TBI rehabilitation service were reviewed. Details for 69 subjects who were functionally dependent at rehabilitation discharge were cross-referenced against the State Government Death Register. The observed mortality rate was compared to an equivalent population sample derived from Australian Life Tables. Twenty-five subjects (36%) were deceased at an average 10.5 years post-injury (SD 5 years; range 1.7-18.8 years). The observed numbers of deaths far exceeded the expected population figure (1.9) for the same period (1989-2007) yielding a standardized mortality rate of 13.2. Mortality trends suggested a bimodal distribution, with more deaths in the first 5 years post-injury followed by no further deaths until 9 years post-injury. Mortality in this functionally-dependent group was significantly associated with age, male sex and degree of disability at discharge. The bimodal distribution of mortality data suggests different contributory mechanisms to early vs. late mortality in this group.
| 19,005,883
|
Melatonin and environmental lighting regulate ALA-S gene expression and So porphyrin biosynthesis in the rat harderian gland.
|
The main porphyrin in rodent Harderian glands (HGs) is the heme precursor protoporphyrin IX (PPIX). Rhythmic variations in PPIX levels have yet to be studied in rodent HGs. Moreover, the mode of regulation of heme biosynthesis in this organ is poorly documented in the rat. The aim of this study was to determine day-night PPIX levels as well as day-night activity and mode of expression of the porphyrinogenic enzymes delta-aminolevulinate synthase (ALA-S) and ferrochelatase (Fech) in the rat HG. The mRNA expression of ABCG2/Bcrp1 was also investigated. Male Wistar rats acclimatized to 12 h light (L): 12 h dark (D) cycles were sacrificed in the middle of both the L and D spans, and HG and liver tissues were collected. We report here that the HG contains an extremely high level of PPIX, 630- to 670-fold higher than in the liver, without a day-night difference, which is the consequence of both low Fech gene expression (5- to 7-fold lower than in the liver) and ALA-S over-expression (4- to 7-fold higher in the HG than liver). Fech and PPIX transporter ABCG2/Bcrp1 do not exhibit day-night variation, whereas HG ALA-S levels are significantly higher during the scotophase. Interestingly, when melatonin (10 mg/kg) is administered in the middle of the light phase, it increases ALA-S mRNA levels in the HG to the ones observed during the middle of the D span. Continuous light exposure abolishes the day-night ALA-S variation in the HG that is observed under standard 12 L:12 D conditions. Our results suggest that melatonin and environmental lighting regulate ALA-S gene expression in the rat HG.
| 19,005,892
|
Novel methods for tendon investigations.
|
Tendon structures have been studied for decades, but over the last decade, methodological development and renewed interest for metabolic, circulatory and tissue protein turnover in tendon tissue has resulted in a rising amount of investigations. This paper will detail the various modern investigative techniques available to study tendons. There are a variety of investigative methods available to study the correlations between mechanics and biology in tendons. The available methodologies not only allow for potential insight into physiological and pathophysiological mechanisms in tendon tissue, but also, to some extent, allow for more elaborate studies of the intact human tendon.
| 19,005,915
|
Correlates of functional fitness in older adults.
|
Self-efficacy has been shown to be both an antecedent and determinant of behaviors such as physical activity and may explain variance in the performance of functional tasks among older adults. The objectives of the current study were: first, to identify potential latent factors of functional fitness (i.e., the ability to perform activities of daily living) among older adults; and second, to determine the extent to which self-efficacy contributed to the variance in functional fitness over and above other known correlates. Older adults (n = 190, M age = 69.4 years) completed a functional fitness test battery, maximal graded exercise test, and demographics and self-efficacy questionnaires. Structural equation modeling supported two latent factors of functional fitness representing "Flexibility" and "Physical Power." Further analyses indicated sex as the sole significant correlate of Flexibility. Greater Physical Power was associated with being male, younger, and having higher self-efficacy. These results support the role of self-efficacy as a correlate of performance on functional tasks. Targeting flexibility and physical power to improve functional fitness among older men and women, respectively, warrants examination.
| 19,005,931
|
Use of MP3 players to increase asthma knowledge in inner-city African-American adolescents.
|
Low-income African-American adolescents suffer a disproportionate burden of asthma morbidity. To evaluate the ability of our intervention, the Adolescents' Disease Empowerment and Persistency Technology (ADEPT) for asthma, to increase asthma knowledge in our target population. This was a 14-week (2-week run-in and 12-week treatment) randomized, double-blind, placebo-controlled pilot study in which 28 inner-city African-American adolescents with asthma, between 10 and 18 years of age, were randomized to receive (1) celebrity asthma messages (experimental group), or (2) general health messages (control group) between music tracks on an MP3 player. The asthma messages were recorded by famous athletes, musicians, and other celebrities popular among this group of teenagers. Asthma knowledge, assessed by the ZAP Asthma Knowledge instrament, was collected pre- and post-intervention. Mean improvement in ZAP score was significantly higher in the experimental group (8.1%, SD 7.2%) than the control group (0.4%, SD 7.2%) (p = 0.05). These findings suggest that this may be an innovative and promising new approach to improving asthma outcomes in this difficult-to-reach population.
| 19,005,935
|
Novel polymeric nanoparticles containing tanshinone IIA for the treatment of hepatoma.
|
Novel polylactic acid nanoparticles containing tanshinone IIA (TS-PLA-NPs) were synthesized by a single oil-in-water emulsion/solvent evaporation method. In this study, the optimized nanoparticles were characterized for morphology, mean particle size, zeta potential, entrapment efficiency, drug-loading content, X-ray diffractometer measurement, and in vitro release. The obtained nanoparticles were spherical and intact. The mean particle size was 192.5 nm with polydispersity index being 0.029 and zeta potential - 26.27 mV. The mean entrapment efficiency and loading of tanshinone IIA (TSIIA) in TS-PLA-NPs were 86.35 and 1.61%, respectively. The in vitro release study was performed at pH 7.4 using a dialysis membrane. Without initial burst effect, the TSIIA sustained release from TS-PLA-NPs for more than 7 days. The mean in vitro cumulative release percentage of TSIIA from TS-PLA-NPs vs. time curve fitted well with the Higuchi Equation (Q = 2.0365 + 13.564 x t(1/2), r = 0.9950). In pharmacokinetics and tissue distribution studies, the concentrations of TSIIA are higher in hepatoma and lower in blood, heart, kidney, spleen, and lung at 2 h after TS-PLA-NPs was administered via caudal vein. TS-PLA-NPs were effective in destroying the human liver cancer cells by the Mono-nuclear cell direct cytotoxicity assay (MTT) assay, and the growth-inhibitory effect of TS-PLA-NPs on human liver cancer cells was concentration and time dependent. The effect of TS-PLA-NPs on hepatoma in mice was also performed. The results of TS-PLA-NPs were markedly more effective than both of TSIIA and blank PLA nanoparticles in preventing tumor growth and increasing survival time of mice with hepatoma. This study provided support for the new paradigm, the application of TSIIA for the treatment of hepatoma.
| 19,005,937
|
Copper (II) and zinc (ii) metal-based salicyl-, furanyl-, thienyl- and pyrrolyl-derived ONNO, NNNO, ONNS & NNNS donor asymmetrically mixed schiff-bases with antibacterial and antifungal potentials.
|
A new series of asymmetric salicyl-, furanyl-, thienyl- and pyrrolyl-derived ONNO, NNNO, ONNS & NNNS donor antibacterial and antifungal Schiff-bases and their copper(II) and zinc(II) metal complexes have been synthesized and characterized. IR spectra indicated the ligands to act as quartdentate towards divalent metal ions via two azomethine-N, deprotonated-O of salicyl, furanyl-O, thienyl-S and/or pyrrolyl-N. The magnetic moments and electronic spectral data suggest octahedral geometry for Cu(II) and Zn(II) complexes. NMR spectral data of the ligands and their diamagnetic zinc(II) complexes well-define their proposed structures/geometries. Elemental analyses data of the ligands and metal complexes agree with their proposed structures/geometries. The synthesized ligands, along with their metal complexes were screened for their antibacterial activity against B. cereus, C. diphtheriae, E. coli, K. pneumoniae, P. mirabilis, P. aeruginosa, S. typhi, S. dysenteriae and S. aureus strains and for in-vitro antifungal activity against T. schoenleinii, C. glabrata, P. boydii, C. albicans, A. niger, M. canis and T. mentagrophytes. The results of these studies show the metal complexes to be more antibacterial/antifungal against one or more species as compared to the uncomplexed ligands. The brine shrimp bioassay was also carried out to study their in-vitro cytotoxic properties. Eight compounds, L(4), (1), (7), (8), (11), (17), (19) and (23) displayed potent cytotoxic activity with LD(50) = 1.445 x 10(- 3), 1.021 x 10(- 3), 7.478 x 10(- 4), 8.566 x 10(- 4), 1.028 x 10(- 3), 9.943 x 10(- 4), 8.730 x 10(- 4) and 1.124 x 10(- 3) M respectively, against Artemia salina.
| 19,005,942
|
A portable method for assessing gastrointestinal motility by simultaneously measuring transit time and contraction frequency.
|
To portably monitor the motility of the total GI tract, a method for assessing GI motility by simultaneously measuring transit time and contraction frequency is put forward. The portable monitoring system is composed of a swallowable telemetric capsule, a portable recorder, magnetizing coils deposited in vitro, and workstation for data processing. The transit time and contraction frequency of the GI tract are deduced by analysing the variation of the position and orientation angles of a telemetric capsule in time domain and frequency domain. AC electromagnetic localization method is used to determine the position and orientation of the telemetric capsule in vivo. In the paper, the localization model based on a quasi-static magnetic field, the method of monitoring GI motility and the set-up of the monitoring system are detailed. Then from static and dynamic experiments, the performances of the system including the accuracy and dynamic response are evaluated. Finally, the electromagnetic safety of the system is verified by simulating electromagnetic radiation to the human body.
| 19,005,962
|
The effect of applied pressure on the electrical impedance of the bladder tissue using small and large probes.
|
There are a number of studies using electrical impedance spectroscopy, a minimally invasive technique, as a tissue characterizing method with different probe sizes (usually with larger probe diameters than that used in this work). In urinary bladder studies the probe size are limited to 2 mm diameter, in order to pass through the working channel of the cystoscope to measure the impedance inside the urinary bladder. Thus, bio-impedance of the human urothelium can only be measured using a small sized probe for in vivo studies. Different pressures were applied with this probe and it was demonstrated that increasing the applied pressure over the probe would increase the measured electrical impedance of the bladder tissue. Therefore, the effect of applied pressure on the resulting electrical impedance was considered in this study (all of the measurements were taken on points that had benign histology). An excessive amount of the applied pressure beyond the first visible indentation (first recordable reading) pressure has a significant effect on the impedance of the bladder tissue (p < 0.001). Then, to reduce the effect of pressure on the measured bio-impedance, the effect of a larger probe (10 mm diameter) was considered (p < 0.001). Increasing the probe contact area is one way to reduce the pressure effect on measurements; however this is difficult in practice in the in vivo situation.
| 19,005,965
|
Lactobacillus fermentum BR11 and fructo-oligosaccharide partially reduce jejunal inflammation in a model of intestinal mucositis in rats.
|
Although probiotics are beginning to enter mainstream medicine for disorders of the colon, their effects on the small bowel remain largely unexplored. We investigated the recently identified probiotic, Lactobacillus fermentum (L. fermentum) BR11 (BR11) and the prebiotic, fructo-oligosaccharide (FOS), both individually and in synbiotic combination, for their potential to alleviate intestinal mucositis. From Days 0-9, rats consumed skim milk (SM; saline + SM), low dose (LD-BR11; 1 x 10(6)cfu/ml), high dose (HD-BR11; 1 x 10(9)cfu/ml), LD-FOS (3%), HD-FOS (6%), or synbiotic (HD-BR11/FOS). On Day 7, rats were injected with 5-fluorouracil (5-FU; 150 mg/kg). All rats were sacrificed on Day 10. Intestinal tissues were collected for quantitative histology, sucrase, and myeloperoxidase (MPO) determinations. 5-FU decreased sucrase activity, villus height, crypt depth, and crypt cell proliferation compared to controls. Compared to 5-FU + SM, histological damage severity scores were increased for all treatments, although all were effective at reducing jejunal inflammation, indicated by reduced MPO activity (P < 0.05). The combination of BR11 and FOS did not provide additional protection. Moreover, HD-FOS and the synbiotic actually increased clinical mucositis severity (P < 0.05). We conclude that L. fermentum BR11 has the potential to reduce inflammation of the upper small intestine. However, its combination with FOS does not appear to confer any further therapeutic benefit for the alleviation of mucositis.
| 19,005,975
|
Effect of Greek raisins (Vitis vinifera L.) from different origins on gastric cancer cell growth.
|
Currants and Sultanas (Vitis vinifera L.) are dried vine products produced in Greece and used broadly in the Mediterranean diet. We aimed to investigate the gastric cancer preventive activity of methanol extracts obtained from currants from three different origins in Greece (Vostizza, Nemea, and Messinia) as well as methanol extracts obtained from Sultanas cultivated in the island of Crete as to inhibition of cell proliferation, induction of apoptosis, and inhibition of inflammation. All extracts from 500 microg dried raisins studied suppressed cell proliferation, significantly those obtained from Sultanas from Crete and currants from Nemea. Flow cytometric analysis of Annexin-V labeled cells indicated that Cretan Sultana, Nemea, and Messinia currants at 500 microg dried product/ml medium significantly induced cell death. All extracts from 500 microg dried raisins statistically decreased protein and mRNA levels of ICAM-1 in TNF-alpha stimulated cells. Measurement of IL-8 protein levels and quantification for IL-8 mRNA showed no significant decrease. These results indicate that the methanol extracts from currants, rich in phenolic compounds, exhibit cancer preventive efficacy by limiting cell proliferation, inducing cell death, and suppressing ICAM-1 levels in AGS cells.
| 19,005,979
|
Inhibition of cell growth and VEGF expression in ovarian cancer cells by flavonoids.
|
Dietary flavonoids have been shown to be protective against various types of cancers. Here we studied the effects of 12 different flavonoids and other substances on cell proliferation and VEGF expression in human ovarian cancer cells, OVCAR-3. Cell growth was determined to pinpoint the best time for drug treatment. By LDH assay, no cytotoxicity was observed for OVCAR-3 cells with all 12 chemicals except mevinolin. Six flavonoids, including apigenin, taxifolin, luteolin, quercetin, genistein, and kaempferol, were shown to inhibit the ovarian cancer cell growth in a dose-dependent manner. From both RT-qPCR and ELISA results, all flavonoids have shown varied degrees of inhibition in VEGF expression. Taxifolin and naringin showed the least inhibition effect. They both lack a double bond in the second ring structure that may be important in inhibiting VEGF expression. The rank order of VEGF protein secretion inhibitory potency was genistein > kaempferol > apigenin > quercetin > tocopherol > luteolin > cisplatin > rutin > naringin > taxifolin. Genistein, quercetin, and luteolin have shown strong inhibition to cell proliferation and VEGF expression of human ovarian cancer cells, and they show promising in the prevention of ovarian cancers.
| 19,005,980
|
[Evidence-based ophthalmology: critical evaluation of the literature in relation to diagnostic tests].
|
In general, articles on diagnostic tests have a very poor methodological quality. If we translate their conclusions to daily practice without a proper analysis it is easy to see a typical trend: physicians use new (and expensive) tests without increasing diagnostic capacity; they only increase the health budget. Evidence-based medicine (EBM) consists of using the best evidence in decision-making. It deals with selected and relevant information, supported by data obtained through the most rigorous scientific method: epidemiology and statistics. Critical evaluation of papers related to diagnostic tests is our aim. We provide with basic skills for evaluation and analysis of papers by means of simple topics on statistics, design of clinical assays and clinical epidemiology. Review of the medical literature. To evaluate papers on diagnostic tests and to use a test correctly, it is necessary to know its diagnostic capacity, the level of certainty to start treatment, the probability of having the disease before using the test and the test capacity to change that probability. The maximum performance of a test is reached when it is used in a maximum uncertainty situation (disease probability 50%). Its highest usefulness is obtained when pre-test probability is maximal, after a careful review of the patient's history and a complete patient examination.
| 19,006,016
|
[The Gerbode defect - a left ventricle to right atrium communication].
|
We present a rare case of left ventricular to right atrial communication - a Gerbode type defect discovered in an adult man with systolic murmur at the left sternal border in physical exam. We report this case because this congenital defect is very rare, more often this pathology was reported after trauma, endocarditis or aortic valve replacement.
| 19,006,037
|
[67-year-old patient with speech disorder and dysphagia].
|
A 67-year-old man who had been heart transplanted ten years before was admitted to our hospital because of diarrhea. During his stay he developed a severe lingual and facial angioedema. After excluding hereditary angioedema caused by a deficiency in functional C1 esterase inhibitor we focused on adverse effects of his drugs. The medication was composed of Aspirin, Enalapril, Diltiazem, Everolimus, Mycophenolate Mofetil, Bisoprolol, Pravastatin, Esomeprazol and Allopurinol. The angioedema disappeared with anti-allergic treatment. The administration of the suspected trigger enalapril was stopped. However weeks later the patient was admitted again with angioedema. Due to missing urticaria Aspirin was unlikely the causer. The only new drug the patient had been medicated with was Everolimus for 30 days. We assumed a link between the angioedema and Everolimus. Consequently we changed the immunosuppressive regime. After stopping Everolimus no angioedema occurred. Everolimus is a potential trigger of angioedema.
| 19,006,046
|
Small-cell neuroendocrine carcinoma originating from the lateral nasopharyngeal wall.
|
A 40-year-old man presented with right-sided nasal blockage and epistaxis of 18 months' duration. Examination revealed a pinkish mass in the right nasal cavity and nasopharynx. Initial biopsy was suggestive of angiofibroma. Complete excision through a lateral rhinotomy approach was performed. The postoperative histopathologic report was suggestive of sinonasal neuroendocrine carcinoma, which was confirmed by immunohistochemistry. To the best of our knowledge, this is the first reported case of sinonasal neuroendocrine carcinoma arising from the lateral wall of the nasopharynx in the English literature. We describe its clinical presentation and management and provide a brief review of the literature.
| 19,006,052
|
Single-cell-based image analysis of high-throughput cell array screens for quantification of viral infection.
|
The identification of eukaryotic genes involved in virus entry and replication is important for understanding viral infection. Our goal is to develop a siRNA-based screening system using cell arrays and high-throughput (HT) fluorescence microscopy. A central issue is efficient, robust, and automated single-cell-based analysis of massive image datasets. We have developed an image analysis approach that comprises (i) a novel, gradient-based thresholding scheme for cell nuclei segmentation which does not require subsequent postprocessing steps for separation of clustered nuclei, (ii) quantification of the virus signal in the neighborhood of cell nuclei, (iii) localization of regions with transfected cells by combining model-based circle fitting and grid fitting, (iv) cell classification as infected or noninfected, and (v) image quality control (e.g., identification of out-of-focus images). We compared the results of our nucleus segmentation approach with a previously developed scheme of adaptive thresholding with subsequent separation of nuclear clusters. Our approach, which does not require a postprocessing step for the separation of nuclear clusters, correctly segmented 97.1% of the nuclei, whereas the previous scheme achieved 95.8%. Using our algorithm for the detection of out-of-focus images, we obtained a high discrimination power of 99.4%. Our overall approach has been applied to more than 55,000 images of cells infected by either hepatitis C or dengue virus. Reduced infection rates were correctly detected in positive siRNA controls, as well as for siRNAs targeting, for example, cellular genes involved in viral infection. Our image analysis approach allows for the automatic and accurate determination of changes in viral infection based on high-throughput single-cell-based siRNA cell array imaging experiments.
| 19,006,066
|
Ultrasound treatment of cutaneous side-effects of infused apomorphine: a randomized controlled pilot study.
|
Apomorphine hydrochloride is a dopamine agonist used in the treatment of advanced Parkinson's disease. Its administration by subcutaneous infusions is associated with the development of nodules that may interfere with absorption of the drug. This pilot study assessed the effectiveness of ultrasound (US) in the treatment of these nodules. Twelve participants were randomly assigned to receive a course of real or sham US on an area judged unsuitable for infusion. Following treatment, no significant change was observed in measures of tissue hardness and tenderness. However, 5 of 6 participants receiving real US rated the treated area suitable for infusion compared with the 1 of 6 receiving sham US. Sonographic appearance improved in both groups, but more substantially in the real US group. Power calculations suggest a total sample size of 30 would be required to establish statistical significance. A full-scale study of the effectiveness of therapeutic US in the treatment of apomorphine nodules is warranted.
| 19,006,068
|
Identification of a MYO18A-PDGFRB fusion gene in an eosinophilia-associated atypical myeloproliferative neoplasm with a t(5;17)(q33-34;q11.2).
|
Chromosomal aberrations of 5q31-33 associated with rearrangements of the platelet-derived growth factor receptor beta (PDGFRB) gene are rare but recurrent in patients with eosinophilia-associated atypical myeloproliferative neoplasms (Eos-MPNs). We used a DNA-based "long-distance inverse PCR" (LDI-PCR) to identify a new MYO18A-PDGFRB fusion gene in an Eos-MPN with associated t(5;17)(q33-34;q11.2). MYO18A is the fourth partner gene after BCR, ETV6 and SPTBN1 that fuses to more than one tyrosine kinase gene. Treatment with imatinib (400 mg/day) led to rapid and sustained complete hematologic, cytogenetic and molecular remission. Patients with PDGFRB fusions genes are excellent candidates for treatment with imatinib; complete cytogenetic and even molecular remissions are common while primary or secondary resistance seems to be very rare.
| 19,006,078
|
CADASIL: extended polymorphisms and mutational analysis of the NOTCH3 gene.
|
CADASIL is a cerebrovascular disease caused by mutations in the NOTCH3 gene. Most mutations result in a gain or loss of cysteine residue in one of the 34 epidermal growth factor-like repeats in the extracellular domain of the Notch3 protein, thus sparing the number of cysteine residues. To date, more than 130 different mutations in the NOTCH3 gene have been reported in CADASIL patients, of which 95% are missense point mutations. Many polymorphisms have also been identified in the NOTCH3 coding sequence, some of them leading to amino acid substitutions. The aim of the present study was to analyze the NOTCH3 gene in a large group of patients affected by leukoencephalopathy and to investigate the presence of genetic variants. The molecular analysis revealed several nucleotide alterations. In particular, we identified 20 different mutations, 22 polymorphisms, and 8 genetic variants of unknown pathological significance never reported previously. We hope that this NOTCH3 gene mutational analysis, performed in such a significant number of unrelated and related patients affected by leukoencephalopathy, will help in molecular screening for the NOTCH3 gene, thus contributing to enlargement of the NOTCH3 gene variation database.
| 19,006,080
|
Presynaptic muscarinic receptors, calcium channels, and protein kinase C modulate the functional disconnection of weak inputs at polyinnervated neonatal neuromuscular synapses.
|
We studied the relation among calcium inflows, voltage-dependent calcium channels (VDCC), presynaptic muscarinic acetylcholine receptors (mAChRs), and protein kinase C (PKC) activity in the modulation of synapse elimination. We used intracellular recording to determine the synaptic efficacy in dually innervated endplates of the levator auris longus muscle of newborn rats during axonal competition in the postnatal synaptic elimination period. In these dual junctions, the weak nerve terminal was potentiated by partially reducing calcium entry (P/Q-, N-, or L-type VDCC-specific block or 500 muM magnesium ions), M1- or M4-type selective mAChR block, or PKC block. Moreover, reducing calcium entry or blocking PKC or mAChRs results in unmasking functionally silent nerve endings that now recover neurotransmitter release. Our results show interactions between these molecules and indicate that there is a release inhibition mechanism based on an mAChR-PKC-VDCC intracellular cascade. When it is fully active in certain weak motor axons, it can depress ACh release and even disconnect synapses. We suggest that this mechanism plays a central role in the elimination of redundant neonatal synapses, because functional axonal withdrawal can indeed be reversed by mAChRs, VDCCs, or PKC block.
| 19,006,081
|
Enriched environment restores hippocampal cell proliferation and ameliorates cognitive deficits in chronically stressed rats.
|
Adult neurogenesis, particularly in the subgranular zone, is thought to be linked with learning and memory. Chronic stress inhibits adult hippocampal neurogenesis and also impairs learning and memory. On the other hand, exposure to enriched environment (EE) is reported to enhance the survival of new neurons and improve cognition. Accordingly, in the present study, we examined whether short-term EE after stress could ameliorate the stress-induced decrease in hippocampal cell proliferation and impairment in radial arm maze learning. After restraint stress (6 hr/day, 21 days) adult rats were exposed to EE (6 hr/day, 10 days). We observed that chronic restraint stress severely affected formation of new cells and learning. Stressed rats showed a significant decrease (70%) in the number of BrdU (5-bromo-2'-deoxyuridine)-immunoreactive cells and impairment in the performance of the partially baited radial arm maze task. Interestingly, EE after stress completely restored the hippocampal cell proliferation. On par with the restoration of hippocampal cytogenesis, short-term EE after stress resulted in a significant increase in percentage correct choices and a decrease in the number of reference memory errors compared with the stressed animals. Also, EE per se significantly increased the cell proliferation compared with controls. Furthermore, stress significantly reduced the hippocampal volume that was reversed after EE. Our observations demonstrate that short-term EE completely ameliorates the stress-induced decrease in cell proliferation and learning deficit, thus demonstrating the efficiency of rehabilitation in reversal of stress-induced deficits and suggesting a probable role of newly formed cells in the effects of EE.
| 19,006,089
|
Immunization with pseudotype baculovirus expressing envelope protein of Japanese encephalitis virus elicits protective immunity in mice.
|
Japanese encephalitis (JE) is a serious infection and disease in southern and eastern Asia. The design and development of safer and more efficacious vaccines against Japanese encephalitis virus (JEV) is a high-priority target in the world. Recently, baculovirus pseudotyped with vesicular stomatitis virus glycoprotein (VSVG) was described as an attractive gene delivery vehicle in mammalian cells and a potential vector for vaccine development. In the present study, we constructed a recombinant pseudotype baculovirus encoding the JEV envelope (E) protein and demonstrated that it could elicit high protective immunity in mice. Recombinant pseudotype baculovirus (BV-G-E) was generated by inserting JEV E gene fragment into pFastBac-VSV/G vector. BALB/c mice were immunized with BV-G-E and challenged with JEV wild-type strain. The neutralization antibody, interferon (IFN)-gamma expression and release, and survival rate were analysed and compared with the group of immunized with inactivated vaccine and DNA vaccine (pc-E) encoding the same gene of JEV. We demonstrated that intramuscular injections of BV-G-E at various doses into mice produced higher levels of JEV-specific neutralizing antibodies, IFN-gamma and better protective efficacy against a lethal challenge with JEV than that of pc-E. Furthermore, BV-G-E could elicit a higher level of cellular immunity response and provide equal protective efficacy against JEV challenge compared to inactivated vaccine. Our data demonstrate that BV-G-E elicited higher levels of protective immunity compared to DNA vaccine and that pseudotype baculovirus-mediated gene delivery can be utilized as an alternative strategy to develop new generations of vaccines against JEV infection.
| 19,006,097
|
Tetralogy of Fallot: the oldest reported survivor of Brock's procedure.
|
We report the case of a 79-y-old male with Tetralogy of Fallot (TOF) who underwent Brock's procedure in his twenties and has survived event-free. Brock's procedure, which entailed infundibular resection and pulmonary valvotomy, has been associated with complications including the need for re-operation, pulmonary regurgitation, and biventricular failure.
| 19,006,112
|
Synthesis of beta-peptides with beta-helices from new C-linked carbo-beta-amino acids: study on the impact of carbohydrate side chains.
|
The design and synthesis of beta-peptides from new C-linked carbo-beta-amino acids (beta-Caa) presented here, provides an opportunity to understand the impact of carbohydrate side chains on the formation and stability of helical structures. The beta-amino acids, Boc-(S)-beta-Caa((g))-OMe 1 and Boc-(R)-beta-Caa((g))-OMe 2, having a D-galactopyranoside side chain were prepared from D-galactose. Similarly, the homo C-linked carbo-beta-amino acids (beta-hCaa); Boc-(S)-beta-hCaa((x))-OMe 3 and Boc-(R)-beta-hCaa((x))-OMe 4, were prepared from D-glucose. The peptides derived from the above monomers were investigated by NMR, CD, and MD studies. The beta-peptides, especially the shorter ones obtained from the epimeric (at the amine stereocenter C(beta)) 1 and 2 by the concept of alternating chirality, showed a much smaller propensity to form 10/12-helices. This substantial destabilization of the helix could be attributed to the bulkier D-galactopyranoside side chain. Our efforts to prepare peptides with alternating 3 and 4 were unsuccessful. However, the beta-peptides derived from alternating geometrically heterochiral (at C(beta)) 4 and Boc-(R)-beta-Caa((x))-OMe 5 (D-xylose side chain) display robust right-handed 10/12-helices, while the mixed peptides with alternating 4 and Boc-beta-hGly-OMe 6 (beta-homoglycine), resulted in left-handed beta-helices. These observations show a distinct influence of the side chains on helix formation as well as their stability.
| 19,006,129
|
Toluene dioxygenase-catalyzed synthesis of cis-dihydrodiol metabolites from 2-substituted naphthalene substrates: assignments of absolute configurations and conformations from circular dichroism and optical rotation measurements.
|
cis-Dihydrodiol metabolites have been isolated from naphthalene and six 2-substituted naphthalene substrates. Their structures and absolute configurations have been determined by a combination of calculated (TDDFT) and experimentally based circular dichroism (CD) and optical rotation (OR) methods. The "inverse" styrene helicity rule is shown to be incorrect for the interpretation of the CD spectra of cis-dihydrodiols. A striking conclusion is that CD spectra correlate directly with the helicity of the styrene chromophore: that is, the sign of the long-wavelength Cotton effect is identical with the sign of styrene torsion angle, whereas the OR sign is dependent on the absolute configuration of the allylic carbon atom. The results demonstrate that a predictive model previously used for the determination of preferred regio- and stereoselectivity associated with TDO-catalyzed cis-dihydroxylation of substituted benzene substrates can now be successfully extended to substituted naphthalene substrates.
| 19,006,170
|
Human embryonic stem cells and cardiac cell fate.
|
Human embryonic stem (HES) cells are pluripotent and give rise to any cell lineage. More specifically, how the first embryonic lineage (i.e., cardiac lineage) is acquired remains in many aspects questionable. Herein, we summarize the protocols that have been used to direct the fate of HES cells toward the cardiomyocytic lineage. We further discuss the regulation of transcriptional pathways underlying this process of differentiation. Finally, we propose perspectives of this research in the near future.
| 19,006,174
|
Stereoselective analysis of labetalol in human plasma by LC-MS/MS: application to pharmacokinetics.
|
Labetalol is clinically available as a mixture of two racemates (four stereoisomers). The stereoisomer (R,R) has as main activity the beta1-antagonism and the stereoisomer (S,R) is highly selective for the alpha1 adrenoceptor and is responsible for most of the alpha-blocker activity. In the present investigation, a method for the analysis of labetalol stereoisomers in human plasma was developed and applied to pharmacokinetic studies. Plasma samples (0.5 ml) were extracted with methyl tert-butyl ether at pH 9.5. The four labetalol stereoisomers were analyzed by LC-MS/MS on a Chirobiotic V column using a mobile phase consisting of methanol, acetic acid, and diethylamine, with a recovery of more than 90% for all four. The quantitation limit was 0.5 ng/ml and linearity was observed at 250 ng/ml plasma for each stereoisomer. Studies of precision and accuracy presented coefficients of variation and percentage inaccuracy of less than 15%, indicating that the method is precise and accurate. The method was applied to the study of the kinetic disposition of labetalol over a period of 12 h after oral administration of a single 100 mg dose to a hypertensive pregnant woman. The clinical study revealed stereoselectivity in the pharmacokinetics of labetalol, with a lower plasma proportion for the active stereoisomers (R,R)-labetalol and (S,R)-labetalol. The stereoselectivity observed after oral administration is due to the hepatic metabolism and the first pass effect, with an AUC(R,R)/AUC(S,S) ratio of 0.5.
| 19,006,203
|
Paternal somatic mosaicism of a TGFBR2 mutation transmitting to an affected son with Loeys-Dietz syndrome.
|
We report on somatic mosaicism of a TGFBR2 missense mutation, c.1336G>A (D446N). The affected son with the heterozygous mutation was previously reported [Sakai et al. (2006); Am J Med Genet A 140A:1719-1725]. Further evaluation indicates his clinical condition is Loeys-Dietz syndrome. Parental blood samples were studied to confirm whether the propositus' mutation was a de novo change, and suggested a trace of the mutation in the father. DNAs extracted from blood leukocytes, buccal cells, hair root cells, and nails in the father indicated 52%, 25%, 0%, and 35% of cells harbored the mutation, respectively. This is the first detailed report of somatic mosaicism of a TGFBR2 mutation.
| 19,006,214
|
Genetic origins and clinical phenotype of familial and acquired erythrocytosis and thrombocytosis.
|
Familial and acquired erythrocytosis and thrombocytosis are characterized by myeloid lineage hyperproliferation, which is either single or multi-lineage in origin. The single lineage disorders exhibit Mendelian inheritance with polyclonal hematopoiesis and often arise from a single genetic defect. In contrast, the multi-lineage disorders exhibit complex patterns of inheritance with multi-genetic origins and clonal hematopoiesis. They have the potential to acquire JAK2 somatic mutations, but this is not the primary event. Identification of the disease-causing genes will enable better classification of familial and acquired erythrocytosis and thrombocytosis. Furthermore, it will provide an insight into the mechanisms regulating myeloid cell proliferation.
| 19,006,225
|
Gender affects survival for medulloblastoma only in older children and adults: a study from the Surveillance Epidemiology and End Results Registry.
|
Males have a higher incidence of medulloblastoma (MB) than females, but the effect of gender on survival is unclear. Studies have yielded conflicting results, possibly due to small sample sizes or differences in how researchers defined MB. We aimed to determine the effect of gender on survival in MB using a large data set and strict criteria for defining MB. A sample of 1,226 subjects (763 males and 463 females) was identified from 1973 to 2002, using the Surveillance Epidemiology and End Results (SEER-9) registry. MB was strictly defined to exclude non-cerebellar embryonal tumors (primitive neuro-ectodermal tumors). Because children <3 years of age are known to have worse survival, patients were stratified by age <3 years at diagnosis (95 males, 82 females) and >3 years (668 males, 381 females). Overall, there was no significant difference in survival between males and females (log rank P = 0.22). However, among subjects >3 years, females had significantly greater survival than males (log rank P = 0.02). In children <3 years, there was a non-significant trend toward poorer survival in females (median survival: males 27 months, females 13 months; log rank P = 0.24). This interaction between age group and gender was statistically significant (P = 0.03). Females with MB have a survival advantage only in subjects >3 years. In children <3 years, females may even have poorer outcome. The effect of gender on survival and incidence in MB warrants additional biologic investigation, and may differ in very young children with MB.
| 19,006,250
|
Bone marrow minimal disseminated disease (MDD) and minimal residual disease (MRD) in childhood T-cell lymphoblastic lymphoma stage III, detected by flow cytometry (FC) and real-time quantitative polymerase chain reaction (RQ-PCR).
|
Despite overlapping features of T-cell lymphoblastic lymphoma (T-LLy) and T-cell acute lymphoblastic leukemia (T-ALL), which respond favorably to T-ALL treatment, clinical and biological differences exist. We retrospectively assessed the prevalence of submicroscopic bone marrow (BM) minimal disseminated disease (MDD) at diagnosis and the early response to treatment (minimal residual disease--MRD) and their prognostic significance in 17 children with stage III T-LLy treated according to Berlin-Frankfurt-Munster (BFM) non-Hodgkin lymphoma protocols. Four-color flow cytometry (FC) was used for lymphoma associated immunophenotype and real-time quantitative polymerase chain reaction (RQ-PCR) for T-cell receptor (TCR beta/delta/gamma) gene rearrangements with at least 0.01% sensitivity. Two markers per patient were identified in all cases using FC and in 80% using RQ-PCR. BM MDD at diagnosis of >or=0.01% was detected by FC and RQ-PCR in 88% and 80% of patients, respectively, and by at least one of the methods in all patients. A significant correlation was achieved between the methods by Pearson correlation analysis (P = 0.004). MRD levels significantly decreased to very low levels on day 33 in 9 out of 10 patients studied. The only patient that remained positive relapsed. MDD was prevalent in stage III T-LLy, for which we could not prove a prognostic significance in the context of ALL-like treatment. This study shows that both FC and RQ-PCR methods are efficient for MDD and MRD analyses in T-LLy.
| 19,006,253
|
Spatial distribution enhancement of sonoluminescence activity by altering sonication and solution conditions.
|
An intensified charge-couped device (CCD) camera was used to capture raw images of multibubble sonoluminescence, generated by 168 and 448 kHz ultrasound. The effect of various air and surfactant concentrations, and pulse conditions on the acoustic pressure distribution, percentage of standing wave component, the structure of the sonoluminescence activity, and speed of streaming was investigated. It was observed that the enhancement in the sonoluminescence intensity by appropriate degassing, pulsing, and addition of sodium dodecylsulfate were closely related to an expansion in the spatial distribution of sonoluminescence activity. This broadening in the spatial distribution is correlated with a high percentage of standing wave component. This effect stems from the reduction in the attenuation of the acoustic field by inhibiting the formation of large coalesced bubbles.
| 19,006,270
|
Distribution of binding energies of a water molecule in the water liquid-vapor interface.
|
Distributions of binding energies of a water molecule in the water liquid-vapor interface are obtained on the basis of molecular simulation with the SPC/E model of water. These binding energies together with the observed interfacial density profile are used to test a minimally conditioned Gaussian quasi-chemical statistical thermodynamic theory. Binding energy distributions for water molecules in that interfacial region clearly exhibit a composite structure. A minimally conditioned Gaussian quasi-chemical model that is accurate for the free energy of bulk liquid water breaks down for water molecules in the liquid-vapor interfacial region. This breakdown is associated with the fact that this minimally conditioned Gaussian model would be inaccurate for the statistical thermodynamics of a dilute gas. Aggressive conditioning greatly improves the performance of that Gaussian quasi-chemical model. The analogy between the Gaussian quasi-chemical model and dielectric models of hydration free energies suggests that naive dielectric models without the conditioning features of quasi-chemical theory will be unreliable for these interfacial problems. Multi-Gaussian models that address the composite nature of the binding energy distributions observed in the interfacial region might provide a mechanism for correcting dielectric models for practical applications.
| 19,006,274
|
Performance of block correlated coupled cluster method with the CASSCF reference function for the prediction of activation barriers, spectroscopic constants in diatomic molecules, and singlet-triplet gaps in diradicals.
|
The spatial orbital formulations of block correlated coupled cluster (BCCC) theory with a general CASSCF reference function (CAS-BCCC in short) is derived and an efficient implementation of this approach at the four-block correlation level (abbreviated CAS-BCCC4) is reported. We have applied the CAS-BCCC4 approach to investigate energy barriers for several reactions (the ring-opening isomerization of the cyclopropyl radical, cyclobutene, cyclobutadiene, and bicyclo[3.1.0]hex-2-ene), spectroscopic constants in several multibond diatomic molecules (C(2), O(2), CO, and N(2)), and singlet-triplet gaps in two diradicals (trimethylenemethane and oxyallyl). A comparison of CAS-BCCC4 results with the experimental data or other theoretical estimates shows that the present approach can provide very satisfactory descriptions for all the studied systems.
| 19,006,279
|
Range separation and local hybridization in density functional theory.
|
Kohn-Sham density functional theory has become a standard method for modeling energetic, spectroscopic, and chemical reactivity properties of large molecules and solids. Density functional theory provides a rigorous theoretical framework for modeling the many-body exchange-correlation effects that dominate the computational cost of traditional wave function approaches. The advent of hybrid exchange-correlation functionals which incorporate a fraction of nonlocal exact exchange has solidified the prominence of density functional theory within computational chemistry. Hybrids provide accurate treatments of properties such as thermochemistry and molecular geometry. But they also exhibit some rather spectacular failures, and often contain multiple empirical parameters. This article reviews our work on developing novel exchange-correlation functionals that build upon the successes of global hybrids. We focus on more flexible functional forms, including local and range-separated hybrid functionals, constructed to obey known exact constraints and (ideally) to incorporate a minimum of empirical parametrization. The article places our work within the context of some other new approximate density functionals and discusses prospects for future work.
| 19,006,280
|
Ion partitioning at the liquid/vapor interface of a multicomponent alkali halide solution: a model for aqueous sea salt aerosols.
|
The chemistry of Br species associated with sea salt ice and aerosols has been implicated in the episodes of ozone depletion reported at Arctic sunrise. However, Br(-) is only a minor component in sea salt, which has a Br(-)/Cl(-) molar ratio of approximately 0.0015. Sea salt is a complex mixture of many different species, with NaCl as the primary component. In recent years experimental and theoretical studies have reported enhancement of the large, more polarizable halide ion at the liquid/vapor interface of corresponding aqueous alkali halide solutions. The proposed enhancement is likely to influence the availability of sea salt Br(-) for heterogeneous reactions such as those involved in the ozone depletion episodes. We report here ambient pressure X-ray photoelectron spectroscopy studies and molecular dynamics simulations showing direct evidence of Br(-) enhancement at the interface of an aqueous NaCl solution doped with bromide. The experiments were carried out on samples with Br(-)/Cl(-) ratios in the range 0.1% to 10%, the latter being also the ratio for which simulations were carried out. This is the first direct measurement of interfacial enhancement of Br(-) in a multicomponent solution with particular relevance to sea salt chemistry.
| 19,006,284
|
Analysis of the critical step in catalytic carbodiimide transformation: proton transfer from amines, phosphines, and alkynes to guanidinates, phosphaguanidinates, and propiolamidinates with Li and Al catalysts.
|
While lithium amides supported by tetramethylethylenediamine (TMEDA) are efficient catalysts in the synthesis of substituted guanidines via the guanylation of an amine with carbodiimide, as well as the guanylation of phosphines and conversion of alkynes into propiolamidines, aluminum amides are only efficient catalysts for the guanylation of amides. Density functional theory (DFT) calculations were used to explain this difference in activity. The origin of this behavior is apparent in the critical step where a proton is transferred from the substrate to a metal guanidinate. The activation energies of these steps are modest for amines, phosphines, and alkynes when a lithium catalyst was used, but are prohibitively high for the analogous reactions with phosphines and alkynes for aluminum amide catalysts. Energy decomposition analysis (EDA) indicates that these high activations energies are due to the high energetic cost of the detachment of a chelating guanidinate nitrogen from the aluminum in the proton transfer transition state. Amines are able to adopt an ideal geometry for facile proton transfer to the aluminum guanidinate and concomitant Al-N bond formation, while phosphines and alkynes are not.
| 19,006,297
|
Silver ion-induced Grob fragmentation of gamma-amino iodides: highly stereoselective synthesis of polysubstituted piperidines.
|
A new concerted silver ion-mediated Grob fragmentation process is described in which a 1,2-dihydropyridinium ion is formed and trapped in situ with Grignard reagents in a highly regio- and diastereoselective fashion. Using this methodology, 2,3,6-trisubstituted piperidines were synthesized in good yields and further derivatized to polysubstituted indolizidine.
| 19,006,316
|
Determination of ground-state hole-transfer rates between equivalent sites in oxidized multiporphyrin arrays using time-resolved optical spectroscopy.
|
Excited-state charge separation in molecular architectures has been widely explored, yet ground-state hole (or electron) transfer, particularly involving equivalent pigments, has been far less studied, and direct quantitation of the rate of transfer often has proved difficult. Prior studies of ground-state hole transfer between equivalent zinc porphyrins using electron paramagnetic resonance techniques give a lower limit of approximately (50 ns)(-1) on the rates. Related transient optical studies of hole transfer between inequivalent sites [zinc porphyrin (Zn) and free base porphyrin (Fb)] give an upper limit of approximately (20 ps)(-1). Thus, a substantial window remains for the unknown rates of ground-state hole transfer between equivalent sites. Herein, the ground-state hole-transfer processes are probed in a series of oxidized porphyrin triads (ZnZnFb) with the focus being on determination of the rates between the nominally equivalent sites (Zn/Zn). The strategy builds upon recent time-resolved optical studies of the photodynamics of dyads wherein a zinc porphyrin is electrochemically oxidized and the attached free base porphyrin is photoexcited. The resulting energy- and hole-transfer processes in the oxidized ZnFb dyads are typically complete within 100 ps of excitation. Such processes are also present in the triads and serve as a starting point for determining the rates of ground-state hole transfer between equivalent sites in the triads. The rate constant of the Zn/Zn hole transfer is found to be (0.8 ns)(-1) for diphenylethyne-linked zinc porphyrins and increases only slightly to (0.6 ns)(-1) when a shorter phenylene linker is utilized. The rate decreases slightly to (1.1 ns)(-1) when steric constraints are introduced in the diarylethyne linker. In general, the rate constants for ground-state Zn/Zn hole transfer in oxidized arrays are a factor of 40 slower than those for Zn/Fb transfer. Collectively, the findings should aid the design of next-generation molecular architectures for applications in solar-energy conversion.
| 19,006,413
|
Interactions between trace metals (Cu, Hg, Ni, Pb) and 2,3,7,8-tetrachlorodibenzo-p-dioxin in the Antarctic fish Trematomus bernacchii: oxidative effects on biotransformation pathway.
|
Biological effects of chemical mixtures are an emerging issue when using biomarkers in field conditions, because synergistic or inhibitory interactions, cascade, and indirect mechanisms can both enhance or suppress responses to specific classes of pollutants. The Antarctic rock cod (Trematomus bernacchii) was exposed to various trace metals (Cu, Hg, Ni, and Pb) and to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), dosed alone or in combination, to generate hypotheses regarding the mechanisms of action at the cellular level. Concentrations of metals significantly increased in liver of T. bernacchii without significant differences between organisms exposed only to the elements or cotreated with TCDD. The marked induction of cytochrome P450 (CYP) by TCDD was greatly suppressed by cotreatment with Cu at both catalytic and protein expression levels, whereas no significant effects were caused by coexposures with Hg, Ni, and Pb. The oxidative status was measured by integrating individual antioxidants with the total oxyradical scavenging capacity toward peroxyl radicals (ROO*) and hydroxyl radicals (*OH). Synergistic oxidative effects appeared in fish coexposed to Cu and TCDD, suggesting that biotransformation efficiency is down-regulated by higher levels of hydrogen peroxide, hydroxyl radicals, and/or mechanisms limiting availability of heme groups. Major oxidative perturbations also were observed in organisms coexposed to TCDD and Hg; in these organisms, however, the marked increase of glutathione content could explain the absence of oxidative inhibition of the CYP system. More limited oxidative effects were caused by Ni and Pb, and the contemporary absence of inhibitory effects on CYP would further confirm the importance of pro-oxidant mechanisms in modulating the biotransformation pathway. The overall results indicate that a wide battery of biomarkers is necessary to assess the impact of chemical mixtures in field conditions.
| 19,006,418
|
Perspectives on health care of adults with developmental disabilities.
|
A focus group study was conducted with individuals with developmental disabilities to understand their perspectives on their health status, health promotion behaviors, and health care services they receive. The majority of participants reported good to excellent health, and all had some form of medical insurance. However, participants reported notable gaps in dental and reproductive health care and age-specific cancer screening. Some adults had good access to medical care, particularly those with a family member or friend who served as their health advocate. Some adults had a sound understanding of their health and health care needs. Program and policy implications are discussed and recommendations are presented to ensure adequate health care for adults with disabilities, including health advocacy training for caregivers.
| 19,006,428
|
Use of erythropoiesis-stimulating agents among chemotherapy patients with hemoglobin exceeding 12 grams per deciliter.
|
Prior to 2007, the erythropoiesis-stimulating agents (ESAs) epoetin alfa and darbepoetin alfa were indicated for use in chemotherapyinduced anemia to achieve target hemoglobin (Hb) levels of approximately 12 grams per deciliter (gm per dL), and treatment was to be withheld if Hb exceeded 13 gm per dL. In March 2007, the FDA changed the labeling of the ESAs to add boxed warnings, updated in November 2007, to include the following key points: (a) ESAs should be used only to treat anemia that occurs in patients with cancer while they are undergoing chemotherapy; (b) treatment with ESAs should be stopped when chemotherapy ends; and (c) dosing ESAs to an Hb target of 12 gm per dL or greater has resulted in more rapid cancer progression or shortened overall survival in patients with breast, head and neck, lymphoid, cervical, and non-small cell lung malignancies. In January 2008, the FDA specified that the increased risk of more rapid tumor growth or shortened survival was associated with ESAs when "administered in an attempt to achieve a Hb level of 12 gm per dL or greater, although many patients did not reach that level." A new black-box warning regarding this association was added to the labels of the ESAs in March 2008, and the FDA mandated further label changes on July 30, 2008, that ESA therapy should not be initiated in patients receiving chemotherapy at Hb levels of 10 gm per dL or higher. To (a) assess the prevalence and predictors of ESA administrations at Hb levels above 12 gm per dL among patients with a diagnosis of solid or hematologic cancer or myelodysplastic syndrome who began their first regimen of conventional myelosuppressive chemotherapy between 2002 and 2006, and (b) describe patterns of ESA treatment subsequent to the first ESA administration at Hb above 12 gm per dL. Using the Health Insurance Portability and Accountability Act (HIPAA)-compliant Varian Medical Oncology database of de-identified electronic medical records from 17 U.S. outpatient oncology practices, adults (aged 18 years or older) with any cancer diagnosis who began chemotherapy between January 1, 2002, and September 30, 2006, were identified. The Hb value associated with each ESA administration was defined as the closest Hb measurement within 7 days prior to the ESA administration. A first ESAHb > 12 was defined as the first time an ESA, either epoetin or darbepoetin, was given with an associated Hb greater than 12 gm per dL during the first chemotherapy regimen recorded in the database for each patient. Hb levels and ESA administrations after the first ESAHb > 12 were determined. Logistic regression models identified predictors of initial receipt of an ESAHb > 12, and of receiving further ESA treatment following the first such administration. Between January 1, 2002, and September 30, 2006, there were 17,731 patients on chemotherapy, the mean (SD) age was 60 (13.2) years; 58.9% were female; 24.6% had breast cancer, 22.2% had lung cancer, 15.8% had colorectal cancer, 11.8% had hematologic cancer, and 25.6% had other or multiple cancers. Of these, 8,086 (45.6%) received an ESA at any time during the regimen, and 7,606 (42.9%) received an ESA at a known Hb level (i.e., Hb measurement within 7 days prior to ESA administration). During the first recorded chemotherapy regimen, 1,844 patients (10.4% of the chemotherapy cohort, 24.2% of ESA users with a known Hb; n = 1,226 epoetin, n = 618 darbepoetin) received an ESAHb > 12. Among patients receiving ESA treatment at a known Hb level, significant predictors of receiving an ESAHb > 12 included treatment in a community-based clinic rather than a hospital-affiliated clinic (odds ratio [OR] = 2.96, 95% confidence interval [CI] = 2.40-3.65), location of practice in the eastern United States (OR for Midwest = 0.67, 95% CI = 0.57- 0.78; OR for West = 0.27, 95% CI = 0.22-0.34), hematologic cancer rather than solid tumor (OR = 1.44, 95% CI = 1.21-1.71), private health insurance (OR for public health insurance = 0.80, 95% CI = 0.70-0.93; OR for other/ unknown insurance = 0.54, 95% CI = 0.47-0.62), and year of regimen 2002- 2003 (ORs = 0.75, 0.74, and 0.71 for 2004, 2005, and 2006, respectively). Following the first ESAHb > 12, 276 (22.5%) of the patients on epoetin and 276 (44.7%) on darbepoetin received no further ESA treatment during the next 6 weeks (Pearson chi-square = 96.1, P < 0.001). This analysis of outpatient oncology practices between 2002 and 2006 revealed that 24% of ESA users with a known Hb level received ESAHb > 12. Dose withholding subsequently occurred in 23%- 45% of those patients. A higher proportion of patients on epoetin than darbepoetin continued ESA treatment after the first administration of ESAHb > 12.
| 19,006,442
|
Self-reported use of pharmaceuticals among patients with irritable bowel syndrome in primary care.
|
Irritable bowel syndrome (IBS) has an estimated 10%-12% prevalence in industrial countries. Studies from the United States have shown that IBS causes notable financial losses for employers. Due to the lack of pathophysiological markers, only a fraction of the pharmacological management of IBS has focused on etiological mechanisms. We hypothesized that there is a high consumption of nonspecific drugs among patients with IBS in their attempts to manage symptoms. To analyze self-reported use of prescription and over-thecounter (OTC) drugs among patients with IBS in primary care compared with controls from the general population. A population-based case-control design was used for the study. IBS cases were identified from the electronic medical records of 3 Swedish primary health care centers from January 1, 1997, through December 31, 2001. A questionnaire containing specific questions about prescription and OTC drugs was mailed in 2003 to 5,015 working-age (18-64 years) individuals (IBS cases and controls) in the Linkping IBS Population Study, a study of primary care patients with controls selected from the general population. After 2 reminders, the overall response rate was 63% (3,074 respondents of 4,913 deliverable surveys); 71% responded for the IBS cases (347/486) and 57% (2,509/4,427) responded for the controls. 72.3% of the IBS respondents and 51.9% of the controls were female. Acid-suppressive agents were the most commonly cited drug category for abdominal complaints reported by IBS patients (13.3%) compared with controls (1.6%) (unadjusted odds ratio [OR] = 9.20, 95% confidence interval [CI] = 5.94-14.25). Antidepressants were the most commonly cited drug category for nonabdominal complaints, reported by 13.3% of IBS patients versus 4.5% of controls (OR = 3.27, 95% CI = 2.27-4.70). An unadjusted univariate correlation analysis revealed that prescription acid-suppressive drugs, fiber and bulking laxatives, and antiflatulents and antidiarrhea drugs, as well as motility-regulating and antispasmodics drugs, were significantly more common among IBS cases compared with controls. In addition to the higher use of antidepressants, there were 3 other drug classes for nongastrointestinal complaints with a higher rate of use among IBS patients compared with controls: sedative hypnotics (OR = 2.49, CI = 1.44- 4.29), analgesics (OR = 2.86, CI = 1.88-4.33), and thyroid hormones (OR = 2.43, CI = 1.39-4.26). There was higher use of antidepressants among patients with IBS compared with controls from the general population. Even though they are not recommended for this patient category, the use of prescription and OTC acid-suppressive drugs is also common among IBS cases in primary care.
| 19,006,443
|
Immunological response to peptide nucleic acid and its peptide conjugate targeted to transactivation response (TAR) region of HIV-1 RNA genome.
|
Anti-human immunodeficiency virus-1 (HIV-1) polyamide (peptide) nucleic acids (PNAs) conjugated with cell-penetrating peptides (CPPs) targeted to the viral genome are potent virucidal and antiviral agents. Earlier, we have shown that the anti-HIV-1 PNA(TAR)-penetratin conjugate is rapidly taken up by cells and is nontoxic to mice when administered at repeat doses of as high as 100 mg/kg body weight. In the present studies we demonstrate that naked PNA(TAR) is immunologically inert as judged by the proliferation responses of splenocytes and lymph node cells from PNA(TAR)-immunized mice challenged with the immunizing antigen. In contrast, PNA(TAR)-penetratin conjugate is moderately immunogenic mainly due to its penetratin peptide component. Cytokine secretion profiles of the lymph node cells from the conjugate-immunized mice showed marginally elevated levels of proinflammatory cytokines, which are known to promote proliferation of T lymphocytes. Since the candidate compound, PNA(TAR)-penetratin conjugate displays potent virucidal and antiviral activities against HIV-1, the favorable immunological response together with negligible toxicity suggest a strong therapeutic potential for this class of compounds.
| 19,006,449
|
Comparison of human placenta- and bone marrow-derived multipotent mesenchymal stem cells.
|
Bone marrow is the traditional source of human multipotent mesenchymal stem cells (MSCs), but placenta appears to be an alternative and more readily available source. This study comprehensively compared human placenta-derived MSC (hpMSC) and human bone marrow-derived MSC (hbmMSC) in terms of cell characteristics, optimal growth conditions and in vivo safety specifically to determine if hpMSC could represent a source of human MSC for clinical trial. MSC were isolated from human placenta (hpMSC) and human bone marrow (hbmMSC) and expanded ex vivo using good manufacturing practice-compliant reagents. hpMSC and hbmMSC showed similar proliferation characteristics in different basal culture media types, fetal calf serum (FCS) concentrations, FCS heat-inactivation experiments, flask types and media replacement responsiveness. However, hpMSC and hbmMSC differed with respect to their proliferation capabilities at different seeding densities, with hbmMSC proliferating more slowly than hpMSC in every experiment. hpMSC had greater long-term growth ability than hbmMSC. MSC from both sources exhibited similar light microscopy morphology, size, cell surface phenotype, and mesodermal differentiation ability with the exception that hpMSC consistently appeared less able to differentiate to the adipogenic lineage. A comparison of both hbmMSC and hpMSC from early and medium passage cultures using single-nucleotide polymorphism (SNP) GeneChip analysis confirmed GTG-banding data that no copy number changes had been acquired during sequential passaging. In three of three informative cases (in which the gender of the delivered baby was male), hpMSC were of maternal origin. Neither hpMSC nor hbmMSC caused any acute toxicity in normal mice when injected intravenously at the same, or higher, doses than those currently used in clinical trials of hbmMSC. This study suggests that human placenta is an acceptable alternative source for human MSC and their use is currently being evaluated in clinical trials.
| 19,006,451
|
Functional analysis of embryonic stem cell-derived glial cells after integration into hippocampal slice cultures.
|
Embryonic stem (ES) cell-derived neural progenitor cells (ESNPs) generated in vitro are multipotent progenitors which can differentiate into oligodendrocytes, astrocytes, and neurons. Given the exciting prospects for ES cell-based treatments of neurological disorders, several studies investigated the migration, integration, and differentiation of grafted ESNPs into neurons and glial cells. However, little is known about the functional properties of transplanted ESNPs on the single cell level. In this study, we combined electrophysiology, single cell reverse transcription polymerase chain reaction (RT-PCR) and immunochemistry to determine the developmental time course of molecular and functional properties of ES cell-derived glial precursors (ESGPs) after deposition onto hippocampal slice cultures. Based on functional criteria, donor cells possessed three different phenotypes. During an observation period of 3 weeks after engraftment, the proportion of donor cells with a passive current pattern (type 3) continuously increased. The majority of these cells expressed astroglial markers. Type 3 host cells underwent similar developmental changes. In contrast, donor and host cells expressing time- and voltage-dependent currents (types 1, 2) displayed different developmental profiles. Importantly, type 2 donor and host cells also differed in the expression of inwardly rectifying K(+) channels. This suggests that despite several similarities in overall current phenotypes and timing of maturation, many donor cells integrated into host tissue but did not acquire the full set of ion channels present in their native counterparts. These findings emphasize the need to carefully characterize ES cell-derived progeny aimed for neural repair and cell-mediated gene transfer strategies.
| 19,006,454
|
Managing neoplastic bone disease with ibandronic acid: a preclinical and clinical data update.
|
Bisphosphonates are the standard of care for treating and preventing the complications of bone metastases. Ibandronic acid is available in effective and well-tolerated oral (50 mg daily) and intravenous (6 mg via > or = 15 min infusion every 3-4 weeks) formulations. This paper reviews the latest preclinical and clinical data supporting the use of ibandronic acid for the prevention and treatment of the skeletal complications of neoplastic bone disease, focusing on metastatic breast cancer. The aim was to update a review of ibandronic acid published in 2004 by the current author. Ibandronate remains the only bisphosphonate with approved oral and intravenous formulations; ibandronate should be considered when designing a bisphosphonate-containing regimen for patients with bone metastases from breast cancer.
| 19,006,482
|
Idiopathic inflammatory myopathies.
|
The idiopathic inflammatory myopathies are a group of systemic autoimmune syndromes characterized by striated muscle inflammation. Here, we discuss the clinical features of this group of conditions and review the recent developments in the understanding of the pathogenesis and immunogenetics of the idiopathic inflammatory myopathies. The role of myositis-specific autoantibodies and their clinical significance and an overview of management are also provided.
| 19,006,486
|
Implantable loop recorders: a viable diagnostic tool in veterinary medicine.
|
The purpose of this study was to investigate whether implantable loop recorders could be used in the diagnosis of unexplained collapse in dogs. The medical records of six dogs presented to the University of Liverpool Small Animal Teaching Hospital between May 2003 and October 2006 for further evaluation of intermittent syncopal episodes, collapse or episodic weakness, were reviewed. All these dogs underwent standard investigations and had implantable loop recorders placed. A provisional diagnosis of supraventricular tachycardia was made in one dog, and diagnoses of exclusion of arrhythmogenic right ventricular cardiomyopathy and idiopathic epilepsy was made in two dogs. One dog suffered no further syncopal episodes, a diagnosis was not reached in another dog and the final dog was lost to follow-up. The implantable loop recorder can be used successfully for the diagnosis of unexplained collapse in dogs.
| 19,006,489
|
Variability in malaria prophylaxis prescribing across Europe: a Delphi method analysis.
|
The indications for prescribing malaria chemoprophylaxis lack a solid evidence base that results in subjectivity and wide variation of practice across countries and among professionals. European experts in travel medicine, who are members of TropNetEurop, participated in a survey conducted using the Delphi method. This technique aims at evaluating and developing a consensus through iterations of questionnaires, controlled feedback, and statistical group responses. A first questionnaire, including questions about controversial issues in prescribing malaria prophylaxis, required responses on a visual scale between 1 and 10. The questionnaire included issues on problematic prescribing, characteristics of drugs, relevance of geography, and importance of insect bite prevention. The repeat questionnaire with the group response from the first round revealed an increasing consensus on most issues. A second survey considered 14 practical scenarios (including two internal standards) and investigated preferred choice of prophylaxis. A significant consensus was noted in 8 of 14 scenarios, which did not increase after a second round. The analysis revealed a wide variation in prescribing choices with preferences grouped by region of practice, and a greater willingness to prescribe in northern and southern Europe than in central Europe. The second round showed a 9.5% change of opinion. The study shows that improving the evidence base on efficacy and tolerability and risk of malaria for prescribing chemoprophylaxis is needed as is further discussion across Europe to achieve harmonization of prescribing practice.
| 19,006,501
|
Leishmaniasis, an emerging imported infection: report of 20 cases from Australia.
|
Leishmaniasis is a protozoan infection rarely reported in Australia. However, with the advent of increased international tourism and migration of refugees from endemic regions, leishmaniasis has emerged as an increasingly imported infection. We report 20 cases (17 cutaneous, 2 visceral, and 1 post-kala-azar dermal leishmaniasis). These data highlight the range of species causing leishmaniasis imported in Australia and demonstrate the importance of species identification in determining proper treatment.
| 19,006,509
|
A patient with paratyphoid A fever: an emerging problem in Asia and not always a benign disease.
|
A 15-year-old Nepalese boy with fever was thought to have enteric fever and started on cefixime. His blood culture grew Salmonella paratyphoid A. On the sixth day, he developed gastrointestinal bleeding, disseminated intravascular coagulation, and later, acute respiratory distress syndrome. He succumbed to his illness despite treatment in the intensive care unit with ceftriaxone, intravenous fluids, and mechanical ventilation. Salmonella paratyphoid A, for which there is no commercial vaccine, may not be a benign disease as perceived, and cefixime that is recommended for enteric fever may be an ineffective choice.
| 19,006,513
|
Plasma levels of asymmetric dimethylarginine in premature neonates: its possible involvement in developmental programming of chronic diseases.
|
The endothel dysfunction in early life may play a role in developmental programming of cardiovascular morbidity. The changes of dimethylarginines' plasma levels during the first month among preterm infants and their determinants had been investigated in our study. Twenty preterm infants of healthy mothers were studied. Mean (+/-SD) birth weight and gestational age were 919.5 +/- 235.5 g and 26.7 +/- 1.6 weeks, respectively. Blood samples were taken by venipuncture at the 3rd, 7th, 14th, 21st and 28th days. Plasma concentrations of L-arginine, asymmetric and symmetric dimethylarginine (SDMA) were measured by liquid chromatography-mass spectrometry method, evaluated by multivariate linear regression analysis. L-arginine (p < 0.001) and asymmetric dimethylarginine (ADMA) levels (p < 0.001) were positively associated with postnatal age. ADMA levels were negatively correlated with gestational age (p = 0.007), dopamine-need on the 3rd day of life (p = 0.015) and late infection (p = 0.038). The higher birth weight was associated with higher L-arginine (p = 0.052) and ADMA (p = 0.002) concentrations. The dopamine-need on the 7th day of life had a significant effect on postnatal elevation of SDMA levels (p = 0.035). The progressive increase of ADMA levels described by our study among preterm infants suggests that early endothel dysfunction may take part in developmental programming of chronic adult diseases.
| 19,006,524
|
The effects of guideline implementation for proton pump inhibitor prescription on two pulmonary medicine wards.
|
It has been demonstrated that 40% of patients admitted to pulmonary medicine wards use proton pump inhibitors (PPIs) without a registered indication. To assess whether implementation of a guideline for proton pump inhibitor (PPI) prescription on pulmonary medicine wards could lead to a decrease in use and improved appropriateness of prescription. This prospective study comprised two periods, i.e. the situation before and after guideline implementation. In each period, 300 consecutive patients were included. We registered patient characteristics, medications and occurrence of upper gastrointestinal-related disorders. After implementation, fewer patients were started on PPIs [21% vs. 13%; odds ratio (OR): 0.56; 95% confidence interval (CI): 0.33-0.97] and more users discontinued their use; however, the latter was not significant (3% vs. 6%; OR for continuation: 0.56; 95% CI: 0.14-2.23). Multivariable logistic regression analysis confirmed that PPI use during hospitalization decreased after implementation (adjusted pooled OR: 0.54; 95% CI: 0.32-0.90). Implementation did not result in a change in reported reasons for PPI prescription. There was no significant difference in the occurrence of upper GI-related disorders in the first 3 months after discharge. Guideline implementation for PPI prescription on two pulmonary medicine wards resulted in a reduction in the number of patients starting PPIs during hospitalization, but appropriateness of prescribing PPIs was not affected. Further studies are needed to determine how appropriateness of PPI prescription on pulmonary medicine wards can be further improved.
| 19,006,542
|
Long-term proton pump inhibitor use and gastrointestinal cancer.
|
Proton pump inhibitors profoundly affect the stomach and have been associated with carcinoid tumors in female rats. There is now sufficient experience with this class of drugs to allow reasonable estimation of their safety in terms of cancer development in humans. Long-term use of proton pump inhibitors is associated with an increase in gastric inflammation and development of atrophy among those with active Helicobacter pylori infections. The actual risk is unknown but is clearly low. However, it can be markedly reduced or eliminated by H. pylori eradication. It is thus recommended that patients being considered for long-term proton pump inhibitor therapy should be tested for H. pylori infection and, if present, this pathogen should be eradicated. Oxyntic cell hyperplasia, glandular dilatations, and fundic gland polyps may develop in patients not infected with H. pylori, but these changes are believed to be reversible and without significant cancer risk.
| 19,006,608
|
Mucolipidosis type IV in a Turkish boy associated with a novel MCOLN1 mutation.
|
Mucolipidosis type IV is a rare neurodegenerative lysosomal storage disorder that usually presents during the first year of life with severe mental retardation, delayed motor milestones and corneal opacities. Mucolipidosis IV is caused by mutations in MCOLN1, a gene encoding mucolipin-1 which is responsible for maintaining lysosomal function. The majority of known patients with this disorders are Ashkenazi Jews, and most have a splice IVS3-2 A>G, or a 6.4kb deletion mutation in MCOLN1. Here, we present a Turkish patient who, in addition to the typical neurological and visceral characteristics of mucolipidosis type IV, also demonstrates defects in the posterior limb of internal capsule by MRI, micrognathia and clinodactyly of the fifth fingers. Direct sequencing of his DNA revealed a homozygous c.1364C>T (S456L) mutation in MCOLN1, which was heterozygous in both consanguineous parents. This mutation, like several previously described, changes the protein sequence in the channel pore domain of the protein. Serine 456 is conserved in mucolipin proteins throughout evolution, therefore the mutation is considered as causative for the severe phenotype of this patient.
| 19,006,653
|
Comparison of daily physical activity between COPD patients from Central Europe and South America.
|
In healthy elderly and adults, lower physical activity level in daily life has been associated with lower socio-economic level and non-Caucasian race. The objective of this study was to determine if this is also applicable in chronic obstructive pulmonary disease (COPD) by comparing physical activity levels in daily life in stable patients from two countries (Austria and Brazil) with different socio-economic and ethnic characteristics. Physical activity in daily life was objectively assessed in 40 Austrian and 40 Brazilian COPD patients. Groups were matched for age, gender, body mass index, disease severity, smoking history, presence of concomitant heart disease, lung function, dyspnea and functional exercise capacity. In addition, climatic conditions were similar during the period of data collection in the two groups. In comparison to Brazilian patients, Austrian patients had a significantly lower walking time (p=0.04), higher sitting time (p=0.02) and lower movement intensity (p=0.0001). The proportion of patients who did not reach an average of 30min of walking per day was 48% in the Austrian group and 23% in the Brazilian group. Austrian patients with COPD showed a significantly lower daily physical activity level in comparison to matched Brazilian patients. Socio-economic and ethnic factors appear to influence stable COPD patients differently than described in previous studies including healthy subjects.
| 19,006,659
|
The combination of docetaxel and cisplatin plus fluorouracil as neoadjuvant chemotherapy in the treatment of T4 stage gastric cancer.
|
The prognosis of local advanced gastric carcinoma is very poor. We evaluated the impact on survival and the effects induced by the triple combination docetaxel-cisplatin-fluorouracil (DCF) as neoadjuvant chemotherapy in 24 T4 stage gastric tumor patients. They received 2-3 cycles DCF chemotherapy, followed by radical gastric resection. Tumor downstaging detected by CT was obtained in 17 out of 24 patients. The overall 3-year survival rate was 68.2%. Patients who received R0 resection (19/22) showed a 3-year survival rate of 78.9%. T downstaged patients (17/22) showed a higher 3-year survival rate of 82.4%. Those who responded to the triple combination of docetaxel-cisplatin-fluorouracil, exhibited T downstaging and subsequently received an R0 resection had a definitely better chance of a cure as compared to surgery alone, according to a complete 3-year follow-up.
| 19,006,661
|
Synthesis and biological activity of previtamin D(3) analogues with A-ring modifications.
|
Synthesis of two novel 6-s-cis analogues of 1alpha,25-dihydroxyvitamin D3 are described using shikimic acid and its 4-epi isomer as versatile chiral starting materials. These derivatives contain a 2beta-(3'-hydroxypropoxy) moiety or a 2beta,3beta-epoxy group into 1alpha,25-OH(2)-19-nor-pre-D3. The synthesized analogues were found to be not suitable for binding to the vitamin D receptor and showed weak binding affinity toward the vitamin D-binding protein. The new derivatives failed to inhibit cell proliferation.
| 19,006,670
|
Structure-activity relationship studies of a new series of imidazo[2,1-f]purinones as potent and selective A(3) adenosine receptor antagonists.
|
We recently described the synthesis of 1-benzyl-3-propyl-1H,8H-imidazo[2,1-f]purine-2,4-diones, new potent and selective A(3) adenosine receptor antagonists containing a xanthine core. The present work can be considered an extension of our SAR studies on related structures in which the effect of different kind of substitutions at the 1-, 3- and 8-positions has been evaluated in order to improve both the potency and the hydrophilicity of the originally synthesised molecules. The A(3) binding disposition of these compounds was also investigated through docking and 3D-QSAR studies.
| 19,006,671
|
Moving beyond "the down low": a critical analysis of terminology guiding HIV prevention efforts for African American men who have secretive sex with men.
|
HIV continues to affect African American populations in the United States at disproportionate levels. Recent reports have described potentially high-risk behaviors of African American men who identify as heterosexual but who engage in secretive sex with other men. These men have been referred to as being "on the Down Low," and this terminology has been used to label subgroups of African American men and explain sexual risks for HIV infection in the African American community. In this paper, we argue that an uncritical use of this terminology for guiding public health and HIV prevention strategies can be problematic and counterproductive because it (a) stigmatizes and exoticizes secretive same-sex sexuality as a unique issue among African American men, and (b) ignores the social conditions under which HIV transmission occurs. We explore some historical roots contributing to current perspectives on African American men's sexuality, describe the use of the term "on the Down Low" and its application to same-sex behavior among African American men, and explain how this term can both clarify and potentially ambiguate efforts to address HIV risk among African American men. Recommendations for research and HIV prevention strategies are also provided.
| 19,006,674
|
Molecular mechanisms of spinal cord dysfunction and cell death in the spinal hyperostotic mouse: implications for the pathophysiology of human cervical spondylotic myelopathy.
|
Cervical spondylotic myelopathy (CSM) is the most common cause of spinal cord dysfunction in adults in Western society. Paradoxically, relatively little is known about the pathobiological mechanisms associated with the progressive loss of neural tissue in the spinal cord of CSM patients. In this report we have utilized the twy/twy mutant mouse, which develops ossification of the ligamentum flavum at C2-C3 and exhibits progressive paralysis. This animal model represents an excellent in vivo model of CSM. This study reports novel evidence, which demonstrates that chronic extrinsic cervical spinal cord compression leads to Fas-mediated apoptosis of neurons and oligodendrocytes which is associated with activation of caspase-8, -9 and -3 and progressive neurological deficits. While surgical decompression will remain the mainstay of management of CSM, molecular therapies, which target Fas-mediated apoptosis could show promise as a complementary approach to maximize neurological recovery in this common spinal cord condition.
| 19,006,686
|
A notch in the toll belt.
|
Two cell response pathways, Toll-like receptor (TLR) and Notch, conserved from Drosophila to mammals are well characterized for distinct roles in innate immunity and cell development, respectively. In this issue of Immunity, Hu et al. (2008) describe and characterize the direct cooperation of these two pathways.
| 19,006,687
|
"Dangerous crystals".
|
Uric acid (UA) crystals are a potent stimulator of inflammation, but how they activate immune cells is not known. In this issue of Immunity, Ng et al. (2008) provide evidence suggesting that UA activates the Syk kinase via membrane cholesterol.
| 19,006,690
|
Retrovirus-specificity of regulatory T cells is neither present nor required in preventing retrovirus-induced bone marrow immune pathology.
|
Chronic viral infections of the hematopoietic system are associated with bone marrow dysfunction, to which both virus-mediated and immune-mediated effects may contribute. Using unresolving noncytopathic Friend virus (FV) infection in mice, we showed that unregulated CD4(+) T cell response to FV caused IFN-gamma-mediated bone marrow pathology and anemia. Importantly, bone marrow pathology was triggered by relative insufficiency in regulatory T (Treg) cells and was prevented by added Treg cells, which suppressed the local IFN-gamma production by FV-specific CD4(+) T cells. We further showed that the T cell receptor (TCR) repertoire of transgenic Treg cells expressing the beta chain of an FV-specific TCR was virtually devoid of FV-specific clones. Moreover, anemia induction by virus-specific CD4(+) T cells was efficiently suppressed by virus-nonspecific Treg cells. Thus, sufficient numbers of polyclonal Treg cells may provide substantial protection against bone marrow pathology in chronic viral infections.
| 19,006,695
|
Intracorneal inlay for the surgical correction of presbyopia.
|
To evaluate the clinical safety and efficacy of the ACI-7000 intracorneal inlay in increasing the depth of field in emmetropic presbyopic patients. Beyoglu Eye Research and Education Hospital, Istanbul, Turkey. This prospective unmasked study comprised 39 presbyopic patients; 12 were naturally emmetropic and 27 had emmetropia resulting from previous hyperopic laser in situ keratomileusis. The intracorneal inlay was placed over the pupil in the patient's nondominant eye after flap lift or creation of a conventional flap using a microkeratome. The inlay was centered on the visual axis. Postoperative follow-up was 1 year. Of the 39 inlays implanted, 3 were explanted during the study. At 1 year, the mean uncorrected near visual acuity improved from J6 (preoperatively) to J1+. All eyes with an inlay had an uncorrected near acuity of J3 or better and 85.3%, of J1 or better. Binocularly, the mean uncorrected near acuity remained J1 or better throughout the study. The mean uncorrected distance visual acuity in eyes with an inlay did not change significantly from preoperatively and remained 20/20 throughout the study period. All 3 eyes with inlay explantation returned to within +/-1.00 diopter of the preoperative refractive state for near and distance vision, with no loss of best corrected distance visual acuity. The ACI-7000 intracorneal inlay showed the potential to provide safe, effective, and reversible treatment of presbyopia.
| 19,006,739
|
Toxic endothelial cell destruction syndrome after intraocular lens repositioning with intracameral epinephrine.
|
A 66-year-old Chinese man developed corneal endothelial decompensation after intraocular lens (IOL) repositioning using intracameral epinephrine was performed. The presentation was compatible with toxic endothelial cell destruction syndrome, which is caused by prolonged, direct exposure of the corneal endothelium to relatively high concentrations of intracameral epinephrine. Despite its effective and immediate mydriatic effect, intracameral epinephrine is not recommended for intraoperative mydriasis in procedures such as IOL repositioning or secondary IOL implantation in which minimal irrigating solution is used.
| 19,006,750
|
Reliability and validity of the German version of "the Patient-rated Wrist Evaluation (PRWE)" as an outcome measure of wrist pain and disability in patients with acute distal radius fractures.
|
The aim was to test the reliability and validity of the German version of the Patient-rated Wrist Evaluation (PRWE) for patients with acute distal radius fractures. To estimate the reliability and construct validity, 44 patients completed a questionnaire booklet containing the German PRWE, the Short Form-36 (SF-36), and the Disability of the Arm, Shoulder, and Hand (DASH) four to six weeks after the fracture, and the PRWE again seven days later. For reliability, the intraclass correlation coefficient (ICC) was 0.94 for the PRWE total score. Its internal consistency was 0.89 (Cronbach's alpha). The PRWE total score showed a moderate correlation with the DASH (0.62) and the SF-36 subscale bodily pain (0.58). Low correlations were found with other scales of the SF-36. Based on our results the German PRWE is a practical, reliable, and valid instrument and can be recommended to measure patient-rated pain and disability in German-speaking patients with acute distal radius fracture.
| 19,006,763
|
Ectopic pregnancy: a pictorial review.
|
Ultrasound has remained the primary modality for investigating the pelvis of women in the reproductive age group, especially in an emergency setting. Recognition of different sonographic presentations, including typical and atypical findings of ectopic pregnancy, is important to determine surgical or nonsurgical management. This pictorial review article will exemplify different sonographic presentations of ectopic pregnancy.
| 19,006,776
|
Cefazolin pharmacokinetics in maternal plasma and amniotic fluid during pregnancy.
|
To study cefazolin pharmacokinetics in maternal plasma and amniotic fluid during pregnancy. Newly collected time-concentrations profiles and reported studies investigating cefazolin disposition (plasma, amniotic fluid) were pooled. Nonlinear mixed effect modeling was applied. A 2-compartment linear disposition model was used to fit cefazolin plasma observations. A third compartment was used to model amniotic fluid concentration. One hundred eighty-seven plasma and 96 amniotic fluid samples were collected in 82 pregnancies (17-40 weeks gestational age). Cefazolin clearance and distribution estimates were 7.44 L/h and 12.04 L without gestational age-dependent trends in maternal plasma. The equilibration half-life (T(eq)) between plasma and amniotic fluid at term gestational age was 4.4 hours, increased with decreasing gestational age, and was 9.09 times longer in patients with polyhydramnios. Cefazolin clearance and distribution volume are increased during pregnancy. The cefazolin T(eq) depends on gestational age and polyhydramnios. On the basis of these observations, dosing regimes to attain higher amniotic fluid concentrations were formulated.
| 19,006,783
|
Surgical treatment of endometriosis: location and patterns of disease at reoperation.
|
To assess the behavior of revised American Fertility Society stages I and II endometriosis after surgical treatment, by observation of location of pelvic involvement at reoperation. Prospective study. Tertiary referral center at a university-based hospital. Thirty-nine women with persistent or recurrent chronic pelvic pain after laparoscopic excision or ablation of histologically confirmed endometriosis who underwent a second laparoscopy. Laparoscopic pelvic mapping and surgical treatment of endometriosis, followed by repeat laparoscopic pelvic mapping of endometriosis at a second laparoscopy. Superficial peritoneal endometriosis (revised American Fertility Society stage I-II) endometriosis recurred in 37% of pelvic regions after surgical treatment. Endometriosis was more likely to recur in a treated pelvic region than an adjacent or distant pelvic region (relative risk 2.54; 95% confidence interval 1.63-3.97). A region adjacent to a previously affected pelvic region that was unaffected by endometriosis at the initial laparoscopy was more likely to have endometriosis at the second laparoscopy than a pelvic region distant from the treated pelvic region (relative risk 1.29; 95% confidence interval 0.84-2.0). Unaffected regions at initial laparoscopy had a low probability of having new endometriosis (11%) in the second laparoscopy. Recurrence of histologically proven endometriosis after surgical excision is more likely to cluster close to the original area of involvement, reflecting either incomplete excision at the initial surgery or a nonrandom favored implantation of new endometrial implants in adjacent peritoneum. Further studies are needed to elucidate the pathophysiology and mechanisms of recurrence of endometriosis.
| 19,006,792
|
[Cytokine profile and level of antibodies after administration of split-vaccine against influenza to adults].
|
Serum concentrations of cytokines (IFN-gamma, TNF-alpha, IL-2, IL-4, IL-6, IL-8) and antibody levels to influenza virus antigens were studied in adults vaccinated with split-vaccine against influenza. Analysis of antibody titers 21 days after vaccination compared with baseline levels revealed high immunogenicity of vaccine in terms of mean geometric titers increase as well as sufficient levels of seroprotection and seroconversion. Study of cytokine profile showed absence of significant changes of IFN-gamma, TNF-alpha, IL-2, IL-4 levels and considerable variability of IL-6 and IL-8 baseline levels as well as their dynamics after vaccination. Direct correlation between IL-6 and IL-8 levels was observed during whole period post-immunization. Inverse correlation between IFN-gamma and fold increase of antibody level was established which can be used as prognostic criterion of influenza prevention effectiveness.
| 19,006,832
|
Polymyalgia rheumatica in a renal transplant patient.
|
A 56-year-old African American woman who was on triple immunosuppressive therapy (which includes tacrolimus, mycophenolate mofetil, and prednisone) for a renal transplant that she had received 10 years ago presented with malaise, low-grade fevers and severe bilateral pain in her shoulder, neck and thigh muscles. There was serological evidence of an acute inflammatory syndrome, including a very high erythrocyte sedimentation rate (ESR) and high interleukin-6 and C-reactive protein levels. An extensive workup for infection and malignancy was negative, and a muscle biopsy was normal. Under a working diagnosis of polymyalgia rheumatica (PMR) her prednisone dose was increased, leading to a complete remission.; her symptoms resolved and the ESR normalized. The occurrence of PMR in an immunosuppressed patient is unusual, but should be considered in the differential diagnosis in the appropriate clinical setting.
| 19,006,913
|
[The 6 top-selling prescription drugs--an interactive evidence-based CME module for GPs on pharmacotherapy].
|
The Bremen General Practitioner's Association developed an interactive education tool about top-selling drugs in the GP setting. The data on various high-priced drugs identified by systematic literature search were processed by small work groups during several training courses for general practitioners and the results presented in plenary sessions. The training courses were systematically evaluated and enhanced. This is a well developed concept for the implementation of clinical evidence in the context of general practice. There will be a randomized controlled trial about the effect of this educational concept on the prescription behavior of general practitioners.
| 19,006,915
|
[Randomised controlled trials (RCTs)].
|
Randomisation is regarded as an essential principle ensuring the internal validity of clinical trials. This is why randomised controlled trials (RCTs) lead every evidence hierarchy of therapeutic interventions. At the same time, there are controversies about the role of RCTs in health research. The article addresses the principle of randomisation and deals with some of the more prominent arguments against RCT.
| 19,006,920
|
The animal-human interface and infectious disease in industrial food animal production: rethinking biosecurity and biocontainment.
|
Understanding interactions between animals and humans is critical in preventing outbreaks of zoonotic disease. This is particularly important for avian influenza. Food animal production has been transformed since the 1918 influenza pandemic. Poultry and swine production have changed from small-scale methods to industrial-scale operations. There is substantial evidence of pathogen movement between and among these industrial facilities, release to the external environment, and exposure to farm workers, which challenges the assumption that modern poultry production is more biosecure and biocontained as compared with backyard or small holder operations in preventing introduction and release of pathogens. An analysis of data from the Thai government investigation in 2004 indicates that the odds of H5N1 outbreaks and infections were significantly higher in large-scale commercial poultry operations as compared with backyard flocks. These data suggest that successful strategies to prevent or mitigate the emergence of pandemic avian influenza must consider risk factors specific to modern industrialized food animal production.
| 19,006,971
|
Animals as early detectors of bioevents: veterinary tools and a framework for animal-human integrated zoonotic disease surveillance.
|
The threat of bioterrorism and emerging infectious diseases has prompted various public health agencies to recommend enhanced surveillance activities to supplement existing surveillance plans. The majority of emerging infectious diseases and bioterrorist agents are zoonotic. Animals are more sensitive to certain biological agents, and their use as clinical sentinels, as a means of early detection, is warranted. This article provides design methods for a local integrated zoonotic surveillance plan and materials developed for veterinarians to assist in the early detection of bioevents. Zoonotic surveillance in the U.S. is currently too limited and compartmentalized for broader public health objectives. To rapidly detect and respond to bioevents, collaboration and cooperation among various agencies at the federal, state, and local levels must be enhanced and maintained. Co-analysis of animal and human diseases may facilitate the response to infectious disease events and limit morbidity and mortality in both animal and human populations.
| 19,006,972
|
Risk factors associated with anthrax outbreak in animals in North Dakota, 2005: a retrospective case-control study.
|
We identified the risk factors associated with the anthrax outbreak Of 2005 in animals in North Dakota. Medical records of the 2005 anthrax outbreak were obtained from the Veterinary Diagnostic Laboratory at North Dakota State University. Additional data were obtained from the North Dakota state veterinarian's office, and supplemental questionnaires were administered to producers. The data obtained included ecological and environmental factors, animal health factors, and management factors. Anthrax occurred from July 1 to October 12, 2005. The cases were located in eastern North Dakota around the Red River Basin. Ransom, LaMoure, and Barnes counties reported most cases (71%). Species affected included cattle, bison, horses, sheep, elk, deer, pigs, and llamas. The predominant symptom was sudden death (38%) followed by bleeding from orifices (17%). Chi-square analysis indicated significant differences between case and control premises on the following variables: death reported on neighboring pasture, vaccination period, dry conditions, wet conditions, antibiotic use, multiple vaccination, and type of predator (coyote). Factors that significantly (p<0.05) predicted anthrax occurrences on the final logistic regression model were vaccination, use of antibiotics during an outbreak, and period of vaccine administration (before or during the outbreak). The characteristics of the anthrax outbreak regarding time and place of occurrence, animals affected, clinical signs reported, and mortality rate were consistent with previous reports of natural anthrax outbreaks in animals. A number of factors that significantly predicted anthrax occurrence in animals in the 2005 outbreak in North Dakota were identified. This information is important in planning appropriate control and prevention measures for anthrax, including recommending the right vaccination and treatment regimens in managing future anthrax outbreaks.
| 19,006,977
|
Brief interventions for alcohol problems: factors that facilitate implementation.
|
Brief interventions are gaining favor as a means of addressing the problems associated with hazardous and harmful drinking. Brief interventions commonly target people whose levels or patterns of use are not diagnosable as alcohol abuse or dependence. These interventions usually are delivered by professionals who do not specialize in alcoholism treatment, and they include treatment elements designed to encourage people to alter their alcohol use without creating resistance. As evidence mounts regarding the efficacy of these interventions, attention has turned to implementing them successfully. New modes of delivery, such as via computers, the Internet, and interactive multimedia presentations, may help to surmount some of the challenges of wide dissemination, such as strains on expertise, time, and resources.
| 19,006,991
|
[Studies on separation and purification of Rhizoma Fagopyri Dibotoryis extract by macroporous resin].
|
To establish a technical process for purification of extract of Rhizoma Fagopyri Dibotoryis. The static adsorption capacity and elution ratio of Mixture of proanthocyanidins tannic condensation were used as evaluation to select the best resin in 3 kinds of macroporous resin. The adsorptive characteristics and elution parameters of selected resin were studied. D-101 resin had good separation performance and was suited to purify priceid in extract of Rhizoma Fagopyri Dibotoryis. The process of applying macroporous resin to absorb and purity priceid in extract of Rhizoma Fagopyri Dibotoryis is feasible.
| 19,007,009
|
[Oral anticoagulation control in a cardiac surgery ward].
|
In patients who undergo cardiac surgery, particularly valvular surgery it is essential to carry out frequent anticoagulation controls during their hospital stay The author questions if it is viable to carry out these controls by means of a portable coagulation meter which, in principle, can provide advantages in patient care. To determine this viability the author evaluates the concordance between the measurements obtained with this device and measurements taken in a laboratory The author compared the INR (prothrombin time, Normalized International Ratio) in 106 pairs of simultaneous blood samples, from both veins and capillaries, taken from 60 patients receiving anticoagulation medicine hospitalized in the cardiac surgery ward at the La Fe Hospital after each underwent surgery The samples taken from veins were processed in a hemostasia laboratory while the capillary samples were processed with a portable coagulation meter, a Roche CoaguChek"S. The statistical analyses applied were Pearson coefficient, intraclass correlation coefficient (CCI) and the method for mean differences (MMD). Numbers for hemocytes and therapy combined with heparine were taken into account. The results showed, in the overall analysis of data, a very good degree of concordance, CCI = 0.939 (confidence interval, IC=95%, 0.902-0.961) and MMD numbers <10%. For hemocytes <32, the concordance decreases, CCI = 0.876 (IC 95% = 0.787-0.930). The author concludes that this coagulation meter is trustworthy therefore using it would improve care for a patient needing anti-coagulation treatment during his/her stay in the ward since using this meter helps to obtain immediate results and reduces the trauma when extracting blood samples, etc. Nonetheless, when dealing with patients having a low hemocyte level, it is more prudent to make use of laboratory results.
| 19,007,028
|
The influence of lamivudine, stavudine and nevirapine on the pharmacokinetics of chlorpropamide in human subjects.
|
Diabetic patients tend to be prone to infections, and multiple drug therapy cannot be ruled out in the management of diabetes. The effect of three routinely prescribed antiretroviral (ARV) drugs on the pharmacokinetic profile of an antidiabetic drug, chlorpropamide, was investigated in 18 human subjects, who had recently been diagnosed positive for human immunodeficiency virus (HIV) infection. The volunteers, aged 22-44 years and weighing 59-66 kg, were randomized into three groups with six subjects in each group. The study was carried out in two phases; in the first phase, all the subjects received chlorpropamide (250 mg) in a fasting state. In the second phase, the subjects received 250 mg of chlorpropamide together with lamivudine (150 mg) or stavudine (40 mg) or nevirapine (200 mg) in a fasting state. Chlorpropamide concentrations in the plasma were determined using a high performance liquid chromatography (HPLC) method developed earlier in our laboratory, while plasma glucose levels were determined using the standard glucose oxidase method. Lamivudine and stavudine decreased significantly (P < 0.05) the mean maximum plasma concentrations (Cmax) and the area under the plasma concentration-time curve (AUC(0-168h)) of chlorpropamide, while both drugs significantly increased the absorption half-life (t(1/2ab)) and elimination half-life (t(1/2el). the apparent volume of distribution (Vd) and the plasma clearance rate (Cl) of chlorpropamide (P < 0.05). The plasma glucose levels were also significantly increased between 0.5 - 4 h post dose (P < 0.05). However, it was found that the pharmacokinetic parameters of chlorpropamide and the blood glucose levels were not significantly altered by the co-administration with nevirapine.
| 19,007,042
|
[The influence of gilt to the retention of the complete metal crown].
|
To research the influence of gilt to the retention of the complete metal crown. Sixty Ni-Cr alloy complete metal crown were divided into three groups, control group (common Ni-Cr alloy complete metal crown), whole gold-plating group (whole gilding on the tissue surface of the inner Ni-Cr alloy complete metal crown), partial gold-plating group (gilding on the tissue surface of 1/3 cervical inner Ni-Cr alloy complete metal crown). The retention force of complete metal crown was measured by tensile force/pressure ergograph. The retention force of control group, partial gold-plating group, whole gold-plating group were (657 +/- 151) N, (632 +/- 139) N, (569 +/- 103) N, respectively. There were significant differences between control group and whole gold-plating group, whole gold-plating group and partial gold-plating group (P < 0.05). There was no significant difference between control group and partial gold-plating group (P > 0.05). The force of retention would decrease after gilding on the tissue surface of the inner Ni-Cr alloy complete metal crown, but have no influence to normal retention requirement of complete crown. Although the retention of partial gold-plating complete metal crown had somewhat decrease, it could be ignored.
| 19,007,070
|
[Comparison of clinical effect of different tapered gutta-percha root filling with warm vertical condensation].
|
To compare the clinical effect of different tapered gutta-percha root filling by warm vertical condensation with immediate postoperative radiographs and one year follow-up. 40 maxillary anterior teeth with single, straight canals were divided into two equal groups. The teeth were instrumented with Hero 642 rotary nickel-titanium files to a master file 0.06 taper No. 30. Group 1 was obturated with 0.02 tapered gutta-percha using System B for downpack and Obtura II for backfilling. Group 2 was the same but 0.06 tapered gutta-percha. Every tooth's X-ray radiographs of immediate postoperative and one year follow-up were taken. In order to compare the quality of root canal filling, the rate of filling material extrusion, and the rate of obturation of lateral canals in each group were evaluated by X-ray radiographs. The clinical effect of one year follow-up's radiographs of the two groups was compared too. There was no significant difference in two groups on the quality of the root canal filling, obturation of lateral canals, and filling material extrusion. The success of the therapy was similar. But the 0.06 tapered gutta-percha group showed more quickly healing trend on apical periodontitis. When single, straight root canals were obturated using warm vertical condensation, adaptively tapered gutta-percha showed better clinical effect.
| 19,007,071
|
[Investigation on dental impression disinfection knowledge grasped by medical staff in stomatological hospitals].
|
To investigate the situation about the dental impression disinfection knowledge of the medical staff in stomatological hospitals. A questionnaire investigation was conducted on 582 medical staff in five Grade A Class Three stomatological hospitals. The investigation items included demographic characteristics and knowledge on dental impression disinfection. Of 582 subjects, 424 subjects (72.85%) thought that the dental impressions should be disinfected. 76 persons chose 75% alcohol to disinfect the dental impressions, 26 persons chose povidone iodine or glutaral, 103 persons chose sterilization machine, 180 persons chose to wash with water, and 197 persons were unknown about the sterilization methods. The status of the staff grasping knowledge on dental impression disinfection was related with the working department. Our results suggest that it is necessary to strengthen the importance of impression disinfection to medical staff in stomatological hospitals. The consciousness of protection should be enhanced to reduce the cross infection in hospitals.
| 19,007,073
|
[Initial study on the discrimination of oral microorganisms with a metabonomics method].
|
To establish the spectra of metabolites that coued be employed in identification of oral pathogenic bacteria, and try to find a convenient and rapid way to discriminate oral microorganisms. Suspensions of Streptococcus mutans ATCC 25175, Streptococcus sanguis ATCC 10556 and Lactobacillus acidophilus ATCC 4356 with same density were preparecd and cultured respectively at improved TPY liquid culture medium. The growth quantity were measured periodically by a turbidimeter. And the growth curves of the inoculated bacteria were completed. The culture solutions in stationary phase of the three bacteria were tested with 1H-nuclear magnetic resonance (1H-NMR) spectroscopy respectively. The data of 1H-NMR spectroscopy results were analyzed by principal components analysis (PCA). The PCA showed the obvious clustering phenomena and the points of three group differentially centralized to three clusters. Therefore, the NMR-based metabonomics profiles could discriminate the three different kinds of bacteria. The metabonomics is a promising new technology for developing to a rapid discrimination method of oral pathogenic bacteria.
| 19,007,080
|
[Effect of estrogen on heat shock protein 70 expression in rat masseter muscle].
|
To investigate the effect of estrogen on heat shock protein (HSP) 70 expression in rat masseter muscle. Sixty twelve-week-old female Sprague-Dawley rats were randomly divided into three groups: Sham surgery group (control group), ovariectomy group (OVX group), ovariectomy with estradiol valerate replacement treatment group (OVX/EV group). Half of the animals were sacrificed at 4 and 8 weeks respectively, then the masseter muscle was removed. Immunohistochemistry (IHC) method was employed to study the HSP70 expression in masseter muscle. Compared to control group and OVX/EV group, the expression of HSP70 was significantly lower at 8 weeks in OVX group (P < 0.05). There were no significantly difference between the HSP70 expression of control group and that of OVX/EV group. Estrogen may affect HSP70 expression in rat masseter muscle, and estrogen replacement therapy may prevent HSP70 reduction.
| 19,007,086
|
Novel naphthalene-N-sulfonyl-D-glutamic acid derivatives as inhibitors of MurD, a key peptidoglycan biosynthesis enzyme.
|
Mur ligases have essential roles in the biosynthesis of peptidoglycan, and they represent attractive targets for the design of novel antibacterials. MurD (UDP-N-acetylmuramoyl-L-alanine:D-glutamate ligase) is the second enzyme in the series of Mur ligases, and it catalyzes the addition of D-glutamic acid (D-Glu) to the cytoplasmic intermediate UDP-N-acetylmuramoyl-L-alanine (UMA). Because of the high binding affinity of D-Glu toward MurD, we synthesized and biochemically evaluated a series of N-substituted D-Glu derivatives as potential inhibitors of MurD from E. coli, which allowed us to explore the structure-activity relationships.The substituted naphthalene-N-sulfonyl-D-Glu inhibitors, which were synthesized as potential transition state analogues, displayed IC50 values ranging from 80 to 600 microM. In addition, the high-resolution crystal structures of MurD in complex with four novel inhibitors revealed details of the binding mode of the inhibitors within the active site of MurD. Structure-activity relationships and cocrystal structures constitute an excellent starting point for further development of novel MurD inhibitors of this structural class.
| 19,007,109
|
Mechanical features of Plasmodium falciparum acyl carrier protein in the delivery of substrates.
|
The Acyl Carrier Protein (ACP) is a key element in the biosynthesis of fatty acids being responsible for the acyl group shuttling and delivery within a series of related enzymes. The molecular mechanism of the delivery process is poorly known, and its characterization is essential for in-depth understanding the biosynthetic machinery. A steered molecular dynamics approach has been applied to shed light on the putative delivery pathway, suggesting the small alpha3-helix act as gatekeeper for the transfer process. Preventing the delivery mechanism would be an innovative strategy for the development of pathway-based antimalarial compounds.
| 19,007,113
|
Phenolic acid nanoparticle formation in iron-containing aqueous solutions.
|
This paper presents results which show that the interaction between two phenolic acids, p-coumaric and caffeic acid, with iron results in the formation of meta-stable colloidal nano particles. The particles are characterized with dynamic light scattering and cryo-transmission electron microscopy. The results show that the nanoparticle formation is an important feature of phenolic acids which is likely to have a large impact on the behavior of these substances as well as their functionality as antioxidants.
| 19,007,124
|
Comparative metabolic profiling reveals secondary metabolites correlated with soybean salt tolerance.
|
High-performance liquid chromatography-ultraviolet-electrospray ionization mass spectrometry (HPLC-UV-ESI-MS) and HPLC-ESI-MS(n) analysis methods were used for metabolic profiling and simultaneous identification of isoflavonoids and saponins in soybean seeds. Comparative targeted metabolic profiling revealed marked differences in the metabolite composition between salt-sensitive and salt-tolerant soybean varieties. Principle component analysis clearly demonstrated that it is possible to use secondary metabolites, for example, isoflavones and saponins, to discriminate between closely related soybean genotypes. Genistin and group B saponins were identified as the key secondary metabolites correlated with salt tolerance. These individual metabolites may provide additional insight into the salt tolerance and adaptation of plants.
| 19,007,129
|
Aromaticity and antiaromaticity in the low-lying electronic states of cyclooctatetraene.
|
The levels of aromaticity of the most important geometries on the ground-state (S(0)), lowest triplet-state (T(1)), and first singlet excited-state (S(1)) potential energy surfaces (PESs) for cycloocta-1,3,5,7-tetraene (COT) are assessed using a wide range of magnetic criteria including nucleus-independent chemical shifts (NICSs), proton shieldings, and magnetic susceptibilities calculated using complete-active-space self-consistent-field (CASSCF) wave functions constructed from gauge-including atomic orbitals (GIAOs). It is shown that the ground state of D(8h) COT (transition state for the pi-bond-shift process on the S(0) PES) is markedly antiaromatic, even more so than the classical example of an antiaromatic system, the ground state of square cyclobutadiene. The CASSCF-GIAO magnetic properties of the ground state of D(4h) COT (transition state for the ring-inversion process on the S(0) PES) strongly suggest that it is much less antiaromatic than the ground state of D(8h) COT, whereas those of the ground state of D(2d) COT (local minimum on the S(0) PES) indicate that it is decidedly nonaromatic. The lowest triplet state and the first singlet excited state of D(8h) COT (local minima on the T(1) PES and the S(1) PES, respectively) exhibit surprisingly similar magnetic properties. These, in turn, are very close to the magnetic properties of benzene, which is a strong indication of a high degree of aromaticity.
| 19,007,145
|
Selenocysteine positional variants reveal contributions to copper binding from cysteine residues in domains 2 and 3 of human copper chaperone for superoxide dismutase.
|
The human copper chaperone for superoxide dismutase binds copper both in an Atx1-like MTCQSC motif in domain 1 and via a multinuclear cluster formed by two CXC motifs at the D3 dimer interface. The composition of the Cu(I) cluster has been investigated previously by mutagenesis of the CXC motif, and by construction of a CXU selenocysteine derivative, which has permitted XAS studies at both Cu and Se absorption edges. Here, we report the semisynthesis and spectroscopic characterization of a series of derivatives with the sequences 243-CACA, 243-CAUA, 243-UACA, and 243-UAUA in the D1 double mutant (C22AC25A) background, prepared by expressed protein ligation of Sec-containing tetrapeptides to an hCCS-243 truncation. By varying the position of the Se atom in the CXC motif, we have been able to show that Se is always bridging (2 Se-Cu) rather than terminal (1 Se-Cu). Substitution of both D3 Cys residues by Sec in the UAUA variant does not eliminate the Cu-S contribution, confirming our previous description of the cluster as most likely a Cu(4)S(6) species, and suggesting that D2 Cys residues contribute to the cluster. As predicted by this model, when Cys residues C141, C144, and C227 are mutated to alanine either individually or together as a triple mutant, the cluster nuclearity is dramatically attenuated. These data suggest that Cys residues in D2 of hCCS are involved in the formation, stability, and redox potential of the D3 cluster. The significance of these finding to the SOD1 thiol/disulfide oxidase activity are discussed in terms of a model in which a similar multinuclear cluster may form in the CCS-SOD heterodimer.
| 19,007,184
|
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.