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The influence of food on the pharmacokinetics of ''biphasic'' nifedipine at steady state in normal subjects. 下载免费PDF全文
G H Rimoy J R Idle N K Bhaskar P C Rubin 《British journal of clinical pharmacology》1989,28(5):612-615
Previous studies following single dose administration have suggested that the pharmacokinetics of various nifedipine formulations could be influenced by the timing of associated food consumption. In order more closely to reflect the clinical situation we have carried out a study at steady state using a 'biphasic' formulation comprising 'rapid' and 'retarded' drug release components. Fifteen normal subjects took 20 mg 'biphasic' nifedipine 12 hourly for 10 days. Studies were carried out on days 4, 7 and 10. On these days the nifedipine was taken 2 h or 1 h before or immediately following a light breakfast. A light breakfast influenced neither the rate nor the extent of nifedipine absorption nor the rate or extent of major metabolite appearance. We conclude that at steady state the timing of a light meal is unlikely to alter in any clinically important manner the pharmacokinetics of nifedipine released from 'biphasic' tablets. 相似文献
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D N Ader A R Seibring P Bhaskar B G Melamed 《Journal of oral and maxillofacial surgery》1992,50(1):27-31; discussion 31-2
Patient response to interactive videodisc preparation for third molar extraction surgery was examined as a function of self-reported information-seeking style. Amount learned was compared among patients informed via an interactive videodisc, noninteractive videotape of the same material, or surgeon only. Anxiety levels and satisfaction with preparation were compared between the videodisc and videotape groups. At consultation, patients (n = 35) were randomly assigned to either the disc- or the tape-viewing group. First, subjects completed a demographic survey, state anxiety scale, quiz on knowledge about third molars and surgery risks and complications, and information-seeking scales. Immediately after viewing the video, subjects completed another anxiety scale and a multiple-choice quiz covering the material presented. Subsequently, another 25 patients undergoing the routine (surgeon-only) consultation procedure were given the same multiple-choice quiz following consultation. Quiz scores differed significantly among the groups; mean percent correct for the tape-viewing subjects was 85; for disc-viewing subjects 72.6; for surgeon-only subjects, 40. Self-rated information seeking was unrelated to amount of video viewed by disc subjects (on average, 64% of the videodisc was viewed), and disc subjects who rated themselves higher in information-seeking achieved the lowest postpreparation quiz scores. Subjects in the disc group were significantly more satisfied with the amount of preparation than the tape group. Although disc group subjects were significantly less knowledgeable following consultation than were tape group subjects, interactive videodisc preparation for third molar extraction appears to have some advantages over more traditional approaches. Further research is needed to determine whether this approach to preparing patients is suitable for widespread clinical use. 相似文献
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Vinay Puri Andrew McQuillin Khalid Choudhury Susmita Datta Jonathan Pimm Srinivasa Thirumalai Robert Krasucki Jacob Lawrence Digby Quested Nicholas Bass Helen Moorey Jenny Morgan Bhaskar Punukollu Gomathinayagam Kandasami David Curtis Hugh Gurling 《Neuropsychopharmacology》2007,61(7):873-879
BACKGROUND: Linkage studies by us and others have confirmed that chromosome 1q23.3 is a susceptibility locus for schizophrenia. Based on this information, several research groups have published evidence that markers within both the RGS4 and CAPON genes, which are 700 kb apart, independently showed allelic association with schizophrenia. Tests of allelic association with both of these genes in our case control sample were negative. Therefore, we carried out further fine mapping between the RGS4 and CAPON genes. METHODS: Twenty-nine SNP and microsatellite markers in the 1q23.3 region were genotyped in the United Kingdom based sample of 450 cases and 450 supernormal control subjects. RESULTS: We detected positive allelic association after the eighth marker was genotyped and found that three microsatellite markers (p = .011, p = .014, p = .049) and two SNPs (p = .004, p = .043) localized in the 700 kb region between the RGS4 and CAPON genes, within the UHMK1 gene, were associated with schizophrenia. Tests of significance for marker rs10494370 remained significant following Bonferroni correction (alpha = .006) for multiple tests. Tests of haplotypic association were also significant for UHMK1 (p = .009) using empirical permutation tests, which make it unnecessary to further correct for both multiple alleles and multiple markers. CONCLUSIONS: These results provide preliminary evidence that the UHMK1 gene increases susceptibility to schizophrenia. Further confirmation in adequately powered samples is needed. UHMK1 is a serine threonine kinase nuclear protein and is highly expressed in regions of the brain implicated in schizophrenia. 相似文献
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Bronchial mucus hypersecretion in acute quadriplegia. Macromolecular yields and glycoconjugate composition 总被引:1,自引:0,他引:1
K R Bhaskar R Brown D D O'Sullivan S Melia M Duggan L Reid 《The American review of respiratory disease》1991,143(3):640-648
In acute quadriplegia we have noted that about one in five patients develops unexplained production of markedly excessive and tenacious bronchial mucus. Spontaneous recovery from mucus hypersecretion usually occurs within weeks to months. Mucus samples collected from 12 patients have been found to be abnormal. Macromolecular contents of single aspirates yielded as much as 500 mg. Analytical ultracentrifuge analysis showed the mucus to contain considerable epithelial glycoprotein (GP) of typical buoyant density; its amino acid and carbohydrate compositions were characteristic of the GP from hypersecretory bronchial mucus such as in chronic bronchitis and cystic fibrosis. In five patients studied after recovery from hypersecretion, there tended to be relatively less GP. The mucus samples contained a high density glycoconjugate (GC): this had sugars of GP but also reacted positively with a monoclonal antibody to keratan sulfate. Its amino acid composition was different from that of GP: threonine was lower and glycine was higher than in GP. In mucus from one patient who died, chondroitin sulfate ABC and hyaluronic acid were identified as well. This suggests proteoglycans are involved in the pathophysiology of mucus hypersecretion. The sudden onset and spontaneous recovery of hypersecretion suggests that it is not due to gland hypertrophy. We speculate that in acute quadriplegia it is due to disturbed neuronal control of bronchial mucus gland secretion, perhaps related to initial disappearance and later reappearance of peripheral sympathetic nervous system tone. 相似文献
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Bioavailability studies on guar gum-based three-layer matrix tablets of trimetazidine dihydrochloride in human volunteers. 总被引:1,自引:0,他引:1
Y S R Krishnaiah R S Karthikeyan P Bhaskar V Satyanarayana 《Journal of controlled release》2002,83(2):231-239
Guar gum-based three-layer matrix tablets of a highly water-soluble drug, trimetazidine dihydrochloride, were evaluated for their in vivo release in healthy volunteers in comparison with commercially available conventional immediate release tablets. Six healthy volunteers participated in the study and a two-way crossover design was followed. The plasma concentration of trimetazidine dihydrochloride was estimated by reverse-phase HPLC. The pharmacokinetic parameters were calculated from the plasma concentration of trimetazidine dihydrochloride versus time data. The delayed T(max), decreased C(max) and K(a), unaltered bioavailability, and prolonged t(1/2) and MRT indicated a slow and prolonged release of trimetazidine dihydrochloride from guar gum three-layer matrix tablets in comparison with the immediate release tablet dosage form. The guar gum three-layer matrix tablets of trimetazidine dihydrochloride may be useful in providing constant drug delivery with minimum fluctuations. 相似文献
9.
Bhaskar Thyagarajan Jennifer L. Cruise Colin Campbell 《Somatic Cell and Molecular Genetics》1996,22(1):31-39
We have characterized homologous DNA recombination activity in nuclear protein extracts prepared from quiescent and regenerating
rat livers. Activity measured in regenerating liver extracts was elevated approximately 35-fold above control, and its appearance
closely mirrored the first wave of DNA synthesis, peaking 24 hours after a regenerative stimulus, and returning fairly rapidly
to basal levels. We also identified a strand-transferase protein of approximately 100 kDa whose presence in these extracts
correlates with homologous recombination activity. Recent evidence suggests that mammalian somatic cells possess a recombinational
DNA repair mechanism analogous to that described in the yeastSaccharomyces cerevisiae. Our results indicate that this recombinational repair process may be regulated in vivo by, or play a role in, progression
through the cell division cycle. 相似文献
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Fulminant hepatic failure induced oxidative stress in nonsynaptic mitochondria of cerebral cortex in rats 总被引:2,自引:0,他引:2
Fulminant hepatic failure (FHF) is a condition with sudden onset of necrosis of hepatocytes and degeneration of liver tissue without any established liver disease. FHF is associated with increased ammonia levels in blood and brain, which is supposed to be neurotoxic, ultimately leading to neuronal death. Evidences from previous studies suggest for mitochondrial dysfunctions under hyperammonemic conditions. In the present investigation, on thioacetamide-induced FHF rat models, studies were undertaken on cerebral nonsynaptic mitochondrial oxidative stress. The results of the present study reveal elevated lipid peroxidation along with reduced total thiol levels in the cerebral cortex mitochondria of experimental animals compared to saline treated control rats. In addition, the enzymatic activities of glutathione peroxidase and glutathione reductase were decreased, with an elevation in Mn-SOD activity. Overall, thioacetamide-induced FHF in rats enhanced the levels of lipid peroxidation coupled with impaired antioxidant defenses in the cerebral nonsynaptic mitochondria. 相似文献