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31.
Naltrexone-3-salicylate (3), a prodrug of naltrexone (1), was prepared by a simple procedure from naltrexone-3-acetylsalicylate (2). The plasma (dog and human) hydrolysis half-life of 3 was found to be approximately 30 min. Compound 2 was previously shown to hydrolyze in dog and human plasma with a fast deacetylation step to 3, followed by slower hydrolysis of 3 to 1 (t
1/2, 30 min). Oral naltrexone bioavailability was greatly improved (30-fold) after oral administration of 3 to dogs, similar to the improvement observed after oral administration of 2. The half-life of naltrexone in dogs after oral administration of 3 was similar to that observed after oral administration of 2 (1 hr). 相似文献
32.
Faiyaz-Ul-Haque M Ahmad W Zaidi SH Hussain S Haque S Ahmad M Cohn DH Tsui LC 《Clinical genetics》2004,66(2):144-151
Multiple hereditary exostoses (HME) is an autosomal dominant developmental disorder exhibiting multiple osteocartilaginous bone tumors that generally arise near the ends of growing long bones. Here, we report two large consanguineous families from Pakistan, who display the typical features of HME. Affected individuals also show a previously unreported feature--bilateral overriding of single toes. Analysis using microsatellite markers for each of the known EXT loci, EXT1, EXT2, and EXT3 showed linkage to EXT1. In the first family, mutation analysis of the EXT1 gene revealed that affected individuals were heterozygous for an in-frame G-to-C transversion at the conserved splice donor site in intron 1. This mutation is predicted to disrupt splicing of the first intron and produce a frameshift that leads to a premature termination codon. In the second family, an insertion of an A in exon 8 is predicted to produce a frameshift at codon 555 followed by a premature termination, a further 10 codons downstream. In both families, an increased number of affected male subjects were observed. In affected females in family 2, phenotypic variability and incomplete penetrance were noted. 相似文献
33.
Rapid exposure of cardiac muscle to high concentrations of caffeine releases Ca(2+) from the sarcoplasmic reticulum (SR). This Ca(2+) is then extruded from the cell by the Na(+)/Ca(2+) exchanger. Measurement of the current carried by the exchanger (I(Na/Ca)) can therefore be used to estimate of the Ca(2+) content of the SR. Previous studies have shown that caffeine, however, can also inhibit K(+) currents. We therefore investigated whether the inhibitory effects of caffeine on these currents could contaminate measurements of I(Na/Ca). Caffeine caused partial inhibition of the inward rectifier K(+) current (I(K1)): the outward current at -40 mV was 1.15+/-0.24 pA/pF in control and decreased to 0.34+/-0.15 pA/pF in the presence of 10 mmol/l caffeine (P<0.05, n=15). This was similar to the effect of caffeine on the holding current observed at -40 mV in the absence of K(+) channel block and could therefore account for the contaminating effects of caffeine observed during measurements of I(Na/Ca). Moreover, caffeine also partially inhibited the transient outward ( I(to)) and the delayed rectifier (I(K)) K(+) currents. 相似文献
34.
Lymphocyte vaccination prevents spontaneous diabetes in the non-obese diabetic mouse. 总被引:2,自引:0,他引:2 下载免费PDF全文
The aim of this study was to investigate whether lymphocyte vaccination can prevent diabetes occurring in the non-obese diabetic (NOD) mouse, an animal model of human insulin-dependent diabetes mellitus (IDDM). The lymphocyte vaccine was composed of lymphocytes isolated from the spleens of diabetic NOD mice, activated in vitro using concanavalin A (Con A) and rendered immunogenic using glutaraldehyde treatment. These cells were used to vaccinate mice at 6 weeks with boosters at weeks 10, 14 and 18. The animals were then monitored for signs of diabetes until week 30. Twenty-eight NOD mice (11 male, 17 female) were T-lymphocyte vaccinated while 35 littermates (14 male, 21 female) were sham vaccinated with the vaccine carrier, as control mice. The percentage of mice remaining non-diabetic was 50% in the T-lymphocyte-vaccinated group compared with 20% in control mice (P < 0.05). When the results were divided according to sex of the mouse the percentage of female NOD mice remaining non-diabetic was 47.1% in the T-lymphocyte-vaccinated group compared to only 9.4% in the controls (P < 0.01), while in the males there was no significant difference between the groups. These results suggest that T-lymphocyte vaccination can prevent diabetes in NOD mice and that it has its greatest effect in females. The therapy is apparently safe and its efficacy indicates that it may be of value in prediabetes in man. 相似文献
35.
R. Blazev M. Hussain A.J. Bakker S.I. Head G.D. Lamb 《Journal of muscle research and cell motility》2001,22(3):277-286
This study investigated the effects of the protein kinase A (PKA) inhibitor, H-89, in mechanically-skinned muscle fibres and intact muscle fibres, in order to determine whether PKA phosphorylation is essential for normal excitation–contraction (E–C) coupling. In skinned EDL fibres of the rat, force responses to depolarization (by ion substitution) were inhibited only slightly by 10M H-89, a concentration more than sufficient to fully inhibit PKA. Staurosporine (1 M), a potent non-specific kinase inhibitor, also had little if any effect on depolarization-induced responses. At 1–2 M, H-89 significantly slowed the repriming rate in rat skinned fibres, most likely due to it deleteriously affecting the T-system potential. With 100 M H-89, the force response to depolarization by ion substitution was completely abolished. This inhibitory effect was reversed by washout of H-89 and was not due to block of the Ca2+ release channel in the sarcoplasmic reticulum (SR). In intact single fibres of the flexor digitorum longus (FDB) muscle of the mouse, 1–3 M H-89 had no noticeable effect on action-potential-mediated Ca2+ transients. Higher concentrations (4–10 M) caused Ca2+ transient failure in fibres stimulated at 20 Hz in a manner indicative of action-potential failure. At 10–100 M, H-89 also inhibited net Ca2+ uptake by the SR and affected the Ca2+-sensitivity of the contractile apparatus in rat skinned fibres. All such effects were proportionately greater in toad muscle fibres. These results do not support the hypothesis that phosphorylation is essential for the Ca2+ release channel to open in response to voltage-sensor activation in skeletal muscle fibres. 相似文献
36.
In anesthetized, artificially ventilated guinea pigs, intranasal and intravenous administration of albuterol produced the same maximum degree of protection against bronchoconstriction induced by bilateral electrical stimulation of the cervical vagal nerves. Intranasal albuterol showed a slower onset of action than intravenous albuterol and exhibited equivalent cardiovascular side effects for the same level of bronchoprotection. Accordingly, intranasal albuterol may represent an alternative to metered-dose inhalation for prophylaxis and treatment of bronchoconstriction in humans. 相似文献
37.
Evaluation of Screening and Commercial Methods for Detection of Methicillin Resistance in Coagulase-Negative Staphylococci 下载免费PDF全文
Zafar Hussain Luba Stoakes Robert Lannigan Susan Longo Barbara Nancekivell 《Journal of clinical microbiology》1998,36(1):273-274
The National Committee for Clinical Laboratory Standards recommends 48 h of incubation by the oxacillin salt agar screen (OSAS) method for the detection of methicillin-resistant coagulase-negative staphylococci (CoNS). An earlier identification of methicillin resistance is desirable. The time to detection of the mecA gene by PCR was compared with the times to detection by OSAS, by the oxacillin disk diffusion (ODD) method, and with MicroScan Gram Positive Combo type 6 panels (MicroScan Inc. Sacramento, Calif.) and Vitek GPS-SA cards (bioMérieux Vitek Inc., Hazelwood, Mo.). The combination of the Vitek card and the ODD method detected 92 of 99 methicillin-resistant strains of CoNS at 24 h; however, 6 mecA-positive strains were phenotypically methicillin susceptible. We conclude that most methicillin-resistant CoNS can be detected and the results can be reported after overnight incubation by a combination of methods. 相似文献
38.
Performance of the TechLab C. DIFF CHEK-60 enzyme immunoassay (EIA) in combination with the C. difficile Tox A/B II EIA kit, the Triage C. difficile panel immunoassay, and a cytotoxin assay for diagnosis of Clostridium difficile-associated diarrhea 下载免费PDF全文
We compared a recently marketed enzyme immunoassay for glutamate dehydrogenase (GDH), TechLab's C. DIFF CHEK-60 (TL-GDH), in combination with the C. difficile Tox A/B II enzyme immunoassay (Tox-A/B) with (i) the Triage C. difficile test, which detects both GDH (TR-GDH) and toxin A (TR-Tox-A); (ii) an in-house cytotoxin assay (C-Tox); and (iii) stool cultures for C. difficile. All C. difficile isolates were tested for the presence of the toxin genes by PCR. If a toxin gene-positive strain of Clostridium difficile was recovered and a toxin was detected by any method, the result was considered to be truly positive. Eighty-seven of 93 and 79 of 93 C. difficile culture-positive samples were also TL-GDH and TR-GDH positive, respectively. No test was able to detect toxin in all samples with true-positive results. Tox-A/B and TR-Tox-A in combination with the GDH detection tests and C-Tox were able to identify 52 and 50 samples with true-positive results. Tox-A/B and TR-Tox-A would have missed 15 and 31% of cases of C. difficile-associated diarrhea, respectively, if used alone. 相似文献
39.
Relevance of apolipoprotein E polymorphism for coronary artery disease in the Saudi population 总被引:8,自引:0,他引:8
Dzimiri N Meyer BF Hussain SS Basco C Afrane B Halees Z 《Archives of pathology & laboratory medicine》1999,123(12):1241-1245
BACKGROUND: The apolipoprotein E alleles epsilon2 and epsilon4 have been reported as independent risk factors for coronary artery disease (CAD) and as predictors for the development of atherosclerosis. METHODS AND RESULTS: We determined by polymerase chain reaction the distribution of apolipoprotein E polymorphism in 320 Saudi blood donors (BD), 96 CAD patients, and 40 control subjects who had undergone angiography. Compared to controls, only epsilon4 was elevated in CAD patients. More than 61% (P <.0001) of the patients had angina, and 52.1% (P <.05) were diabetic; both of these factors were strongly associated with the presence of allele epsilon2. The epsilon2 allele was also associated with hypertension, elevated serum triglycerides, and total cholesterol. On the other hand, the allele epsilon4 appeared to be associated with increased risk of CAD and was also associated with hypertension, 3-vessel disease, and restenosis. CONCLUSIONS: Accordingly, epsilon4 may be associated with increased risk of CAD, whereas epsilon2 appears to be a predictor of several risk factors for atherosclerosis. 相似文献
40.
Heterologously expressed Staphylococcus aureus fibronectin-binding proteins are sufficient for invasion of host cells 总被引:8,自引:0,他引:8 下载免费PDF全文
Sinha B Francois P Que YA Hussain M Heilmann C Moreillon P Lew D Krause KH Peters G Herrmann M 《Infection and immunity》2000,68(12):6871-6878
Staphylococcus aureus invasion of mammalian cells, including epithelial, endothelial, and fibroblastic cells, critically depends on fibronectin bridging between S. aureus fibronectin-binding proteins (FnBPs) and the host fibronectin receptor integrin alpha(5)beta(1) (B. Sinha et al., Cell. Microbiol. 1:101-117, 1999). However, it is unknown whether this mechanism is sufficient for S. aureus invasion. To address this question, various S. aureus adhesins (FnBPA, FnBPB, and clumping factor [ClfA]) were expressed in Staphylococcus carnosus and Lactococcus lactis subsp. cremoris. Both noninvasive gram-positive microorganisms are genetically distinct from S. aureus, lack any known S. aureus surface protein, and do not bind fibronectin. Transformants of S. carnosus and L. lactis harboring plasmids coding for various S. aureus surface proteins (FnBPA, FnBPB, and ClfA) functionally expressed adhesins (as determined by bacterial clumping in plasma, specific latex agglutination, Western ligand blotting, and binding to immobilized and soluble fibronectin). FnBPA or FnBPB but not of ClfA conferred invasiveness to S. carnosus and L. lactis. Invasion of 293 cells by transformants was comparable to that of strongly invasive S. aureus strain Cowan 1. Binding of soluble and immobilized fibronectin paralleled invasiveness, demonstrating that the amount of accessible surface FnBPs is rate limiting. Thus, S. aureus FnBPs confer invasiveness to noninvasive, apathogenic gram-positive cocci. Furthermore, FnBP-coated polystyrene beads were internalized by 293 cells, demonstrating that FnBPs are sufficient for invasion of host cells without the need for (S. aureus-specific) coreceptors. 相似文献