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991.
Moses MA Wiederschain D Wu I Fernandez CA Ghazizadeh V Lane WS Flynn E Sytkowski A Tao T Langer R 《Proceedings of the National Academy of Sciences of the United States of America》1999,96(6):2645-2650
Cartilage is an avascular and relatively tumor-resistant tissue. Work from a number of laboratories, including our own, has demonstrated that cartilage is an enriched source of endogenous inhibitors of angiogenesis. In the course of a study designed to identify novel cartilage-derived inhibitors of new capillary growth, we have purified an inhibitory protein that was identified by peptide microsequencing and protein database analysis as troponin I (TnI). TnI is a subunit of the troponin complex (troponin-C and troponin-T being the other two), which, along with tropomyosin, is responsible for the calcium-dependent regulation of striated muscle contraction; independently, TnI is capable of inhibiting actomyosin ATPase. Because troponin has never previously been reported to be present in cartilage, we have cloned and expressed the cDNA of human cartilage TnI, purified this protein to apparent homogeneity, and demonstrated that it is a potent and specific inhibitor of angiogenesis in vivo and in vitro, as well as of tumor metastasis in vivo. 相似文献
992.
993.
Rapid scale-up of antiretroviral therapy at primary care sites in Zambia: feasibility and early outcomes 总被引:10,自引:1,他引:9
Stringer JS Zulu I Levy J Stringer EM Mwango A Chi BH Mtonga V Reid S Cantrell RA Bulterys M Saag MS Marlink RG Mwinga A Ellerbrock TV Sinkala M 《JAMA》2006,296(7):782-793
Context The Zambian Ministry of Health has scaled-up human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) care and treatment services at primary care clinics in Lusaka, using predominately nonphysician clinicians. Objective To report on the feasibility and early outcomes of the program. Design, Setting, and Patients Open cohort evaluation of antiretroviral-naive adults treated at 18 primary care facilities between April 26, 2004, and November 5, 2005. Data were entered in real time into an electronic patient tracking system. Intervention Those meeting criteria for antiretroviral therapy (ART) received drugs according to Zambian national guidelines. Main Outcome Measures Survival, regimen failure rates, and CD4 cell response. Results We enrolled 21 755 adults into HIV care, and 16 198 (75%) started ART. Among those starting ART, 9864 (61%) were women. Of 15 866 patients with documented World Health Organization (WHO) staging, 11 573 (73%) were stage III or IV, and the mean (SD) entry CD4 cell count among the 15 336 patients with a baseline result was 143/µL (123/µL). Of 1142 patients receiving ART who died, 1120 had a reliable date of death. Of these patients, 792 (71%) died within 90 days of starting therapy (early mortality rate: 26 per 100 patient-years), and 328 (29%) died after 90 days (post-90-day mortality rate: 5.0 per 100 patient-years). In multivariable analysis, mortality was strongly associated with CD4 cell count between 50/µL and 199/µL (adjusted hazard ratio [AHR], 1.4; 95% confidence interval [CI], 1.0-2.0), CD4 cell count less than 50/µL (AHR, 2.2; 95% CI, 1.5-3.1), WHO stage III disease (AHR, 1.8; 95% CI, 1.3-2.4), WHO stage IV disease (AHR, 2.9; 95% CI, 2.0-4.3), low body mass index (<16; AHR,2.4; 95% CI, 1.8-3.2), severe anemia (<8.0 g/dL; AHR, 3.1; 95% CI, 2.3-4.0), and poor adherence to therapy (AHR, 2.9; 95% CI, 2.2-3.9). Of 11 714 patients at risk, 861 failed therapy by clinical criteria (rate, 13 per 100 patient-years). The mean (SD) CD4 cell count increase was 175/µL (174/µL) in 1361 of 1519 patients (90%) receiving treatment long enough to have a 12-month repeat. Conclusion Massive scale-up of HIV and AIDS treatment services with good clinical outcomes is feasible in primary care settings in sub-Saharan Africa. Most mortality occurs early, suggesting that earlier diagnosis and treatment may improve outcomes. 相似文献
994.
Sattanathan P Babu JM Vyas K Reddy RB Rajan ST Sudhakar P 《Journal of pharmaceutical and biomedical analysis》2006,40(3):598-604
During the impurity profile of risperidone (RSP), a more polar impurity (RSP-1) and a more non-polar impurity (RSP-2) were detected in LC-MS with respect to risperidone. These impurities were isolated, enriched and were subjected to mass and NMR spectral studies. Based on the spectral data, RSP-1 and RSP-2 were characterized as risperidone N-oxide and 9-methylene risperidone, respectively. The formation of these impurities is rationalized. The structures of both the impurities were unambiguously confirmed by single crystal XRD Studies. 相似文献
995.
Vasu Dev R Moses Babu J Vyas K Sai Ram P Ramachandra P Sekhar NM Mohan Reddy DN Srinivasa Rao N 《Journal of pharmaceutical and biomedical analysis》2006,40(3):614-622
During the process development of docetaxel, two polar impurities (Impurities I and II) and two non-polar impurities (Impurities III and IV) were detected by high performance liquid chromatography (HPLC). All the impurities were isolated by Medium Pressure Liquid Chromatography (MPLC). The Impurities I, II, III and IV were identified as 13-[(4S,5R)-2-oxo-4-phenyl-oxazolidine-5-carboxy]-10-deacetyl baccatin III ester, 2'-epi docetaxel, 7-epi docetaxel and 13-[(4S,5R)-2-oxo-4-phenyl-oxazolidine-3,5-dicarboxyl-3-tert-butyl)]-10-deacetyl baccatin III ester, respectively, based on one- (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) spectroscopy data. The Impurity IV was crystallized and the structure was solved by single crystal X-ray diffraction (XRD). Two impurities (Impurities II and III) were found to be process related, while the remaining two impurities (Impurities I and IV) turned out to be isomers. The formation of these impurities was discussed. 相似文献
996.
Improved quality control method for Danshen products--consideration of both hydrophilic and lipophilic active components 总被引:5,自引:0,他引:5
The current study intends to provide an improved quality control analysis for Danshen product-a representative herbal product with known active components that are both hydrophilic and lipophilic in nature. A simple HPLC method with photodiode-array (PDA) ultraviolet detection was developed for the simultaneous determination of three major lipophilic components (cryptotanshinone, tanshinone I and tanshinone IIA) and three major hydrophilic components (danshensu, protocatechuic aldehyde and salvianolic acid B) of Danshen (Salvia miltiorrhiza). These six components were successfully separated using Radial-pak C18 cartridge with the elution gradient consisting of 0.5% acetic acid in water and 0.5% acetic acid in acetonitrile at a flow rate of 1 ml/min. The intra-day and inter-day precisions of the analysis were within 2.32 and 2.0%, respectively. The detection limits were 0.02, 0.01, 0.01, 0.05, 0.005 and 0.02 microg/ml for cryptotanshinone, tanshinone I, tanshinone IIA, danshensu, protocatechuic aldehyde and salvianolic acid B, respectively. The developed method has been applied to the simultaneous determination of above six major components in Fufang Danshen Tablet and Dripping Pill products by extraction with methanol and water. It has been demonstrated that salvianolic acid B and danshensu are the major components among the eight commercial Fufang Danshen products studied. The current developed method with methanol as extraction solvent provides a simple and efficient method for simultaneous detection of both lipophilic and hydrophilic major components in Danshen products. 相似文献
997.
998.
The present study determined the interindividual and intrandividual variability of the urinary 6beta-hydroxycortisol/cortisol ratio, a useful marker for CYP3A induction and inhibition in Chinese subjects. The study consisted of 2 parts. In part I, 82 healthy male Chinese subjects underwent 3 study sessions, each separated by a 1-week interval. In part II, 20 subjects who initially completed part I underwent another 3 sessions over a period of 3 to 4 months. During each session, a first-morning urine specimen was collected from each subject for the quantification of urinary concentrations of cortisol and 6beta-hydroxycortisol. There were no significant differences in the mean 6beta-hydroxycortisol/cortisol ratios among the 3 sessions (P > .05, 1-way analysis of variance) for both part I and part II of the study. A normal distribution of the 6beta-hydroxycortisol/cortisol ratio was observed (P = .849, Kolmogorov-Smirnov test). This ratio varied 30-fold (range, 0.76-23.23) among the study subjects. The mean intraindividual variabilities during the short (3-week) and long (3- to 4-month) periods were 30.9% +/- 17.5% and 32.2% +/- 17.1%, respectively. The genetic fraction contributing to the observed variability in the 6beta-hydroxycortisol/cortisol ratio was estimated to be 0.91. The genetic component is likely to contribute significantly to the variability of the 6beta-hydroxycortisol/cortisol ratio, and such variability should be considered when the ratio is used to evaluate CYP3A induction or inhibition in a given ethnic population. 相似文献
999.
The pharmacokinetic profile of solifenacin succinate (YM905; Vesicare), a new once-daily bladder-selective muscarinic receptor antagonist, was examined in 2 controlled trials of healthy young men. A single-dose study evaluated 5-, 10-, 20-, 40-, 60-, 80-, and 100-mg doses. A multidose study evaluated 5-, 10-, 20-, and 30-mg doses. In the single-dose study, mean time to maximal concentration and elimination half-life ranged from 3.3 to 4.8 and from 40.2 to 57.6 hours, respectively; in the multidose study, the corresponding ranges were 2.9 to 5.8 and 45.0 to 64.8. Plasma concentration and area under the curve increased linearly with single doses in both trials. At steady state, a less regular increase was seen, with higher values in the 20-mg group than in the 30-mg group. All doses in the single-dose study were well tolerated. At steady state, only the 30-mg dose was not well tolerated. The most commonly reported adverse events were dry mouth, blurred vision, and headache. Solifenacin 5 and 10 mg, either as single doses or at steady state, had minimal effect on salivary flow, visual nearpoint, and the incidence of adverse events. Solifenacin was well tolerated up to single doses of 100 mg and after multiple doses of 20 mg. Its pharmacokinetic profile makes it suitable for qd administration. 相似文献
1000.
O'Neil J Orchard T Swarankar RC Blanchard JF Gurav K Moses S 《Social science & medicine (1982)》2004,59(4):851-860
This paper discusses the results of two ethnographic studies with female sex workers in rural areas of Karnataka and Rajasthan, India. In particular, we focus on women whose socio-economic status, and religious and occupational practices, are part of sex work systems that have historical precedents such that they can be termed "traditional" sex workers. The approach taken in the ethnographic work was informed by current critical approaches in medical anthropology and public health. The paper argues that in the context of an expanding HIV/AIDS epidemic in rural areas of India, understanding the historical and structural factors that operate to perpetuate female sex work as a culturally "sanctioned" occupation is critical if interventions intended to reduce the risk of HIV transmission are to succeed. We conclude that interventions designed to empower women collectively in these communities that are consistent with cultural traditions are needed to lead to healthier sexual behaviours and reduced risk of HIV/AIDS infection. 相似文献