Drugs online research references
Diabetes Care. 2002 Feb;25(2):303-8.
A health economic model to assess the long-term effects and cost-effectiveness of orlistat in obese type 2 diabetic patients.
Lamotte M, Annemans L, Lefever A, Nechelput M, Masure J.
Health Economics and Disease Management, Brusselsteenweg 91, B-1860 Meise, Belgium.
OBJECTIVES: Obesity is a common condition in type 2 diabetic patients. Treating obesity may enhance hypoglycemic treatment and contribute to the reduction of long-term microvascular and macrovascular complications. Orlistat reduces cardiovascular risk factors in obese type 2 diabetic patients. The objectives of this study were to estimate the long-term clinical consequences of this weight loss and the resulting cost-effectiveness of treating obese type 2 diabetic patients with orlistat. RESEARCH DESIGN AND METHODS: A Markov model was developed to predict, over a 10-year period, the complication rates and mortality with and without a 2-year orlistat treatment, assuming a 5-year catch-up period after treatment. A stepwise approach was used to obtain the clinical data. First, the impact of weight loss with orlistat on HbA(1c), blood pressure, and cholesterol was assessed; then, the impact on mortality and micro- and macrovascular complications of decreasing these risk factors was applied. Four subgroups were studied based on the presence of risk factors. RESULTS: Cost-effectiveness varies between 3,462 Euro/life-year gained (LYG) for obese diabetic patients with hypertension and hypercholesterolemia and 19,986 Euro/LYG for obese diabetic patients without other risk factors. The latter result is not robust according to sensitivity analyses. CONCLUSIONS: Our results suggest that orlistat is cost-effective in the management of obese type 2 diabetic patients, especially in those with the presence of hypercholesterolemia and/or hypertension. Evidence on longer-term benefits of orlistat (>2 years) will be of importance for future decision-making.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11815500&dopt=Abstract
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Obes Surg. 2002 Feb;12(1):113-7.
Impact of orlistat therapy on weight reduction in morbidly obese patients after implantation of the Swedish adjustable gastric band.
Zoss I, Piec G, Horber FF.
Hirslanden Clinic, Witellikerstr. 40, CH-8008 Zurich, Switzerland.
BACKGROUND: Adjustable gastric banding (AGB) is frequently performed to treat morbid obesity. One problem which can occasionally develop after a restrictive procedure is consumption of a high calorie liquid diet, which may prohibit further weight loss. Orlistat, a newly developed intestinal lipase inhibitor, prevents absorption of about one-third of ingested fat. It is unknown whether patients no longer losing weight after AGB, despite further band restriction, may lose weight with addition of orlistat. METHODS: 38 patients were selected who had stopped losing weight 3 months before the initiation of the study, 18 +/- 6 months (mean +/- SEM) after laparoscopic AGB. Subjects were divided into 2 groups, matched for age, sex, filling volume of the band and body mass index (BMI) both at the time of surgery and start of the study (18 +/- 6 months after AGB). RESULTS: Patients in group A received dietary counseling and orlistat 120 mg TID for 8 months, while patients in group B received only dietary counseling. During the following 8 months of study, subjects in group A lost 8 +/- 3 kg in weight, whereas subjects in group B lost 3 +/- 2 kg (p < 0.01, months 18 vs 26 of study; p < 0.03, group A vs B). In 15 patients from group A the study was further extended 9 months, but interestingly, weight remained stable independent of whether orlistat was continued (n = 8) or stopped (n = 7). 4 subjects were excluded from the extension study because of additional malabsorptive bypass surgery. Subjects taking orlistat encountered only minor GI side-effects. CONCLUSION: Orlistat appears to be useful when added in patients after AGB who are no longer losing weight, perhaps due to a high-calorie liquid diet rich in fat.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11868286&dopt=Abstract
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J Org Chem. 2002 Mar 8;67(5):1536-47.
Serine and threonine beta-lactones: a new class of hepatitis A virus 3C cysteine proteinase inhibitors.
Lall MS, Ramtohul YK, James MN, Vederas JC.
Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2G2.
Hepatitis A virus (HAV) 3C enzyme is a cysteine proteinase essential for viral replication and infectivity and represents a target for the development of antiviral drugs. A number of serine and threonine beta-lactones were synthesized and tested against HAV 3C proteinase. The D-N-Cbz-serine beta-lactone 5a displays competitive reversible inhibition with a K(i) value of 1.50 x 10(-6) M. Its enantiomer, L-N-Cbz-serine beta-lactone 5b is an irreversible inactivator with k(inact) = 0.70 min(-1), K(Iota) = 1.84 x 10(-4) M and k(inact)/K(Iota) = 3800 M(-1) min(-1). Mass spectrometry and HMQC NMR studies using (13)C-labeled 5b show that inactivation of the enzyme occurs by nucleophilic attack of the cysteine thiol (Cys-172) at the beta-position of the oxetanone ring. Although the N-Cbz-serine beta-lactones 5a and 5b display potent inhibition, other related analogues with an N-Cbz side chain, such as the five-membered ring homoserine gamma-lactones 14a and 14b, the four-membered ring beta-lactam 33, 2-methylene oxetane 34, cyclobutanone 36, and 3-azetidinone 39, fail to give significant inhibition of HAV 3C proteinase, thus demonstrating the importance of the beta-lactone ring for binding.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11871884&dopt=Abstract
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