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Cancer Res. 2004 Mar 15;64(6):2070-5.
Kridel SJ, Axelrod F, Rozenkrantz N, Smith JW.
Cancer Research Center, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Orlistat is a novel inhibitor of fatty acid synthase with antitumor activity.
Here the author wrote about effect of orlistat and how this novel inhibitor of fatty acid synthase with antitumor activity. The researchers find out a new molecular target and a potential new application for Orlistat. It has the power to halt tumor cell proliferation, tempts tumor cell apoptosis, and inhibits the growth of PC-3 tumors.
One of the fundamental principles of pharmacology is that most drugs have side effects. Although considerable attention is paid to detrimental side effects, drugs can also have beneficial side effects. Given the time and expense of drug development, it would be particularly exciting if a systematic method could be applied to reveal all of the activities, including the unappreciated actions, of a potential drug. The present study takes the first step along this path. An activity-based proteomics strategy was used to simultaneously identify targets and screen for their inhibitors in prostate cancer. Orlistat, a Food and Drug Administration-approved drug used for treating obesity, was included in this screen. Surprisingly, we find a new molecular target and a potential new application for Orlistat. Orlistat is a novel inhibitor of the thioesterase domain of fatty acid synthase, an enzyme strongly linked to tumor progression. By virtue of its ability to inhibit fatty acid synthase, Orlistat halts tumor cell proliferation, induces tumor cell apoptosis, and inhibits the growth of PC-3 tumors in nude mice.
Metabolism. 2004 Apr;53(4):430-4.
Valsamakis G, McTernan PG, Chetty R, Al Daghri N, Field A, Hanif W, Barnett AH, Kumar S.
Department of Diabetes and Endocrinology, Birmingham Heartlands Hospital, Birmingham, UK.
Modest weight loss and reduction in waist circumference after medical treatment are associated with favorable changes in serum adipocytokines.
Positive changes in serum adipocytokines may result in modest weight loss and reduction in waist circumference. The researchers observed the effect of modest weight loss on serum adipocytokines and their association with changes in anthropometric and metabolic parameters within a period of 6 months. Reduction of waist is connected with a modification in serum resistin
Modest weight loss if maintained is associated with significant metabolic benefits and reduction in cardiovascular risk. Adipose tissue secretes cytokines believed to contribute to the pathogenesis of insulin resistance and cardiovascular risk. We therefore observed the effect of modest weight loss on serum adipocytokines and their relationship with changes in anthropometric and metabolic parameters within a period of 6 months in the setting of a routine obesity hospital clinic after various medical treatments. In this prospective, nonrandomized, nonblinded observational study, patients were first given treatment (sibutramine or orlistat) as decided by the treating clinician and then allocated into 1 of 2 groups according to the treatment prescribed. The first group included 21 Caucasian nondiabetic female subjects, with a mean (+/-SD) age of 43 +/- 11 years and a mean body mass index (BMI) of 46 +/- 8.6 kg/m(2); subjects were treated with sibutramine 10 or 15 mg/d for weight loss. The second group included 20 Caucasian nondiabetic female subjects, mean age 42 +/- 9 years and mean BMI 45.2 +/- 5.2 kg/m(2); orlistat was introduced after 1 month on a low-fat (5%) after medical treatment in a routine obesity hospital clinic is associated with improvements in insulin sensitivity and lipid profile. Modest weight loss is also associated with potentially favourably changes in serum adipocytokines, particularly in a rise of serum adiponectin. Reduction of waist circumference is associated with a change in serum resistin.
Int J Obes Relat Metab Disord. 2005 Mar 01.
Ruof J, Golay A, Berne C, Collin C, Lentz J, Maetzel A.
[1] 1Health Services Research Unit, Division of Rheumatology, Center of Internal Medicine, Hannover Medical School, Hannover, Germany [2] 2Global Health Economics Department, Roche Pharmaceuticals, Basel, Switzerland.
Orlistat in responding obese type 2 diabetic patients: meta-analysis findings and cost-effectiveness as rationales for reimbursement in Sweden and Switzerland.
A study to find out the effect of orlistat in responding obese patients with type 2 diabetes. This meta-analysis finding is the basic factor to get reimbursement in Sweden and Switzerland. During the study, a group of patients treated with orlistat and another group of patients given placebo were eligible for the intent-to-treat analysis.
OBJECTIVE:: The aim of this study is to review the clinical and economic rationale for the reimbursement of orlistat in responding obese patients with type 2 diabetes. METHODS:: Data from seven randomized controlled clinical trials of orlistat in overweight and obese patients with type 2 diabetes were pooled. A subgroup analysis involving patients who achieved a response (defined as a weight loss of >/=5% after 12 weeks of treatment) was conducted. The outcomes of the pooled analysis were then used to construct a Markov health economic model covering an 11-y period. The incidences of diabetes-related micro- and macrovascular complications were derived from the United Kingdom Prospective Diabetes Study. The effects of changes in body mass index, and the impact of micro- and macrovascular complications on utilities were derived from published sources. Publicly available cost data were used and are presented here in 2001 Euros. Discounting of 3% was applied. A probabilistic sensitivity analysis was conducted to examine the robustness of results. RESULTS:: A total of 1249 patients treated with orlistat and 1230 given placebo were eligible for the intent-to-treat analysis. At the end of the study period, 23% of orlistat patients achieved a weight reduction of >/=5%. These patients showed a mean decrease in HbA1C of 1.16%, a weight reduction of 8.6 kg, a reduction in total cholesterol of 5.3% and a reduction in systolic blood pressure of 5.2 mmHg. The base-case economic analysis revealed costs per quality-adjusted life year gained of \[euro]14 000 in Sweden and \[euro]13 600 in Switzerland. CONCLUSION:: The data presented here support the utilization and reimbursement of orlistat in overweight and obese diabetic patients who respond to the treatment.International Journal of Obesity advance online publication, 1 March 2005; doi:10.1038/sj.ijo.0802925.
BMC Fam Pract. 2005 Jan 29;6(1):5.
Feigenbaum A, Pasternak S, Zusk E, Sarid M, Vinker S.
Department of Family Medicine, Sackler School of Medicine, Tel Aviv University; Tel Aviv, Israel.
Influence of intense multidisciplinary follow-up and orlistat on weight reduction in a primary care setting.
Here the author shed light on the influence of intense multidisciplinary follow-up and orlistat on weight reduction in a primary care setting. The motto of the research was to examine if effective weight-reducing treatment can be given by a family physician. It evaluates usual treatment with rigorous treatment that includes close follow-up and orlistat treatment.
BACKGROUND: Obesity is the most common health problem in developed countries. Recently, several physicians' organizations have issued recommendations for treating obesity to family physicians, including instructions in nutrition, physical activity and medications. The aim of this study was to examine if effective weight-reducing treatment can be given by a family physician. It compares regular treatment with intensive treatment that include close follow-up and orlistat treatment. METHODS: The study was conducted in three primary care clinics. 225 patients were divided into three groups according to their choice. Group A received a personal diet with fortnightly meetings with the family physician and dietitian and orlistat treatment. Group B received a general diet, monthly meetings with the family physician only and orlistat treatment. Group C received a personal diet, monthly meetings with the dietitian only and no drug treatment. The primary endpoint was reduction of at least 5% of the initial weight during the study period. RESULTS: A greater percentage of patients in group A achieved their weight reduction goals than in other groups (51%, 13% and 9% in groups A, B and C, respectively, p < 0.001). There was a significant reduction in triglycerides in all groups, a significant reduction of low density lipids (LDL) in groups A and B and no significant difference in high density lipids (HDL) in any group. CONCLUSIONS: Significant weight reduction was obtained in a family physician setting. Further research is needed to evaluate if, by providing the family physician with the proper tools, similar success can be achieved in more clinics.
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Drug category:Weight loss and gaining agents
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