Establishment of a discrinatory dissolution method for orlistat capule and evalution of the similarity of dissolution curue / 中国药师

Objective To establish a discriminative dissolution test method for orlistat capsules and evaluate the similarity of dissolution curves of 6 domestic enterprises and imported orlistat capsules.Methods The HPLC method was used,the chromatographic column was Thermo Hyersil GOLD C18(150 mm×4.6 mm,5 μm)column,the mobile phase was acetonitrile and water(85∶15),the flow rate was 1.0 mL·min-1,the detection wavelength was 195 nm,the column temperature was 30℃,and the injection volume was 20 μL.The effects of different concentrations of sodium dodecyl sulfate,different concentrations of sodium chloride and different pH dissolution media on the dissolution curve were investigated,and the best dissolution conditions were selected.The similarity of the dissolution curve was evaluated using the dissolution curve similarity factor method.Results Orlistat had good linear relationship within the range of 5.989-179.697 μg·mL-1(r=0.999 8),and its average recovery rate was 100.4％,with an RSD of 1.1％(n=9).The optimal dissolution conditions selected were as follows:the pH 6.0 phosphate buffer solution containing 1.0％sodium dodecyl sulfate and 0.5％sodium chloride was as dissolution medium;the conduct dissolution tests conducted under conditions of paddle method,75 r·min-1 and medium 1 000 mL.Only one domestic enterprise had a similar dissolution curve between the product and the reference formulation,while the other five enterprises had inconsistent dissolution behavior between the product and the reference formulation.Conclusion This measurement method can effectively distinguish the dissolution behavior of products from different enterprises,and has certain reference significance to evaluate the consistency of the quality and efficacy of orlistat capsules in China.

Effects of orlistat on the viability of human gallbladder cancer cells / 中华消化外科杂志

Objective:To investigate the effects of orlistat on the viability of human gall-bladder cancer (GBC) cells.Methods:The experimental study was conducted. The human GBC NOZ cells with high expression of FSAN was screened out through in vitro cultivating human GBC-SD, SGC-996 and NOZ cells. The cell proliferation assay, clone formation assay and protein detection experiment were used to analysis of the effects of orlistat on the viability of human GBC cells. Cell grouping: NOZ cells cultured with medium were set as the control group, cultured with medium + 10 μmol/L orlistat were set as the low-dose orlistat group, cultured with medium + 100 μmol/L orlistat were set as the high-dose orlistat group, respectively. Observation indicators: (1) expression of FASN protein in human GBC cells; (2) effects of orlistat on the proliferation of human GBC NOZ cells; (3) effects of orlistat on apoptosis of human GBC NOZ cells. Measurement data with normal distribution were represented as Mean± SD, the ANOVA test was used for comparison between groups and the least significant difference method was used for pairwise comparison. Results:(1) Expression of FASN protein in human GBC cells. Results of western blot showed that the relative expression of FASN protein in human GBC NOZ, GBC-SD and SGC-996 cells was 0.57±0.06, 0.12±0.04 and 0.10±0.02, respectively, showing a significant difference among them ( F=115.67, P<0.05). There were significant differences between the NOZ cells and the GBC-SD or the SGC-996 cells ( P<0.05), and there was no significant difference between the GBC-SD cells and the SGC-996 cells ( P>0.05). (2) Effects of orlistat on the proliferation of human GBC NOZ cells. ① Results of cell proliferation assay showed that the absorbance value of NOZ cells was 2.34±0.12, 1.57±0.08 and 1.07±0.13 in the control group, low-dose orlistat group and high-dose orlistat group, respectively, showing a significant difference among them ( F=205.88, P<0.05). ② Results of clone formation assay showed that the number of NOZ cells clones was 257±23, 153±11 and 83±11 in the control group, low-dose orlistat group and high-dose orlistat group, respectively, showing a significant difference among them ( F=92.64, P<0.05). ③Results of western blot showed that the relative expression of Cyclin-D1 protein of NOZ cells was 2.31±0.10, 1.52±0.05 and 1.23±0.11 in the control group, low-dose orlistat group and high-dose orlistat group, respectively, showing a significant difference among them ( F=120.73, P<0.05). The relative expression of CDK-4 protein of NOZ cells was 1.58±0.04, 1.21±0.02 and 1.19±0.04 in the control group, low-dose orlistat group and high-dose orlistat group, respectively, showing a signifi-cant difference among them ( F=110.45, P<0.05). (3) Effects of orlistat on apoptosis of human GBC NOZ cells. Results of western blot showed that the relative expression of Bcl-2 protein of NOZ cells was 1.07±0.03, 0.36±0.03 and 0.15±0.02 in the control group, low-dose orlistat group and high-dose orlistat group, respectively, showing a significant difference among them ( F=1 242.93, P<0.05). The relative expression of Bax protein of NOZ cells was 0.51±0.03, 0.38±0.05 and 1.38±0.04 in the control group, low-dose orlistat group and high-dose orlistat group, respectively, showing a signifi-cant difference among them ( F=583.51, P<0.05). Conclusion:Orlistat can inhibit the growth of human GBC NOZ cells and promote their apoptosis.

Comparison of orlistat and orlistat plus metformin therapy between diabetic and nondiabetic groups

SUMMARY OBJECTIVE: The objective of this study was to examine the effects of orlistat use on metabolic control and weight loss in diabetic and nondiabetic patients. METHODS: A total of 119 patients with body mass index≥40 kg/m2 and receiving orlistat therapy, who applied to the Endocrinology polyclinic between January 2016 and October 2019, were included. The patients' weight changes and biochemical values (i.e., fasting glucose, HbA1c, ALT, creatinine, and lipid parameters) were evaluated at the drug beginning and the last polyclinic control. The patients were divided into groups, whether they had diabetes or used metformin, and compared. RESULTS: The mean age of the 119 patients in the study was 45.3±11.5 years. A total of 94.1% of the patients were females and 5.9% were males. A total of 38.7% of the patients had diabetes and 29.4% had prediabetes. When the patients were compared to whether they had diabetes or used metformin, there was a statistically significant difference between the groups according to weight loss. The mean weight change of patients without diabetes and receiving metformin and orlistat was statistically significantly higher than that of patients with diabetes and receiving metformin and orlistat. DISCUSSION: It was determined that the weight loss effect of orlistat in obesity was seen in all groups, but this effect decreased in the diabetic group.

Advanced therapy of overweight or obese polycystic ovary syndrome:a prospective study / 《全球健康杂志（英文）》

Objective:To investigate the effects of orlistat combined with drospirenone/ethinylestradiol tablets(DRSP/EE)on anthropometric indices,sexual hormones,hepatorenal function parameters of overweight or obese patients with polycystic ovary syndrome(PCOS).Methods:75 overweight or obese PCOS patients[body mass index(BMI)＞24 kg/m2]were recruited within the Department of Gynecological Endocrinology,Beijing Obstetrics and Gynecology Hospital,Capital Medical Uni-versity,from April 2019 to January 2020,for a prospective,randomized,open-labelled comparing study.They were numbered one by one according to the order of recruitement and randomly divided into two groups,group 1 included 50 patients,orlistat plus DRSP/EE;group 2 included 25 patients treated with DRSP/EE alone.Both groups got the same comprehensive intervention in terms of individualized,standardized managment and mon-itoring of life-style like diet and exercise.The changes of anthropometric indices,sexual hormones,hepatorenal function parameters before and after three months of treatment in the two groups were compared.Results:After three months of treatment,body weight,waist circumference(WC),hip circumference(HC)and BMI of both groups were significantly decreased(P＜0.05).The decrease of body weight,WC,HC and BMI in group 1 was significantly greater than those in group 2(P＜0.05).Free testosterone and sex hormone-binding globulin in both groups were significantly changed(P＜0.05).There was no significant difference in the hepatorenal function parameters between the two groups after three months treatment(P＞0.05).Conclusion:To our knowledge our study is the first to investigate the effects of orlistat combined with DRSP/EE in overweight or obese PCOS patients comparing with the effect of using DRSP/EE alone.Orlistat combined with DRSP/EE was better than use DRSP/EE alone in getting weight loss,which provides an evidence for the choice of rational drug use in clinical practice.

Effects of orlistat and metformin on metabolism and gonadal function in overweight or obese patients with polycystic ovary syndrome / 中华内科杂志

The aim of this study was to assess the effects of orlistat or metformin treatment on lipid and glucose metabolism, and gonadal function in obese/overweight women with polycystic ovary syndrome (PCOS). A total of 39 patients diagnosed with PCOS were randomly (digital table method) divided into orlistat treatment group (20 cases) and metformin treatment group (19 cases). Compared with those before, treatment with either orlistat or metformin significantly reduced body weight, body mass index (BMI), hip circumferences, and serum insulin levels of the PCOS patients both at the end of 3 months and 6 months ( P<0.05). No significant differences could be viewed between orlistat and metformin treated subjects. Moreover, orlistat treatment significantly lowered the levels of low-density lipoprotein cholesterol, total cholesterol, fasting blood glucose, and homeostasis model assessment-insulin resistance (HOMA-IR) ( P<0.05), while there were no significant changes in above parameters with metformin treatment. The improvement of menstrual cycle was observed after 6-month treatment in both groups ( P<0.05). However, changes in polycystic ovarian morphology by ultrasound were only observed in orlistat treated group. In conclusion, orlistat is comparable with metformin in weight loss and improvement of insulin resistance and menstrual cycle, and is superior to metformin in improvement of lipid metabolism in overweight/obese PCOS patients.

Orlistat induces ferroptosis-like cell death of lung cancer cells / 医学前沿

Aberrant de novo lipid synthesis is involved in the progression and treatment resistance of many types of cancers, including lung cancer; however, targeting the lipogenetic pathways for cancer therapy remains an unmet clinical need. In this study, we tested the anticancer activity of orlistat, an FDA-approved anti-obesity drug, in human and mouse cancer cells in vitro and in vivo, and we found that orlistat, as a single agent, inhibited the proliferation and viabilities of lung cancer cells and induced ferroptosis-like cell death in vitro. Mechanistically, we found that orlistat reduced the expression of GPX4, a central ferroptosis regulator, and induced lipid peroxidation. In addition, we systemically analyzed the genome-wide gene expression changes affected by orlistat treatment using RNA-seq and identified FAF2, a molecule regulating the lipid droplet homeostasis, as a novel target of orlistat. Moreover, in a mouse xenograft model, orlistat significantly inhibited tumor growth and reduced the tumor volumes compared with vehicle control (P < 0.05). Our study showed a novel mechanism of the anticancer activity of orlistat and provided the rationale for repurposing this drug for the treatment of lung cancer and other types of cancer.

Efficacy of orlistat in the treatment of patients with non-alcoholic fatty liver

Background: Nonalcoholic fatty liver disease (NAFLD) is a reversible condition of fat accumulation that is associated with liver inflammation and can disrupt the normal activity of the liver. People with a diagnosis of NAFLD have a higher risk of all- cause mortality than the general population. The purpose of the present study was to determine, the efficacy of orlistat in the treatment of patients with NAFLD.Methods: This semi-experimental study was performed on 45 fatty liver patients of the gastroenterology clinic of Imam Khomeini Hospital in Ardabil city in April 2016 to April 2017. Data was collected by a checklist which included demographic and clinical data such as age, sex, body mass index (BMI), alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), cholesterol and result of ultrasound before and after orlistat consumption.Results: The mean decrease in the variables examined was as follows: weight 8.3 kg, BMI 3.5 kg/m2, ALT 31.6 U/l, AST 18.1 U/l, cholesterol 15.5 mg/dl and TG 33.1 mg/dl. All of the upper indexes were decreased significantly following received drug.Conclusions: Orlistat therapy was associated with significant decreases in ALT, AST, TG and cholesterol level. Orlistat is effective in weight loss, body mass index reduction and can be used to treat non-alcoholic fatty liver disease.

Suppression of Feed Intake in Response to Rice Bran Oil Supplementation in Normal Rat

@#Introduction: Rice bran oil (RBO) is used in Asian countries as a daily dietary supplement. RBO is known in particular for its hypolipidemic effect. There has been increasing interest recently in the use of RBO as a means to maintain body weight and prevent obesity, though the mechanism of how this happens is still not well understood. We have investigated the effect of RBO on expression of genes that might influence energy homeostasis and feed intake. Methods: This study assessed Sprague-Dawley male rats at 12-weeks that were split into three groups over a 28-day period. A control group was fed a diet of standard rat chow, a standard group was fed standard rat chow with Orlistat (10.8 mg/kg bw/day), and a treatment group was fed standard rat chow with RBO (57.6 mg oryzanol/day). All supplementation was given by oral gavage. Possible adiposity was investigated through a histological analysis of adipocytes size measurement of intra-abdominal white adipose tissue in the rats. Changes in gene expression in the liver were determined by microarray. Results: The data suggest that RBO supplementation of a regular diet did not result in excess body weight and adiposity. A microarray analysis of the rats’ livers found that RBO altered the expression of genes related to energy homeostasis and feeding behavior, by upregulating genes such as Olr522, RGD1561231 and Rgs16. Conclusion: It is suggested that RBO supplementation can be used to maintain body weight by lowering appetite.

Protective Effects of Orlistat on Lipid Profile, Cardiac Oxidative Stress Biomarkers and Histology in High-fat Diet-induced Obese Rats

@#Introduction: Orlistat is a widely used drug in treating obesity as it promotes weight reduction. The aim of this study was to determine the protective effects of orlistat (10 mg/kg/day) on cardiovascular parameters and oxidative stress biomarkers in high-fat diet (HFD)-induced obese rats. Methods: Twenty-four male rats Sprague Dawley rats were divided into three groups and fed with normal diet (N), HFD and HFD with orlistat (HFD+O). Orlistat was administered daily by oral gavage and after six weeks, all rats were sacrificed. Results: Administration of orlistat along with HFD (HFD+O) has brought significant decreases in Lee obesity index and LDL level compared to HFD group. Activities of cardiac superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) were significantly higher, whereas level of oxidised LDL was significantly lower in HFD+O group compared to HFD group. HFD group had significantly higher necrotic patch area in myocardium while minimal histological changes were seen in HFD+O group. Conclusion: This study may suggest that administration of orlistat at 10 mg/kg/day for 6 weeks may have protective effects against the changes on Lee obesity index, lipid profiles, cardiac oxidative stress biomarkers and histology of myocardium in HFD-induced obese rats possibly through its hypolipidaemic and antioxidant actions.

Efficacy and Safety of Orlistat versus Metformin in Reducing Body Weight of Overweight or Obese Patients:A Meta-analysis / 中国药房

OBJECTIVE: To evaluate therapeutic efficacy and safety of orlistat versus metformin in reducing body weight of overweight or obese patients, and to provide evidence-based reference.METHODS: Retrieved from PubMed, Embase, Ovid, Web of Science, Cochrane Library, Chinese Journal Full-text Database, Wanfang database and VIP, RCTs about orlistat alone or combined with metformin (trial group) versus metformin alone (control group) in reducing body weight, BMI and the incidence of ADR of overweight or obese patients were collected. Meta-analysis was performed by using Rev Man 5. 3 statistical software after data extraction and quality evaluation with modified Jadad scale. RESULTS: A total of 9 RCTs were included, involving 502 patients. The results of Meta-analysis showed that, when orlistat combined with metformin, the reduction of BMI in trial group was significantly better than control group, with statistical significance [SMD= -0. 74, 95％CI (- 1. 22,-0. 26),P=0. 002]. There was no statistical significance in the reduction of body weight [SMD= -0. 04, 95％CI (-0. 27,0. 20), P=0. 76] or the incidence of ADR [RR=1. 07, 95％CI (0. 68, 1. 68), P=0. 78] between 2 groups. CONCLUSIONS: Both orlistat and metformin can reduce body weight with good safety. Combined use of these two drugs can reduce body weight more significantly.

Características demográficas, clínicas y reacciones adversas de personas con sobrepeso y obesidad: consumidores de orlistat atendidos por centro de atención telefónica (2009 ­ 2017) / Demographic and clinical characteristics, and adverse reactions of people with overweight and obesity consumers of orlistat, attended by a call center (2009 ­ 2017)

Resumen Introducción Las enfermedades crónicas van en ascenso y están asociadas al incremento ponderal. Se requieren estrategias multidisciplinarias para su control. Métodos El diseño es descriptivo, observacional y retrospectivo. Los objetivos de esta comunicación son describir las características demográficas, clínicas y reacciones adversas de personas con sobrepeso y obesidad consumidores de orlistat, atendidos por un centro de atención telefónica durante el periodo 2009 a 2017; e identificar al profesional de la salud más consultado por ellos. La información se obtuvo desde una base de datos existente de un programa de atención a personas con sobrepeso u obesidad, interesadas en usar orlistat (prospectos) o usuarios (pacientes). El estudio se llevó a cabo en México y duró siete años. Las variables estudiadas fueron demográficas, clínicas y reacciones adversas. Resultados Se reunieron 311 913 solicitudes de 126 607 sujetos (104 711 prospectos interesados en consumir orlistat y 21 896 pacientes que ya lo tomaban). Las principales actividades fueron llamadas al sujeto (35,9%). Hubo 104 711 solicitudes: 82 810 (79,1%) prospectos y 21 896 (20,9%) pacientes. El 79,9% fue de sexo femenino. El intervalo de edad predominante fue de 32 a 45 años. Se detectaron 43 reacciones adversas (0,02%); las más comunes fueron dolor abdominal (0,05%) y cefalea (0,03%). Conclusiones La población más interesada en el control ponderal en este estudio es la femenina (79,9%) y el grupo etario de 32 a 45 años. El profesional más consultado fue el nutriólogo. Solo se obtuvo el índice de masa corporal (29,2 kilogramos por metro cuadrado) de los sujetos que desarrollaron 43 reacciones adversas, las más comunes fueron dolor abdominal y cefalea.

Introduction Chronic diseases are on the rise and are associated with weight gain. Multidisciplinary strategies are required for its control. Methods The design was descriptive, observational and retrospective. The objectives of this communication were to describe the demographic and clinical characteristics and adverse reactions of overweight and obese people who were consumers of orlistat, attended by a call center during the period 2009 to 2017; and to identify the healthcare professional most consulted by them. The information was obtained from an existing database of a program of attention to people with overweight or obesity, interested in using orlistat (prospects) or users (patients). The study was carried out in Mexico and lasted seven years. The variables studied were demographic, clinical and adverse reactions. Results A total of 311,913 requests were collected from 126 607 subjects (104 711 prospects interested in consuming orlistat and 21 896 patients who already took it). The main activities were phone calls to the subject (35.9%). There were 104 711 requests: 82 810 (79.1%) prospects and 21 896 (20.9%) patients. 79.9% of all were female. The predominant age interval was 32 to 45 years. 43 adverse reactions (0.02%) were detected; the most common were abdominal pain (0.05%) and headache (0.03%). Conclusions The population most interested in weight control in this study was the female population (79.9%) and the age group from 32 to 45 years. The most consulted healthcare professional was the nutritionist. Only the body mass index (29.2 kilograms per square meter) of the subjects who developed 43 adverse reactions was obtained. There were 43 adverse reactions, the most common being abdominal pain and headache.

Saffron Extract and Crocin Reduced Biomarkers Associated with Obesity in Rats Fed a High-Fat Diet

This study aimed to investigate the effect of saffron extract and crocin on blood biomarkers associated with obesity using the rat model. Methods: Obesity was induced by feeding a high-fat diet to 42 male Sprague-Dawley rats for 12 weeks, after which they were equally distributed into seven groups. Three groups served as controls namely, normal diet (ND), high-fat diet (HFD), and high-fat diet plus orlistat (HFD + ORL), while the remaining four treatment groups consisted of HFD added low or high dose (40 and 80 mg/kg/day) of either saffron extract or crocin in the food. At the end of 8 weeks, blood samples were collected by cardiac puncture for biochemical analysis. Results: Obese rats treated with a high dose of saffron extract and crocin showed significantly lower plasma glucose levels (5.26 and 5.67 mmol/L respectively) than the HFD rats (6.92 mmol/L). Saffron extract and crocin at a high dose showed significantly lower levels of plasma insulin (3.97 and 3.88 ng/mL respctively) compared to HFD control (5.41 ng/mL). Adiponectin levels significantly increased in obese rats fed saffron extract and crocin at high doses (7.44 and 7.92 µg/mL respectively) compared to HFD control (5.34 µg/mL). Ghrelin level significantly increased from 419.10 to 284.10 pg/mL,while leptin level significantly decreased from 8.08 to 5.68 ng/mL for the high dose crocin groups compared to HFD control. No significant differences in plasma serotonin levels were found among the groups. Conclusion: Saffron extract and crocin show potential in reducing blood biomarkers associated with obesity as well as anti-inflammatory and regulatory potential of adipocytokines in an animal model.

Safety of Anti-Obesity Drugs Approved for Long-Term Use

Because of the widespread use of ant-obesity medications, bariatricians need to be aware not only of common adverse events but also uncommon serious events in the pharmacotherapy of obesity. Safety and tolerability must be considered in selecting the drug, titrating the dosage, and monitoring patients. In Korea, orlistat and lorcaserine are the two anti-obesity drugs that can be used for long-term treatment, and in the US, liraglutide, phentermine/topiramate, and naltrexone/bupropion have been recently approved. In general, all of these drugs have very good safety and tolerability profiles. Common adverse events of these drugs are well understood, and they can be coped with or prevented by adjusting the dosage properly. In addition, patients can recover from serious events by stopping the medication. However, there are other serious side effects that need to be monitored for. These include liver injury, acute kidney injury, and pancreatitis for orlistat; valvulopathy for lorcaserine; thyroid C-cell pathology and pancreatitis for liraglutide; metabolic acidosis, urolithiasis, acute angle closure glaucoma, and teratogenic effects for phentermine/topiramate; and severe nausea and heart disease for naltrexone/bupropion.

Review of fatty acid synthase inhibitor and its anti-tumor effect / 中国现代医生

It has been proved that FAS is a potent oncogene. Its expression and activity is normal in most of the non-neoplastic cells, but it is over-expressed and associated with poor prognosis in several human malignancies. Recent studies show that FAS inhibitor can induce significant anti-tumor effect. It reduces cell proliferation,enhances apopto-sis,inhibits tumor invasion and metastasis,while it is also an chemosensitization for other chemotherapy drugs. In this paper, the anti-tumor mechanism of FAS inhibitors is reviewed to prospect the research direction of its anti-tumor ef-fect.

Hypolipidemic and hypoglycemic effects of Centella asiatica (L.) extract in vitro and in vivo.

In vitro study revealed that pancreatic lipase inhibitory activity of C. asiatica extract was significantly higher than rutin but lower than orlistat, an anti-obesity drug. α-Amylase inhibitory activities of C. asiatica extract and rutin were significantly lower than acarbose, an anti-diabetic drug. Inhibition of α-glucosidase activity by C. asiatica extract, rutin, and acarbose was not different. The in vivo study substantiated the in vitro results. C. asiatica extract (1000 and 2000 mg/4 mL/kg), rutin (1000 mg/4 mL/kg), and orlistat (45 mg/4 mL/kg) significantly decreased plasma glucose, triglyceride and total cholesterol levels in lipid emulsion-induced hyperlipidemic rats at 3 h. However, plasma aspartate aminotransferase and alanine aminotransferase levels did not show significant change. The present work further supports that the C. asiatica extract and its bioactive rutin may help managing hypolipidemic and hypoglycemic effects.

Effects of Orlistat and Herbal Mixture Extract on Renal Function and Oxidative Stress Biomarkers in a Rat Model of High Fat Diet.

This study was designed to assess the effectiveness of herbal mixture extracts of pumpkin seed oil, peanuts shell and Orlistat on renal function and oxidative stress biomarkers in male albino rats administrated high fat diet (HFD). Study Design: Fifty male rats were divided into four groups: 1st a normal diet, 2nd HFD, 3rd HFD with Orlistat and 4th HFD with herbal mixture. Place and Duration of Study: Biochemistry-Chemistry department, Faculty of Science, Beni-Suef University for two years. Methodology: A group of rats were fed with a standard control diet (1st control group) and another group of rats were fed with a diet containing 35% fat (2nd HFD) for 16 weeks. Then, this group of HFD was divided into 3 groups for the following 6 weeks: 1st group hadHFD only, 2nd group had HFD plus 2 mg/kg bw/day Orlistat and 3rd group had HFD plus 5 mg/kg bw/day pumpkins and 2 mg/kg bw/day nutshell extract. Blood and renal tissues were collected for biochemical assays. Results: HFD group showed a very high significant increase (***P<0.001)in feed intake from low (216.9+/-12.25) to high (327.5 +/-22.00), body weight and body mass index. HFD affect the kidney by increasing serum uric acid (**P<0.01)(1.964+/-0.251) to (3.106+/- 0.161), urea, creatinine, (***P<0.001) for low density lipoproteins and total cholesterol (16.71+/-2.27 to 55.78+/-4.40 and 70.30+/-2.75 to118.10+/-6.35) respectively, triacylglycerol (**P<0.01) (54.60+/-6.42 to 80.00+/-0.65) and malondialdehyde (***P<0.001) (35.48 +/- 3.52 to 63.03 +/-1.48). These changes improved by the treatments with Orlistat and herbal mixture that decreased the oxidative stress biomarkers. Conclusion: Rats that fed with HFD showed hypertriglyceridemia, increased oxidative stress and renal alteration. Moreover, suggesting association between lipid peroxidation, obesity and nephropathy, while treatment with Orlistat and herbal mixture ameliorated the harmful effects of the HFD and reduce feed intake.

ELISA protocol for rapid screening of potential antitubercular drugs based on antigenic reactivity of mycobacterial ES-31 serine protease - a drug target supported by axenic culture of Mycobacterium tuberculosis H37 Ra strain in the presence of inhibitor.

Background: Mycobacterial ES-31 serine protease has been reported to be a drug target using protease and lipase inhibitors in axenic and macrophage cultures. Simple screening techniques are needed for rapid testing of anti-tubercular drugs. Aim: To demonstrate the usefulness of ELISA protocol based on antigenic reactivity of mycobacterial serine protease by indirect ELISA for detecting anti-tubercular activity. Material and Methods: Indirect ELISA for assessment of antigenic reactivity of mycobacterial ES-31 serine protease was standardized using ES-31Ag and anti-DSS-goat-serum and assessed the inhibition of the antigenic reactivity by isoniazid, an anti-tubercular drug and serine protease inhibitor and orlistat, a lipase inhibitor. Results: Optimal antigenic reactivity of mycobacterial ES-31 serine protease was observed at 5μg/well of ES-31 antigen and at 1:25 dilution of anti-DSS-goat-serum. Isoniazid showed 42% inhibition of ES-31 serine protease at 0.4μg/well, while orlistat showed inhibition of 60% at 0.5μg/well. Inhibition of Mtb H37Ra bacilli is further confirmed in axenic culture. 35% and 29% inhibition by isoniazid at 0.4μg/well and orlistat at 0.5μg/well were observed respectively on bacterial growth. Conclusion: Simple ELISA protocol based on assay of antigenic reactivity of mycobacterial ES-31 serine protease, a drug target, has been standardized for rapid screening of potential anti-tubercular drugs.

Inhibitory effect of isoniazid and orlistat combination on mycobacterial ES-31 serine protease in vitro and on the growth of M.tb bacilli in axenic culture.

Background: Isoniazid and orlistat were reported to have inhibitory effect on mycobacterial ES-31 serine protease in vitro and bacterial cell growth in axenic culture. Aim: To study the cumulative effect and understand drug - drug interaction, if any, when isoniazid and orlistat used in combination. Material and Methods: Inhibition of mycobacterial ES-31 serine protease by different combinations of orlistat and isoniazid together and individually were studied using azocasein assay. Inhibition of secretion of excretory secretory ES- 31 antigen in Sautan culture medium was studied under axenic condition and growth of M.tuberculosis H37Ra bacilli by CFU count on LJ-medium. Results: Orlistat and isoniazid both showed inhibitory activity of ES-31 serine protease in in vitro as well as in vivo. Individually, isoniazid showed 90% inhibition at 200 ng/ml while orlistat at 250 ng/ml showed 65% inhibition of mycobacterial ES-31 serine protease in vitro. A combination of orlistat (250 ng/ml) and isoniazid (200 ng/ml) showed 86% inhibition in vitro while 73% inhibition was observed by orlistat (25 ng/ml) and isoniazid (200 ng/ml) on bacterial growth in axenic culture. Conclusion: Significant inhibition by orlistat suggests that it could be tried in patients with intolerance to isoniazid or in those already developed isoniazid resistance. It may also be explored in the suspected TB patients as initial medication in place of antibiotics for clinical relief.

Lorcaserin: a selective serotonin receptor (5-HT2C) agonist for the treatment of obesity.

Lorcaserin is a selective serotonin receptor (5-HT2C) agonist that recently received the U.S. Food and Drug Administration (FDA) approval for chronic weight management. The efficacy of this drug in reducing body weight and improving metabolic parameters of obese patients has been demonstrated in three phase-3 clinical trials. The available evidence indicates that this drug does not show heart valve abnormalities, and the treatment improves the risk factors for type 2 diabetes and cardiovascular diseases. However, the drug’s manufacturer will be required to conduct postmarketing studies, including a long-term cardiovascular outcomes trial to assess the effect of Lorcaserin on the risk for major adverse cardiac events such as heart attack and stroke.

Pancreatitis Aguda como consecuencia del uso de Orlistat / Acute Pancreatitis as consequence of the use of Orlistat

La pancreatitis aguda es un proceso inflamatorio del páncreas desencadenada por la auto digestión ante la activación de sus pro fermentos, tiene un manejo urgente ya que pone en peligro la vida del paciente. El reciente ingreso de Orlistat, un fármaco inhibidor de la lipasa gástrica y pancreática para tratar la obesidad, a través de su venta creciente sin receta se ha estado traduciendo en una mayor frecuencia de eventos adversos sobre todo gastrointestinales (diarrea grasa, esteatorrea, incontinencia, pero con insignificantes efectos sistémicos) con complicaciones por un mal uso, entre éstos la pancreatitis cuyo mecanismo causal no está aún determinado en su totalidad. Hasta la fecha se han reportado a la Administración de Alimentos y Medicamentos de Estados Unidos (FDA) 99 casos de pancreatitis aguda relacionadas con el uso de Orlistat, no habiéndose encontrado reportes de casos similares en América Latina. En el caso clínico una adolescente de 15 años de edad, desencadenó un cuadro típico de severa pancreatitis aguda con necrosis de más del 50% asociada a colección peripancrática clasificada como Baltazar D- E, Ranson de 5 a 6, secundaria al consumo de Orlistat para su obesidad grado III, apoyando esto con los criterios de probabilidad de Naranjo.

Acute pancreatitis is an inflammatory process of the pancreas, triggered by self digestión before activation of their pro ferments, it has a urgent management because it endangers the life of the patient.The recent accession of Orlistat, an inhibitor drug of lipase gastric and pancreatic to treat obesity, through its growing sale without a prescription has been translated in a greater frequency of especially gastrointestinal adverse events (fatty diarrhea, steatorrhea, incontinence, but with negligible systemic effects) with complications from misuse, among these pancreatitis whose causal mechanism is not yet determined in its entirety.To date, the U S Food and Drug Administration (FDA) have been reported 99 cases of acute pancreatitis associated with the use of Orlistat, not having found reports of similar cases in Latin America. In the clinical case a 15-year-old teenager, triggered a typical pattern of severe acute pancreatitis with more than 50% necrosis associated with peripancreática collection classified as Baltazar D-E, Ranson of 5-6, secondary to the use of Orlistat for his obesity grade III, supporting this with the criteria of probability of Naranjo.