Gastrointestinal Lipase Inhibitor Research Articles

Protective effect of grape seed extract and orlistat co-treatment against stroke: Effect on oxidative stress and energy failure

Ischemic stroke is a major health concern and a leading cause of mortality worldwide. Oxidative stress is an early event in the course of stroke inducing neuro-inflammation and cell death. Grape seed extract (GSE) is a natural phytochemical mixture exhibiting antioxidant, anti-inflammatory and neuroprotective properties. Orlistat (ORL) is an anti-obesity agent and a gastro-intestinal lipase inhibitor which showed recently beneficial effects on brain lipotoxicity. Recent studies reported the increase of lipase activity upon stroke which led us to investigate the neuroprotective effect of ORL on rat brain I/R injury as well as the putative synergism with GSE. I/R insult infarcted the brain parenchyma as assessed by TTC staining, induced an oxidative stress as revealed by increased lipoperoxidation along with alteration of antioxidant enzymes activities which was corrected using the cotreatment of ORL + GSE. I/R also disturbed the main metabolic pathways involved in brain fueling as glycolysis, neoglucogenesis, glycogenolysis, TCA cycle and electron transfer chain (ETC) complexes. These disturbances were also corrected with the cotreatment ORL + GSE which maintained energetic activities near to the control level. I/R also disrupted transition metals distribution, along with associated enzymes as tyrosinase, LDH or glutamine synthetase activities and induced hippocampal inflammation as revealed by glycogen depletion from dentate gyrus area along with depressed anti-inflammatory IL1β cytokine and increased pro-inflammatory CD68 antigen. Interestingly almost all I/R-induced disturbances were corrected either partially upon ORL and GSE on their own and the best neuroprotection was obtained in the presence of both drugs (ORL + GSE) enabling robust neuroprotection of the sub granular zone within hippocampal dentate gyrus area.

Protective effect of (Xenical+GSF) against I/R-induced blood brain barrier disruption, ionic edema, lipid deregulation and neuroinflammation

Ischemic stroke is a leading cause of mortality worldwide that occurs following the reduction or interruption of blood brain supply, characterized by a cascade of early events as oxidative stress and ensuing neuro-inflammation, energy failure and the burst of intracellular Ca++ resulting in activation of phospholipases and large increase in FFA including arachidonic acid, ultimately leading to nervous cell death. Grape Seed Flour (GSF) is a complex polyphenolic mixture harboring antioxidant, anti-inflammatory and neuroprotective properties. Orlistat (Xenical ™,Xe) is a gastro-intestinal lipase inhibitor and an anti-obesity agent. In an earlier study we reported the higher efficiency in neuroprotection against HFD-induced brain lipotoxicity when combining the two drugs (GSF + Xe). As a result repurposing Xe as an adjunct to GSF therapy against stroke appeared relevant and worthy of investigation. I/R insult disrupted the blood brain barrier (BBB) as assessed by EB dye extravasation, increased water and Na+ within the brain. Ultrastructurally I/R altered the brain blood capillaries at the vicinity of hippocampus dentate gyrus area as assessed by transmission and scanning electron microscopy. I/R altered lipid metabolism as revealed by LDL/HDL ratio, lipase activity, and FFA profiles. Moreover, I/R induced neuro-inflammation as assessed by down-regulation of anti-inflammatory CD 56 and up-regulation of pro-inflammatory CD 68 antigen. Importantly almost all I/R-induced disturbances were retrieved partially upon Xe or GSF on their own, and optimally when combining the two drugs. Xe per se is protective against I/R injury and the best neuroprotection was obtained when associating low dosage Xe with high dosage GSF, enabling neuroprevention and cell survival within hippocampus dentate gyrus area as revealed by increased staining of Ki 67 proliferation biomarker.

Characteristic features of correcting testosterone deficiency syndrome in young men with obesity

Aim. To assess the approaches to treatment of testosterone deficiency syndrome (TDS) in fertile (young) men with obesity.
 Materials and methods. Comparative analysis of peculiarities of TDS correction in 120 men aged 21–35, suffering from class III abdominovisceral obesity, was performed taking into account the personified approach. Testosterone deficiency syndrome was detected in all the examined men. The examined patients were divided into two completely comparable groups: in group I, androgen replacement therapy was administered to patients, in group II – individual balanced diet, combined with individual physical loads and course of inhibitor of gastrointestinal lipases.
 Results. In both groups, identical efficiency of TDS therapy in young men with obesity was established: when applying androgen replacement therapy and body mass decreasing therapy. However, the most favorable conditions for restoration of fertility are created when using complex multifactor therapy without testosterone preparations, since along with correction of erectile dysfunction, there is observed optimization of spermogram indices.
 Conclusions. Differentiated approach to correction of testosterone deficiency syndrome among patients with obesity permits to optimize financial expenditure for treatment and preserve reproductive function. The body mass decrease leads to liquidation of testosterone deficiency syndrome, normalization of erectile function and lipid spectrum.

Effect of orlistat on obese women with polycystic ovary syndrome

Abstract Polycystic ovary syndrome (PCOS) is a common gynecological endocrine syndrome characterized by metabolic abnormality and reproductive dysfunction, including ovulation abnormality, hyperandrogenism and polycystic ovarian manifestations. Most PCOS patients are overweight or obese, particularly the central type. This aggravates the clinical manifestations of PCOS and ultimately increases the risk of infertility. Orlistat is the only weight loss drug approved by the US Food and Drug Administration. As a long-lasting gastrointestinal lipase inhibitor, orlistat can effectively reduce the absorption of lipid and increase lipid excretion, thereby achieving weight loss. In obese PCOS patients, orlistat can reduce weight, improve lipid metabolism and insulin resistance, improve sex hormone disorder, and have a positive effect on pregnancy outcome. This review summarizes the impact of orlistat treatment on metabolism and fertility in obese women with PCOS.

Macrocytic Anemia and Thrombocytopenia Induced by Orlistat

Introduction:The overall incidence of obesity and its prevalence is increasing continuously. The obesity is a cardiovascular risk factor whose importance is increasing too. It is associated with many chronic conditions such as type II diabetes mellitus or cardiovascular diseases. The obesity is also implicated as a risk factor for several kinds of cancer such as esophagus, pancreas, colon, rectum, breast cancer in menopausal women. The treatment of the obesity may reduce the incidence of these diseases. The mainstray of the treatment of obesity is changing the lifestyles, but obesity´s treatment may need drug therapy or even though surgical treatment.Orlistat is a specific inhibitor of gastrointestinal lipases, which stops fat absortion. It is used along with a hypocaloric diet, for obesity´s treatment. The beneficial effects of orlistat include weight loss, the improvement of blood pressure´s control, it may delay the development of diabetes mellitus, and it may reduce HbA1c.Case Report:Besides the interaction with other drugs (mainly warfarin and amiodarone).Orlistat´s mainly side effects are gastrointestinal disorders such as the existence of oily spotting from the rectum, abdominal pain or discomfort, fecal urgency. There are also side effects at other levels, like flu symptoms, hypoglycemia, heathache or upper respiratory infections. There are other side effects with very low incidence but clinically relevant like pancreatitis, subacute liver failure, severe liver disease, myopathy, or tubular necrosis secondary to oxalate nephropathy induced by Orlistat.Discussion:In this case report appears a new adverse effect of Orlistat that has not been described above: thrombopenia and macrocytic anemia.

Acute Oxalate Nephropathy Associated with Orlistat: A Case Report with a Review of the Literature

Orlistat is a gastrointestinal lipase inhibitor used for weight reduction in obese individuals. Enteric hyperoxaluria caused by orlistat leads to oxalate absorption. Acute oxalate nephropathy is a rare complication of treatment with orlistat. Herein we report a patient presenting with acute renal failure which improved minimal with intravenous hydration. She was found to have oxalate crystals on renal biopsy. Patient admitted orlistat use over the counter for weight reduction on further questioning. The purpose of this case review is to increase awareness among patients since they are more focused on losing weight. This case also calls for the provider attention to educate patients regarding side effects of orlistat because of easy availability of orlistat over the counter.

Cetilistat for the treatment of obesity

Obesity is a modern plague in industrialized and developing countries, and currently overweight and obesity cause more deaths worldwide than underweight. Cetilistat is a novel, orally active, gastrointestinal and pancreatic lipase inhibitor. In in vitro studies cetilistat inhibited human pancreatic lipase with an IC50 in the low nanomolar range. In phase II clinical tials in obese patients and in obese patients with type 2 diabetes, cetilistat administered for 12 weeks significantly reduced body weight, serum low-density lipoprotein (LDL) cholesterol and total cholesterol in comparison to placebo. The proportion of obese patients reaching a reduction in baseline body weight of at least 5% was greater in all active arms in comparison to placebo. In obese diabetic patients the levels of glycosylated hemoglobin (HbA1c) were also significatively reduced. Cetilistat showed mild to moderate adverse events, predominantly of gastrointestinal nature (steatorrhea), with an incidence lower than orlistat. It was recently approved in Japan for the treatment of obesity with complications.

An Integrated Analysis of Liver Safety Data from Orlistat Clinical Trials

Objective: Orlistat is an oral gastrointestinal lipase inhibitor and is indicated for treatment of obesity in combination with a hypocaloric diet. Post-marketing reports of adverse reactions revealed hints for possible drug-induced liver injury which has prompted changes to the product information. Orlistat’s development program, involving over 30,000 patients, did not indicate a hepatic safety issue. Methods: We analyzed liver function test data from randomized clinical trials of orlistat, using i) meta-analysis of published study safety data, ii) time-to-event analysis for individual patients, and iii) a novel and more sensitive method derived from the US Food and Drug Administration’s (FDA) Evaluation of Drug-Induced Serious Hepatotoxicity (eDISH) technique. Over 10,000 subjects were included. Results: The combined odds ratio from a simple summary-level fixed-effects meta-analysis of treatment-emergent abnormalities in serum alanine aminotransferase (ALT) (defined as greater than the upper level of normal for 2 successive measurements) was 1.09 (95% CI 0.93–1.28), and in total bilirubin 1.24 (95% CI 1.03–1.49). Part of the small apparent effect was due to longer exposure to orlistat than to placebo, on average. A patient-level display, adjusting for regression towards the mean, and Kaplan-Meier analysis of changes in ALT and bilirubin, taking account of different exposure, showed no significant difference between orlistat and placebo. This shows that there is no signal for hepatic damage in clinical studies of orlistat. Conclusion: While idiosyncratic liver injury following exposure to orlistat cannot be excluded, it is likely to be extremely rare.

The 2′,4′,6′-Trihydroxyacetophenone Isolated fromMyrcia multifloraHas Antiobesity and Mixed Hypolipidemic Effects with the Reduction of Lipid Intestinal Absorption

This study evaluated the hypolipidemic and antiobesity effects of phloroacetophenone (2',4',6'-trihydroxyacetophenone, THA) isolated from Myrcia multiflora and their relationship with triglyceride (TG) intestinal absorption and pancreatic lipase activity inhibition. The hypolipidemic effect of THA was evaluated by acute (Triton WR-1339 treatment) and chronic assay (high-fat diet treatment), the antiobesity effect was evaluated by chronic assay (high-fat diet treatment), while the inhibition of enzymatic activity of pancreatic lipase was measured in the intestinal tissue of mice treated with high olive oil concentration. In the acute assay, THA caused greater total cholesterol (37 %) and triglyceride (46 %) serum level reduction than lovastatin (32 and 1 %), a HMG-CoA reductase inhibitor or orlistat (26 and 34 %), a gastrointestinal lipase inhibitor. In addition, in the chronic assay with a high-fat diet, THA reduced cholesterol and triglyceride levels (32 and 61 %, respectively) while lovastatin showed a decrease of 35 and 49 %, respectively. THA also caused a reduction in weight gain very similar to orlistat (40 and 38 %, respectively) when the animals were submitted to a high-fat diet. Moreover, THA showed a stronger and continuous pancreatic lipase inhibitory activity when compared with orlistat, causing inhibition of this enzyme during 6 hours associated to a significant reduction of triglyceride serum levels. The IN VIVO antiobesity and hypolipidemic effects of THA may be partly mediated by delaying the intestinal absorption of dietary fat by inhibiting pancreatic lipase activity.

Progressos recentes e novas perspectivas em farmacoterapia da obesidade

Obesity prevalence has risen dramatically over the past decades, which poses a great number of patients at risk of metabolic and cardiovascular complications. Long-term efficacy of lifestyle modification isolated has shown to be modest which, therefore, urges the need of more aggressive interventions such as adjuvant pharmacotherapy or the more radical surgical approach. Bariatric surgery has proven to date to be the most effective treatment, although it may be associated with nutritional and metabolic complications not yet completely recognized. By contrast, there is limited availability of antiobesity agents currently in the market, as well as historical facts involving the suspension of previously existing medications due to safety concerns. This article aims to present recent data on clinical trials of novel weight-loss drugs with short perspective to enter the market, if approved by the regulatory agencies. This review will discuss the efficacy and safety of these compounds, which include lorcaserin (selective serotonin 5-HT2c agonist), tesofensine (triple monoamine reuptake inhibitor), liraglutide (GLP-1 analogue) and cetilistat (gastrointestinal lipase inhibitor), as well as the combination therapies of bupropion/naltrexone, bupropion/zonisamide, phentermine/topiramate and pramlintide/metreleptin.

Nanosized particles of orlistat with enhanced in vitro dissolution rate and lipase inhibition

Orlistat is locally acting inhibitor of gastrointestinal lipases which has been developed for the treatment of obesity. The present study was designed with the intent to formulate orlistat in a different way compared to the current practice and investigate its inhibition of gastrointestinal lipases. Orlistat is considered as a technologically problematic and unmanageable substance because of waxy nature, low melting point and low chemical stability. The manuscript presents the critical issues regarding engineering of its nanosuspension with controlled particle size by melt emulsification and high pressure homogenization. In order to formulate dry product, lactose was dissolved in nanosuspension as filler and spray drying has been performed for obtaining the final powder product. Laser diffraction, scanning electron microscopy and atomic force microscopy have been used for orlistat nanosuspension characterization, dissolution studies and lipase inhibition studies were performed to characterize the in vitro efficacy of formulated orlistat. The advantage of selected technological procedures is nanosized orlistat with elevated in vitro dissolution rate in comparison to raw drug, physical mixture and marketed product. Furthermore, nanosuspension demonstrated significantly higher in vitro lipase inhibition in comparison to references. To conclude, the results show new technological solution and remarkable increase of pharmacological effect which could potentially lead to decreasing the dose and consequently dose dependent side effects.

Bifidobacterium as an oral delivery carrier of oxyntomodulin for obesity therapy: inhibitory effects on food intake and body weight in overweight mice

Oxyntomodulin (OXM) is a gut hormone released from intestinal L cell. Synthetic OXM and its analog reduce food intake and body weight in both rodents and human beings by being administered intravenously. However, people find intravenous administration difficult because of its side effects and inconvenience. The aim of this study is to develop a novel oral delivery system for OXM and its analog using genetically engineered Bifidobacterium as the carrier. An OXM gene expression vector pBBADs-OXM for the Bifidobacterium genus was constructed. Human OXM sequence was fused with extracellular exo-xylanase (XynF) signal peptide (Xs) from Bifidobacterium longum under the control of the pBAD promoter. B. longum NCC2705 was transformed with the recombinant plasmid pBBADs-OXM by electroporation, and the transformed B. longum was selected using MRS plates containing 60 microg ml(-1) ampicillin. The OXM expression in vitro was identified by western blot and enzyme-linked immunosorbent assay (ELISA) assay after L-arabinose induction. Overweight BALB/c mice were treated with B. longum transformed with OXM after 0.2% L-arabinose induction every day for 4 weeks to investigate the effects of OXM-transformed B. longum on food intake and body weight by oral administration. The B. longum transformed with the green fluorescent protein (GFP) gene was used as negative control; orlistat, a gastrointestinal lipase inhibitor, was used as positive control; Normal saline (NS, 0.9% saline) was used as blank control. The food intakes of each group were measured every day, and body weights were measured once a week. Normal BALB/c (2 months old) mice were treated with OXM-transformed B. longum after induction by intragastric administration every day for 6 days to reveal the mechanism of transformed B. longum, with OXM exerting its biological function by oral administration. Plasma OXM, plasma ghrelin and the OXM of intestinal contents were detected by the ELISA method. Plasma glucose and triglyceride levels were analyzed using the Automatic Biochemistry Analyzer. Transformed B. longum with OXM was selected and identified without biological and morphological alteration. An approximately 4-5 kDa OXM peptide was detected in both the supernatant and the cell pellet of transformed B. longum after L-arabinose induction in vitro. The food intake, body weight and blood triglyceride level of overweight mice treated with OXM-transformed B. longum were all significantly reduced compared with that of the GFP negative control group and NS control group (P<0.01). Interestingly, the plasma triglyceride level of the GFP group was significantly decreased compared with that of the NS control group (P<0.01). The OXM level in the intestinal contents of the OXM group was significantly increased compared with that of the GFP negative control group and the NS group (P<0.05). The plasma ghrelin level of the OXM group was significantly decreased compared with that of the GFP and NS groups (P<0.01). Unexpectedly, the ghrelin level of the GFP group was significantly increased compared with that of the NS control group (P<0.01). A novel oral delivery system of Bifidobacterium for human OXM has been successfully established. The expression of recombinant OXM can be detected in the supernatant and cell pellet of transformed B. longum. OXM-transformed B. longum reduces food intake, body weight and plasma lipid level in overweight mice by oral administration.

Pharmacotherapy for obesity.

Obesity is associated with increased risk of conditions such as hypertension, dyslipidaemia, diabetes mellitus, and obstructive sleep apnoea. Pharmacotherapy for obesity should be considered in combination with lifestyle changes in obese patients, or overweight patients with other conditions that put them at risk of developing heart disease. Sibutramine and orlistat are the only two anti-obesity medications approved for long-term use. Sibutramine is a serotonergic and adrenergic drug that reduces food intake. Orlistat is a gastrointestinal lipase inhibitor that interferes with fat absorption. However, it commonly causes flatulence and diarrhoea. Rimonabant is the first of a series of endocannabinoid receptor antagonists. It was approved by the Committee for Medicinal Products for Human Use of the European Medicines Agency (EMEA) as an adjunct to diet and exercise in treating obesity in 2006. However, despite the extensive clinical trial data, EMEA announced in 2008 that it has recommended suspension of rimonabant because of its psychiatric side effects. Studies evaluating the long-term safety and efficacy of anti-obesity agents are needed.

An unusual complication of treatment with orlistat

We report an unusual complication of orlistat, a gastrointestinal and pancreatic lipase inhibitor used in the treatment of obesity. A 66-year-old man with history of Type 2 diabetes and obesity presented to our hospital with recurrent episodes of hypoglycemia over 2 weeks. His medications included twice daily biphasic insulin and 3 months previously he was prescribed orlistat as treatment for his obesity. On admission he was in acute renal failure with a creatinine concentration of 405 micromol/l. His renal function 4 months previously was normal. Urinalysis revealed neither blood nor protein, but microscopy of his urine revealed moderate amounts of crystals. A renal biopsy revealed normal glomeruli, but there were features of acute tubular necrosis associated with oxalate crystal deposition. Over the next few days his renal function declined and needed hemodialysis. 3 weeks after his admission he continued to require hemodialysis and he unexpectedly had a cardiac arrest and died. Our patient had acute tubular necrosis secondary to orlistat-induced acute oxalate nephropathy. The identification of high risk patients treated with orlistat and regular monitoring of their renal function might reduce the risk of renal failure due to acute oxalate nephropathy.

Reduction of dietary fat absorption by the novel gastrointestinal lipase inhibitor cetilistat in healthy volunteers

To assess the efficacy, pharmacodynamics, safety and tolerability of a range of doses of cetilistat, a novel inhibitor of gastrointestinal lipases, in healthy volunteers. Three Phase I, randomized, placebo-controlled, parallel-group studies were conducted. Enrolled subjects in the three studies (n = 99) received a controlled calorie diet (total intake 2160 calories daily, 30% from fat). Twenty-four subjects were randomized to placebo and 66 were randomized to the following cetilistat doses: 50 mg three times daily [t.i.d. (n = 7)], 60 mg t.i.d. (n = 9), 100 mg t.i.d. (n = 7), 120 mg t.i.d. (n = 9), 150 mg t.i.d. (n = 16), 240 mg t.i.d. (n = 9) and 300 mg t.i.d. (n = 9). Nine subjects received the approved orlistat dose (120 mg t.i.d.). Treatment was for 5 days, with a 2-day run-in period and 1-day post-treatment follow-up. The primary outcome measure was daily faecal fat excretion. Secondary outcomes included plasma lipid levels, tolerability [gastrointestinal adverse events (AEs)] and safety. Cetilistat increased faecal fat excretion relative to baseline at all doses. Cetilistat was well tolerated, with gastrointestinal AEs the most common (51%). Steatorrhoea (oily stool) was more frequent in the orlistat group (4.11 events per subject) than in any cetilistat dose group (0.14-1.81 events per subject). Most AEs (98%) were mild or moderate in intensity. Cetilistat increased dietary fat excretion in healthy volunteers receiving a controlled calorie diet. Cetilistat was well tolerated at all doses examined and tolerability appeared to be improved relative to orlistat. Faecal fat excretion in the cetilistat groups was at least comparable to the orlistat 120 mg t.i.d. group.

The effects of diet and orlistat on body weight and lipid profiles in high risk Chinese patients with coronary artery disease, obesity and hypercholesterolemia

Orlistat is a gastrointestinal lipase inhibitor approved for use in obesity. So far, no evidence has been reported on the use of orlistat in obese patients with coronary artery disease (CAD). To investigate the effect of orlistat on body weight and lipid profiles in obese patients with CAD and hypercholesterolemia. Thirty non-diabetic patients with CAD, body mass index (BMI) > or = 25 kg/m(2) and low-density lipoprotein cholesterol (LDL-C) > or = 2.6 and < 4.1 mmol/L were put on diet for 12 weeks. Those still having a BMI > or = 25 kg/m(2) received orlistat 120 mg thrice daily for another 24 weeks. BMI was significantly reduced by 1.7% after 12 weeks of dietary treatment. The 24-week orlistat treatment resulted in further significant reduction in BMI (-2.8%) and LDL-C (-7.0%). Diet and orlistat treatment significantly reduced BMI and improved LDL-C in obese patients with CAD and hypercholesterolemia.

Inhibition of human pancreatic lipase by tetrahydrolipstatin: Further kinetic studies showing its reversibility

Tetrahydrolipstatin (THL, Orlistat) is a potent inhibitor of gastrointestinal lipases. Using the pH-stat technique we report that, in the absence of substrate, THL (at a molar excess of 100) inhibits rapidly (after few minutes of incubation) human pancreatic lipase (HPL). Bile salts over their critical micellar concentration (CMC) were found to accelerate the inhibition process. At variance with the generally accepted model of a covalent and quasi-irreversible acyl-lipase complex, we showed here that the inhibition of HPL could be rapidly and partially reversed in the presence of an emulsion of short- or long-chain triacylglycerols, as indicated by a kinetic reactivation process. The presence of bile salts in the incubation medium, containing THL and HPL, was found to stabilise the covalent complex as reflected by a decrease in the reactivation rate. Paradoxically, the presence of bile salts in the lipase assay enhanced this reactivation process probably by forming mixed micelles between bile salts and THL, which accelerates the deacylation phenomenon. On the basis of this kinetic study, a general model is proposed to describe the inhibition of lipases by THL in the aqueous phase as well as its partial reactivation process at the lipid–water interface.

Evaluation of Urinary Oxalate Levels in Patients Receiving Gastrointestinal Lipase Inhibitor

The purpose of this study was to examine the possible effects of a gastrointestinal lipase inhibitor "Orlistat (Xenical)" on the intestinal absorption of oxalate and thereby on the urinary levels of oxalate excretion in overweight patients. Long-term follow-up data of 95 cases (57 men, 38 women; M/W=1.5) were documented. Patients were randomly assigned into two groups. While the patients in group I (n=55) were treated with orlistat (Xenical) for 6 months, patients in group II (n=40) received no specific medication. Calcium, oxalate, and citrate levels were determined in a 24-h urine collection from each patient. To evaluate the significance in the groups as well as the differences between the two groups, ANOVA test was performed and the results were given as mean +/- s.d. Comparative evaluation of urinary oxalate levels during 3-month follow-up clearly showed that urinary oxalate excretion significantly increased in 34/55 patients (61.8%) in the first group (P<0.05). Of these 34 patients, 30 (88.2%) continued to have increased urinary oxalate excretion during 6-month follow-up (P=0.001). However, our data did not show any significant effect of this medication on urinary citrate and calcium levels during 3- and 6-month follow-up evaluation (P=0.05). Our results suggest that increased intestinal absorption of dietary oxalate due to this type of medication in obese patients could make a substantial contribution to urinary oxalate excretion and may increase the risk of stone formation.

Experience of using Xenical for pilots

Lack of exercise, hypoxia, stress, constant psychological stress, longer shifts, a violation of the feeding process contribute to the development of metabolic disorders. Thus, persons Summer Special can be seen as a model for the study of risk factors for type 2 diabetes and the development of optimal preventive measures that determined the relevance and purpose of the study. The purpose of research - to evaluate the effectiveness of the correction of overweight and disorders of carbohydrate and lipid metabolism in patients with risk factors for type 2 diabetes. For the correction of body weight was used Orlistat (Xenical) - specific inhibitor of gastrointestinal lipases, acting locally in the lumen of the gastrointestinal trakta.Materialy and methods The study was performed at the Central Clinical Hospital of Civil Aviation. The study found that those aircrew who are overweight are at high risk of developing type 2 diabetes, which is due on the one hand, metabolic disorders due to abdominal obesity, and on the other - especially the professional activity (physical inactivity, a violation of the process food, emotional stress). As an effective therapy to persons aircrew appropriate to recommend treatment with Xenical against the background of a moderately hypocaloric diet combined with the expansion of physical activity.

Regulation of Fat-Stimulated Neurotensin Secretion in Healthy Subjects

Cholecystokinin (CCK) and neurotensin are stimulated during meal intake by the presence of fat in the small intestine. The sequence of events suggests that fat hydrolysis is crucial for triggering the release. The aim of this study was to investigate whether CCK mediated the effect of intraduodenal (ID) fat on neurotensin secretion via CCK-1 receptors. This was a single center study; 34 male volunteers were studied in consecutive, randomized, double-blind, cross-over studies. CCK and neurotensin release were quantified in: 1) 12 subjects receiving an ID fat infusion with or without 60 mg orlistat, an irreversible inhibitor of gastrointestinal lipases, in comparison to vehicle; 2) 12 subjects receiving ID long chain fatty acids (C18s), ID medium chain fatty acids, or ID vehicle; and 3) 10 subjects receiving ID C18 with and without the CCK-1 receptor antagonist dexloxiglumide or ID vehicle plus iv saline (placebo). Hormone concentrations were measured by specific RIA systems. ID fat induced a significant increase in CCK and neurotensin concentrations (P < 0.001-0.002). Inhibition of fat hydrolysis by orlistat abolished both effects. C18 stimulated CCK and neurotensin release (P < 0.001, respectively), whereas medium chain fatty acid was ineffective. Dexloxiglumide administration partially blocked the effect of C18 on neurotensin; the effect was only present in the first phase of neurotensin secretion. Generation of C18 through hydrolysis of fat is a critical step for fat-induced stimulation of neurotensin in humans; the signal is in part mediated via CCK release and CCK-1 receptors.