Single-blind, placebo controlled randomised clinical study of chitosan for body weight reduction.

BACKGROUND: Chitosan is a dietary fibre which acts by reducing fat absorption and thus used as a means for controlling weight. Weight loss clinical trial outcomes, however, have contradictory results regarding its efficacy. The primary objective of the present study was to evaluate the efficacy and safety of a chitosan from fungal origin in treatment of excess weight in the absence of dietary restrictions. METHODS: A phase IV, randomised, multicentre, single-blind, placebo-controlled, clinical study was conducted by administering chitosan capsules (500 mg, five/day) and indistinguishable placebo capsules as daily supplements to 96 overweight and obese subjects for 90 days. The study participants were divided in 2:1 ratio to receive either chitosan (n = 64) or placebo (n = 32). Efficacy was assessed by measuring body weight, body composition parameters, anthropometric measurements, HbA1C level and lipid profile at day 45 and day 90. Also, short form-36 quality of life (QoL) questionnaire was assessed to evaluate improvement in life-style and dietary habits were recorded for calorie intake. Safety was assessed by evaluating safety parameters and monitoring adverse events. RESULTS: The mean changes in body weight were -1.78 ± 1.37 kg and -3.10 ± 1.95 kg at day 45 and day 90 respectively in chitosan group which were significantly different (p < 0.0001) as compared to placebo. BMI was decreased by10.91 fold compared to placebo after 90 day administration. In concert with this, there was also reduction in body composition and anthropometric parameters together with improvement in QoL score. Chitosan was also able to reduce HbA1C levels (below 6 %) in subjects who had initial higher values. The mean caloric intake shows that there was no change in dietary habits of subjects in both groups. Lipid levels were unaffected and all adverse events were mild in nature and unrelated to study treatment. CONCLUSION: Chitosan from fungal origin was able to reduce the mean body weight up to 3 kg during the 90 day study period. Together with this, there was also improvement in body composition, anthropometric parameters and HbA1C, reflecting overall benefits for the overweight individuals. Additionally, there was also improvement in QoL score. It was safe and well tolerated by all subjects. TRIAL REGISTRATION: CTRI/2014/08/004901.

A randomized two way cross over study for comparison of absorption of vitamin D3 buccal spray and soft gelatin capsule formulation in healthy subjects and in patients with intestinal malabsorption.

BACKGROUND: Vitamin D deficiency has been proposed to contribute to the development of malabsorption diseases. Despite this, the vitamin D status of these patients is often neglected. The objective of the present work was to compare the absorption of vitamin D3 through the oral route by comparing a 1000 IU soft gelatin capsule and a 500 IU buccal spray (delivering 1000 IU in two spray shots) in healthy subjects and in patients with malabsorption disease. METHODS: An open label, randomized, two-periods, two-way cross over study was conducted, first in healthy subjects (n = 20) and then in patients with malabsorption syndrome (n = 20). The study participants were equally divided and received either of the treatments (buccal spray, n = 7; soft gelatin capsule, n = 7; control, n = 6) in Period I for 30 days. After washout of another 30 days, the treatments were changed in crossover fashion in Period II. Fasting blood samples were collected to measure baseline 25-hydroxyvitamin D [25(OH)D] levels in all participants at day 0 (Screening visit), day 30 (completion of period I), day 60 (end of wash out and initiation of period II) and day 90 (completion of period II). Safety was evaluated by hematology and biochemistry analyses. Statistical analyses was performed using differences of mean and percentage change from baseline of 25(OH)D levels between two formulation by two tailed Paired t-test with 95% confidence interval. RESULTS: In healthy subjects, the mean increase in serum 25(OH)D concentration was 4.06 (95% CI 3.41, 4.71) ng/ml in soft gelatin capsule group and 8.0 (95% CI 6.86, 9.13) ng/ml in buccal spray group after 30 days treatment (p < 0.0001). In patients with malabsorption disease, the mean increase in serum 25(OH)D concentration was 3.96 (95% CI 2.37, 5.56) ng/ml in soft gelatin capsule group and 10.46 (95% CI 6.89, 14.03) ng/ml in buccal spray group (p < 0.0001). CONCLUSION: It can be concluded from the results that the buccal spray produced a significantly higher mean serum 25(OH)D concentration as compared to the soft gelatin capsule, in both healthy subjects as well as in patients with malabsorption syndrome over a period of 30 days administration in a two way cross over study. Treatments were well tolerated by both subject groups TRIAL REGISTRATION: CTRI/2013/06/003770.

Plasma analysis of celiprolol by HPTLC: a useful technique for pharmacokinetic studies.

A rapid and sensitive high performance, thin-layer chromatographic (HPTLC) method has been developed for the measurement of celiprolol in human plasma and its use in pharmacokinetic studies has been evaluated. Detection and quantitation were performed without using an internal standard. A simple extraction procedure was followed for extracting celiprolol from plasma and a known amount of the extract was spotted on precoated silica gel 60 F254 plates using a Camag Linomat IV autosampler. Celiprolol was quantitated using a Camag TLC Scanner 3. The average recovery of authentic analytes (20 to 200 ng/mL) added to plasma was 72.06 +/- 2.8% and the lowest amount of celiprolol that could be detected was 10 ng/mL. The method provides a direct estimate of the amount of celiprolol present in plasma. Pharmacokinetic parameters of 2 marketed preparations have also been determined after oral administration to 12 healthy human volunteers.

High performance thin-layer chromatographic method for the determination of sparfloxacin in human plasma and its use in pharmacokinetic studies.

A rapid and sensitive high-performance thin-layer chromatographic (HPTLC) method has been developed for the measurement of sparfloxacin in human plasma and its use for pharmacokinetic study has been evaluated. Detection and quantitation were performed without using an internal standard. A single stage extraction procedure was followed for extracting sparfloxacin from plasma and a known amount of the extract was spotted on precoated silica gel 60 F254 plates using a Camag Linomat IV autosampler. Sparfloxacin was quantified using a Camag TLC Scanner 3. The recovery study of authentic analytes added to plasma at 0.1 to 0.8 microgram ml-1 was 94.9 +/- 0.98% and the lowest amount of sparfloxacin that could be detected was 50 ng ml-1 plasma. The method provides a direct estimate of the amount of sparfloxacin present in plasma. The method was used for the determination of plasma levels as well as pharmacokinetic parameters of sparfloxacin after oral administration of two marketed preparations to healthy volunteers.

Effect of long-term treatment with enalapril in streptozotocin diabetic and DOCA hypertensive rats.

We studied the effects of long-term treatment with enalapril (5 mg/kg/day orally) on various biochemical and cardiovascular complications in streptozotocin (STZ) diabetic and deoxycorticosterone acetate (DOCA) hypertensive rats. Female Wistar rats made diabetic or hypertensive or both by streptozotocin (STZ; 45 mg/kg) or deoxycorticosterone acetate (DOCA; 10 mg/kg, p.o., daily) or both. Enalapril (5 mg/kg) was administered daily by the oral route for 6 weeks. At the end of 6 weeks, blood samples were taken to analyze glucose, insulin, and lipids. Blood pressure and heart rate were recorded by a noninvasive technique, and cardiac functions were recorded by Neely's working heart preparation. Injection of STZ produced severe glycosuria (>2%), hyperglycemia, hypoinsulinemia, and loss of body weight. It also produced hypercholesterolemia, hypertriglyceridemia, hypertension, bradycardia, and decreased left ventricular developed pressure (LVDP) and increase in angiotensin-converting enzyme (ACE) in left ventricular tissue. DOCA by itself did not produce any change in blood glucose but reduced serum insulin levels in nondiabetic animals. However, in the diabetic group, DOCA reduced blood sugar levels. Treatment with enalapril prevented an increase in the blood pressure and the heart weight. Decrease in the heart rate, reduction in LVDP, and increase in intracardiac activity were observed in diabetic rats; these were also prevented by enalapril treatment. Enalapril had no effect on plasma glucose and did not modify plasma insulin levels in diabetic animals. The effects of STZ and DOCA together were not additive on the investigated parameters, and enalapril was similarly efficient in diabetic and diabetic hypertensive animals.

Beneficial effects of clonidine in streptozotocin-induced diabetes and DOCA-hypertensive rats.

This investigation was undertaken to study the effects of chronic treatment with clonidine on cardiovascular complications in streptozotocin-induced diabetes and DOCA-hypertensive rats. Injection of streptozotocin induced glucosuria, hyperglycaemia, hypoinsulinaemia, hypothyroidism, hypercholesterolaemia, hypertriglyceridaemia, bradycardia and a decrease in left ventricular developed pressure (LVDP). DOCA by itself did not induce any change in blood-glucose levels in non-diabetic animals. However, in diabetic animals DOCA significantly reduced blood-glucose levels. Treatment of diabetic and diabetic hypertensive animals with clonidine (25 micrograms kg-1 every day for six weeks) significantly prevented diabetes-induced loss of body weight, bradycardia, cardiac hypertrophy and hypothyroidism. It also partially, but significantly, prevented diabetes-induced hyperglycaemia and hypoinsulinaemia in both diabetic and diabetic-hypertensive animals. There was a significant reduction in diabetes-induced elevation of cholesterol and triglyceride levels and an improvement in LVDP at higher filling pressure in diabetic and diabetic hypertensive animals. This investigation shows that chronic treatment with clonidine produces a number of beneficial effects such as prevention of hyperlipidaemia and hypothyroidism and improvement in cardiomyopathy and glycaemic control in diabetic and diabetic hypertensive rats.

High-performance thin-layer chromatography for the determination of nimesulide in human plasma, and its use in pharmacokinetic studies.

A rapid and sensitive high-performance thin-layer chromatographic assay has been developed for the measurement of nimesulide in human plasma. Its use for pharmacokinetic studies has been evaluated. The method includes a single-stage extraction procedure without the use of an internal standard. Analysis was performed on plasma containing known amounts of the drug, on drug-free plasma, and on plasma containing an unknown quantity of the drug. Known amounts of extract and nimesulide (100 and 200 ng, as external standard) were spotted on precoated silica-gel 60F254 plates by means of a Camag Linomat IV autosampler. Quantification was achieved using a Camag TLC scanner 3. The recovery of the method was 97.10 +/- 2.22%. The method was applied for the determination of plasma levels and pharmacokinetic parameters of nimesulide after oral administration of two formulations (100 mg) in healthy volunteers. The method is a sensitive, economical, rapid and specific assay for nimesulide in human plasma, and is suitable for pharmacokinetic studies after therapeutic doses.

High-performance thin-layer chromatographic method for the detection and determination of lansoprazole in human plasma and its use in pharmacokinetic studies.

A rapid and sensitive high-performance thin-layer chromatography (HPTLC) method has been developed for the measurement of lansoprazole in human plasma and its use for pharmacokinetic study has been evaluated. Detection and quantitation were performed without using an internal standard. A single stage extraction procedure was followed for extracting lansoprazole from plasma and a known amount of the extract was spotted on precoated silica gel 60 F254 plates using a Camag Linomat IV autosampler. Lansoprazole was quantified using a Camag TLC Scanner 3. The recovery study of authentic analytes added to plasma at 0.05 to 0.25 microg/ml was 95.37+/-2.15% and the lowest amount of lansoprazole that could be detected was 20 ng/ml plasma. The method provides a direct estimate of the amount of lansoprazole present in plasma. The method was used for the determination of plasma levels as well as pharmacokinetic parameters of lansoprazole after oral administration of two marketed preparations to healthy volunteers.

Effect of chronic treatment with hydralazine on various in vitro preparations of rat.

Effect of chronic treatment with hydralazine (40 mg/kg/day) on isolated heart, anococcygeus muscle and myometrial preparations from rats has been studied. The treatment for 6 weeks caused a significant increase in isoprenaline induced positive inotropic response in rat heart. However, isoprenaline induced positive chronotropic effects were not altered significantly by chronic hydralazine treatment. Chronic hydralazine treatment also failed to alter noradrenaline induced contractile effects on rat anococcygeus muscle. However, on myometrial preparations from hydralazine treated rats showed an increase in adrenaline induced relaxations. The results of the present study can be explained on the basis of the effect of hydralazine on adenylate cyclase-cyclic adenosine monophosphate (cAMP).

Sensitive high-performance thin-layer chromatography method for detection and determination of ranitidine in plasma samples.

A high-performance thin-layer chromatographic procedure has been developed for the determination of ranitidine, a H2-receptor antagonist, in plasma. The detection and quantification were performed without using internal standards. A single-stage extraction procedure was followed for extracting ranitidine from plasma, and a known amount of the extract was spotted on precoated silica gel F254 plates. Ranitidine was quantified using a Shimadzu CS930 dual-wavelength TLC scanner. The method provides a direct estimate of total ranitidine present in the plasma.

Effects of enalapril on lipid profile in diabetic and non-diabetic essential hypertensive patients.

Effectiveness of enalapril was studied in hypertensive patients with or without diabetes-mellitus. All the patients received enalapril, 5-20 mg per day for 9 months. Enalapril effectively controlled the blood pressure and favourably altered the lipid levels and did not affect the glucose level in diabetics as well as non-diabetics. Enalapril may be considered as a better therapeutic option for the treatment of hypertension associated with diabetes mellitus.

Effects of chronic nifedipine treatment on streptozotocin-induced diabetic rats.

We studied the effects of 6-week treatment with nifedipine (35 mg/kg/day orally, p.o.) on streptozotocin (STZ)-induced diabetic rats. Injection of STZ [45 mg/kg intravenously, (i.v.) single dose] produced a significant increase in blood pressure (BP), bradycardia, hyperglycemia, hypoinsulinemia, hyperlipidemia, hypothyroidism, depression in left ventricular developed pressure (LVDP), cardiomyopathy, and nephropathy. Treatment of diabetic rats with nifedipine normalized the BP and prevented bradycardia. Insulin levels were decreased after nifedipine treatment in diabetic as well as nondiabetic rats. However, serum glucose levels were also partially decreased in diabetic animals by nifedipine treatment. In control animals as well, glucose levels were in the normal range despite lower insulin levels observed after nifedipine treatment. Nifedipine treatment significantly prevented STZ-induced increase in cholesterol and triglyceride levels. Nifedipine treatment significantly prevented STZ-induced hypothyroidism and also prevented STZ-induced cardiac depression and cardiomyopathy. Our data indicate that nifedipine increases insulin sensitivity and has some beneficial effects on cardiovascular parameters. It may therefore be considered a preferred drug in the treatment of hypertension associated with diabetes mellitus.

Comparative effects of atenolol versus nifedipine on serum lipids and other biochemical parameters in diabetic and non-diabetic hypertensive subjects.

A controlled clinical trial on 65 patients was performed to compare the effects of nifedipine and atenolol in diabetic and non-diabetic hypertensive patients. Patients were from 45 to 70 years in age. The diabetic hypertensive patients and non-diabetic essential hypertensive patients randomly received atenolol (50-100 mg per day) or nifedipine (10-20 mg per day) for 9 months. Both the drugs effectively controlled the blood pressure throughout the therapy. Atenolol treatment significantly increased triglyceride levels and decreased the HDL-cholesterol levels after 9 months in both groups. However, nifedipine therapy did not alter lipid levels to any significant extent. Both drugs did not alter blood glucose, serum creatinine and blood urea levels. It may be concluded from the present study that nifedipine is preferable to atenolol as it does not alter lipid profile to any significant extent in diabetic and non-diabetic hypertensive patients.

Detection and determination of total amlodipine by high-performance thin-layer chromatography: a useful technique for pharmacokinetic studies.

A novel analytical method for determination of the total plasma levels (free and protein bound) of the calcium channel blocking agent amlodipine has been developed using a high-performance thin-layer chromatographic (HPTLC) procedure. Detection and quantitation were performed without internal standards. In previously described methods for the estimation of amlodipine by gas chromatography and high-performance liquid chromatography, only the free levels in plasma and serum were quantified at 7% of the total amlodipine level, with the remaining 93% bound to plasma protein and tissue. The present method employs proteolysis of the plasma proteins by incubating plasma for 2 h in pepsin solution. After proteolysis amlodipine is extracted and a known amount of the extract is spotted on precoated silica-gel 60 F254 plates using a Camag Linomat IV autosampler. Amlodipine was quantified using a dual-wavelength TLC scanner. The method provides a direct estimate of the total amlodipine present in plasma.

Evidence for catecholamine-depleting action of fluoxetine.

The present investigation was undertaken to study the interaction of fluoxetine with 5-hydroxytryptamine (5-HT) and noradrenaline (NA) in rat anococcygeus muscle and vas-deferens. In rat anococcygeus muscle responses to NA were significantly potentiated after 30 min and 60 min incubation with fluoxetine (2.9 x 10(-9) M). The responses to 5-HT were however, inhibited after 30 min incubation with fluoxetine in this preparation. On rat vas-deferens also, the responses to NA were potentiated after 30 min incubation with fluoxetine. The response to 5-HT were not altered significantly. In rats pretreated with fluoxetine (5 mg/kg, ip) for seven days, the responses to NA were significantly potentiated in rat anococcygeus muscle. Whereas the responses to 5-HT and tyramine were significantly inhibited. The inhibited responses to 5-HT restored back to normal when the anococcygeus muscle was pre-incubated with NA for 30 min.