Objective : The aim of the present work was to evaluate the anxiolytic effect of an ethanolic extract of Nymphaea alba Linn. in mice. Materials and Methods : The elevated plus maze test (EPMT), light and dark test (L and DT) and open field test (OFT) were used to assess the anxiolytic activity of the ethanolic extract of N. alba Linn. in mice. In addition, aggressive behavior and motor coordination was also assessed by foot shock induced aggression test (FSIAT) and rota rod test (RRT). Diazepam 1 mg/kg served as a standard anxiolytic drug, administered orally. Results : The ethanolic extract of N. alba (100 and 200 mg/kg, p.o.) significantly increased the percentage of time spent and number of entries in open arm in EPMT. In L and DT, the extract produced significant increase in time spent, number of crossing and decrease in the duration of immobility in light box. In OFT, the extract showed significant increase in number of rearings, assisted rearings and number of square crossed, all of which are demonstrations of exploratory behavior. In FSIAT, N. alba extract attenuated aggressive behavior related to anxiolytic activity, such as number of vocalization, leaps, rearing, biting/attacks and facing each other in paired mice. Furthermore, the extract produced skeletal muscle relaxant effect assessed by RRT. Conclusion : The results of the present study suggest that an ethanolic extract of N. alba may possess anxiolytic activity and provide a scientific evidence for its traditional claim.

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Objectives : This study was conducted to determine the effect of ethanolic extract of the dried stems of Tinospora crispa in a male rat model of hepatic fibrosis caused by the hepatotoxin, thioacetamide. Materials and Methods : The extract was gavaged daily to the rats, at doses of 100 and 200 mg/kg along with thioacetamide at a dose of 200 mg/kg twice weekly. To assess the effectivity of extract, against thioacetamide, the activity of aminotransferases (alanine aminotransferase, aspartate aminotransferase), alkaline phosphatase (AP); and bilirubin were measured, together with morphological and histopathological indices in the liver of healthy and thioacetamide-treated rats. Results : A significant increase in the activity of liver enzymes, bilirubin and G-glutamyl transferase and gross and histopathological changes were determined. Although previous in vitro study established that this extract had strong antioxidant activity, this in vivo study establishes that this extract contains hepatotoxins whose identity may be quite different from those compounds with antioxidant properties. Conclusion : The study confirms that complete reliance on data obtained using in vitro methodologies may lead to erroneous conclusions pertaining to the safety of phytopharmaceuticals.

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Benign prostatic hyperplasia (BPH) is the most common condition in aging men, associated with lower urinary tract symptoms (LUTS). A better understanding of the prostate physiology, function, and pathogenesis has led to the development of promising agents, useful in the management of LUTS in men. The specific approach used to treat BPH depends upon number of factors like age, prostrate size, weight, prostate-specific antigen level, and severity of the symptoms. 5α-reductase inhibitors decrease the production of dihydrotestosterone within the prostate, which results in decreased prostate volume, increased peak urinary flow rate, improvement of symptoms, decreased risk of acute urinary retention, and need for surgical intervention. α₁ -adrenergic receptor (α₁ -AR) antagonists decrease LUTS and increase urinary flow rates in men with symptomatic BPH, but do not reduce the long-term risk of urinary retention or need for surgical intervention. Clinical efficacy of either 5α-reductase inhibitor or α₁ -AR antagonist has been further improved by using combination therapy; however, long-term outcomes are still awaited. Many more potential new therapies are under development that may improve the treatment of BPH. This article gives a brief account of rationale and efficacy of different treatment options presently available in the management of BPH.

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Objectives : Adverse drug reactions (ADRs) to psychotropic agents are common and can lead to noncompliance or even discontinuation of therapy. There is paucity of such data in the Indian context. We deemed it worthwhile to assess the suspected ADR profile of psychotropic drugs in an ambulatory setting in a public teaching hospital in Kolkata. Materials and Methods : A longitudinal observational study was conducted in the outpatient department (OPD) of the concerned psychiatry unit. Twenty consecutive patients per day, irrespective of their psychiatric diagnosis, were screened for suspected ADRs, 2 days in a week, over 15 months. Adverse event history, medication history and other relevant details were captured in a format as adopted in the Indian National Pharmacovigilance Programme. Causality was assessed by criteria of World Health Organization-Uppsala Monitoring Center (WHO-UPC). Results : We screened 2000 patients (68.69% males, median age 34.4 years), of whom 429 were suspected of having at least one ADR; 84 cases had insufficient evidence about causality (WHO-UMC causality status "unlikely") and were excluded from further analysis. Thus, 17.25% (95% confidence interval: 15.59-18.91%) of our study population reported ADRs with at least "possible" causality. Of 352 events recorded, 327 (92.90%) were "probable" and the rest "possible". None was labeled "certain" as rechallenge was not performed. Patients received a median of 3.2 psychotropic drugs each. Thirty-three different kinds of ADRs were noted, including tremor (19.60%), weight gain (15.34%) and constipation (14.49%). Among the incriminated drugs, antipsychotics represented the majority (57.10%), with olanzapine topping the list. Conclusions : This study offers a representative profile of ADRs to be expected in psychiatry out-patients in an Indian public hospital. Establishment of a psychotropic drug ADR database can be a worthy long-term goal in the Indian context.

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Aim : Ulcerative colitis and Crohn's disease are chronic recurrent inflammatory bowel disease (IBD) of unknown origin. Oxidative stress is believed to be a key factor in the pathogenesis and perpetuation of the mucosal damage in IBD. Materials and Methods : Ethanolic extract of Fragaria vesca (EFFV) fruits was prepared by percolation method and subjected to oral toxicity testing using OECD guidelines. Albino rats were pretreated orally for 5 days with 3% gum acacia in control, EFFV 500 mg/kg in test and 5-aminosalisylic acid (5-ASA) 100 mg/kg in standard groups. Colitis was induced by transrectal administration of 4% acetic acid on 5 ^th day. All the animals were sacrificed with ether overdose 48 hours after colitis induction, and 10 cm colon segment was resected from proximal end. Colon was weighed (for disease activity index) and scored macroscopically and microscopically after histological staining. Biochemical assessments included myeloperoxidase (MPO) and tissue catalase (CAT), glutathione (GSH) and superoxide dismutase (SOD) measurements. Statistical analysis was done using one-way analysis of variance (ANOVA) followed by Dunnett's "t" test. Results : EFFV showed significant (P < 0.05) prevention of increase in colon weight and disease activity index along with decrease in macroscopic and microscopic lesion score as compared to control group. Significant improvement was observed in the levels of MPO, CAT and SOD, except GSH (P < 0.05). However, the effect of EFFV was significantly less than 5-ASA (P < 0.05). Conclusions : EFFV at 500 mg/kg showed significant amelioration of experimentally induced IBD, which may be attributed to its antioxidant and anti-inflammatory properties.

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Objectives : To investigate the effect of the aqueous extract of Phyllanthus niruri (Aq.E.PN) against doxorubicin (Dox)-induced myocardial toxicity in rats. Materials and Methods : Cardiotoxicity was produced by Dox administration (15 mg/kg for 2 weeks). Aq.E PN (200 mg/kg, orally) was administered as pretreatment for 2 weeks alternated with Dox for the next 2 weeks. The general observations, mortality, histopathology, biomarker enzymes like lactate dehydrogenase (LDH), creatinine phosphokinase (CPK) and alkaline phosphatase, diagnostic enzyme markers like aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and antioxidants such as glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) were monitored after 3 weeks of the last dose. Results : Pretreatment with the Aq.E.PN significantly (P < 0.01) protected the myocardium from the toxic effects of Dox by reducing the elevated level of biomarker and diagnostic enzymes like LDH, CPK, AST and ALT to the normal levels. Aq.E PN increased the GSH, SOD and CAT levels and decreased the MDA levels in cardiac tissue. Administration of Dox caused cardiomyopathy associated with an antioxidant deficiency. Conclusion : These results suggest a cardioprotective effect of P. niruri due to its antioxidant properties.

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Objectives : To evaluate the effect of various herbal adaptogens such as shade-dried powders of Withania somnifera, Ocimum sanctum, Asperagus recemosus, Andrographis paniculata, Asphaltum panjabinum (Shilajith), Gymnema sylvestre, Spirulina platensis, and Panex ginseng on cadmium (Cd)-induced oxidative stress and its accumulation in broiler chicken. Materials and Methods : A total of 80 male broiler chicks of day old age were randomly assigned to 10 equal groups. Group 1 birds were fed with basal diet throughout the experiment (1-42 days). Group 2-10 chicks were fed with basal diet containing cadmium at 100 ppm from day 1 to day 28 (4 weeks). From 29 ^th to 42 ^nd day (2 weeks), basal diet alone was fed to group 2 chicks which acted as toxic control and group 3-10 birds were fed with feed containing 0.1% powder of W. somnifera, O. sanctum, Aspe. recemosus, An. paniculata, Asph. panjabinum (Shilajith), G. sylvestre, S. platensis, and P. ginseng, respectively. Body weight gain, levels of non-enzymatic antioxidants such as reduced glutathione (GSH), lipid peroxidation markers such as thiobarbituric acid reacting substances (TBARS), liver functional markers such as serum alanine transaminase (ALT), kidney functional markers such as blood urea nitrogen (BUN) and serum creatinine and concentration of cadmium in liver and kidney were investigated. Results : Body weight gains were significantly decreased in birds of groups 2-10 compared to group 1 at the end of 4 ^th week. Supplementation of various medicinal herbs in feed after 4 ^th week significantly improved the body weight gain compared to that in group 2 chicks. The increase in TBARS and decrease in GSH concentrations of liver and kidney tissues in cadmium intoxicated birds were significantly reversed by the above-said herbs. The liver and kidney functional markers were also restored to normal levels. Highest concentration of cadmium was found accumulated in kidney, followed by liver in birds of group 2. Herbal supplementation in groups 3-10 prevented Cd bioaccumulation which was most evident in liver, followed by kidney. Conclusions : Administration of herbal adaptogens at the rate of 0.1% in feed significantly prevented the bioaccumulation of Cd and reversed the Cd-induced oxidative tissue damage.

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Objective : To evaluate the antidiabetic effects of the aqueous extract of Elaeocarpus ganitrus (EAG) in experimental animals. Materials and Methods : The hypoglycemic activity of the EGA was evaluated in normoglycemic rats by single dose at three graded dose levels, viz. 250, 500 and 1000 mg/kg of body weight. Antihyperglycemic activity of the extract was also evaluated at the same dose levels in streptozotocin (STZ) (60 mg/kg, i.p.)-induced diabetic rats during a 30-day treatment period. Metformin (500 mg/kg) was used as the reference drug. Fasting blood glucose and lipid parameters, viz. triglycerides, total cholesterol, high-density lipoprotein and low-density lipoprotein levels were measured. Acute oral toxicity of the EGA extract was carried out in Swiss albino mice. Results : In normoglycemic rats, EGA showed a significant (P < 0.01) hypoglycemic effect at 2 h. In STZ-induced diabetic rats, the EGA treatment significantly (P < 0.05) decreased the blood glucose level in a dose-dependent manner during the 30 days of treatment period. EGA modulated lipid profile changes in STZ-diabetic rats in a dose-dependant manner. In the acute oral toxicity study, EGA showed no mortality till the 5 g/kg dose in mice. Conclusion : The present investigation shows that EAG seeds has potential antidiabetic effects.

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Objective : To study the anticonvulsant activity and neurotoxicity of ethanolic extract and ethyl acetate fraction of the rhizome of Smilax china (EESC and EAF, respectively) in mice. Materials and Methods : The anticonvulsant activities of EESC and EAF were studied against maximal electroshock (MES) and pentylenetetrazole (PTZ)-induced seizures in mice and neurotoxicity was determined using rotarod test. Results : The duration of hindleg extension in MES test was reduced significantly (P < 0.001) by EESC at a dose level of 400 mg/kg and EAF at both higher dose levels (200 and 400 mg/kg). In PTZ model, the seizure latency was prolonged by all the test groups. Conclusion : The EESC and EAF may help to control petit mal and grand mal seizures.

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Background : No pricing formula has been implemented from November 2002 to date in Sri Lanka. Therefore, we initiated a study in 2003 to determine the prices, availability and affordability of medicines in the private sector of Sri Lanka in the absence of a price control. Materials and Methods : The World Health Organization/Health Action International methodology was used. The study was conducted in retail pharmacies (Rajya Osu Sala) of State Pharmaceuticals Corporation (semigovernment) and privately owned retail pharmacies (n = 15) in 2003, 2006 and 2009 in a geographical area. Essential medicines (n = 28) were studied and, for each medicine, innovator, most sold generic and cheapest generic were monitored. The medicine's median price was compared with the international reference prices (IRP) to obtain the median price ratio. The daily wage of the lowest-paid government worker was used to calculate affordability. Results : Innovators were five to six-times the IRP at privately owned pharmacies and four to seven-times at the Rajya Osu Sala. The prices of generics were ≤1 the IRP during 6 years in privately owned and Rajya Osu Sala pharmacies. Cheapest generics were high in availability (>80%) throughout the study period. Innovators cost more than a day's wage of the lowest-paid government worker; in contrast, generics were always less than one day's wage. There seems to be no difference in affordability between privately owned or semigovernment pharmacies. Conclusion : In Sri Lanka, generic medicines have effective pricing and are available and affordable. No drastic changes in prices of medicine in the private sector were observed over the 6 years despite removal of price control.

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Objective : Present study was carried out to evaluate effect of esomeprazole on the pharmacokinetics of carbamazepine in rabbits. Materials and Methods : Study was conducted at Department of Pharmacology, Postgraduate Institute of Medical Education and Research from March to October 2007. In a parallel design study, carbamazepine 40 mg/kg/day was given orally for 14 days. On day 15, blood samples were taken at various time intervals between 0 and 24 hours. In esomeprazole group, carbamazepine was administered for 14 days as above. On day 8, esomeprazole 2.8 mg/kg/day along with carbamazepine 40 mg/kg/day was administered till 14 days and blood samples were drawn on 15 ^th day. Plasma levels of carbamazepine were assayed by high-performance liquid chromatography and pharmacokinetic parameters were calculated. Results : In all groups there was a decrease in the AUC _0-24 when carbamazepine was coadministered with esomeprazole. The decrease in AUC _0-24 (22.78 ± 4.71 to 10.46 ± 2.29), C _max (2.76 ± 0.77 to 1.412±1.08), T _max (2.83 ± 0.17 to 3 ± 0.40) was statistically significant (P < 0.05) when esomeprazole was given along with carbamazepine. Additionally, absorption and elimination constant were also altered significantly. Conclusions : These results suggest that concomitant use of esomeprazole alters the pharmacokinetics of carbamazepine. Confirmation of these results in human studies will warrant changes in carbamazepine dose or frequency when esomeprazole is coadministered.

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Nevirapine, a non-nucleoside reverse transcriptase inhibitor (NNRTI), is widely prescribed as a part of the combination therapy of human immunodeficiency virus (HIV) infection because of its efficacy and good tolerability. Here, we report a case of Stevens-Johnson syndrome (SJS) secondary to nevirapine. The patient had a diffuse, exfoliating exanthema with generalized bullous eruptions that involved the face, trunk and both extremities with elevated hepatic alanine aminotransferase and aspartate aminotransferase enzyme activities. The condition improved with stoppage of nevirapine-based highly active antiretroviral therapy (HAART) regimen, so we attributed this adverse event to nevirapine. A strict vigilance of adverse drug reaction is required in HAART.

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Objective : To test Antarth, a polyherbal phytomedicine, for its efficacy and safety in patients with osteoarthritis (OA) and compared with placebo. Material and Methods : A total of 90 male or female adult patients who were diagnosed clinically and radiologically with OA were recruited in the study. Antarth or placebo was given 2 capsules b.i.d. for 3 months and the patients were assessed every month for its efficacy. Diclofenac sodium was allowed to be taken as rescue medication. Results : After 3 months of treatment, the reduction in severity of pain on Visual Analog Scale (VAS) was more in Antarth group compared to placebo but the difference between the two groups was not significant. However, pain during functioning of disabled joints while walking distance, squatting, sitting cross-legged and climbing steps were significantly reduced in Antarth group compared to placebo (P < 0.05). Reduction in consumption of rescue medication, diclofenac sodium, was more in Antarth than in placebo group. Conclusions : In Patients' Global Assessment, patients treated with Antarth were more satisfied than the ones treated with placebo. Observations were similar in Physicians' Global Assessment too. There were no adverse events in both the groups.

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H ₂ antagonist ranitidine causing thrombocytopenia is a rare drug phenomenon. Here we present a case of 55 year old female of pustular psoriasis who presented with fever and vomiting. Patient. was started on roxithromycin, iv ondensetron, paracetamol and iv ranitidine. Complete blood count revealed neutrophilia with normal blood picture. However repeat investigations showed falling WBC and platelet count. After excluding other causes of pancytopenia we concluded that ranitidine was the cause for this atypical drug reaction, more so when the blood picture improved within 72 hrs of ranitidine withdrawal.

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Objective : Acute exacerbation of chronic bronchitis (AECB) is a commonly encountered problem and those suspected to be due to bacterial infections require antibiotic therapy. This randomized, controlled trial was designed to evaluate the effectiveness and safety of gemifloxacin, a new fluoroquinolone, versus cefpodoxime, an oral third-generation cephalosporin, for the treatment of mild to moderately severe cases of AECB. Materials and Methods : Adult subjects diagnosed with chronic bronchitis with clinical symptoms suggestive of an Anthonisen type II acute exacerbation (any two of the following criteria - increased dyspnea, cough, sputum purulence) were eligible and those fulfilling the subject selection criteria were randomized to receive either gemifloxacin 320 mg once daily or cefpodoxime 200 mg twice daily orally for 7 days. The primary outcome measure was clinical success rate at day 14 visit and the secondary outcome measures were changes in Clinical Global impression (CGI) scales and incidence of adverse events (AEs). Fifty-two subjects were enrolled: 26 in gemifloxacin group and 24 in the other and 2 were lost to follow-up. Results : The clinical success rates were comparable (84.6% in gemifloxacin group versus 83.3% in cefpodoxime group) and no statistically significant difference was observed between the groups. AEs were mild, self-limiting and few (two in gemifloxacin and three in cefpodoxime arm) and tolerability was also good. Conclusion : The results of this randomized, single-blind trial demonstrated that a 7-day course of gemifloxacin is therapeutically comparable to cefpodoxime in terms of both clinical effectiveness and safety for the treatment of type II Anthonisen category AECB patients.

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Milk-alkali syndrome was once considered to be of historic interest and a rare cause of hypercalcemia. Currently, it should be an important consideration in the differential diagnosis of hypercalcemia, after malignancies and primary hyperparathyroidism. The resurgence is in part due to the easy availability of over the counter (OTC) calcium preparations. We describe a 50-year-old man who presented with severe hypercalcemia on two occasions associated with renal failure and metabolic alkalosis. Extensive investigations during the first admission failed to unravel a specific cause of hypercalcemia but a thorough history during his subsequent admission helped to confirm the diagnosis of milk-alkali syndrome.

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Therapeutic dose of methylphenidate is known to cause adverse effects (psychosis or mania), albeit in a small number of cases. Signs and symptoms of adverse effects usually disappear on stopping the medicine. Data regarding the safety of methylphenidate in comorbid attention deficit hyperactivity disorder (ADHD) and mental retardation are nonexistent. We describe a case of an 11-year-old girl with ADHD and mental retardation treated with methylphenidate, who developed mania like symptoms requiring inpatient treatment. The index case required psychopharmacological intervention with sodium valproate and olanzapine as the symptoms did not subside even after 3 days. This case highlights the fact that one has to exercise caution while prescribing methylphenidate in patients with comorbid ADHD and mental retardation.

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This paper reviews the critical issues in the control and design of antihypertension (anti-HT) clinical trials. The international guidelines and current clinical and biostatistical practices were reviewed for relevant clinical, design, end-point assessments and regulatory issues. The results are grouped mainly into ethical, protocol and assessment issues. Ethical issues arise as placebo-controlled trials (PCTs) for HT-lowering agents in patients with moderate to severe HT are undertaken. Patients with organ damage due to HT should not be included in long-term PCT. Active-control trials, however, are suitable for all randomized subsets of patients, including men and women, and different ethnic and age groups. Severity subgroups must be studied separately with consideration to specific study design. Mortality and morbidity outcome studies are not required in anti-HT trials except when significant mortality and cardiovascular morbidity are suspected. Generally, changes in both systolic and diastolic blood pressures (BP) at the end of the dosing interval from the baseline are compared between the active and the control arms as the primary endpoint of anti-HT effect. Onset of the anti-HT effect can be studied as the secondary endpoint. For maintenance of efficacy, long-term studies of ≥6 months need to be undertaken. Error-free measurement of BP is a serious issue as spontaneous changes in BP are large and active drug effect on diastolic BP is often small. Placebo-controlled short-term studies (of ~12 weeks) for dose-response and titration are very useful. Safety studies must be very vigilant on hypotension, orthostatic hypotension and effects on heart. In dose-response studies, at least three doses in addition to placebo should be used to well characterize the benefits and side-effects.

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Clarithromycin is a macrolide antibiotic. In clinical trials, adverse drug reactions of clarithromycin are usually mild and transient. Only 1% of the adverse reactions are severe. Herein, we present a case with vesiculobullous skin reaction and vein thrombosis caused by administration of intravenous clarithromycin.

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