Toxicity testing of new compounds is essential for drug development process. The preclinical toxicity testing on various biological systems reveals the species-, organ- and dose- specific toxic effects of an investigational product. The toxicity of substances can be observed by (a) studying the accidental exposures to a substance (b) in vitro studies using cells/ cell lines (c) in vivo exposure on experimental animals. This review mainly focuses on the various experimental animal models and methods used for toxicity testing of substances. The pre-clinical toxicity testing helps to calculate "No Observed Adverse Effect Level" which is needed to initiate the clinical evaluation of investigational products.

Objectives: To investigate the effect of ethanolic extract of fruit pulp of Tamarindus indica Linn. (Family: Caesalpiniaceae) on obesity in rats using cafeteria diet-induced obesity and antipsychotic drug (sulpiride)-induced obesity. Materials and Methods: Cafeteria diet was administered for 40 successive days to male Wistar rats and sulpiride (20 mg/kg, i.p.) was administered for 28 successive days to female Wistar rats. In separate groups of animals, the ethanolic extract (50 and 100 mg/kg p.o.) of Tamarindus indica fruit was administered along with cafeteria diet for 40 successive days to Wistar male rats and along with sulpiride for 28 successive days to Wistar female rats. Results: Cafeteria diet alone significantly increased body weight, serum total cholesterol, triglycerides, and glucose levels and decreased HDL cholesterol in male rats as compared to control. Sulpiride per se significantly increased the levels of glucose, triglycerides, cholesterol and there was no significant effect on HDL-cholesterol in female rats as compared to control. Ethanolic extract showed a significant decrease in body weight, serum cholesterol, and triglycerides and a significant increase in HDL-cholesterol in cafeteria diet- and sulpiride-induced obese rats as compared to their respective control groups. Conclusions: Thus, the ethanolic extract of Tamarindus indica fruit pulp showed a significant weight-reducing and hypolipidemic activity in cafeteria diet- and sulpiride-induced obese rats.

Objective: To evaluate the reporting of the statistical methods in articles published in two Indian pharmacology journals. Materials and Methods: All original articles published since 2002 were downloaded from the journals' (Indian Journal of Pharmacology (IJP) and Indian Journal of Physiology and Pharmacology (IJPP)) website. These articles were evaluated on the basis of appropriateness of descriptive statistics and inferential statistics. Descriptive statistics was evaluated on the basis of reporting of method of description and central tendencies. Inferential statistics was evaluated on the basis of fulfilling of assumption of statistical methods and appropriateness of statistical tests. Values are described as frequencies, percentage, and 95% confidence interval (CI) around the percentages. Results: Inappropriate descriptive statistics was observed in 150 (78.1%, 95% CI 71.7-83.3%) articles. Most common reason for this inappropriate descriptive statistics was use of mean ± SEM at the place of "mean (SD)" or "mean ± SD." Most common statistical method used was one-way ANOVA (58.4%). Information regarding checking of assumption of statistical test was mentioned in only two articles. Inappropriate statistical test was observed in 61 (31.7%, 95% CI 25.6-38.6%) articles. Most common reason for inappropriate statistical test was the use of two group test for three or more groups. Conclusion: Articles published in two Indian pharmacology journals are not devoid of statistical errors.

Objective: To investigate the short-term effects of ormeloxifene on systemic hemodynamics, coagulation profile, and serum antioxidant activity in vivo in comparison with raloxifene. Materials and Methods: Colony-bred adult female Sprague-Dawley rats were randomized into 19 groups of 10 each and received either ormeloxifene or raloxifene (0.25, 1.25, or 3 mg/kg/day) for 7, 15, or 30 days by the oral route. Animals of control group received vehicle (gum-acacia in distilled water) alone in a similar manner. Systemic hemodynamics and serum total antioxidant activity were assessed 24 h after the last treatment. Results: There was no significant effect of ormeloxifene administered at these doses and schedules on hemodynamic parameters or antioxidant activity, except for increase in amplitude of R wave in rats treated with 3 mg/kg/day dose for 30 days. This effect with raloxifene was evident only 7 days after treatment at this dose. Overall response was, however, almost similar with both the agents. Conclusion: The findings demonstrate comparable pharmacological profile of ormeloxifene and raloxifene on short-term administration to rats. Based on changes observed in the ECG (R wave), long-term studies may lead to justifiable comparison of beneficial and harmful effects of ormeloxifene and raloxifene in relation to cardiovascular effects.

Objective: To collect information on the availability of five essential children's medicines in the public health facilities of India. Materials and Methods: A snap shot survey of the availability of five essential medicines for children was conducted. Five medicines which are included in the National Rural Health Mission (NRHM) list for subcentres were selected, i.e., vitamin A liquid solution, syrup cotrimoxazole, oral rehydration salt (ORS), syrup paracetamol, and zinc sulphate (oral liquid or tablets). Information about this survey was posted in two e-groups for pharmacologists and pharmacists and volunteers were requested to collect data on the availability of these five medicines and fill up a data sheet which was emailed back to the organizers. Data was collected from February 14 to 21, 2010. Results: Data were collected from 129 public health facilities spanning 17 states, two union territories and NCT Delhi. The overall median availability was 80% (range: 0%-100%). Punjab, Tamilnadu, and Jharkhand showed 100% median availability (range: 40%-100%). Ninety percent of the facilities have ORS, paracetamol, and cotrimoxazole whereas zinc was available in only 36% of the public health facilities. Syrup cotrimoxazole and ORS have 100% availability in all states except in four and paracetamol has nearly 100% availability in all but six states. Conclusion: The availability of essential medicines for children in public health facilities is not satisfactory and needs to be improved.

Aim: To monitor and evaluate the pattern of ADRs to oseltamivir in pediatric population suffering from H1N1 influenza at a tertiary care hospital. Materials and Methods: Children offered oseltamivir for treatment and chemoprophylaxis were monitored for adverse events by direct questioning for symptoms and clinical examination on day 5 and day 10. Assessment of neurological events was done by asking the parents or guardians regarding development of specific symptoms. Adverse events obtained were analyzed for severity, causality and age-group wise. Results: Out of 191 children (median age, 3 years), 69 (36.1%) developed ADRs. Most common symptoms were vomiting (16.2%) followed by diarrhea (12.0%), ear disorders (8.9%), and insomnia (6.8%). The incidence of neuropsychiatric symptoms was 12.6% which were mild-to-moderate on severity scale. There was no significant difference in the incidence of adverse events between children less than 1 year and other age groups. Conclusion: Oseltamivir is well tolerated in Indian children with suspected or confirmed H1N1 influenza. Our study also indicates safety of oseltamivir in infants.

Objective: To study the effect of brimonidine on intraocular pressure (IOP) following capsulotomy among Indian subjects. Materials and Methods: The study was a nonrandomized trial with open label. Results: 80% of the subjects showed a decrease in IOP after instilling 0.2% brimonidine (1 hour pre capsulotomy). No such decrease was observed in control. After 1 and 4 h post capsulotomy a statistically significant decrease in IOP ranging between 1-10 mmHg was found in 73.3% of the treatment group. Conclusions: In the present study 0.2% brimonidine has been proven effective to counteract the increase in IOP following Nd-YAG laser capsulotomy in Indian setting.

Sexual dysfunction affects patients' quality of life. It can occur secondary to physical or mental disorders, substance abuse and treatment with prescription drugs like antidepressants. We wanted to study the prevalence of sexual dysfunction associated with antidepressant use in the psychiatric unit of a tertiary care hospital and assess for causality, severity and preventability. We did a retrospective data collection from case records of patients on antidepressants from the Psychiatry outpatient clinic of a tertiary care teaching hospital during the period 1 ^st January 2006 to 31 ^st December 2006, excluding those with complaints of sexual dysfunction prior to treatment. Data are presented as a case series. Documented adverse events were subjected to analysis for causality, severity and preventability using Naranjo's, modified Hartwig and Siegel and modified Schumock and Thornton's Preventability scales respectively. Out of 169 patients, four patients developed sexual dysfunction (2.36%) associated with duloxetine, mirtazapine, trazodone and sertraline. We observed a possible causal relationship of mild to moderately severe ADR (sexual dysfunction) which was not preventable. Prevalence of antidepressant associated sexual dysfunction was lower than quoted in Western literature probably due to the retrospective nature of our study design. Active monitoring and intervention can greatly improve the quality of life and compliance to treatment.