Drug development is an activity that is long, complex and expensive. In 2004, attrition in the drug development paradigm prompted the US Food and Drug Administration (FDA) to introduce its 'Critical Path' document, which highlighted the serious discordance between major scientific advances and limited drug development process. One issue addressed was that of microdosing. The concept of microdosing involves the use of extremely low, nonpharmacologically active doses of a drug to define the pharmacokinetic profile of the medication in human subjects. Microdosing, thus, appears as a new viable concept in the 'toolbox' of the drug development activity. It appears that microdosing strategy could complement standard animal-to-human scaling, redefining the existing concept of phase I clinical research. In future, when research methods and technology involved in Phase 0 studies become more sophisticated, human microdosing may be applied to a number of drugs developed subsequently.

Objectives: To study the prescription pattern at the different levels of public health facilities of Lucknow district and to assess the average cost of drugs prescribed. Methods: Multi-stage stratified random sampling was done to select 1625 prescriptions of the patients attending the different level of public health facilities in Lucknow district, from August 2005 to September 2006, which was used for the development of study tools, collection of data and analysis. Results: The important components of prescription viz. examination findings, weight of the child, follow up visit and the signatures of the prescribers were absent in the prescriptions at the primary level. Polypharmacy was common (3.1 ± 1.6 drugs per prescription). The prescription of drugs by generic name was low (27.1%). The prescriptions at the secondary level health facilities were incomplete with respect to mentioning the suffix/prefix of the drug, full name, dose, frequency and strength of the drugs, and directions specifying the route and duration of the treatment. The average cost of drugs/prescription/day in US$ (Mean, SD) was found to be the highest at the tertiary level (0.34, 0.43), which decreased significantly at the primary level health facilities. Conclusion: The pattern of prescription in terms of completeness and rationality was poor. There is an urgent need to improve the standards of drug prescription.

Objective: To assess the effects of sodium valproate on intratesticular testosterone and lactic dehydrogenase level in rats. Methods: Male Wistar rats (12 weeks old) were treated with sodium valproate and sacrificed at the end of the 2 ^nd , 4 ^th , 5 ^th , 7 ^th , 10 ^th and 15 ^th week, after the last exposure to sodium valproate. The testes were removed, weighed and processed for biochemical analysis. Results: The intratesticular testosterone level was significantly (P<0.001) reduced in 200 mg/kg and 400 mg/kg treated rats. The intratesticular lactate dehydrogenase (LDH) level was significantly (P<0.001) increased by valproate in a time dependent manner. Conclusion: Valproate causes reversible change in intratesticular testosterone and LDH level.

Objectives: To assess the knowledge of final year medical students in Nigeria, about good prescribing and the application of this knowledge to their prescribing skills. Materials and Methods: Thirty four final year medical students of the Lagos State University College of Medicine (LASUCOM), Ikeja, were interviewed with a structured questionnaire that assessed their knowledge on the principles of good prescribing. They were also requested to write a prescription, based on a paediatric clinical scenario of malaria and upper respiratory tract infection. The prescription was used to assess their prescribing skills. Results: Thirty one (91.18%) students knew that rational prescribing involved prescribing correct dosage of an appropriate medicine formulation. Factors considered important by the students to prescribe rationally were: Potential benefit : risk ratio of a medicine - 33 (97.06%); good knowledge of pharmacology - 29 (85.29%) and pathophysiology of the disease to be treated - 24 (70.59%); and safety of an alternative medicine to be used - 24 (70.59%). An average of 3.71 medicines was prescribed for a child suspected to have malaria. Antimalarials (38.24%) and paracetamol (20%) were the most frequently prescribed medicines. The name and signature of the prescriber were available in 51.61% and 58.06% prescriptions, respectively. Less than 50% prescriptions had the name, case file number, age and gender of the patient. Conclusion: The final year medical students of LASUCOM would require theoretical and practical teaching of principles of rational prescribing to improve their prescribing knowledge and skills.

Objective: To identify the antihyperglycemic activity of various extracts, petroleum ether (60-80 ^o ), chloroform, acetone, ethanol, aqueous and crude aqueous, of the flower buds of Michelia champaca, and to identify the antidiabetic activity of active antihyperglycemic extract. Materials and Methods: Plant extracts were tested for antihyperglycemic activity in glucose overloaded hyperglycemic rats. The effective antihyperglycemic extract was tested for its hypoglycemic activity at two-dose levels, 200 and 400 mg/kg respectively. To confirm its utility in the higher model, the effective extract of M. champaca was subjected to antidiabetic study in alloxan induced diabetic model at two dose levels, 200 and 400 mg/kg respectively. The biochemical parameters, glucose, urea, creatinine, serum cholesterol, serum triglyceride, high density lipoprotein, low density lipoprotein, hemoglobin and glycosylated hemoglobin were also assessed in the experimental animals. Results: The ethanolic extract of M. champaca exhibited significant antihyperglycemic activity but did not produce hypoglycemia in fasted normal rats. Apart from this extract, the crude aqueous and petroleum ether extracts were found active only at the end of the first hour. Treatment of diabetic rats with ethanolic extract of this plant restored the elevated biochemical parameters significantly (P<0.05) (P<0.01) and the activity was found dose dependent. Conclusion: This study supports the traditional claim and the ethanolic extract of this plant could be added in traditional preparations for the ailment of various diabetes-associated complications.

In the present study, the effect of garlic (Allium sativum) extract on ischemic preconditioning and ischemia-reperfusion induced cardiac injury has been studied. Hearts from adult albino rats of Wistar strain were isolated and immediately mounted on Langendorff's apparatus for retrograde perfusion. After 15 minutes of stabilization, the hearts were subjected to four episodes of 5 min ischemia, interspersed with 5 min reperfusion (to complete the protocol of ischemic preconditioning), 30 min global ischemia, followed by 120 min of reperfusion. In the control and treated groups, respective interventions were given instead of ischemic preconditioning. The magnitude of cardiac injury was quantified by measuring Lactate Dehydrogenase and creatine kinase concentration in the coronary effluent and myocardial infarct size by macroscopic volume method. Our study demonstrates that garlic extract exaggerates the cardio protection offered by ischemic preconditioning and per se treatment with garlic extract also protects the myocardium against ischemia reperfusion induced cardiac injury.

Aim: The antioxidant effect of the methanol-methylene chloride extract of Terminalia glaucescens (Combretaceae) leaves was investigated in streptozotocin (STZ)-induced oxidative stress. Methods: Oxidative stress was induced in mice by a daily dose of STZ (45 mg/kg body weight i.p.) for five days. From day one, before STZ injection, normal and diabetic-test mice received an oral dose of the extract (100 or 300 mg/kg b.w.) daily. Plasma metabolites, lipid peroxidation, and antioxidant enzymes in the liver were assessed and gain in body weight recorded. Results: In normal mice the plant extract reduced food and water intake, blood glucose and LDL-C level and body weight gain, did not affect the lipid peroxidation in the liver, while the antioxidant enzyme activities seemed increased. Blood glucose was decreased (P < 0.05) in normal mice treated with 300 mg/kg extract. Diabetic mice pretreated with 100 mg/kg extract as diabetic control mice (DC) showed significant (P < 0.001) body weight loss, polyphagia and polydipsia, high plasma glucose level, decrease in the liver catalase, peroxidase, and superoxide dismutase activities, and increase in lipid peroxidation. The HDL-C level was lowered (P < 0.05) whereas LDL-C increased. In 300 mg/kg extract-pretreated diabetic mice the extract prevented body weight loss, increase of blood glucose level, lipid peroxidation in liver, food and water intake, and lowering of plasma HDL-C level and liver antioxidants; this extract prevented LDL-C level increase. Conclusion: These results indicate that T. glaucescens protects against STZ-induced oxidative stress and could thus explain its traditional use for diabetes and obesity treatment or management.

Objectives: The antiulcer activity of Benincasa hispida (Thunb.) Cogn. fruit was evaluated in rats against ethanol-induced gastric mucosal damage, pylorus ligated (PL) gastric ulcers, and cold restraint-stress (CRS)-induced gastric ulcer models. Methods: Petroleum ether and methanol extracts were administrated orally at the dose of 300 mg/kg, and omeprazole (reference standard) at the dose of 20 mg/kg. Ulcer index was common parameter studied in all the models. Further, vascular permeability was evaluated in ethanol model, and effect on lipid peroxidation, viz. melondialdehyde (MDA) content, superoxide dismutase (SOD), and catalase (CAT) levels were studied in CRS model. Results: Both the extracts produced significant reduction in ulcer index (P < 0.05) in all the models and the results were comparable with that of omeprazole-treated group. Further, significant reduction in vascular permeability (P < 0.05) was observed. In CRS model, MDA content was significantly reduced along with increase in CAT levels as compared to control group. Conclusions: Petroleum ether and methanol extracts of B. hispida possess significant antiulcer as well as antioxidant property.

The effect of TNF-α and TNF-α antagonists on semen quality in men is controversial. TNF-α levels are usually low in seminal plasma, but they tend to increase in inflammatory and infectious diseases. Etanercept is a highly-specific antagonist of TNF-α. In this report, we describe the development of pregnancy in a couple with a previously infertile husband, who received etanercept for ankylosing spondylitis.

Topiramate, an antiepileptic drug is reported to cause various ocular adverse effects like acute onset myopia, glaucoma. Visual field defect is an uncommon, serious treatment emergent adverse effect. We are reporting two cases of suspected topiramate induced visual field defects. Both the cases were on topiramate for more than 6 months as add-on therapy at daily doses ranging from 100-150mg. The presenting complaints were insidious onset visual disturbances. Diagnosis was based of temporal association with drug intake, clinical examination and investigations. Automated perimetry revealed bilateral superior quadrantic and arcuate field defects in the two cases respectively. Marked improvement with drug dechallenge was noted which was also corroborated by perimetry. Using Naranjo's ADR Probability Scale, both cases revealed a "probable" association with topiramate. This report intends to improve awareness amongst clinicians to facilitate early diagnosis and intervention.