Objective : The objective of the present study was to evaluate the adaptogenic property of the ethyl acetate-soluble fraction of methanol extract of Morus alba roots against a rat model of chronic stress (CS). Materials and Methods : Rats were exposed to stress procedure for 21 days. The stress procedure was mild, unpredictable footshock, administered for 1 h once daily for 21 days. Rats were administered with the ethyl acetate soluble fraction of methanol extract of M. alba roots (25, 50 and 100 mg/kg p.o) 1 h before footshock for 21 days and behavioral parameters were evaluated for cognitive dysfunction and depression using elevated plus maze and despair swim test, respectively. On day 21, rats were sacrificed immediately after stress and blood was collected for biochemical estimation. The adrenal gland and spleen were dissected for organ weight and the stomach was dissected for ulcer score. Results : CS significantly induced cognitive deficit, mental depression and hyperglycemia and increased blood corticosterone levels, gastric ulcerations and adrenal gland weight, but decreased the splenic weight. Pre-treatments with the ethyl acetate soluble fraction of methanol extract of M. alba roots (25, 50 and 100 mg/kg, p.o.) significantly attenuated the CS-induced perturbations. Diazepam (1 mg/kg, p.o.) was used as the standard antistress drug. Conclusion : The results indicate that M. alba possesses significant adaptogenic activity, indicating its possible clinical utility as an antistress agent.

Background : Diabetic nephropathy (DN) is one of the most common causes of end-stage renal failure. The pathogenesis of progressive renal damage is multifactorial and the mechanism by which hyperglycemia causes microangiopathy in diabetic glomeruli is still poorly understood. Because the renin angiotensin system has been reported to be an important contributory factor in the pathophysiology of DN, exogenous administration of angiotensin II receptor antagonist may be beneficial in counteracting some biochemical or functional changes of DN. Aims : The present study was therefore undertaken to evaluate the preventive role of irbesartan in streptozotocin (STZ)-induced DN in rats. Methods and material : STZ-induced DN in rats was assessed biochemically by measuring urine volume, protein and electrolytes as well as blood urea and creatinine clearance. Results : Marked hyperglycemia, polyuria, proteinuria and uremia along with a reduction in urine electrolytes and creatinine clearance were observed in STZ diabetic rats. Pre-treatment with irbesartan (20 mg/kg, p.o. 5 days prior to STZ and continued for 16 weeks) also significantly altered these parameters towards normal, except blood glucose. Conclusion : Pre-treatment with insulin reversed the parameters of DN. The data suggest that irbesartan prevents the development of STZ-induced DN in rats.

Aim : Gastric dysfunctions are commonly seen after scorpion envenomation, and the underlying mechanisms are not clear. Therefore, the present study was undertaken to investigate the effect of Indian red scorpion (Mesobuthus tamulus, MBT) venom on gastric fundus muscle contraction and the underlying mechanisms involved. Materials and Methods : In vitro isometric contraction was recorded from gastric fundus muscle strips on a chart recorder. The tissue was exposed to different concentrations of serotonin or crude MBT venom. The contractile responses to venom were expressed as the percentage of maximum contraction produced by serotonin at the beginning of each experiment. The contractile responses to 1.0 µg/ml of crude MBT venom were ascertained in the absence or presence of serotonin antagonist, methysergide. Results : Serotonin produced concentration-dependent fundus contractions (0.004-4.0 µM), and maximum contractile response was observed at 4.0 µM of serotonin. Hence, the contractile response obtained at 4.0 µM of serotonin was taken for normalization. The crude MBT venom (0.1-1.0 µg/ml) produced a concentration-dependent increase in fundus contractions (as % of maximum fundus contraction produced by serotonin at 4.0 µM). The maximum response was observed at 1.0 µg/ml of crude venom and a further increase in the concentration, up to 3.0 µg/ml, did not increase the response. In a separate series of experiments, pre-treatment with methysergide (1.0 µM) significantly attenuated the contractile response elicited by the venom (1.0 µg/ml) (P<0.05) and blocked the serotonin (4.0 µM) response. Conclusion : The results suggest that the crude MBT venom produces gastric fundus contractions by partially involving serotonin.

Objective : To evaluate the in vivo antimalarial activities of ethanolic leaf and stembark extracts of Anthocleista djalonensis used traditionally as malarial remedy in Southern Nigeria in mice infected with Plasmodium berghei berghei. Methods : The ethanolic extracts of the A. djalonensis leaf (1000 - 3000 mg/kg/day) and stembark (220 - 660 mg/kg/day) were screened for blood schizonticidal activity against chloroquine-sensitive P. berghei in mice. The schizonticidal effect during early and established infections was investigated. Results : The A. djalonensis leaf extract (1000 - 3000 mg/kg/day) exhibited a significant antiplasmodial activity both in the 4-day early infection test and in the established infection with a considerable mean survival time, which was incomparable to that of the standard drug, chloroquine (5 mg/kg/day). The stembark extract (220 - 660 mg/kg/day) also demonstrated a promising blood schizontocidal activity in early and established infections. Conclusion : These plant extracts possess considerable antiplasmodial activities, which justify their use in ethnomedicine and can be exploited in malaria therapy.

Background : High cholesterol levels have been positively correlated with a higher incidence of memory impairment and dementia. Aim : The study was undertaken to investigate the potential of the lipid-lowering drug, ezetimibe, in memory deficits associated with dementia of Alzheimer's (AD) type in mice. Methods : Dementia was induced with chronic administration of a high-fat diet (HFD) or intracebroventricular streptozotocin (ICV STZ, two doses of 3 mg/kg) in separate groups of animals. The memory of the animals was assessed by employing a Morris water maze. Brain thio barbituric acid-reactive species and reduced glutathione levels were measured to assess the total oxidative stress. Brain acetyl cholinesterase (AChE) activity and total serum cholesterol levels were also measured. Results : STZ/HFD produced a significant impairment of memory along with an increase in brain AChE activity and oxidative stress. HFD mice also showed an increase in cholesterol levels. Ezetimibe (10 mg/kg, orally for 15 days) significantly attenuated STZ/HFD-induced memory deficits and biochemical changes. It also prevented HFD-induced rise in the cholesterol level. Conclusions : The memory-restorative effect of ezetimibe can be attributed to its cholesterol-dependent as well as cholesterol-independent effects. The study highlights the potential of ezetimibe in memory dysfunctions associated with dementia of AD.

Objectives : To study the effect of oral magnesium oxide supplementation alone and on the activity of standard anti-epileptic drugs in the animal models of maximal electroshock seizures (MES) and chemically (pentylenetetrazole [PTZ])-induced seizures. Methods : Healthy male albino rats were given magnesium oxide (MgO) supplementation orally in various doses (500, 750 and 1000 mg/kg /day) for 4 weeks (day 1 to day 28). On day 0 and day 29, response to MES (180 mA for 0.2 s) was tested 1 h after pre-administration of phenytoin or carbamazepine orally. Similarly, in the other groups, the response to PTZ 40 mg/kg i.p. was tested 1 h after pre-administration of oral sodium valproate. Results : Oral administration of MgO in a low dose (500 mg/kg) for 4 weeks in healthy rats appears to exert protective effect against MES. High oral doses of MgO (750 and 1000 mg/kg) appear to enhance the activity of phenytoin and carbamazepine in the MES model. MgO supplementation was seen to decrease the latency of PTZ-induced seizures. Conclusion : The dose of oral MgO appears to have an inverse relation with the protective effect in MES-induced seizure model. High doses of MgO supplementation given orally appear to enhance the activity of standard anti-epileptic drugs in the MES-induced seizure model.

Objective : To evaluate the effect of petroleum ether (60-80), chloroform, acetone, ethanol and aqueous extracts of Plumbago rosea leaves on the estrous cycle and to identify the estrogenic activity of active acetone and ethanol extracts in female albino rats. Methods : Plant extracts were tested for their effect on the estrous cycle at two dose levels: 200 and 400 mg/kg, respectively. The effective acetone and ethanol extracts were further studied on estrogenic activity in rats. Histological studies of the uterus were carried out to confirm their estrogenic activity. Results : The acetone and ethanol extracts were most effective in interrupting the normal estrous cycle of the rats (P<0.05, <0.01, <0.001). These later exhibited prolonged diestrous stage of the estrous cycle with consequent temporary inhibition of ovulation. The antiovulatory activity was reversible on discontinuation of treatment. Both the extracts showed significant estrogenic and antiestrogenic activity. Conclusion : The acetone and ethanolic extracts of P. rosea leaves have an antifertility activity.

Objective: Adrafinil and modafinil have received wide publicity and have become controversial in the sporting world when several athletes were discovered allegedly using these drugs as doping agents. By acknowledging the facts, the World Anti-Doping Agency (WADA) banned these drugs in sports since 2004. The present study explores the possibility of differentiating adrafinil and modafinil and their major metabolites under electron impact ionization in gas chromatograph-mass spectrometer (GC-MSD) and electrospray ionization in liquid chromatograph-mass spectrometer (LC-MS/MS) by studying the fragmentation pattern of these drugs. Materials and Methods: Adrafinil, modafinil and their major metabolite, modafinilic acid were analyzed on EI-GC-MSD and ESI-LC-MS/MS using various individual parameters on both the instruments. The analytical technique and equipment used in the analysis were an Agilent 6890N GC with 5973 mass selective detector for the GC-MSD analysis and an Agilent 1100 HPLC with API-3200 Triple quadrupole mass spectrometer for the LC-MS/MS analysis. Validation of both methods was performed using six replicates at different concentrations. Result and Discussion: The results show that adrafinil, modafinil and their major metabolite modafinilic acid could be detected as a single artifact without differentiation under EI-GC-MSD analysis. However, all drugs could be detected and differentiated under ESI-LCMS/MS analysis without any artifaction. The GC-MSD analysis gives a single artifact for both the drugs without differentiation and thus can be used as a marker for screening purposes. Further, the Multiple Reaction Monitoring (MRM) method developed under LC-MS/MS is fit for the purpose for confirmation of suspicious samples in routine sports testing and in forensic and clinical analysis.

Gynecomastia results from conditions that cause an imbalance of estrogenic and androgenic effects on the breast, resulting in an increased or unopposed estrogen action on breast tissue. Approximately 4 to 10% cases of gynecomastia are due to drugs. Both Digoxin and Furosemide are also reported to cause the same condition. Although, chances of gynecomastia could be more if these two drugs are coadministered, but no case report of this adverse effect is ever reported when both are prescribed concurrently. Here we report a case of gynecomastia suspected to have resulted from the coadministation of both the drugs. Probability of the adverse effect due to drug interaction was evaluated by DIPS, which suggests that the adverse drug reaction (ADR) due to DI is "Possible."