Diabetic neuropathy (DN) is a multifactor complication of diabetes. It is a late finding in type 1 diabetes, but can be an early finding in type 2 diabetes. The cause of DN is still unclear and, like other complications of diabetes, it may be the result of various pathological conditions. Animal models and biomarkers of DN have been extensively used in neuropathic research. The most useful model of DN should exhibit the key feature present in human pathology. Diabetic rodents show behavioral, functional, structural and molecular biomarkers and they are widely used as models to investigate the etiology of DN as well as to screen the efficacy of the potential therapeutic interventions. We have reviewed the different animal models and biomarkers of neuropathy in diabetic rodents of either type 1 or type 2 diabetes.

Background : Uncontrolled anger while being most commonly associated with personality disorders could also be part of many other conditions such as chronic low back ache and post-traumatic stress disorder. The intensity of anger as an emotional state at a particular time is known as "State Anger," whereas how often angry feelings are experienced over time is known as "Trait Anger." Anger could also manifest as expression of anger toward other persons or objects in the environment (Anger-Out), holding in or suppressing angry feelings (Anger-In) and controlling angry feelings by preventing the expression of anger toward other persons or objects in the environment or controlling suppressed angry feelings by calming down or cooling off (Anger Control). Objective : To prove the effectiveness of topiramate in the control of anger as compared to placebo and to disprove that its use leads to psychiatric adverse events by systematically reviewing the available randomized controlled trials. Materials and Methods : The basic search was performed in MEDLINE (1966 through November 2008) combined with the optimal search strategy for randomized controlled trials described in the Cochrane Reviewers' Handbook. To update this search, we regularly screened citations from PubMed till November 2008 for eligible studies or reviews that might include eligible studies. The Cochrane Central Register of Controlled Trials (CENTRAL) was searched using the terms "topiramate" and "anger or aggression." In addition, we screened bibliographies of reviews and identified articles. Randomized clinical trials wherein study participants were aggressive adults were included. Results : We could arrive at a weighted mean difference of -3.16 (-3.64 to -2.68) in State Anger. The reduction in the score was highest in borderline personality disorder (BPD) patients as compared to those with low back ache. Trait Anger dropped by -2.93 (-3.49 to -2.37), especially in female BPD patients. Anger In reduced more or less uniformly across the studies by -1.43 (-1.84 to -1.03). Anger Out decreased by -2.8 (-3.19 to -2.42). This effect was minimal among the male BPD patients. Anger Control uniformly increased across the four studies by 2.32 (2.00-2.64). There is sufficient evidence to suggest that topiramate is significantly effective in stabilizing the "trait anger" while reducing the "state anger." "Anger Out" and "hostility" were significantly reduced. "Anger In" was the feature that was the least affected, although this was significant. This suggests that topiramate is effective in controlling anger. There was no suggestion of topiramate precipitating psychomorbidity. Conclusions : Topiramate appears to be a safe and effective drug in the management of anger/aggression. Additional research is needed to determine whether these results can be reproduced and how long lasting are the benefits of long-term treatment with topiramate.

Objective : To study the effect of saturated fatty acid (SFA)-rich dietary vegetable oils on the lipid profile, endogenous antioxidant enzymes and glucose tolerance in type 2 diabetic rats. Materials and Methods : Type 2 diabetes was induced by administering streptozotocin (90 mg/kg, i.p.) in neonatal rats. Twenty-eight-day-old normal (N) and diabetic (D) male Wistar rats were fed for 45 days with a fat-enriched special diet (10%) prepared with coconut oil (CO) - lauric acid-rich SFA, palm oil (PO) - palmitic acid-rich SFA and groundnut oil (GNO) - control (N and D). Lipid profile, endogenous antioxidant enzymes and oral glucose tolerance tests were monitored. Results : D rats fed with CO (D + CO) exhibited a significant decrease in the total cholesterol and non-high-density lipoprotein cholesterol. Besides, they also showed a trend toward improving antioxidant enzymes and glucose tolerance as compared to the D + GNO group, whereas D + PO treatment aggravated the dyslipidemic condition while causing a significant decrease in the superoxide dismutase levels when compared to N rats fed with GNO (N + GNO). D + PO treatment also impaired the glucose tolerance when compared to N + GNO and D + GNO. Conclusion : The type of FA in the dietary oil determines its deleterious or beneficial effects. Lauric acid present in CO may protect against diabetes-induced dyslipidemia.

Objectives : To study the effect of centchroman, a non-steroidal oral contraceptive, coadministration on the pharmacokinetics of metformin in rats. Materials and Methods : The pharmacokinetic interaction of metformin was studied in normal Sprague-Dawley female rats with and without centchroman coadministration. Blood samples were analyzed using a validated high-performance liquid chromatography method to generate the pharmacokinetic profile of metformin. The C _max and t _max were directly read from the concentration-time data. Other pharmacokinetic parameters were estimated using non-compartmental analyses. Results : Metformin was monitored up to 10 h, and it exhibited a double-peak phenomenon. The C _{max 1,} 2.62 ± 0.32 μg/ml, and C _{max 2,} 2.96 ± 0.65 μg/ml, occurred after 0.75 and 3 h post-dose, respectively. The mean residence time (MRT), AUC _{0-4 h} and volume of distribution (Vd/F) were 4.20 ± 0.30 h, 8.53 ± 1.89 μg.h/ml and 14.24 ± 5.42 L/kg, respectively. Following centchroman coadministration, metformin showed significantly (P < 0.05) higher C _max (C _{max 1,} 3.96 ± 0.55 μg/ml and C _{max 2,} 5.21 ± 0.59 μg/ml), AUC _{0-4 h} (12.28 ± 0.73 μg.h/ml) and Vd/F (18.29 ± 1.19 L/kg), but lower MRT (3.19 ± 0.36 h) than the values obtained after metformin dosing alone. However, AUC_0-t (17.74 ± 5.58 μg.h/ml) and clearance (3.76 ± 0.80 L/h/kg) remained unchanged. Conclusions : The results indicate that centchroman coadministration increases the rate but not the extent of absorption of metformin in rats. However, it does not seem to alter the pharmacokinetics of metformin to clinically significant levels.

Objective : The Delhi State Drug Policy was adopted in 1994 following which the first Essential Medicines List (EML) was developed in 1996. The Delhi State Essential Medicines Formulary was brought out in 1997. A need was felt to revise the formulary to match with the EML as the EML is renewed every 2 years. Materials and Methods : A survey was undertaken to elicit the opinions of the doctors practicing in the state on the usefulness of the formulary before revising and printing the updated version. The survey covered dispensaries, 10-20 bedded hospitals, 100-bedded hospitals and two tertiary care hospitals. Discussions were focused on questionnaires on attitudes toward adopting Essential Medicines Formulary using a 10-point scale. Results : Of the 200 doctors approached, only 90 doctors completed the questionnaire. Sixty-nine respondents (76.6%) had received the copy of the formulary. Most practitioners welcomed the formulary and were satisfied with the coverage and selection of the medicines. Most respondents (76.9%) agreed that a well-developed formulary would improve the quality of the public health care system, although they had reservations about the authority, relevance and effect on professional autonomy. Conclusion : About 74% of the respondents used the formulary in clinical practice as a source of medicine information, which makes its regular revision necessary.

Background : Theoretically, angiotensin II receptor blockers (ARBs) have certain advantages over angiotensin-converting enzyme inhibitors, but the contribution of these advantages to the clinical effect of ARBs is not known. Objective : To compare the efficacy and tolerability of telmisartan with enalapril in patients of essential hypertension. Materials and Methods : Patients of mild to moderate hypertension were randomized to receive either 40 mg of telmisartan or enalapril 10 mg once a day orally for 12 weeks. At each visit, the systolic blood pressure (BP), diastolic BP and heart rate of each patient were recorded. Investigations such as hemogram hemoglobin, total leucocytes count (Hb, TLC), serum creatinine, serum glutamic oxaloacetic transaminase, serum glutamic pyruric transaminase (SGOT, SGPT) random blood sugar and urine examination were performed at baseline and after 12 weeks of the treatment period. Results : The mean reduction in systolic BP in the telmisartan/enalapril group was 26.38 ± 10.98/26.74 ± 8.24 mmHg while the mean reduction in diastolic BP in the telmisartan/enalapril group was 14 ± 2.98/9.71 ± 4.23 mmHg, respectively, at 12 weeks. When the reduction in systolic BP in the two groups was compared, there was no significant difference between the groups (P > 0.05). However, the mean reduction in diastolic BP achieved with telmisartan at 12 weeks was significantly higher (P < 0.001) than that achieved with enalapril after the corresponding period. The overall frequency of adverse-effects was similar. However, in the enalapril group, the incidence of dry cough was higher as compared to that in the telmisartan group (11.43% vs. 0%, respectively; P < 0.05). Conclusion : Telmisartan produces a greater reduction in diastolic BP than enalapril and is free from the adverse-effect of dry cough that is commonly encountered with enalapril.

Objective : The present study was performed to evaluate the preventive and curative antidiarrheal effects of the methanol extract, fractions and compound from the stem bark of Trilepisium madagascariense in rats. Materials and Methods : The methanol extract from the stem bark of T. madagascariense, its fractions (n-hexane, ethyl acetate, n-butanol and aqueous residue) and compound (obtained from further column chromatography of the ethyl acetate fraction) were evaluated for the antidiarrheal activity in rats. These test samples (at 100, 200 and 400 mg/kg for the extract and fractions and 2.5 mg/kg for compound) were assayed on the latent periods, purging indices and fecal frequencies in castor oil-induced diarrhea. Gastrointestinal transit and castor oil-induced enteropooling assays were conducted. Shigella-induced diarrhea was assayed. Blood chemistry and fecal Shigella load were examined. Results : The fractionation of the ethyl acetate fraction from the methanol extract of T. madagascariense afforded a known compound [isoliquiritigenin (1)]. Compound 1 increased the latent period of diarrhea induction (179.40 min) compared to the saline control (60.80 min). The purging indices, fecal frequencies and intestinal enteropooling decreased with an increase in the dose of test samples. The blood cell counts, sera creatinine and fecal Shigella load decreased significantly (P ≤ 0.05) in the plant extract-treated rats compared to the saline control. Conclusion : The results of our study, being reported for the first time, provide clear evidence that the methanol extract, fractions and isoliquiritigenin from T. madagascariense stem bark possess antidiarrheal activities.

The present study was undertaken to explore the potential of stevioside in memory dysfunction of rats. Memory impairment was produced by scopolamine (0.5 mg/kg, i.p.) in animals. Morris water maze (MWM) test was employed to assess learning and memory. Brain acetylcholinestrase enzyme (AChE) activity was measured to assess the central cholinergic activity. The levels of brain thiobarbituric acid-reactive species (TBARS) and reduced glutathione (GSH) were estimated to assess the degree of oxidative stress. Scopolamine administration induced significant impairment of learning and memory in rats, as indicated by a marked decrease in MWM performance. Scopolamine administration also produced a significant enhancement of brain AChE activity and brain oxidative stress (increase in TBARS and decrease in GSH) levels. Pretreatment of stevioside (250 mg/kg dose orally) significantly reversed scopolamine-induced learning and memory deficits along with attenuation of scopolamine-induced rise in brain AChE activity and brain oxidative stress levels. It may be concluded that stevioside exerts a memory-preservative effect in cognitive deficits of rats possibly through its multiple actions.

Objective : Cognitive disorders such as amnesia, attention deficit and Alzheimer's disease are emerging nightmares in the field of medicine because no exact cure exists for them, as existing nootropic agents (piractam, tacrine, metrifonate) have several limitations. The present study was undertaken to investigate the effect of Prunus amygdalus (PA) nuts on cognitive functions, total cholesterol levels and cholinesterase (ChE) activity in scopolamine-induced amnesia in rats. Materials and Methods : The paste of PA nuts was administered orally at three doses (150, 300 and 600 mg/kg) for 7 and 14 consecutive days to the respective groups of rats. Piracetam (200 mg/kg) was used as a standard nootropic agent. Learning and memory parameters were evaluated using elevated plus maze (EPM), passive avoidance and motor activity paradigms. Brain ChE activity and serum biochemical parameters like total cholesterol, total triglycerides and glucose were evaluated. Results : It was observed that PA at the above-mentioned doses after 7 and 14 days of administration in the respective groups significantly reversed scopolamine (1 mg/kg i.p.)-induced amnesia, as evidenced by a decrease in the transfer latency in the EPM task and step-down latency in the passive avoidance task. PA reduced the brain ChE activity in rats. PA also exhibited a remarkable cholesterol and triglyceride lowering property and slight increase in glucose levels in the present study. Conclusion : Because diminished cholinergic transmission and increase in cholesterol levels appear to be responsible for the development of amyloid plaques and dementia in Alzheimer patients, PA may prove to be a useful memory-restorative agent. It would be worthwhile to explore the potential of this plant in the management of Alzheimer's disease.

Objectives : Regulated on activation, normal T cell expressed and secreted (RANTES) is a chemokine that is produced by fibroblasts, lymphoid and epithelial cells of the mucosa in response to various external stimuli. RANTES expression has been demonstrated in a variety of diseases characterized by inflammation, including asthma, transplantation-associated accelerated atherosclerosis, endometriosis and fibrosis. RANTES mRNA is quickly up-regulated by tumor necrosis factor (TNF)-α stimulation. Cyclosporine A (CsA) is widely used in organ transplant patients, often causing various side-effects including gingival overgrowth, which is fibrotic in nature. This study was carried out to assess the mRNA expression of TNF-α and RANTES in healthy individual, chronic periodontitis and CsA-induced gingival overgrowth tissues. Materials and Methods : Gingival tissue samples were collected from chronic periodontitis, CsA-induced gingival overgrowth patients and healthy individuals. Total RNA was isolated and reverse transcription polymerase chain reaction (RT-PCR) was performed for TNF-α and RANTES expression. Results : The results suggest that CsA-induced gingival overgrowth tissues expressed significantly increased TNF-α and RANTES compared to control and chronic periodontitis. Conclusion : The findings of the present study suggest that CsA can modify the expression of TNF-α and RANTES in drug-induced human gingival overgrowth.

Background and Purpose : A water decoction of the poisonous shrub Cleistanthus collinus is used for suicidal purposes. The mortality rate is 28%. The clinical profile includes distal renal tubular acidosis (DRTA) and respiratory failure. The mechanism of toxicity is unclear. Objectives : To demonstrate features of C. collinus toxicity in a rat model and to identify its mechanism(s) of action. Materials and Methods : Rats were anesthetized and the carotid artery was cannulated. Electrocardiogram and respiratory movements were recorded. Either aqueous extract of C. collinus or control solution was administered intraperitoneally. Serial measurements of blood gases, electrolytes and urinary pH were made. Isolated brush border and basolateral membranes from rat kidney were incubated with C. collinus extract and reduction in ATPase activity was assessed. Venous blood samples from human volunteers and rats were incubated with an acetone extract of C. collinus and plasma potassium was estimated as an assay for sodium-potassium pump activity. Results : The mortality was 100% in tests and 17% in controls. Terminal event in test animals was respiratory arrest. Controls had metabolic acidosis, respiratory compensation _, acidic urine and hyperkalemia. Test animals showed respiratory acidosis, alkaline urine and low blood potassium as compared to controls. C. collinus extract inhibited ATPase activity in rat kidney. Plasma K ⁺ did not increase in human blood incubated with C. collinus extract. Conclusions and Implications : Active principles of C. collinus inhibit proton pumps in the renal brush border, resulting in type I DRTA in rats. There is no inhibition of sodium-potassium pump activity. Test animals develop respiratory acidosis, and the immediate cause of death is respiratory arrest.

Objectives : To study the ulcer protective property of sodium cromoglycate in pylorus-ligated rats and the biochemical role in ulcer protection by various biochemical tests. Materials and Methods : The ulcer protective effect of sodium cromoglycate was studied using a Pyloric Ligation Model using Wistar albino rats. The antiulcer effect of sodium cromoglycate 40 mg/kg b.w., i.p., was compared with the reference drug ranitidine 27 mg/kg b.w., i.p. The ulcer index was calculated and other biochemical parameters like free acidity, total acidity, pH, mucin, pepsin and volume of gastric juice were determined. Results : Pylorus ligation showed a significant (P < 0.01) reduction in gastric volume, free acidity, total acidity and ulcer index as compared to the control. Conclusion : Sodium cromoglycate has activity equipotent to ranitidine.

Hematological abnormalities are frequent among human immunodeficiency virus (HIV)-infected patients and may be directly attributable to the virus or may be caused by opportunistic infections, neoplasms or drugs that cause bone marrow suppression or hemolysis. Pure red cell aplasia (PRCA) is an uncommon hematological disorder that causes anemia. We report a 37-year-old male with HIV infection who developed PRCA 6 weeks after commencing Zidovudine and recovered following cessation of the drug. This is the first case of Zidovudine-induced PRCA reported from the Indian subcontinent.