Ketamine but not glycine potentiates antidepressant like action of citalopram in mice exposed to chronic mild stress

Background: The present study was designed to investigate the effect of citalopram, ketamine, glycine and their combinations on animal models of depression. Methods: Swiss Albino male mice were subjected to chronic mild stress for 6 weeks for inducing depression, and randomly divided into different groups: citalopram (5 and 10 mg/kg), ketamine (17.5 and 35 mg/kg), glycine (50 and 100 mg/kg), ketamine (17.5 mg/kg) + citalopram (5 mg/kg) and ketamine (17.5 mg/kg) + glycine (50 mg/kg). Two behavioural tests were utilized for the assessment of depression, namely tail suspension test (TST) and forced swim test (FST). Immobility time was recorded for 6 min, before and after administration of drug. Results: Citalopram (10 mg/kg) administration caused significant decrease in the immobility time in TST model only but not in FST. Citalopram (5 mg/kg) and ketamine (17.5 mg/kg) caused insignificant decrease in immobility time in both the models. Moreover, ketamine in combination with Citalopram significantly reduced the immobility time in both the models. Glycine at a dose of 100 mg/kg (but not 50 mg/kg) significantly increased the immobility time in both the models as compared to control group. Further, ketamine when administered with glycine caused increase in the immobility time on both the paradigms, though insignificant. Conclusions: Ketamine demonstrated antidepressant like action in both TST and FST models. Moreover, it potentiated the antidepressant effect of citalopram that might be due to the role of NMDA receptors.

Protective effect of pioglitazone on cardiomyocyte apoptosis in low-dose streptozotocin & high-fat diet-induced type-2 diabetes in rats.

Background & objectives: Cardiomyocyte apoptosis is one of the pathologic phenomena associated with diabetes and related conditions including obesity, insulin resistance and hyperlipidaemia. In the present study, the protective effects of pioglitazone on cardiomyocyte apoptosis was evaluated in experimental diabetes induced by low dose of streptozoticin (STZ) combined with high fat diet (HFD) in rats. Methods: Male Wistar rats (150-200 g) were injected with low-dose STZ (45 mg/kg, i.v., single dose) and orally fed with a HFD (20 g/day/rat) for a period of 28 days and simultaneously treated with pioglitazone (20 mg/kg/p.o.) for a period of 21 days (from 8th day to 28th day). On 29th day blood was collected, serum separated and used for biochemical parameters. Heart tissue was used for cardiomyocyte apoptosis measurement and also for histopathological examination. Results: Pioglitazone treatment resulted in a decrease in cardiomyocyte apoptosis as revealed by a decrease in cardiac caspase-3, lactate dehydrogenase (LDH) levels and DNA fragmentation, and an increase in Na+K+ATPase levels in diabetic rats. Cardiac histology of diabetic control rats showed dense focal fatty infiltration in the myocardial cells whereas normal architecture with regular morphology and well preserved cytoplasm was observed with pioglitazone treatment. Pioglitazone treatment significantly reduced the heart rate, mean arterial blood pressure, body mass index (BMI) and levels of serum glucose, leptin, insulin, HOMA-IR, total cholesterol (TC) and triglycerides (TGs), apoliproprotein-B glycosylated haemoglobin (HbA1c) levels and atherogenic index, and increased the levels of serum high density lipoprotein cholesterol (HDL-C) and cardiac antioxidant enzymes. Interpretation & conclusions: The present study results suggest that pioglitazone possesses cardiac anti-apoptotic potential in diabetic rat model and can be further explored for its use for treatment of diabetic cardiomyopathy.

Current status of TNF blocking therapy in heart failure.

Recent experimental studies have shown that tumor necrosis factor alpha (TNF-alpha) has deleterious cardiovascular effects. Tumor necrosis factor alpha antagonists bind to TNF-a and functionally inactivate this cytokine and thereby reverse some of these effects. Various clinical studies of TNF-alpha antagonists have reported conflicting results. The present review analyses all reported clinical trials of TNF-alpha antagonists in congestive heart failure (CHF). The effect of these agents on clinical composite score, CHF hospitalizations, and mortality were compared. Early clinical studies of blocking TNF in patients with heart failure demonstrated promising results. However, recent large-scale, placebo-controlled trials have failed to show any improvement in the clinical status of heart failure. There have in fact, been some reports of worsening of heart failure with these agents. It may be concluded that TNF-alpha antagonists could adversely affect the clinical condition of patients with moderate to severe heart failure.

Adverse drug reaction monitoring: knowledge, attitude and practices of medical students and prescribers.

BACKGROUND: Adverse drug reactions (ADRs) contribute to excessive health care costs through increased patient morbidity and mortality. Thus, there is an urgent need to create awareness among physicians towards ADR monitoring. The present study was designed to assess the knowledge, attitude and practices of fifth semester undergraduate students and prescribers (interns, junior residents and senior residents) towards the recording and reporting of ADRs. METHODS: The fifth semester MB,BS undergraduate students (n=107) and prescribers (n=l 17) working in different disciplines of Lady Hardinge Medical College and associated hospitals were given a questionnaire to answer. The responses of the undergraduate students were compared with those of prescribers. RESULTS: Knowledge about definition, classification, objectives and methods of ADR monitoring was found to be comparable in both groups. Spontaneous and intensive methods of ADR monitoring were known to the majority of participants of both groups. Attitude and practices of the prescribers were significantly (p<0.01 ) better with regard to the status of ADR monitoring in the institute. A significantly higher (p<0.001) proportion of prescribers (82%) as compared to the undergraduate students (64.5%), felt that ADRs should be reported both when it causes inconvenience to the patient as well as death. ADRs were encountered by both undergraduates (46%) and prescribers (66%) during their clinical project exercises and patient care, respectively. Commonly encountered ADRs were allergic reactions, symptoms of upper gastrointestinal irritation, extrapyramidal symptoms and hepatitis. The common offending groups of drugs causing these ADRs were non-steroidal anti-inflammatory drugs, antidopaminergics and chemotherapeutic agents. A majority of ADRs were suspected and subsided on their own by either stopping the drug or reducing its dose. CONCLUSIONS: The knowledge, attitude and practices of both undergraduates and prescribers were comparable but need further improvement. This suggests the need for suitable changes in the undergraduate teaching curriculum. Further, the prescribers also need periodic reinforcement regardingADR monitoring.

Study of drug utilization pattern in dental OPD at tertiary care teaching hospital.

Irrational prescribing is a global phenomenon. The objective of the study was to find out the prescribing practices of dental prescribers in a tertiary care teaching hospital with special emphasis on the utilization of antimicrobial agents. A prospective study was conducted in the month of March 2000. A total of 491 prescriptions were collected randomly. Prescribing pattern was analyzed using WHO basic drug indicators. The average number of drugs for prescription was 2.4. 78.8% of all prescriptions contained antimicrobial agents. It was most commonly prescribed (40.37%) group of drugs followed by anti-inflammatory and analgesics (33.8%). Fixed dose combination of ampicillin and cloxacillin was most commonly prescribed antimicrobial agents. Prophylactic use of AMA (78%) was more than therapeutic purpose (21.9%). Prophylactic use of antimicrobial agents was irrational in all the cases as duration for the use of antimicrobial agents was 5.1 +/- 0.5 days. Fixed dose combinations (45%), drugs by brand name (98.5%) were frequently used. Drug prescribed from Essential Drug List was maximum when one drug was prescribed. Results indicate that there is a scope for improving prescribing habits and minimizing the use of antimicrobial agents. This could be facilitated by periodic education to the prescribers.

Comparative bioavailability of two formulations of azithromycin.

AIM: To compare the bioequivalence of two brands of azithromycin capsules in healthy male volunteers for regulatory purpose. METHOD: A single oral dose of 500 mg of either test (Panacea Biotec Ltd.) or reference (Pfizer India Ltd.) preparation of azithromycin was administered to 12 volunteers in double blind randomised cross over fashion. Serum levels of azithromycin were analysed using microbiological assay. The pharmacokinetic parameters studied were Cmax, Tmax, AUC, t1/2, Ke, CL and MRT. In vitro dissolution tests were conducted for both the preparations and compared with in vivo absorption. RESULTS: The mean peak serum azithromycin concentration of 0.516 +/- 0.008 microgram/ml was observed at 2.33 +/- 0.22 h with test brand and was similar to that of reference brand with Cmax of 0.494 +/- 0.011 microgram/ml at 2.71 +/- 0.26 h. The statistical difference between all the other paharmacokinetic parameters were insignificant. CONCLUSION: Both the brands of azithromycin can be considered to be bioequivalent on the basis of results obtained.

Effect of alcohols and their potentiating responses on acetylcholine induced contractures on frog rectus abdominis.

Ethanol, propanol and butanol cause contraction and potentiate the responses of acetylcholine (Ach) on frog's rectus muscle. These actions are minimum with ethanol and maximum with butanol. Various drugs acting at different levels of neuromuscular transmission inhibited the responses of alcohol itself and also its potentiating responses of Ach. The results show that these effects are partly due to enhanced release of Ach at neuromuscular junction and partly due to release of sarcoplasmic calcium suggesting that more than one mechanism may be responsible for these actions.

Mechanism of haloperidol-induced miosis.

Haloperidol administration (iv) has been shown to produce miosis in dogs. In the present study on rabbits, haloperidol administration (iv) produced dose-related miosis but when administered intracerebroventricularly, it failed to produce any change in pupillary size. Higher degree of miosis was observed when haloperidol was administered directly into the anterior chamber of eye. Haloperidol pretreatment failed to significantly modify the mydriasis produced by phenylephrine or atropine. These observations suggest that the miosis produced by haloperidol is a peripheral effect, and also that the miosis is not mediated through the blockade of alpha adrenoceptors of radial muscles or stimulation of cholinoceptors of circular muscles of iris.