Comparison of pre- and post-ischemic treatment of telmisartan and nimodipine combination in experimentally induced cerebral ischemia.

Time dependent intervention plays a crucial role in preventing neurodegeneration after ischemic insult. The intensity of excitotoxicity is greater in the secondary reperfusion phase (2-4 h) compared to the primary occlusion phase (2 h), which could be attributed to secondary elevation of excitatory amino acids (EAA) in cerebral ischemia. In the present study, we tried to assess the neuroprotective effects of telmisartan and nimodipine (TM-NM) combination on the secondary reperfusion phase. The drug treatments were made immediately after reperfusion and their effects were compared with pre-treatment. The neuroprotective effect was studied using middle cerebral artery occlusion (MCAo) transient ischemic model in rats. On the 7th day after reperfusion, the rats were subjected to behavioral studies. The brain was dissected out on the 9th day to measure neurobiochemical alterations and for histopathological observations. The results have shown that TM-NM (5 mg/kg) attenuated the EAA release in different brain regions with partial restoration of energy levels in secondary reperfusion phase. Similarly, it normalized the behavioral alteration and the effect was comparable to pre-ischemic treatment (2.5 mg/kg). Pre-ischemic treatment of TM-NM (2.5 mg/kg) protected the neurons from ischemic reperfusion injury by energy dependent EAA regulation. It can be concluded from the study that, even though the pre- and post-treatment of TM-NM show similar results, the post-ischemic treatment of TM-NM combination is beneficial due to better EAA control. Since hypertension is the primary risk factor for stroke, clinical incidents of stroke in hypertensive patients receiving angiotensin receptor blockers (ARBs) can be further investigated to understand the present study in the clinical situation.

Elucidation of neuroprotective role of endogenous GABA and energy metabolites in middle cerebral artery occluded model in rats.

The excitatory amino acids (EAA) like glutamate, aspartate and inhibitory neurotransmitter GABA (gama amino butyric acid) play an important role in the pathophysiology of cerebral ischemia. The objective of the present study is to elucidate the role of endogenous GABA against EAA release in different regions during ischemia. The transient focal ischemia was induced in rats by using middle cerebral artery occlusion model (MCAo). The results indicate gradual elevation of brain glutamate, aspartate and GABA level at different brain regions and attained peak level at 72 h of ischemic reperfusion (IR). At 168 h of IR the EAA levels declined to base line but GABA level was found to be still elevated. The biochemical analysis shows the depleted brain ATP, Na+K+ATPase content and triphasic response of glutathione activity. It can be concluded that time dependent variation in the EAA and GABA release, endogenous GABA can be neuroprotective and earlier restoration of energy deprivation is essential to prevent further neurodegeneration. To have efficient treatment in ischemic condition, multiple approaches like energy supply, antagonism of EAA, controlling calcium function are essential.

Behavioural and neurochemical evaluation of Perment® an herbal formulation in chronic unpredictable mild stress induced depressive model.

Perment®, a polyherbal Ayurvedic formulation that contains equal parts of Clitoria ternatea Linn., Withania somnifera Dun., Asparagus racemosus Linn., Bacopa monniera Linn., is used clinically as mood elevators. The aim of the present study was to explore the behavioural effects and to understand possible mode of action of Perment® in stress induced depressive model. Chronic unpredictable mild stress (CUMS) was used to induce depression in rats. Open field exploratory behaviour, elevated plus maze, social interaction and behavioural despair tests were used to assess behaviour. Using standard protocols plasma noradrenaline, serotonin, corticosterone and brain/adrenal corticosterone levels were measured to support the behavioural effects of Perment®. Exposure to CUMS for 21 days caused anxiety and depression in rats, as indicated by significant decrease in locomotor activity in the open field exploratory behaviour test and increased immobility period in the behavioural despair test. Perment® predominantly exhibited antidepressant action than anxiolytic activity. Further Perment® increased the plasma noradrenaline and serotonin levels in stressed rats. No significant alteration in the brain corticosterone level in stressed rats was observed with Perment® treatment. However the adrenal corticosterone level is decreased with Perment®. It can be concluded that the Perment® formulation exhibited synergistic activity, has a significant antidepressant and anxiolytic activity, which may be mediated through adrenergic and serotonergic system activation. Currently the formulation is clinically used as anxiolytic but the present results suggest that the formulation can also be indicated in patients affected with depression.

Lipid lowering activity of ethanolic extract of leaves of Aegle marmelos (Linn.) in hyperlipidaemic models of Wistar albino rats.

Lipid lowering effect of 50% ethanolic extract of the leaves of A. marmelos (Linn.) was evaluated in triton and diet induced hyperlipidaemic models of Wistar albino rats. The extract at 125 and 250 mg/kg dose levels inhibited the elevation in serum cholesterol and triglycerides levels on Triton WR 1339 administration in rats. The extract at the same dose levels significantly attenuated the elevated serum total cholesterol and triglycerides with an increase in the high-density lipoprotein cholesterol in high-fat diet- induced hyperlipidaemic rats. The standard drugs atorvastatin in the former and gemfibrozil in the latter studies showed slightly better effects.

Diagnosis of anomalous origin of left coronary artery from pulmonary artery in an adult by 64-slice CT angiography.

Anomalous origin of Left Coronary Artery from Pulmonary Artery (ALCAPA) presenting in adult age is a rare entity. We report an adult patient with exertional angina, who was diagnosed to have ALCAPA conclusively and non-invasively by 64-slice CT angiography.

Leptospirosis: clinical presentation and correlation with serovars.

A total of 2400 patients with pyrexia of unknown origin and or suspected leptospirosis were included in this study. Dark field microscopy detected Leptospira in 690 cases, Leptospira serological Investigations proved positive in 570 out of these 690 patients. Among them 212 had the classical icteric and the other 358 had anicteric type of presentation. Notably eptospira interrogans serovar ictero haemorrhagiae infection was encountered in 212 patients. In 30 patients, who had multi organ dysfunction which included renal failure, hepatic dysfunction or meningitis was due to Leptospira interrogans Serovar cannicola. Coexsistense of leptospirosis and hepatitis B virus infection were noted in 15 patients. Antibody to Leptospira interrogans was demonstrated by Micro agglutination test (MAT) in addition to dark field microscopy positivity in these cases. Similarly HIV antibody was demonstrated in 30 of the 330 anicteric patients. 554 out of 570 cases responded to intra venous penicillin (216), and oral Doxycycline (182) and Augmentin (156), and the remaining 16 patients succumbed to death.

Neuroprotective evaluation of standardized extract of Centella asciatica in monosodium glutamate treated rats.

The effect of chloroform: methanolic (80:20) extract of C. asiatica (CA; 100 and 200 mg/kg), was evaluated on the course of free radical generation and excitotoxicity in monosodiumglutamate (MSG) treated female Sprague Dawley rats. The extract showed significant improvement in catalase, super oxide desmutase and lipid peroxides levels in hippocampus and striatum regions. Glutathione level was not altered with CA treatment. Similar observation was made with dextromethorphan. The general behavior, locomotor activity and CAl a region of the hippocampus was significantly protected by CA indicating neuroprotective effect of CA in MSG induced excitotoxic condition. Hence it can be concluded that CA protected MSG induced neurodegeneration attributed to its antioxidant and behavioural properties. This activity of CA can be explored in epilepsy, stroke and other degenerative conditions in which the role of glutamate is known to play vital role in the pathogenesis.

Reactivation of trigeminal neuralgia following distraction osteogenesis in an 8-year-old child: report of a unique case.

Trigeminal neuralgia is extremely rare in children. No concrete treatment protocols seem to be available for management of this condition in the pediatric population. Although trigeminal neuralgia may achieve remission, the possibility of reactivation of a hitherto quiescent condition cannot be ruled out. We present a case of pediatric trigeminal neuralgia following distraction osteogenesis of the mandible.

Effect of losartan and enalapril on cognitive deficit caused by Goldblatt induced hypertension.

The present study was designed to evaluate the learning and memory, in an altered physiological state associated with increased blood pressure and activated renin angiotensin system in Wistar rats. The role of angiotensin in cognitive function was assessed by treatment with angiotensin converting enzyme (ACE) inhibitor enalapril (2 mg/kg), angiotensin 1 receptor (AT(1)) antagonist losartan (5 mg/kg) and their combination. The experimental renal hypertension was induced by the method of Goldblatt. Learning and memory was assessed using the radial arm maze test. Acetylcholine esterase (AChE) levels in the pons medulla, hippocampus, striatum and frontal cortex were measured as a cholinergic marker of learning and memory. Results indicate that in comparison to normotensive rats, renal hypertensive rats committed significantly higher number of errors and took more trials and days to learn the radial arm maze learning and exhibited memory deficit in the radial arm maze retrieval after two weeks of retention interval, indicating impaired acquisition and memory. Treatment with enalapril, losartan and their combination attenuated the observed memory deficits indicating a possible role of renin angiotensin system in cognitive function. AChE level was reduced in hippocampus and frontal cortex of renal hypertensive rats which could be attributed to the observed memory deficit in hypertensive rats. It can be concluded that, renal hypertensive rats had a poor acquisition, retrieval of the learned behavior, perhaps a possible disturbance in memory consolidation process and that this state was reversed with ACE inhibitor enalapril and AT 1 receptor antagonist losartan.

Bacteriology of diabetic foot lesions.

Clinical grading and bacteriological study of 107 patients with diabetic foot lesions revealed polymicrobial aetiology in 69 (64.4%) and single aetiology in 21 (19.6%). Among 107 patients 62 had ulcer. Of these 31 had mixed aerobes. Twenty six patients with cellulitis and 12 with gangrene had more than 5 types of aerobes and anaerobes such as E.coli, Klebsiella spp., Pseudomonas spp., Proteus spp., Enterobactor spp., Enterococci spp., Clostridium perfringens, Bacteroides spp., Prevotella spp. and Peptostreptococcus spp. It was noted that 50 out of 62 patients with ulcer, and all the patients with cellulitis and gangrene were given surgical management and treated with appropriate antibiotics based on antimicrobial susceptibility testing.

Evaluation of cognitive function of fluoxetine, sertraline and tianeptine in isolation and chronic unpredictable mild stress-induced depressive Wistar rats.

Depressive illness is generally associated with cognitive impairment. Serotonergic selective antidepressant drugs, fluoxetine (FLX), sertraline (SER) and tianeptine (TIA), are claimed to have less or no effect on cholinergic system, the key system involved in memory. In the present study, these drugs were evaluated for their influence on cognitive behavior in both depressive and non-depressive animals. Depression was induced by two models, (i) 60 days social isolation of litter; and ii) by applying chronic unpredictable mild stress for 21 days. Depression in the rats was confirmed by behavioral despair test. Transfer latency on elevated plus maze and inflexion ratio in passive avoidance step through behavior were employed to assess learning and memory. The results indicated that administration of fluoxetine; sertraline and tianeptine attenuated the cognitive deficits observed in depressive rats. In non-depressive rats these drugs produced retention deficit, which was found to be parameter and model dependent. Data suggested that, FLX and SER (SSRI's) effectively attenuated the isolation-induced depression and cognitive deficit, whereas TIA (SSRE) produced better effect in stress-induced depressive conditions. It was concluded that behavioral profiles of fluoxetine, sertraline and tianeptine on cognition were model and parameter dependent.

Hyperglycaemia in pregnancy: effects on the offspring behaviour with special reference to anxiety paradigms.

Maternal hyperglycemic effect was studied on the offspring behaviour. Offspring were obtained from diabetic rats by mating a normal father with a diabetic mother (NFDM), diabetic father with normal mother (DFNM) and diabetic father with diabetic mother (DFDM). Rats were rendered diabetic by injecting streptozotocin (STZ, 50 mg/kg i.p.) in citrate buffer. Offspring were subjected to various anxiety parameters including open field exploratory behaviour, elevated plus maze and zero maze behaviours, and the social interaction tests at the age of 8 weeks. The results indicate that offspring of NFDM and DFDM showed anxiogenic activity on the elevated plus maze zero maze and the social interaction test. Offspring of NFDM and DFDM exhibited hyper and emotional activity in the open field behaviour test. The behavioural alterations observed in the offspring were comparable to the behavioural alterations noted in STZ diabetic rat as reported earlier. Further offspring of NFDM and DFDM exhibited mild hyperglycaemia. No significant behavioural alterations in the offspring of DFNM were observed. It may be concluded, that exposure of offspring to diabetic environment in their foetal life can lead to anxiogenic/emotional behaviours in adult life.

Superoxide dismutase, catalase and glutathione peroxidase activities in the brain of streptozotocin induced diabetic rats.

Brain antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) levels were studied in the brains of early diabetic (72 hr) and long term diabetic (one month) rats. Diabetes was induced by injecting streptozotocin (50 mg/kg, i.p.) in citrate buffer. One group of diabetic rats was treated with insulin (1U/day/animal). The results indicate that early diabetic rats exhibit increased SOD and CAT activities with no alteration in the GPX activity. On the contrary, increased CAT decreased GPX activities with no alteration in the SOD activity, was noted in the long-term Diabetic rats. Insulin treatment reversed these alterations in both the groups. It can be concluded that, in diabetic condition antioxidant enzyme levels are elevated and insulin treatment attenuated these changes. Hence, diabetes mellitus, if left untreated, may initiate degenerative processes and other CNS complications due to accumulation of oxidative free radicals.

Experimental methods for evaluation of psychotropic agents in rodents: II-Antidepressants.

Rodent models of clinical depression are extensively used for the evaluation of putative antidepressants. In the present review, the available experimental methods which can be utilized by most laboratories involved in preclinical screening of antidepressants, have been discussed. The methods have been categorized on the basis of induction of the depressive state or on the assumption that monoamine deficiency leads to depression. These methods have been critically validated in terms of efficacy of standard antidepressants in these tests and, in some cases, by the neurochemical basis of depression, namely, the deficient monoaminergic theory of clinical depression.