Comparative interaction of few antihypertensive drugs with cyclosporine-A in rats.

The maximal endothelial dependent relaxation of isolated aortic rings to cumulative doses of acetylcholine was significantly decreased in the Cyclosporine-A (CSA, 20 mg kg(-1) day(-1)) treated animals compared to olive oil (CSA vehicle) treated control. Administration of antihypertensive drugs like diltiazem, enalapril or propranolol to CSA treated animals augmented the endothelial damage induced by CSA. These drugs also increased the bioavailability of CSA. However, administration of losartan to CSA treated animals produced a significant increase in endothelial dependent relaxation as compared to CSA treated control but did not affect the bioavailability of CSA significantly. The results suggest that losartan is safer compared to other antihypertensives for the treatment of CSA induced hypertension.

Analgesic activity of new synthetic thiazolidine-4-ones derivatives.

Ten new synthetic thiazolidine-4-ones derivatives (5 chlorothiazolidine-4-ones, 3 methoxythiazolidine-4-ones and 2 hydoxythiazolidine-4-ones) having different substituents at R1, R2 and R3 were evaluated for their analgesic activity using different animal models and their structure activity relationship was also elucidated. Chlorothiazolidine-4-ones and methoxythiazolidine-4-ones exhibited analgesic activity in tail flick test, tail immersion test and acetic acid writhing test. C-III (chloride substituents at R1 and R2) produced higher latencies than any other compounds in tail flick test and C-I (no substituents at R1 and R2) was not effective in acetic acid writhing test. Hydroxythiazolidine-4-ones did not show analgesic activity in any of the animal models used. In conclusion, the character of substituents at R3 of thiazolidine moiety position may have an effect on the analgesic activity of thiazolidine-4-ones and either chloride or methoxy substitution may be necessary to produce analgesic activity. Two chloride substituents in a compound may increase the central analgesic activity of the compound.

A perspective of smooth muscle contractility through actions of vanadium compounds.

Smooth muscle contraction has a characteristic step-response with successive additions of stimulating compounds, and instant reversal on withdrawing the stimulus, indicative of an equilibrium situation wherein continuous, rapid reactions are occurring. Vanadium compounds, ortho- and meta-vanadates, decavanadate and peroxovanadate, were found to contract a variety of smooth muscles. Their actions were analyzed with respect to activation of receptors, increase in the intracellular calcium concentration, and increase in calmodulin-dependent myosin light chain phosphorylation leading to contraction. A new perspective of smooth muscle contractility has emerged from the studies with vanadium compounds suggesting control mechanisms involving phosphorylation for contraction and redox for relaxation.

Correlation between the severity of symptoms in organophosphorus poisoning and cholinesterase activity (RBC and plasma) in humans.

This study was undertaken to examine the correlation, if any, between the inhibition of red blood cell cholinesterase (RBC ChE), plasma cholinesterase (PChE) and cerebrospinal fluid acetyl cholinesterase (CSF AChe) and the severity of symptoms in patients poisoned with organophosphorus (OP) compounds. Baseline values of the cholinesterases (RBC, Plasma & CSF) were established in our laboratory using a modified colorimetric method. OP poisoned patients were divided into 3 groups - mild, moderate and severe based on clinical symptoms. We observed a severity dependent inhibition of both RBC ChE and PChE, in acute poisoning. Sequential post exposure estimations of the ChEs upto 5 days not reveal any rise in the values though there was substantial clinical improvement. Our findings therefore indicate that the correlation of ChE values with severity of symptoms are applicable only in the initial stages of acute poisoning. AChE could not be detected in CSF in two severely neurotoxic patients who subsequently expired. The clinical significance of this observation needs to be examined further.

Felodipine potentiates morphine analgesia in control and streptozotocin diabetic female rats.

Tolerance to morphine analgesia was seen in diabetes. Calcium channel blockers potentiate opioid analgesia while calcium agonists antagonize. Therefore, the present study using thermal pain threshold was taken up to find out, whether felodipine, altered morphine analgesia in experimental diabetes. From the end of 6th week of streptozotocin-diabetes, felodipine was administered po for 2 week to half of the control and diabetic female rats. Morphine analgesia was recorded 1 hr after the first (acute effect) and last dose (chronic effect) of felodipine. Significant elevation of pain threshold was seen in the first 6 weeks in diabetic rats compared to controls. No tolerance was seen to morphine (2 mg/kg, sc) analgesia in diabetic rats. In both control and diabetic rats acute administration of felodipine produced significant analgesia while both acute and chronic administration of felodipine produced significant potentiation of morphine analgesia in control diabetic rats. The results suggest that prior felodipine may enhance morphine analgesia, and that this needs to be explored further in various types of pain.

The isolated air perfused rat heart.

A simple method has been developed for continuous monitoring of metabolic activity of an isolated, perfused rat heart by O2/CO2 respirometer. Since respirometer provides vital data on oxygen consumption and carbon dioxide production of a preserved organ on a continuous basis over a long period of time, it will be possible to use this method to monitor viability of not only isolated heart but also any given donor organ under preservation.

A comparative study of prescribing pattern at different levels of health care delivery system in Bangalore district.

A study of prescribing pattern in tertiary, primary and urban general practice levels of the Indian health care delivery system was undertaken by analyzing 1810 prescriptions for 3932 drugs. The study evaluated feasibility of data acquisition methods and compared the prescribing frequency of various drug groups and of individual drugs in three commonly used categories. The mean number of drugs per prescription was highest in urban general practice (2.41). The four most frequently prescribed drug groups were antibacterials, vitamins, nonsteroidal antiinflammatory drugs (NSAIDs) and respiratory drugs. The study delineates the differences in prescribing frequency of drug groups and individual drugs across the three levels of health care and the results suggest intervention strategies to promote rational drug therapy.

Effect of felodipine on cholinergic responses of the colonic smooth muscle of streptozotocin induced diabetic rats.

In streptozotocin induced diabetic rats, irrespective of felodipine treatment (5 mg/kg/day po for 4 weeks), a reduction in contractile response of colonic smooth muscle in vitro was observed. Similarly, in both control and diabetic rats treated with felodipine, contractile response was reduced. However, in felodipine treated diabetic rats there was a significant increase in response to exogenous acetylcholine. It may be of interest to study the effect of felodipine, on gastro-intestinal motility in vivo in diabetic rats, to enable extrapolation of the present results to the effect of felodipine on gastrointestinal complications of diabetes mellitus.

Effect of felodipine on myocardial function and cholinergic responses in short term streptozotocin diabetes in rats.

Cardiovascular complications of diabetes mellitus account for 80% of deaths among diabetics. Autonomic neuropathy increases the susceptibility of the diabetic myocardium to arrhythmias. Decreased contractility of diabetic myocardium is associated with intracellular calcium overload. However, the relationship between calcium levels and myocardial cholinergic responses is not known. This study was undertaken to observe the effect of felodipine 5 mg/kg on myocardial function and cholinergic responses of the spontaneously working isolated heart of rats with short term streptozotocin-diabetes. Felodipine was administered (po) for 4 week to rats with streptozotocin-diabetes of 4 week duration. Felodipine did not alter the blood glucose levels. The increased cardio-somatic ratio in diabetic rats was attenuated by felodipine. Diabetic status was associated with decreased coronary flow and felodipine increased coronary flow in diabetic rat hearts both before and after ACh. It may be concluded that felodipine favourably altered the adverse myocardial pathology in experimental diabetes, and this strengthens its use as an antihypertensive in diabetics.

Correlation of time course of blood cholinesterase activity and toxic manifestations of acute methylparathion in antidote treated rats.

Study was conducted to find out the correlation between red blood cholinesterase (RBC ChE) and plasma butyryl cholinesterase (BuChE) activities and toxic signs of oral methylparathion (MPT) and their recovery pattern with or without atropine treatment in female rats. Enzyme activity was estimated before and after an oral dose of MPT (7.5 mg/kg-1) at various time intervals upto 120 hr. Antidote groups received atropine (10 mg/kg-1, i.p.), either alone or with diazepam (2.5 mg/kg-1, i.p.), at the onset of toxic signs. Inhibition of enzyme activity served as definite index of acute toxicity of MPT. RBC ChE activity correlated with the intensity of toxic signs in no-antidote rats, while in atropine treated groups, there was no correlation. BuChE levels did not correlate with toxic signs in any of the groups except in the fatal group. The resynthesis of both the enzymes was complete in 120 hr study and did not synchronize with the recovery pattern of animals from toxic signs. Compared to BuChE, RBC ChE activity was found to be a more sensitive indicator for the diagnosis of severity of MPT toxicity.

A preliminary audit of practice--antibacterial prophylaxis in general surgery in an Indian hospital setting.

As a major proportion of antibacterials used in hospital practice are for surgical prophylaxis, an audit of practice in relation to antibacterial prophylaxis in general surgery was undertaken over a four week period in a teaching hospital to assess the extent to which principles governing surgical antibacterial prophylaxis were practised and to provide a feedback to the clinicians. The extent of use of anti-bacterial agents in surgical prophylaxis was 90%. The timing of administration was more than 2 h before surgery in 21% of the cases. Intravenous route was used in 97% of the cases. The duration of prophylaxis was more than 72 h in 48% of cases. Cefazolin was the most frequently prescribed either alone or in combination with metronidazole. The study indicated inappropriateness in the timing and duration of administration of surgical antibacterial prophylaxis.

Species variation in the specificity of cholinesterases in human and rat blood samples.

Acetylthiocholine iodide (ATC) as a common substrate in the combined assay of red blood cell cholinesterase (RBC ChE) and butyrylcholinesterase (BuChE) do not provide the accurate individual enzyme activities. Hence, in the present study the two enzyme activities in the same sample were assayed with the help of two different substrate, ATC and butyrylthiocholine iodide (BTC). Specificity of BTC towards BuCHE was found in blood, plasma and serum, while ATC is nonspecifically hydrolysed by both RBC ChE and BuChE. ATC gives significantly higher enzyme activity (P < 0.001) in rat plasma/serum and significantly lower enzyme activity (P < 0.0001; P < 0.001) in human plasma/serum. The possible reasons are discussed for substrate specity in various species in the assay of ChEs.

Effects of ECT-dothiepin combination on learning in rats.

Electroconvulsive therapy (ECT) and antidepressant drugs are each known to impair learning and memory. No information is available on their effects on cognition when used concurrently in the treatment of depression, as is frequent in India. In the present study, therefore, the effects of electro-convulsive shocks (ECS) and dothiepin, separately and in combination, were studied in an animal model employing a complex maze operant learning paradigm. ECS were given on alternate days (3/week) for 2 weeks. Dothiepin (10 mg/kg, ip) was administered once daily for 2 weeks. Learning was assessed on days 2-10 post-treatment ECS produced greater initial impairment in learning while dothiepin produced a more sustained impairment. While impairment was maximum in the combined treatment group, the statistical significances that emerged to proscribed the combination were but weak.

Effect of felodipine on serum lipid profile in short term streptozotocin-diabetes in rats.

Lipid lowering effect of calcium antagonists is well documented in high fat fed rats and in hypertensive patients. In order to study their effect on lipid profile in experimental diabetes, felodipine 5 mg/kg/day per oral for 4 week was given to rats with streptozotocin-diabetes of 8 week duration. Serum total cholesterol and triglycerides were estimated in non-fasting rats at the end of the study period using Ranbaxy diagnostic kits. Diabetic rats had a significant elevation of both total cholesterol and triglycerides. In diabetic rats felodipine treatment produced a significant reduction of the serum triglycerides while there was no change in the serum total cholesterol. In control rats the drug did not produce any significant alteration in the levels of both total cholesterol and triglycerides.

Improved colorimetric method for cholinesterase activity.

A modified colorimetric method for the estimation of cholinesterase activity has been worked out using two different substrates, acetylthiocholine iodide for total cholinesterase and a specific substrate, butyrylthiocholine iodide for pseudocholinesterase in the same sample. This is a modification of the method described by Voss and Sachsse (1970) wherein acetylthiocholine iodide was used for both total and pseudo cholinesterase activities. The pseudocholinesterase obtained with acetylthiocholine iodide was significantly higher (P < 0.0001) than that with butyrylthiocholine iodide either in whole blood or serum samples. Acetylthiocholine iodide while reacting with pseudocholinesterase in serum or plasma samples might also be interacting with the small quantities of acetylcholinesterase present. It is therefore suggested that butyrylthiocholine iodide and acetylthiocholine iodide may be used to determine pseudocholinesterase and total cholinesterase activities respectively. The use of two substrates with a few more alterations in the experimental conditions increased the validity of this simple and rapid colorimetric method.

Erythrocyte and plasma cholinesterase activity in normal pregnancy.

Erythrocyte acetylcholinesterase and plasma cholinesterase was estimated in 50 normal pregnant women and 22 age matched normal non-pregnant women. Plasma cholinesterase was significantly decreased while erythrocyte cholinesterase was significantly increased during pregnancy. These changes may be related to altered haemodynamics and or other inter-related changes occurring in pregnancy.

Effect of inhalation of insecticide spray on learning and memory in rats.

Acute exposure to insecticide (Baygon-spray; 5 ml/animal/5 min) inhalation in rats did not affect the learning process but produced a significant loss of memory (P less than 0.01 less than 0.001) whereas chronic exposure (one exposure per day for three weeks) produced a significant delay in learning (P less than 0.05) and memory (P less than 0.01). Acetylcholinesterase activity in brain after acute and chronic exposure declined significantly (P less than 0.01) during the learning process but returned to normal after 24 hr.

Acetylcholinesterase activity of rat brain and heart in starvation and protein restriction.

AChE activity was determined in the brain and heart of normal, acute totally starved, chronically semi-starved and chronically protein restricted groups of adult male rats. Neither acute total starvation nor chronic semi-starvation produced significant changes in AChE activity and protein content of the brain, while AChE activity and protein content in the heart were significantly decreased (P less than 0.01) after semi-starvation. Protein restriction, however, produced a significant decrease in AChE activity and protein content of both brain (P less than 0.01) and heart (P less than 0.001).