Biomedical subjects
Publications and source records attributed to B V Venkataraman.
Wedelolactone (WL) and demethylwedelolactone (DWL) isolated from Eclipta alba were tested in the trypsin inhibition bioassay (in vitro). Both compounds showed potent activity. IC(50) values of WL and DWL were found to be 2.9 and 3.0 microg/mL respectively.
Successive extracts of Tribulus terrestris prepared using petroleum ether, chloroform, 50% methanol and water were tested for anthelmintic activity in-vitro using the nematode Caenorhabditis elegans. The activity could be detected only in 50% methanol extract which on further bioactivity guided fractionation and chromatographic separation yielded a spirostanol type saponin, tribulosin and beta-sitosterol-D-glucoside. Both the compounds exhibited anthelmintic activity with ED50 of 76.25 and 82.50 microg/ml respectively.
Previous research found that the administration of verapamil and felodipine immediately before electroconvulsive shocks (ECS) attenuated ECS-induced retrograde amnesia. This study examined whether sodium nitroprusside, an antihypertensive drug that does not affect calcium channels, has a similar action. Adult male Sprague-Dawley rats received nitroprusside (0.5 mg/kg ip) or saline 3 minutes before each of three once-daily true or sham ECS. Retention of pre-ECS learning was studied 1 day after ECS using a passive avoidance task. Nitroprusside was associated with increased seizure duration in ECS-treated rats, and with enhanced recall in both true and sham ECS groups. The latter finding suggests that nitroprusside nonspecifically improves cognitive functions, and does not support the hypothesis that ECS-induced cognitive impairment is a result of blood-brain barrier breach. Nitric oxide mechanisms may underlie the benefits purveyed by nitroprusside.
Phenylephrine is a nonselective alpha-receptor agonist. This study examined whether the administration of phenylephrine immediately before electroconvulsive shocks (ECS) attenuated ECS-induced retrograde amnesia. Adult male Wistar rats received phenylephrine (0.25 mg/kg i.p.) or saline 3 min before each of three once-daily true or sham ECS. Retention of pre-ECS learning was studied 1 day after the ECS course using a passive avoidance task. Phenylephrine increased seizure duration in ECS-treated rats, and also enhanced recall in both true and sham ECS groups. The latter finding suggests that phenylephrine nonspecifically improves cognitive functions, perhaps through adrenergic mechanisms that improve memory consolidation and storage. Since phenylephrine increases blood pressure, its cognitive effects also weaken the hypothesis that ECT-induced cognitive impairment results from the seizure-related hypertensive surge.
During the last decade the use of herbal medicinal substances in the attenuation of anterograde and retrograde amnesia induced by electroconvulsive shock (ECS) has been studied using animal research. We will discuss the background of herbal medicine in India, review the research findings on herbal medicines for ECS-induced amnestic deficits, and examine the applications and limitations of animal models in this context. We will focus on our own research and insights, with particular emphasis on practical issues.
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.
Oxidative damage to crucial biomolecules due to excess generation of reactive oxygen species has been implicated as a major cause of organ damage and hence compounds capable of negating such damage have potential benefits. Using hydrogen peroxide (H2O2) as a model pro-oxidant to induce oxidative stress, we have examined the ability of natural food supplement Maharishi Amrit Kalash (MAK-4) to decrease oxidative damage in potassium-arrested isolated rat hearts. The protocol was that hearts isolated from male Sprague-Dawley rats were retrograde-perfused with Krebs-Henseleit (K-H) solution for 30 min for equilibration. After this period, the hearts were subjected to cardioplegia with high potassium (26-30 mM), followed by reperfusion with K-H solution in the presence or absence of 200 microM H2O2. As expected, H2O2 treatment following cardioplegia induced a high degree of oxidative stress as assessed by release of lactate dehydrogenase (LDH, a marker of plasma membrane damage) and total glutathione (GSH + GSSG). H2O2 also impaired the ability of heart to regain developed tension during the testing period. However, addition of MAK-4 in the perfusate containing H2O2 decreased oxidative stress in terms of release of LDH and glutathione. In parallel with these biochemical studies, in a few experiments the cardiac function was assessed by measuring developed contractile tension. These preliminary studies also showed that in the presence of MAK-4 the H2O2-treated hearts were able to regain better developed tension. Further in vitro studies to examine the possible mechanisms of MAK-4 action reveal that this formulation contains H2O2 binding activity which resulted in the decreased availability of H2O2 itself. Our studies hence reveal that the ayurvedic food supplement MAK-4 may have potential benefits in reducing oxidative stress.
Decavanadate, an inorganic polymer of vanadate, produced contraction of rat aortic rings at a relatively high concentration compared to phenylephrine, an agonist of alpha-adrenergic receptor. This effect was blocked by two known alpha-adrenergic receptor antagonists, prazosin and phenoxybenzamine. Decavanadate, formed by possible dimerization of V5 under acid conditions, possessed a structural feature of two pairs of unshared oxygen atoms at a distance of 3.12 A, not found in its constituents of V4 or V5. A structural motif of O..O..O using such oxygen atoms is recognized in decavanadate. This matches with a similar motif of N..O..O that uses the essential amino and hydroxyl groups of the side-chain and the m-hydroxyl group in trans-beta form of noradrenaline. The interaction of such a structural motif with the membrane receptor is likely to be the basis of the unusual noradrenaline-mimic action of decavanadate.
Two once-daily electroconvulsive shocks (ECS) produced retrograde amnesia in rats trained on a Hebb-Williams maze; Verapamil (12.5 mg/kg, i.p.) or felodipine (10 mg/kg, p.o.) administered half an hour before each ECS attenuated this ECS-induced amnesia. Hence, these drugs may hold promise for the containment of amnesia induced by electroconvulsive therapy (ECT). Speculatively, one or more of several mechanisms may be involved: cerebral vasodilatation, enhancement of cholinergic tone, and inhibition of calcium-mediated impairment of neuronal function. These drugs may also act by attenuating the systolic surge in blood pressure during ECT, thereby decreasing edema due to cerebral hyperperfusion, as well as decreasing the possible transfer of potentially neurotoxic macromolecules through a putative breach in the blood-brain barrier.
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.
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.
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.
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.
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.
BR-16A is an herbal (non-allopathic) medication used in India to enhance cognition. Sixty adult male Sprague Dawley rats received either BR-16A (200 mg/kg/day) or vehicle alone for 16 days. During the first 7 days, the rats were trained in a spatial memory task using the Hebb Williams complex maze. Once a day for the next 2 days, rats in BR-16A and control groups received either true or sham electroconvulsive shock (ECS). During the last 7 days of the study, the rats were reexposed to the maze to assess recall of pre-ECS training and to evaluate further improvement in learning scores. BR-16A-treated rats performed better than controls both before and after ECS. It is concluded that BR-16A facilitates learning and that this effect extends to a protection against ECS-induced anterograde and retrograde amnesia. BR-16A may hence hold promise in the restriction of ECT-induced cognitive compromise. An unexpected observation in this study was that BR-16A attenuated seizure duration; implications and mechanisms are discussed.
BR-16A is an herbal (non allopathic) medication used in India to enhance cognition. In experiment 1, 28 Wistar rats received either BR-16A (200 mg/kg/day) or vehicle alone for 3 weeks. During the third week, the rats were tested for learning in the Hebb Williams complex maze. BR-16A-treated rats showed significantly better learning than did controls. Experiment 2 was conducted identically except that during the second week all of 32 rats additionally received six once-daily electroconvulsive shocks (ECS). An advantage for learning was again demonstrated for the BR-16A group. It is concluded that BR-16A facilitates learning, and that this effect extends to a protection against ECS-induced anterograde amnesia. Cognitive deficits induced by electroconvulsive therapy are a major disadvantage of the treatment and, to-date, no drug has been found to offer satisfactory protection against such deficits. It is suggested that BR-16A may hold promise in the containment of electroconvulsive therapy (ECT)-induced cognitive compromise.
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.
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.