Preparation of [Al(hfip)4](-)-based ionic liquids with siloxane-functionalized cations and their physical properties in comparison with their [Tf2N]- analogues.

Two new ionic liquids (ILs) with siloxane-functionalized cations and the weakly coordinating tetraalkoxyaluminate [Al(hfip)(4)](-) (hfip=hexafluoroisopropoxy) are prepared and characterized by nuclear magnetic resonance (NMR), infrared (IR) and Raman spectroscopy. With melting points below 0 °C they qualify as room temperature ILs (RTILs). Their temperature-dependent viscosities and conductivities, together with those of two [Tf(2)N](-) ILs with the same cations and a further siloxane-functionalized [Tf(2)N](-) IL, are measured between 0 and 80 °C, and all are described by the Vogel-Fulcher-Tammann (VFT) equations. We note that the [Al(hfip)(4)](-) ILs have lower viscosities than their [Tf(2)N](-) analogues at all measured temperatures and higher conductivities at room temperature.

Understanding the polarity of ionic liquids.

The polarities of a wide range of ionic liquids have been determined using the Kamlet-Taft empirical polarity scales α, ß and π*, with the dye set Reichardt's Dye, N,N-diethyl-4-nitroaniline and 4-nitroaniline. These have been compared to measurements of these parameters with different dye sets and to different polarity scales. The results emphasise the importance of recognising the role that the nature of the solute plays in determining these scales. It is particularly noted that polarity scales based upon charged solutes can give very different values for the polarity of ionic liquids compared to those based upon neutral probes. Finally, the effects of commonplace impurities in ionic liquids are reported.

Knowledge, attitudes and practices (KAP) regarding the management of diarrhea by pharmacists and licensed drug sellers in eastern Nepal.

Diarrhea constitutes a major cause of morbidity and mortality in developing countries. Inappropriate drug prescribing is common in diarrhea, resulting in an increase in cost and adverse drug reactions. In Nepal, drug sellers often act as the first contact persons for the underprivileged. No information has been available regarding their knowledge, attitudes and practices (KAP) regarding diarrhea management. Using a structured questionnaire, between the 1st of January and the 31st of December 2003, 109 drug sellers in eastern Nepal were interviewed about their educational status, patient/attendant presentation at the outlet and their advice to patients/attendants. Only 2.7% of drug sellers were qualified in health education. Eighty percent of the patients/attendants sought advice from the drug sellers, only 20% presented to the outlet with prescriptions. The data reveals that about half of them were taking note of the nature of the diarrhea. Although 62 (56.8%) of them were aware of dehydration, only 2 (1.8%) of them knew all three signs of dehydration (dry tongue, non-elastic skin and sunken eyes). Sixty-six (60.5%) of them knew about oral rehydration solution (ORS), its principle and the required period of administration. About 50 to 60% of them were aware of the implications resulting from dehydration from uncontrolled diarrhea and of the importance of ORS in its management. Only 20% of the drug sellers advised ORS alone, otherwise it was dispensed along with drugs, such as antimotility agents (AMA) or metronidazole. As a result of the above findings, it is important to educate the drug sellers by conferring knowledge about the ethical aspects of drugs in the management of diarrhea.

Evaluation of pre-ECS antihypertensive drug administration in the attenuation of ECS-induced retrograde amnesia.

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.

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.

Herbal pharmacotherapy for the attenuation of electroconvulsive shock-induced anterograde and retrograde amnestic deficits.

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.

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.

BR-16A protects against ECS-induced anterograde amnesia.

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.

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.

Relationship between rate of administration of electroconvulsive shocks and rate of learning in rats: implications for the practice of ECT.

Number of electroconvulsive therapy (ECT) treatments administered and severity of psychopathology confound the interpretation of clinical studies that address the relationship between the rate of administration of ECT and cognitive morbidity occasioned by the treatment. A preclinical study was therefore conducted to address the issue. Three groups (n = 8/group) of adult male Sprague-Dawley rats received six electroconvulsive shocks (ECS) in daily ECS, 3 ECS/week, and 2 ECS/week schedules; a fourth group (control; n = 8) received only sham ECS. From days 2 to 7 after the conclusion of the ECS/sham ECS course, the rats were monitored for learning on the Hebb-Williams complex maze. The control, 2 ECS/week, and 3 ECS/week groups showed significant learning by days 3, 5, and 7, respectively, while the daily ECS group showed no significant learning during the assessment period. This indicates that even when the cumulative effect of ECS on learning is controlled for, more frequent ECS is associated with slower learning. Extrapolating to clinical settings, it is suggested that wider spacing of ECT may lessen ECT-induced cognitive morbidity.

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.

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.

ECT-induced anterograde amnesia: can the deficits be minimized?

To date, no pharmacological agent has been confirmed to lessen electroconvulsive therapy (ECT)-induced memory deficits. BR-16A is an herbal preparation, containing various organic extracts, used in India for the enhancement of cognition (among other applications). In the present study, adult male Sprague-Dawley rats received six once-daily electroconvulsive shocks (ECSs). Half the animals were treated with BR-16A (200 mg/kg/day) for 1 week before ECS, during the ECS course, and during the post-ECS learning assessment phase; the remaining animals received vehicle alone. In experiment 1, rats (n = 16/treatment group) were preassessed for learning on days 3 and 5 of exposure to the Hebb-Williams complex maze and were reassessed after comparable exposure to the maze starting from the second day post-ECS. In experiment 2, rats (n = 9/treatment group) were preassessed for number of trials to satisfactory learning and number of wrong arm entries in a T-maze and were reassessed on the second day post-ECS. The learning preassessments were conducted just prior to the commencement of the BR-16A/vehicle treatments. In both experiments, rats receiving BR-16A performed significantly better than controls. It is concluded that BR-16A protects against ECS-induced anterograde amnesia. BR-16A may therefore have scope in minimizing ECT-induced learning deficits.

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.

Effect of dothiepin on nociceptive response in diabetic rats.

In alloxan-diabetic rats of 4 wk duration with blood glucose levels of about 300 mg/100 ml, the tail flick reaction time (TFRT) to thermal stimuli was significantly elevated (P less than 0.25), indicating hypoalgesia. Intraperitoneal dothiepin, injections of 25 mg & 50 mg/kg body weight per day did not significantly alter the TFRT, either in control or in diabetic rats, following either acute (one dose), or short term (once a day for five days) administration. It is concluded that at least in the dosage schedule used herein, dothiepin does not influence hypoalgesia of diabetic neuropathy.