Pesticides `contamination of lactating mothers’ milk in the north-western Himalayan region of India

Aim: The objective of the study was to develop and characterize the properties of sago (sabudana) from cassava based reconstituted dry starch with addition of pre-gelatinized starch and wet starch as binders.Methodology: The dry starch was soaked for 12 hrs at 30 % concentration and then sago was prepared at 40% moisture content with addition of pre-gelatinized starch and wet starch as binders in different treatment combinations. Results: The sago developed from the combination of reconstituted dry starch (75%) and wet starch (25%) had an optimal commercial size (3.36 mm) and shape (sphericity value, 76 %). The swelling power (5.98%) was high in reconstituted dry starch sago and solubility (13.42 %) was high in wet starch sago without the addition of any binders. The increase in cooking time (10.37%) and decrease in cooking loss (1.73%) were observed for sago developed with pre-gelatinized starch as binder. The lowest oil absorption index (0.45 g g-1) was noticed for sago prepared with wet starch as a binder. The storage modulus was comparatively lower for sago paste prepared using wet starch and thus the sago gel behaved like a dilute solution with increase in storage modulus and phase angle. Interpretation: The physico-functional properties of the cassava -based reconstituted dry starch sago can be improved by adding wet starch as a binder due to less retrogradation rate. Further, the addition of pre-gelatinized starch as a binder with reconstituted cassava dry starch can reduce the cooking loss in sago.

Possible involvement of leptin in a Mas-receptor agonist, AVE-0991-induced improvement in dyslipidemia and cardiomyopathy in STZ-induced diabetic rats.

Present study was designed to investigate the possible involvement of leptin in the pharmacological activation of Mas–receptor in STZ-diabetic rats, with cardiomyopathy. A single administration of STZ (50 mg/kg, i.p.) produced diabetes which leads to cardiomyopathy after 8 weeks. Estimation of serum glucose has been used as a marker of hyperglycemia. Cardiomyopathy was assessed by measuring LV collagen content, absolute LV weight, LVW/BW ratio, LVDP, dp/dtmax and dp/dtmin. Furthermore, serum triglyceride, serum cholesterol and serum HDL levels were estimated as an index of dyslipidemia. Rat serum leptin was quantitatively estimated by using enzyme-linked immunosorbent assay (ELISA) kit. STZ-diabetic rats were associated with significant hyperglycemia, hypertriglyceridemia, decreased cardiac functions and decreased serum leptin level. Both the low and high dose AVE-0991 treatment, significantly decreased hyperglycemia and increased serum leptin level in diabetic rats. Whereas, AVE-0991 only at high dose significantly improved lipid profile and cardiac function. on the basis of above, it may be concluded that downstream activation of leptin may be responsible for the beneficial effect of AVE-0991, a Mas-receptor agonist in STZ-induced diabetic cardiomyopathy in rats.

Possible Involvement of "Phosphatidylinositol-3 kinase and endothelial nitric oxide synthase' in experimental obesity induced vascular endothelium dysfunction.

This study was designed to investigate the possible role of Phosphatidylinositol-3 kinase (PI3K) and endothelial nitric oxide synthase (eNOS) in obesity-induced vascular endothelium dysfunction. Wistar rats were fed high fat diet (HFD) for 12 weeks to induce obesity. HFD induce obesity significantly increased parameters employed viz body weight, basal metabolic index (BMI), total fat pad and lipid profile. Furthermore vascular endothelial dysfunction was assessed in terms of decrease in endothelium dependent relaxation and serum nitrate/nitrite level and increase in mean arterial blood pressure. Atorvastatin (30mg/kg,i.p.) was employed in the present study as standard drug to improve vascular endothelial dysfunction. YS-49 (1.6 mg/kg, i.p.) a specific activator of PI3K and atorvastatin in obese rats significantly improves the lipid profile and markedly improved acetylcholine induced endothelium dependent relaxation, serum nitrite/nitrate concentration and mean arterial blood pressure. However, this ameliorative effect of YS-49 has been prevented by L-NAME (25 mg/kg, i.p.), an inhibitor of eNOS. Further wortmannin (100μg/kg, i.p.),a specific PI3K inhibitor improves the anthropometric parameters and lipid profile but did not show any significant effect on acetylcholine dependent relaxation, serum nitrate/nitrite level and mean arterial blood pressure. Therefore, it may be concluded that PI3K and eNOS pathway is dysregulated in obesity induced vascular endothelial dysfunction and YS-49, a PI3K activator improves vascular endothelial function in eNOS and nitric oxide dependent manner. Abbreviations (Ach): Acetylcholine, (Ang-II): Angiotensin II, (BMI): Body Mass Index, (Enos): Endothelial Nitric Oxide, Synthase, (HO-1): Heme Oxygenase, (Kcl): Pottesium Cloride, (MAP): Mean Arterial Pressure, (NO): Nitric Oxide, (PI3K): Phosphatidylinositol 3-Kinase, (SNP ): Sodium Nitroprusside, (VED): Vascular Endothelium Dysfunction

Role of noradrenaline uptake inhibition and alpha-adrenoceptors in reperfusion ventricular arrhythmias in vivo and in vitro.

In view of the importance of sympathetic nervous system in the genesis of cardiac arrhythmias during reperfusion following coronary occlusion, the role of noradrenaline uptake inhibitor desipramine in the prevention of reperfusion arrhythmias was investigated in intact rabbit heart and isolated rat heart. For both the paradigms, ischaemia was produced by coronary artery ligation for 30 min followed by reperfusion for 60 min with drug administration at the time of reperfusion. Desipramine was used at three dose levels (0.2, 0.6 and 2.0 mg/kg) in the in vivo study while in vitro it was used at a concentration of 7 microM. Further, to investigate the status of adrenergic receptors during ischaemia and reperfusion, ischaemia was simulated by superfusing lactate physiological solution in isolated rabbit aortic strip preparation, which has well characterized alpha-receptors. Cumulative dose response curves (DRC) of selective alpha 1 agonist, phenylepherine (PE) were recorded during normal, ischaemic and reperfused conditions. Desipramine showed dose dependent anti-arrhythmic effect in vivo as well as in vitro. In intact heart studies desipramine offered protection against reperfusion arrhythmias in a dose related manner i.e. 50, 67.5 and 100% whereas in isolated studies, 50% protection was observed in the overall incidence of arrhythmias. DRC of PE shifted towards right during both ischaemia and reperfusion with a significant elevation of maximal response only during reperfusion.

Evaluation of antimuscarinic activity in human volunteers: a teaching aid in clinical pharmacology.

The antimuscarinic activity of oxyphenonium bromide, diphenhydramine hydrochloride and astemizole were evaluated in six volunteers. The parameters used were salivary secretion, heart rate and pupillary size. The results indicated that the changes in heart rate and pupillary size and measurements were not convenient parameters for class room demonstration. However, salivary secretion and dryness of mouth were found to be reliable parameters for measurement. It was concluded that simple procedures like evaluation of antimuscarinic activity could be introduced as teaching aids in clinical pharmacology for undergraduate students.

Possible mechanism of endosulfan-induced enhancement of memory acquisition and retention in mice.

The effects of pre-training and post-training administration of endosulfan on retention of a step-down passive avoidance task was studied in mice. Endosulfan at doses of 1.0 mg/kg(ip) and 2.0 mg/kg(ip) enhanced memory acquisition and retention. This effect of endosulfan was possibly mediated by interaction with cholinergic neurotransmission, as scopolamine (0.5 mg/kg, ip) significantly antagonized the memory enhancing effects of endosulfan. Clonidine (0.05 mg/kg, ip) did not have any effect on enhancement of memory produced by endosulfan, thus indicating possibly no role of noradrenergic system.

A study on withdrawal related haemodynamic response in chronic propranolol treated conscious rats.

Single dose of propranolol hydrochloride (5 mg/kg, i.p.) caused significant fall in heart rate (HR) but not in systolic blood pressure (SBP) in normotensive conscious rats. Multiple doses of propranolol (5 mg/kg, i.p., twice-a-day for 5 wk) caused significant fall in both HR and SBP at 2 wk and 4 wk in normotensive conscious rats. Sudden withdrawal of propranolol at 5 wk caused a significant blood pressure upswing and tachycardia between 12-24 h followed by normalization of both blood pressure and heart rate. The study documents a possible model of rebound hypertension in normotensive conscious rats.

Effects of ranitidine alone and in combination with chlorpheniramine on histamine-induced wheal and flare and psychomotor performance.

Some reports suggest that addition of an H2 antagonist increases the efficacy of H1 antagonist but the influence on the side effect profile of antihistamines are largely unknown. The effects of ranitidine, chlorpheniramine, their combination and placebo on histamine induced wheal and flare, psychomotor performance and subjective symptoms were studied in 6 healthy male volunteers in a double blind randomized and cross-over (Latin square) study. Ranitidine significantly reduced the histamine induced wheal at 4 hrs (P < 0.05). Chlorpheniramine and the combination significantly reduced both histamine induced wheal and flare at 2 hrs and at 4 hrs (P < 0.05). Addition of ranitidine reduced the feeling of sleepiness produced by chlorpheniramine, though other subjective symptoms were not affected. None of the treatment schedules produced any consistent change in the psychomotor performance of the volunteers.

A preliminary study on the interaction between ethanol and propranolol in normal human subjects.

Ethanol significantly increased the steady-state peak concentration of propranolol while propranolol significantly reduced the total body clearance of ethanol in healthy human volunteers. Ethanol per se caused tachycardia and rise in systolic blood pressure while propranolol administration resulted in bradycardia. In combinations, ethanol and propranolol caused significant fall in diastolic blood pressure without any significant changes in the heart rate and systolic blood pressure compared to the control readings of four healthy male volunteers. The kinetic and haemodynamic interactions observed between ethanol and propranolol in the preliminary study are of clinical relevance and need further exploration.

Effect of fatty diet on pharmacokinetics and pharmacodynamics of a liquid theophylline preparation in volunteers.

The effect of a standard breakfast and a fatty breakfast on the pharmacokinetics and pharmacodynamics of a theophylline liquid preparation (160 mg-single dose) was examined in 6 healthy, non-smoking male volunteers. The plasma theophylline concentrations after both standard and fatty diet were found to be comparable at each point of time and pharmacokinetic parameters like Cmax, Tmax, T1/2a, T1/2 beta and AUC0-alpha, were also comparable. However, the time taken to attain the therapeutic plasma concentration was earlier and sustained along with the standard breakfast in comparison to that with fatty breakfast. Peak change in PEFR and pulse rate was also observed earlier with the standard diet than with fatty diet. The plasma theophylline concentrations produced after both diets were insufficient to produce any detectable change in subjective symptoms like tremor palpitation, heart burn, nausea, restlessness and tenseness. However, theophylline after fatty breakfast was better tolerated than that after a standard breakfast.

Patients' attitude towards health care at a teaching hospital in India.

Using a questionnaire, 362 patients attending the outpatients services of Internal Medicine of Nehru Hospital attached to our institution were randomly interviewed. Seventy per cent of the patients were in the 21-50 years age range; 50% came from rural and 50% from urban areas. Forty per cent travelled more than 30 Km; 72% used a public transport to reach hospital. Most patients had an income less than Rs. 1000/-. Ninety per cent had already consulted another medical practitioner earlier. The largest number of complaints related to the gastrointestinal, cardiovascular and respiratory systems. On an average 1-2 drugs were prescribed per patient; only 13% of these were available at the hospital dispensary. Most patients were willing to purchase the prescribed drugs from the market.

Effect of subacute insecticide exposure on body weight, drug responses & electrical convulsions in mice.

Effect of subacute insecticide exposure was studied in male albino mice treated with phosphamidon, propoxur or aldrin at 1/40 LD50 dose intraperitoneally daily for 8 wk. The parameters studies included body weight, pentobarbitone (50 mg/kg) sleeping time, chlorpromazine (6 mg/kg) induced motor incoordination and convulsions induced by leptazol (100 mg/kg) and electrical stimulation (18 mA for 0.2 msec). While body weight and electrically induced convulsions were not affected, the effect of various drugs was significantly decreased. The observed changes may be due to the induction of hepatic drug metabolising enzymes by the insecticides. The study suggests that certain dose adjustment of drugs may be necessary in those exposed to insecticides over long periods.

Effect of subacute DDT on pharmacokinetics of isoniazid and liver function in rabbits.

DDT administration (30 mg/kg per day, po, for 21 consecutive days) to rabbits showed an increase in peak plasma concentration and a decrease in time to reach peak plasma concentration of isoniazid whereas no change was observed in elimination rate constant and area under the plasma concentration-time curve. DDT treatment caused increased absorption of isoniazid. Early signs of hepatic damage were also observed. Since there was no change in the levels of serum glutamate oxaloacetate transaminase and serum glutamate pyruvate transaminase, it can be concluded that DDT does not significantly affect liver function at the dosage used. The observed elevated levels of alkaline phosphatase could be due to direct activation of the enzyme. Leukopaenia and neutropaenia with relative lymphocytosis indicated that DDT might have suppressant effect on granulocyte cell line of WBCs.

Effects of morphine, buprenorphine, pentazocine and nalorphine on acquisition and extinction of active avoidance responses in rats.

The effects of subcutaneous administration of morphine, buprenorphine, pentazocine and nalorphine were studied at two dose levels in rats (low dose x 10 and high dose x 20 of equivalent human dose) on the performance of active avoidance responses using a shuttle box. Pretraining injections of both doses of pentazocine and low dose nalorphine impaired acquisition on day 1 and day 2. Morphine and buprenorphine (at both dose levels) and high dose nalorphine did not affect the acquisition process. Post-training administration of morphine (high dose) and buprenorphine (both doses) delayed extinction of active avoidance responses. Low dose of morphine, high dose of pentazocine and both doses of nalorphine did not appreciably affect the extinction process. Mu opioid receptor agonists probably act as reinforcers to facilitate memory.

Acute neurobehavioural toxicity of phosphamindon and its drug-induced alteration.

Phosphamidon, a systemic organophosphate insecticide, (1.4 mg/kg - dose 1/4th of LD50 given ip), produced several autonomic, neurological and behavioral effects in mice with peak effects being at 15 min. Similar dose in rats also abolished conditioned avoidance response. Pre-treatment with atropine, iproniazid, alpha-methyl-p-tyrosine, p-chlorophenylalanine or thiosemicarbazide reduce many of these effects. This suggests that phosphamidon toxicity involves the central cholinergic, adrenergic, serotonergic and GABAergic systems in addition to peripheral cholinergic effects.