Effect of Ocimum sanctum fixed oil on vascular permeability and leucocytes migration

Ocimum sanctum fixed oil significantly inhibited the rise in protein concentration and dye leakage in peritoneal fluid in experimentally induced peritoneal inflammation in mice. In carrageenan-induced pleurisy in rats, the fixed oil showed significant inhibition of leucocytes migration in the pleural exudate. The results suggest that the fixed oil can inhibit enhancement of the vascular/capillary permability and leucocyte migration following inflammatory stimulus.     

Biochemical and immunological changes on oral glutamate feeding in male albino rats

 High altitude stress leads to lipid peroxidation and free radical formation which results in cell membrane damage in organs and tissues, and associated mountain diseases. This paper discusses the changes in biochemical parameters and antibody response on feeding glutamate to male albino Sprague Dawley rats under hypoxic stress. Exposure of rats to simulated hypoxia at 7576 m, for 6 h daily for 5 consecutive days, in an animal decompression chamber at 32±2° C resulted in an increase in plasma malondialdehyde level with a concomitant decrease in blood glutathione (reduced) level. Supplementation of glutamate orally at an optimal dose (27 mg/kg body weight) in male albino rats under hypoxia enhanced glutathione level and decreased malondialdehyde concentration significantly. Glutamate feeding improved total plasma protein and glucose levels under hypoxia. The activities of serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) and the urea level remained elevated on glutamate supplementation under hypoxia. Glutamate supplementation increased the humoral response against sheep red blood cells (antibody titre). These results indicate a possible utility of glutamate in the amelioration of hypoxia-induced oxidative stress. Received: 23 March 1998 / Accepted: 19 October 1998     

Mating activity and fitness of a few wild type strains of Drosophila ananassae

Courtship time, duration of copulation and fertility were tested in six wild type strains of D. ananassae originating from different geographical localities. The results indicate that there is significant variation among the strains tested with respect to courtship time, duration of copulation and fertility. The strains showing a longer duration of copulation produce more progeny. These findings suggest that there is a positive correlation between duration of copulation and fertility in D. ananassae.     

State of pregnancy modifies lead toxicity in mice

Toxicity of lead acetate after administration through the oral route at 0-50 mg/kg body weight of animal has been assessed in the liver of pregnant mice and compared with the effect in the liver of nonpregnant dams. Analysis showed that the basal level of hepatic lead is considerably reduced during pregnancy as compared to that in nonpregnant state. After administration of Pb-acetate, deposited lead in liver of nonpregnant mice was 3- to 4-fold while in pregnant mice was, it was 1.8- to 3.0-fold over their respective control values. Although hepatic Fe, Cu, and Zn levels had a tendency to be lowered during pregnancy, it appeared that the added trace quantity of lead prior to and during pregnancy helped in the retention of these metals, which either remained unaffected (as Fe) or declined (Cu and Zn) after lead administration during the nonpregnant state. The effect of lead on Mn diminution, however, was visible at the dose of 50 mg/kg body wt of lead-acetate. Alkaline phosphatase, which increased during pregnancy along with Mn, was reversed between the pregnant and nonpregnant states after oral administration of lead. On the other hand, the level of delta-aminolevolunic acid dehydratase, which declined during normal pregnancy, continued to fall further after lead exposure. It is concluded that the distribution of basal or administered lead and its effect on enzyme activities and trace metal composition in liver depends on the pregnant and nonpregnant states of female hosts.     

Actions of butyrophenones and other antipsychotic agents at NMDA receptors: relationship with clinical effects and structural considerations

Haloperidol inhibits NMDA receptors with higher affinity for NMDA receptors composed of NR1/2B compared with NR1/2A. To assess whether the clinical effects of haloperidol and other antipsychotic agents are mediated through this site on NMDA receptors and to examine structure activity relationships at this site, we examined the ability of a variety of drugs with neuroleptic actions to inhibit NMDA receptor function. Many antipsychotic agents inhibit 125I-MK 801 binding to the NMDA receptor with IC50 values in the micromolar range. The rank order of potency for inhibition of binding to adult rat forebrain was trifluperidol (TFP) > clozapine = fluphenazine = reduced haloperidol = spiperone = trifluoperazine = butaclamol > pimozide = risperidone = sulpiride. These findings match the molecular biological specificity of the agents, with trifluperidol having a marked preference for NR1/2B (epsilon2) receptors. Mutations at epsilon2E201, which alter the effects of haloperidol, also decrease the affinity of TFP but not other modulators, showing that the effect of TFP but not other modulators is mediated by this residue of the NMDA receptor. The present results demonstrate that while TFP acts on NMDA receptors in a manner similar to haloperidol, other antipsychotic agents do not share the specific pharmacological properties of this action, suggesting that their clinical mechanism is not mediated by this receptor.     

Synergistic effects in enzymic reactions

It has been shown that when two enzymes showing similar actions act in close proximity of each other they influence each other synergistically. The phenomenon of synergism is, however, not observed if the two enzymes are of dissimilar action type. The condition of closest proximity has been simulated by conducting the enzymic reactions inside the reversed micelles. In the present study we have experimented with alpha-amylase and invertase both hydrolysing enzymes and also with peroxidase and invertase which do not show similar actions.     

Effect of lithium on thyroidal 131iodine uptake, its clearance, and circulating levels of triiodothyronine and thyroxine in lead-treated rats

The influence of lead acetate (50 mg per kg body weight) on the 131iodine (131I) biokinetics (uptake and retention) in rat thyroid and serum levels of triiodothyronine (T3) as well as thyroxine (T4) was evaluated as a function of time and in combination with lithium treatment. The 2-h and 24-h uptake of 131I in the thyroid was stimulated significantly by lead treatment. The 24-h uptake showed a maximum stimulation after 4 months of lead treatment. Lithium supplementation, however, showed the opposite effect by reducing the iodine uptake whereby the maximum decrease was noticed after 2 months of treatment. Further, simultaneous lead and lithium treatment resulted in an even more pronounced increase of 2-h 131I uptake with a maximum after 3 months. However, the 24-h uptake after 3 months and 4 months of treatment did not differ significantly from the lead treated reference groups. The thyroidal biological half-life of 131I (Tbiol) was found to have clearly increased following the lead/lithium treatment. Interestingly, the combined lead/lithium treatment applied for 4 months caused a further growth of Tbiol, thus reflecting an increased retention of 131I. A maximum increase of Tbiol was seen after 2 months of combined treatment. A progressive decline of the circulating T3 and T4 levels following lead or lithium treatment was noticed and was more pronounced after combined treatment.     

Effect of insulin on exocrine pancreatic secretion in healthy and diabetic anaesthetised rats

This investigation characterised the effects of exogenous insulin on exocrine pancreatic secretion in anaesthetised healthy and diabetic rats. Animals were rendered diabetic by a single injection of streptozotocin (STZ, 60 mg kg(-1) I.P.). Age-matched controls were injected citrate buffer. Rats were tested for hyperglycaemia 4 days after STZ injection and 7-8 weeks later when they were used for the experiments. Following anaesthesia (1 g kg(-1) urethane I.P.), laparotomy was performed and the pancreatic duct cannulated for collection of pure pancreatic juice. Basal pancreatic juice flow rate in diabetic rats was significantly (p < 0.001) increased whereas protein and amylase outputs were significantly (p < 0.001) decreased compared to control rats. Insulin (1 IU, I.P.) produced in healthy rats significant increases in pancreatic flow rate, amylase secretion and protein output compared to basal (p < 0.05). Insulin action also included a reduction in blood glucose (152.7 +/- 16.9 mg dl(-1), n = 6, prior to insulin and 42.0 +/- 8.4 mg dl(-1), n = 4, 100 min later). In fact, flow rate and glycaemia showed a strong negative correlation (p < 0.01, Pearson). Pretreatment with atropine (0.2 mg kg(-1), I.V.) abolished the effects of insulin on secretory parameters despite a similar reduction in glycaemia; in this series of experiments the correlation between flow rate and blood glucose was lost. In diabetic rats, insulin (4 IU, I.P.) did not modify exocrine pancreatic secretion. There was a fall in blood glucose (467.6 +/- 14.0 mg dl(-1), n = 10, prior to insulin and 386.6 +/- 43.6 mg dl(-1), n = 7, 120 min later). Rats, however, did not become hypoglycaemic. Similar results were observed in diabetic atropinized rats. The results of this study indicate that the effects of insulin on exocrine pancreatic secretion in anaesthetised healthy rats are mediated by hypoglycaemia-evoked vagal cholinergic activation.     

Physiological effects and biochemical properties of a serum protein that produces positive inotropic and chronotropic effects on isolated guinea pig atria

Isolated left and right guinea pig atria were used as a bioassay for the detection of an endogenous cardioactive substance in bovine serum. Serum, buffer exchanged to Krebs-Henseleit solution, produced positive inotropic and chronotropic effects on the isolated guinea pig atria. The cardiotonic effects were unaffected by the combined presence of propranolol and methysergide (both 10(-6)M) and were also dissimilar in time course from other known cardiotons such as catecholamines and cardiac glycosides. Following ultrafiltration (using XM100A Amicon membranes), activity was found solely in the retentate fractions and was therefore probably due to a large molecular weight (> 100 kDa) substance or a small molecule bound to a large protein. The cardioactive factor (CF) in the whole serum was heat labile, sensitive to acidification, exposure to potassium bromide and equilibration to physiological buffers of a low ionic strength. Isolation by conventional protein purification techniques was unsuccessful due to the labile nature of the active molecule(s) when exposed to non-physiological experimental conditions. Physical and biochemical properties of the CF which may help avoid inactivation are discussed for future experiments aimed at elucidating the nature and identity of the cardiotonic principle.     

Momordica charantia fruit juice stimulates glucose and amino acid uptakes in L6 myotubes

The fruit of Momordica charantia (family: Cucurbitacea) is used widely as a hypoglycaemic agent to treat diabetes mellitus (DM). The mechanism of the hypoglycaemic action of M. charantia in vitro is not fully understood. This study investigated the effect of M. charantia juice on either ³H-2-deoxyglucose or N-methyl-amino-a-isobutyric acid (¹⁴C-Me-AIB) uptake in L6 rat muscle cells cultured to the myotube stage. The fresh juice was centrifuged at 5000 rpm and the supernatant lyophilised. L6 myotubes were incubated with either insulin (100 nM), different concentrations (1–10 g ml^–1) of the juice or its chloroform extract or wortmannin (100 nM) over a period of 1–6 h. The results were expressed as pmol min^–1 (mg cell protein)^–1, n= 6–8 for each value. Basal ³H-deoxyglucose and ¹⁴C-Me-AIB uptakes by L6 myotubes after 1 h of incubation were (means ± S.E.M.) 32.14 ± 1.34 and 13.48 ± 1.86 pmol min^–1 (mg cell protein)^–1, respectively. Incubation of L6 myotubes with 100 nM insulin for 1 h resulted in significant (ANOVA, p < 0.05) increases in ³H-deoxyglucose and ¹⁴C-Me-AIB uptakes. Typically, ³H-deoxyglucose and ¹⁴C-Me-AIB uptakes in the presence of insulin were 58.57 ± 4.49 and 29.52 ± 3.41 pmol min^–1 (mg cell protein^–1), respectively. Incubation of L6 myotubes with three different concentrations (1, 5 and 10 g ml^–1) of either the lyophilised juice or its chloroform extract resulted in time-dependent increases in ³H-deoxy-D-glucose and ¹⁴C-Me-AIB uptakes, with maximal uptakes occurring at a concentration of 5 g ml^–1. Incubation of either insulin or the juice in the presence of wortmannin (a phosphatidylinositol 3-kinase inhibitor) resulted in a marked inhibition of ³H-deoxyglucose by L6 myotubes compared to the uptake obtained with either insulin or the juice alone. The results indicate that M. charantia fruit juice acts like insulin to exert its hypoglycaemic effect and moreover, it can stimulate amino acid uptake into skeletal muscle cells just like insulin. (Mol Cell Biochem 261: 99–104, 2004)