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Biomedical subjects

M Dikshit

Publications and source records attributed to M Dikshit.

67 records · Page 4Linked to original sources

Effect of centbucridine & lignocaine on biochemical changes in isoproterenol induced ischemia in rats.

Effect of lignocaine and centbucridine against isoproterenol-induced biochemical changes was studied in the rat. Isoproterenol (40 mg/kg twice) increased the heart weight, level of manolaldehyde (MDA) and activity of acid phosphatase, but decreased the myocardial phospholipid content at 48 h. In addition, increase in plasma triglyceride, cholesterol, MDA and creatine phosphokinase activity was observed. Pretreatment of the animals with lignocaine (10 mg/kg) or centbucridine (1, 3 and 10 mg/kg) protected the animals against these biochemical changes. However, increase in heart weight consequent to isoproterenol treatment could not be prevented. Total protection against creatine phosphokinase release in the blood was also not observed. The results suggest that the two drugs inhibit lipolysis. They may also inhibit phospholipases leading to protection against ischemia-induced changes in the rat.

Acid Phosphatase↗

Evidence for the presence of a new plasma factor which acts synergistically to ADP induced platelet aggregation.

The existence of a new factor (AF) in mice acting synergistically with known proaggregatory stimuli has been suggested by the present study in the plasma of mice challenged with intravenous collagen and adrenaline. Indomethacin, nordihydroguaretic acid (NDGA), BW 755C, phentolamine, cimetidine and ketanserin could not block the response of AF. Activity of the factor remained unaltered after treatment with pancreatic phospholipase A2, collagenase, CP/CPK, trypsin and heparin. Fractionation of the plasma indicated the presence of AF in acetone precipitate. Activity was destroyed by pronase and it was lost after dialysis and charcoal treatment. Existence of such a factor which is heat resistant, is of low molecular weight and is proaggregatory in nature in the thrombotic mice plasma and which requires calcium ions for the expression of its activity, has not been reported earlier.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗

Role of free radicals in pulmonary thromboembolism in mice.

Involvement of free radicals and their scavenging enzymes in mice pulmonary thromboembolism, induced by intravenous infusion of collagen and adrenaline, has been studied. Malonaldehyde (MDA) and activities of xanthine oxidase (XO), catalase (CAT) and superoxide dismutase (SOD) were estimated in platelets, heart and lung homogenates. MDA increased in all the tissues sharply, while animals showed 70-80% thrombocytopenia. Xanthine oxidase activity in these animals increase significantly in heart. However, increased SOD activity and decreased catalase activity was observed in platelets. Intravenous administration of superoxide dismutase (5 mg/kg), catalase (5 mg/kg) and mannitol (200 mg/kg) protected the mice against pulmonary thromboembolism. The importance of free radicals in mice pulmonary thromboembolism has been demonstrated.

Animals↗

A flowcytometric method for evaluation of acid secretion from isolated rat gastric mucosal cells.

Studies on the gastric proton pump are mostly performed on the H(+), K(+)-ATPase enzyme in the microsomal preparation or by aminopyrine accumulation in the gastric parietal cells. H(+), K(+)-ATPase activity is estimated by both spectrophotometric and fluorimetric methods. In the present study, quenching or augmentation in acridine orange (AO) fluorescence was monitored on a flowcytometer in rat gastric mucosal cells. Rat gastric mucosal cells were isolated by the standard pronase--EDTA method. The effect of oleic acid, a proton pump inhibitory was evaluated on gastric parietal cell activity and was compared with its effect on proton transport, H(+), K(+)-ATPase, and p-nitrophenyl phosphatase (p-NPPase) activity in gastric microsomes. In addition, the effect of histamine and carbachol, gastric acid release inducers, was also investigated by flowcytometry in isolated parietal cells. Histamine and carbachol, in a dose-dependent manner, stimulated acid release from isolated gastric cells. Oleic acid also dose-dependently inhibited the basal and stimulated acid release from the cells, as well as in all three enzyme preparations associated with gastric proton pump activity. Thus, the results suggest that flowcytometric method might be used to study basal, as well as stimulated, proton pump activity in isolated gastric parietal cells.

4-Nitrophenylphosphatase↗

Interferon-inducer polyriboinosinic-polyribocytidylic acid: a potent anti-gastric ulcer agent and inhibitor of the gastric proton pump in rats.

1. Polyriboinosinic-polyribocytidylic acid (Poly I:Poly C), an interferon inducer was studied for its effect on gastric ulceration in rats. Polyriboinosinic-polyribocytidylic acid (1, 2 and 4 mg/kg, i.m.) showed a dose-dependent inhibition of gastric ulcers induced by aspirin, cold restraint stress and pylorus ligation (Shay's model). Protective dose (PD50) +/- SEM values of Poly I:Poly C on these models of ulcers were 1.9 +/- 0.2, 2.3 +/- 0.4 and 2.8 +/- 0.4 (mg/kg, i.m.) respectively. 2. Polyriboinosinic-polyribocytidylic acid (10-60 micrograms) produced dose-dependent inhibition of gastric proton pump (H+/K(+)-ATPase) activity in the gastric parietal microsomal fraction. The concentration of Poly I:Poly C causing a 50% inhibition (IC50) +/- SEM was found to be 17.6 +/- 1.2 micrograms. 3. Polyriboinosinic-polyribocytidylic acid caused a significant decrease in free and total acid and pepsin and an increase in mucin content in Shay (pylorus-ligated) rat. 4. Polyriboinosinic-polyribocytidylic acid did not exert a significant influence on isolated tissue preparations for anti-cholinergic (acetylcholine-induced contraction of guinea-pig ileum) and H2-anti-histaminic (histamine-induced contraction of rat uterus and guinea-pig auricle) activities. 5. Thus, the present study indicates that Poly I:Poly C may possess anti-gastric ulcer activity as a result of inhibition of the gastric proton pump.

Animals↗

Inhibition of platelet aggregation by rat trophoblasts.

OBJECTIVE: To determine the effect of rat trophoblast cell suspensions on adenosine diphosphate (ADP)-induced platelet aggregation. MATERIALS AND METHODS: The trophoblasts were isolated from ectoplacental cones (a preplacental tissue very rich in trophoblasts) developed in rat embryos on day 12 of pregnancy (normal period of gestation: 22-23 days). Platelet-rich plasma (PRP) was obtained from adult male rats. The trophoblasts were preincubated (37 degrees C, 30 min), suspended in the medium, and then re-incubated with PRP for 3-5 min. RESULTS: 5 x 10(4) and 7 x 10(4) trophoblasts inhibited ADP-induced platelet aggregation by 10 and 18%, respectively. When the trophoblast cell concentration was increased to 1-2 x 10(5) cells, a proaggregatory phenomenon was observed, even in the absence of ADP. However, there was no inhibition of aggregation or promotion of aggregation when fixed trophoblasts or live endometrial stromal cells were incubated with PRP. CONCLUSION: The results indicate that the aggregation inhibition response was cell specific and concentration dependent. A 68-kD protein was detected in the medium when it was conditioned with 5-7 x 10(4) but not with 1-2 x 10(5) trophoblasts. However, the inhibitory or stimulatory effect does not seem to be dependent on the presence of this protein.

Adenosine Diphosphate↗

Free radical scavenger mechanisms in experimentally induced ischemia in the rabbit heart and protective effect of verapamil.

The protective effect of verapamil on the free radical generation in the ischemic myocardium of rabbit has been studied. A significant decrease of the lactate dehydrogenase activity in the ischemic zone was observed compared to the nonischemic control myocardial tissue. The level of malondialdehyde was found to be elevated in the ischemic zone and in other parts of the myocardium. However, there was no alteration in glutathione content in both zones. In addition, an increase in the activity of myeloperoxidase was observed in the ischemic part of the myocardium. At lower doses (30 micrograms/kg), verapamil protected the animals from ischemic changes but did not do so at higher doses (100 micrograms/kg). These results suggest that, in the rabbit, the free radical scavenging mechanism of the heart is not adversely affected during ischemia.

Animals↗

Effect of alpha-adrenergic receptor blockers on the vulnerability of cat heart to ventricular fibrillation.

Recently, alpha-adrenergic receptors have been implicated in the precipitation of arrhythmias associated with myocardial ischemia and reperfusion. The present investigation has been undertaken to study the effect of alpha-adrenoceptor antagonists on electrically induced ventricular fibrillation. The effect of ventricular fibrillation on the alpha-adrenergic receptor population in myocardium and its modification by phentolamine pretreatment has also been investigated. Phentolamine and prazosin raised the ventricular fibrillation threshold significantly. However, yohimbine was protective at high doses only (3 and 5 mg/kg). There was no change in alpha-receptor population and affinity after ventricular fibrillation. Cyclic AMP levels increased in the fibrillating myocardium. Pretreatment with phentolamine did not prevent the decrease in blood flow observed after electrically induced ventricular fibrillation. It is concluded that alpha 1-adrenergic receptor blockade is protective against ventricular fibrillation in cats.

Adrenergic beta-Antagonists↗

Study on the involvement of the L-arginine/nitric oxide pathway in the central cardiovascular regulation in the chloralose-anaesthetized cat.

The role of the L-arginine/nitric oxide pathway in mediating the central control of blood pressure and heart rate, has been investigated in chloralose-anaesthetized cats. L-arginine (10 micrograms to 10 mg), administered intracerebroventricularly into a lateral ventricle, produced a dose-dependent rise in mean blood pressure (7 to 28%) and heart rate (4 to 34%). D-arginine (1 mg), on the other hand, did not produce any change. The effect of L-arginine (100 micrograms) was dose-dependently inhibited by pretreatment with either L-NAME (1 mg) or methylene blue (400 micrograms). Sodium nitroprusside (1 microgram to 10 micrograms, intracerebroventricularly), a spontaneous source of nitric oxide, produced a dose-dependent fall in mean blood pressure (6 to 19%) with a moderate rise in heart rate (3 to 10%). The effect of nitroprusside was markedly inhibited by methylene blue, but not by L-NAME. The results suggest that the L-arginine/nitric oxide pathway in the central nervous system is involved in the blood pressure regulation in the cat.

Anesthesia↗