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Biomedical subjects

K Prasad

Publications and source records attributed to K Prasad.

At least 145 records · Page 8Linked to original sources
PubMed1994

Botulinum toxin A in blepharospasm and hemifacial spasm.

We report the first Indian experience of botulinum toxin A in the treatment of blepharospasm and hemifacial spasm. Sixteen patients, 7 with essential blepharospasm, 5 with Meige syndrome and 4 with hemifacial spasm received botulinum toxin A injection. One patient received 3 courses of injections, 2 received 2 courses and the rest received only one course. The effect was observed after a latent period of less than 48 hours in all patients and lasted for a mean of 16.65 weeks. More than 70% improvement occurred after 17/20 injections (85%). Poor response was more often seen when blepharospasm was associated with oromandibular dystonia (2/5 injections). Though the duration of response and subjective score of improvement was best in patients with hemifacial spasm, the numbers were very small for any statistical evaluation. The side effects were local, transient, mild and well tolerated. The commonest side effect was blepharoptosis.

Adult↗
PubMed1994

Pulmonary vascular effects of endotoxin in canine lobes pretreated with dapsone.

Endotoxin results in a granulocyte mediated loss of hypoxic pulmonary vasoconstriction (HPV). Dapsone blocks the granulocyte respiratory burst and might, therefore, preserve HPV following endotoxin. Isolated-perfused canine lobes (n = 6) were pretreated with 18 mg/kg dapsone (dapsone group), and compared to six lobes which did not receive dapsone (control group). Total pulmonary vascular resistance (Rtot) and arterial, middle (Rm), and venous segmental resistances were calculated by a vascular occlusion technique. We then administered endotoxin (2 mg/kg) and repeated measurements at 5, 30, and 90 min. The increase in Rm during 3% O2 compared to 35% O2 ventilation was used to define the presence of HPV. In the control group, following endotoxin, values of Rm did not change (P > 0.05) during 3% O2 ventilation (0.011 +/- 0.006 cm H2O/ml/min) compared with 35% O2 ventilation (0.014 +/- 0.005 cm H2O/ml/min). In the dapsone group, following endotoxin, values of Rm increased (P < 0.05) during 3% O2 ventilation (0.06 +/- 0.026 cm H2O/ml/min) compared with 35% O2 ventilation (0.03 +/- 0.015 cm H2O/ml/min). Changes in 6-keto PGF1 alpha or thromboxane B2 do not explain these observations. We conclude that in this experimental preparation, pretreatment with dapsone prevents the loss of HPV associated with endotoxin.

Animals↗
PubMed1994

Neutrophil-mediated acute lung injury after extracorporeal perfusion.

A pulmonary injury of varying severity occurs routinely after cardiopulmonary bypass. We studied the pulmonary complications of partial cardiopulmonary bypass in four groups of dogs to better define the injury and to evaluate the efficacy of two interventions (addition of a leukocyte filter or cyclooxygenase inhibition) on preservation of systemic oxygenation. All animals received a standard anesthetic (pentobarbital, morphine, and vecuronium) and, after sternotomy, three groups of animals received 3 hours of partial cardiopulmonary bypass. The animals were randomized to receive partial bypass alone (n = 6), indomethacin and bypass (n = 5), or a leukocyte filter and bypass (n = 5). A fourth group (n = 5) did not receive bypass and served as a time control. We measured blood gases and also obtained histologic samples to assess the degree of lung injury. We found that bypass alone caused a significant reduction (p < 0.05) in arterial oxygen tension 1 hour after the conclusion of bypass (175 +/- 53 mm Hg) compared with prebypass values (357 +/- 41 mm Hg). Pretreatment with indomethacin ameliorated the decrease in arterial oxygen tension from prebypass to postbypass values (477 +/- 50 mm Hg versus 339 +/- 57 mm Hg, respectively). Similarly use of a leukocyte filter reduced the decline in arterial oxygen tension from prebypass to postbypass values (440 +/- 71 mm Hg versus 311 +/- 73 mm Hg, respectively). We believe that indomethacin ameliorates the decline in systemic oxygenation associated with bypass by augmentation of hypoxic pulmonary vasoconstriction and that the leukocyte filter acted to reduce pulmonary edema and thereby minimized intrapulmonary shunt.

Animals↗
PubMed1993

A protein cofactor is required for uncoating of clathrin baskets by uncoating ATPase.

Immediately after clathrin-coated pits pinch off from the cell membrane to form clathrin-coated vesicles, clathrin dissociates from the vesicles. In vitro studies suggest that this dissociation is carried out by the uncoating ATPase, a constitutive member of the 70-kDa heat shock family. Aside from the requirement for ATP, nothing is known about the regulation of the uncoating process. We now show that clathrin baskets prepared from highly purified clathrin and AP2, the assembly protein associated with plasma membrane coated vesicles, cannot be uncoated by the bovine brain uncoating ATPase alone. A 100-kDa protein cofactor, which was isolated from coated vesicles, is essential for uncoating by the uncoating ATPase. This cofactor restores normal uncoating when present at a molar ratio of about 1 to 10 to clathrin and uncoating ATPase.

Adenosine Triphosphatases↗
PubMed1993

Oxygen free radicals and hypercholesterolemic atherosclerosis: effect of vitamin E.

We investigated the effects of a high-cholesterol diet in the presence and absence of vitamin E on the lipid peroxidation product malondialdehyde of blood and aortic tissue, the oxygen-free-radical-producing activity of polymorphonuclear leukocytes (PMNs) (PMN chemiluminescence), and the blood lipid profile in rabbits. The animals were divided into four groups each of which comprised 10 rabbits. Rabbits in group I received a regular rabbit chow diet; those in group II received vitamin E; those in group III received high cholesterol + vitamin E; and those in group IV received a high-cholesterol diet. Blood concentrations of triglycerides, total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), very low-density lipoprotein cholesterol (VLDL-C), malondialdehyde, and PMN chemiluminescence were measured. The aorta of each rabbit was removed at the end of the protocol for assessment of atherosclerotic changes (gross and microscopic) and malondialdehyde. Serum triglycerides, total cholesterol, HDL-C, LDL-C, and VLDL-C increased while HDL/LDL ratio decreased in groups III and IV but remained unchanged in group I. There was an increase in the HDL-C component and HDL/LDL ratio and a decrease in the LDL-C component and triglycerides in group II. Blood and aortic tissue malondialdehyde increased in group IV but decreased in groups II and III. PMN chemiluminescence increased in groups III and IV. Atherosclerotic changes were marked in group IV as compared with those in group III. However, histologic changes in the aortas were similar in groups III and IV. The increased levels of blood and aortic tissue malondialdehyde and PMN chemiluminescence, which were associated with development of atherosclerosis, suggest a role of oxygen free radicals in the pathogenesis of hypercholesterolemia-induced atherosclerosis. The protection afforded by vitamin E, which was associated with a decrease in blood and aortic tissue malondialdehyde concentration in spite of hypercholesterolemia, supports the hypothesis that oxygen free radicals are involved in the development of hypercholesterolemic atherosclerosis.

Animals↗
PubMed1993

Antioxidant enzymes in hypercholesterolemia and effects of vitamin E in rabbits.

We investigated the effects of high cholesterol diet in the absence and presence of vitamin E on the activity of antioxidant enzymes [superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px)] in rabbits. The animals were divided into 4 groups each comprising of 10 rabbits. Group I, regular rabbit chow diet; Group II, regular rabbit chow diet with added vitamin E; Group III, high cholesterol diet; and Group IV, high cholesterol diet+vitamin E. Antioxidant enzymes of blood were measured in each group before and after 1, 2, 3, and 4 months on the experimental diets. The aorta was removed at the end of the protocol for measurement of antioxidant enzymes. There was a decrease in activity of SOD and GSH-Px and an increase in activity of catalase in blood of Group III. Vitamin E produced a decrease in blood SOD, catalase and GSH-Px activity in Group II and prevented the decrease in SOD and GSH-Px activity in Group IV but did not affect the changes in the catalase activity. SOD, catalase and GSH-Px activity of aortae from Group III increased significantly, while catalase activity increased and GSH-Px activity decreased in those from Group II. Vitamin E prevented the cholesterol-induced rise in catalase and GSH-Px activity in aorta but did not prevent the rise in SOD activity. These results suggest that the activity of antioxidant enzymes in blood is affected differently from that in aortic tissue. There appears to be a mutually supportive interaction among the antioxidant enzymes which provide defense against oxidant injury. The protective effects of vitamin E against hypercholesterolemic atherosclerosis may not be due to changes in the antioxidant enzymes but may be mainly mediated through its chain-breaking antioxidant activity.

Animals↗
PubMed1993

Influence of hydroxyl radical on rabbit airway smooth muscle chronically exposed to H2O2 in vivo.

The effects of .OH on the isolated tracheal smooth muscles (TSM), from control, polyethylene glycol (PEG)-glucose oxidase (GO)-, and GO+PEG catalase-treated rabbits were investigated. GO or GO+catalase were given intravenously each week for 4 mo. .OH produced relaxation of basal and ACh-precontracted tension in TSM of control rabbits. The relaxant effect was attenuated by removal of epithelium, whereas it was converted to contraction in the indomethacin-pretreated muscle. .OH produced contraction of TSM and ACh-precontracted muscle in GO-treated rabbits. The contractile response was abolished in preparations denuded of epithelium or pretreated with indomethacin. .OH produced relaxation in basal tension, but a small contraction in ACh-precontracted muscle of GO+catalase-treated rabbits. The contractile response to .OH was unaffected by indomethacin pretreatment; however, it was converted to relaxation in the preparations denuded of epithelium. Contractile response of TSM to ACh was augmented in deepithelialized, indomethacin-, or GO-treated preparations. H2O2 damaged the tracheal epithelium. These results suggest that 1) .OH-induced relaxation/contraction of TSM is partly epithelium dependent and is mediated by bronchodilator/bronchoconstrictor arachidonic acid metabolites, 2) the airway smooth muscle with healthy epithelium responds to .OH differently from those with dysfunctional or damaged epithelium, and 3) hyperresponsiveness of the airways to ACh may be related to the epithelial dysfunction.

Acetylcholine↗
PubMed1993

Cardiac depressant effects of oxygen free radicals.

In many clinical situations, including cardiac ischemia/reperfusion, elective cardiac arrest, and renal dialysis, the chances of increased production of oxygen free radicals (OFR) exist. OFR have been implicated as a causative factor of cell damage in several pathologic conditions. The effects of exogenous OFR, generated by xanthine plus xanthine oxidase, in the absence and in the presence of OFR scavenger (superoxide dismutase [SOD]) on the contractility of isolated perfused heart of rabbit were studied. OFR produced concentration-dependent decreases in the contractility of perfused heart. SOD prevented the OFR-induced decreases in the left ventricular contractility. Xanthine produced an increase in the contractility of isolated perfused rabbit's heart. Xanthine oxidase produced a marked decrease in the left ventricular contractility. Repeated administration of xanthine oxidase produced accelerated and greater decreases in the contractility of perfused heart when compared with that of the initial administration of the drug. Effects of xanthine or xanthine oxidase on the cardiac function and contractility were also studied in anesthetized dogs. Xanthine alone had no significant effect on the cardiac function and indices of myocardial contractility. However, xanthine oxidase produced a marked decrease in the mean aortic pressure, left ventricular work index, heart rate, cardiac index, left ventricular systolic pressure, left ventricular end-diastolic pressure, (+) and (-) dp/dt of left ventricular pressure, and other indices of myocardial contractility [(dp/dt)/PAW (pulmonary arterial wedge pressure)]; and an increase in the total systemic and pulmonary vascular resistance. Repeated administration of xanthine oxidase in anesthetized dogs had lesser effects on the cardiovascular system when compared with those from the initial dose of the drug. These results suggest that OFR are cardiac depressant. Clinical situations wherein there is an increased production of OFR or increased formation of xanthine and xanthine oxidase may be associated with decreased cardiac function and contractility. Scavengers of OFR may protect the heart from the deleterious effects of OFR in such clinical conditions.

Animals↗
PubMed1993

Ocular myasthenia--factors predictive for generalisation.

A retrospective analysis was done from case records of 186 patients with myasthenia. Ninety patients had purely ocular symptoms at the onset. Thirty six of these patients continued to have ocular myasthenia while 54 patients developed features of generalised disease. There were no significant difference between the two groups as regards age at onset, sex distribution, response to repetitive stimulation, radiologic evidence of thymic enlargementor associated thyroid disease. The median time for generalisation was 3 months. A later age of onset seemed to prognosticate for early generalisation.

Adult↗
PubMed1992

Detection of ischemia-reperfusion cardiac injury by cardiac muscle chemiluminescence.

Various methods have been used in the past to assess the implication of oxygen free radicals (OFR) in ischemia-reperfusion-induced cardiac injury. Luminol-enhanced tert-butyl-initiated chemiluminescence in cardiac tissue reflects oxidative stress and is a very sensitive method. It was used to elucidate the role of OFR in cardiac injury due to ischemia and reperfusion. Studies were conducted on perfused isolated rabbit hearts in three groups (n = 8 in each): I, control; II, submitted to global ischemia for 30 min; III, submitted to ischemia for 30 min followed by reperfusion for 60 min. The heart tissue was then assayed for chemiluminescence (CL); content of malondialdehyde (MDA), an indicator of OFR-induced cardiac injury; and activity of tissue levels of antioxidants [superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px)]. The control values for left and right ventricular CL and malondialdehyde were 81.1 +/- 15.4 (S.E.) and 182.4 +/- 50.3 (S.E.), mv.min.mg protein-1; and 0.024 +/- 0.006 (S.E.) and 0.324 +/- 0.005 (S.E.) nmoles.mg protein-1 respectively. Ischemia produced an increase in the cardiac CL (3.3 to 4.4 fold) and MDA content (2 to 2.6 fold). Reperfusion following ischemia also produced similar changes in CL and MDA content. The control values for activity of left ventricular SOD, catalase, and GSH-Px were 45.77 +/- 1.73 (S.E.) U.mg protein-1, 5.35 +/- 0.51 (S.E.) K.10(-3).sec-1.mg protein-1, and 77.50 +/- 7.70 (S.E.) nmoles NADPH.min-1.mg protein-1 respectively. Activities of SOD and catalase decreased during ischemia but were similar to control values in ischemic-reperfused hearts. The GSH-Px activity of left ventricle was unaffected by ischemia, and ischemia-reperfusion. GSH-Px activity of the right ventricle increased with ischemia, and ischemic-reperfusion. These results indicate that cardiac tissue chemiluminescence would be a useful and sensitive tool for the detection of oxygen free radical-induced cardiac injury.

Animals↗
PubMed1992

Oxygen free radical producing activity of polymorphonuclear leukocytes in patients with Parkinson's disease.

Oxygen free radicals (OFRs) have been suggested in the pathogenesis of Parkinson's disease (PD). These free radicals exert their cytotoxic effect by peroxidation of lipid membrane resulting in the formation of malondialdehyde (MDA). Polymorphonuclear (PMN) leukocyte is one of the major sources of OFR. However, the oxygen free radical producing activity of PMN leukocytes in patients with PD is not known. We therefore studied the oxygen free radical producing activity of polymorphonuclear leukocytes and MDA levels in the serum of healthy subjects and in patients with Parkinson's disease. The oxygen free radical producing activity of PMN leukocytes in blood and the MDA content in serum were significantly higher in patients with Parkinson's disease than in healthy subjects. These results indicate a possible role of oxygen free radicals in the pathogenesis of Parkinson's disease.

Aged↗
PubMed1992

Serum antioxidant enzyme activity in Parkinson's disease.

The activities of superoxide dismutase (SOD; EC 1.15.1.1) and glutathione peroxidase (GSHPx; EC 1.11.1.9), the enzymes that metabolize the superoxide anion and hydrogen peroxide, respectively, were measured in serum from healthy subjects and patients with Parkinson's disease (PD). The activities of SOD and GSHPx in patients with PD were higher than those in normal healthy individuals. These results suggest that the increased activities of these enzymes could be due to oxidative stress in the initial stages of this disease.

Aged↗
PubMed1992

Oxygen free radicals in volume overload heart failure.

It has been suggested that oxygen free radicals (OFR) depress the excitation-contraction coupling in cardiac muscle. It is possible that a decrease in the cardiac contractility in the failing heart may be due to an increased OFR producing activity of polymorphonuclear (PMN) leukocytes. We studied the OFR producing activity (chemiluminescence) of PMN leukocytes from blood in dogs with heart failure due to chronic volume overload. The animals were divided into two groups: I) normal, (n = 10): II) dogs with mitral insufficiency (MI) of 6 to 9 months duration, (n = 10). Hemodynamic studies were done to establish the presence of heart failure. Blood samples were collected to measure PMN leukocyte chemiluminescence. There was a decrease in the cardiac index and index of myocardial contractility (dp/dt/IIP) and an increase in the left ventricular end-diastolic pressure in dogs with MI indicating left ventricular failure. The peak chemiluminescent activity of the PMN leukocytes in blood of dogs with failure was about four folds greater than that in the blood from normal dogs. These results suggest that there may be an increased OFR generation in dogs with volume overload heart failure. The decrease in the myocardial contractility in the failing heart might be due to an increase in the OFR produced by the PMN leukocytes.

Animals↗