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Biomedical subjects

K Prasad

Publications and source records attributed to K Prasad.

At least 163 records · Page 9Linked to original sources

Increased oxygen free radical activity in patients on cardiopulmonary bypass undergoing aortocoronary bypass surgery.

Cardiac dysfunction after cardiopulmonary bypass (CPB) has been reported by various investigators. Oxygen free radicals have been shown to depress cardiac function and contractility. To evaluate the possible role of oxygen free radicals (OFR) in post-pump cardiac dysfunction, measurements of cardiac function, OFR producing activity of polymorphonuclear (PMN) leukocytes (PMN chemiluminescence) and malondialdehyde (MDA), a lipid peroxidation product, in blood were made at induction of anesthesia (T1), before cross clamping of the aorta (T2), after closure of the chest (T3), and 24 hours postoperatively (T4) in 21 patients undergoing aortocoronary bypass surgery. The total OFR-derived chemiluminescence at T1, T2, T3, and T4 was 1590 +/- 156, 3169 +/- 338, 1972 +/- 214, and 2614 +/- 366 mv.min.10(6) PMN-1, respectively. Superoxide dismutase (SOD)-inhibitable chemiluminescence at T1, T2, T3, and T4 was 1214 +/- 129, 2674 +/- 328, 1752 +/- 215, and 2139 +/- 292 mv.min.10(6) PMN-1, respectively. Superoxide anion at T1, T2, T3, and T4 was 0.99 +/- 0.14, 1.30 +/- 0.17, 1.07 +/- 0.14, and 1.19 +/- 0.12 nmol.10(6) PMN-1.30 min-1, respectively. Blood MDA at T1, T2, T3, and T4 was 0.17 +/- 0.02, 0.25 +/- 0.03, 0.20 +/- 0.03, and 0.23 +/- 0.02 nmol/ml, respectively. OFR-derived and SOD inhibitable chemiluminescence, superoxide anion, and blood MDA increased significantly during CPB and postoperatively. There were decreases in the blood pressure and stroke volume, and increases in the central venous pressure, capillary wedge pressure, and heart rate during CPB and postoperatively. Cardiac output remained unchanged during this procedure. There was leukopenia during CPB.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Echocardiographic variables affecting surgical outcome in patients undergoing closed mitral commissurotomy.

We studied, by transthoracic cross-sectional echocardiography, the influence of subvalvar pathology on the early hemodynamic result of closed mitral commissurotomy in 132 patients with severe rheumatic mitral stenosis (56 males, 76 females, mean age 25.2 yr, range 10-55) in our tertiary care hospital in North India from July 89 to December 91. The mitral subdistance ratio was calculated by dividing the distance between the papillary muscle tip and mitral valve in systole (apical 4-chamber view) by left ventricular diastolic length (apical long axis view). Nineteen patients with mild subvalvar pathology (mitral subdistance ratio > 0.18) and 71 patients with moderate, achieved a larger valve area (2.26 cm2 SD 0.54) than 42 patients with severe subvalvar pathology (mitral subdistance ratio < 0.12, postoperative valve area 2.09 cm2 SD 0.6, p < 0.05). In addition, 9 of these 42 patients (21%) developed significant mitral regurgitation (4 deaths), in contrast to 1/19 with mild and 6/71 with moderate subvalvar pathology. We conclude that echocardiography identifies patients with severe subvalvar pathology who fare poorly after closed mitral commissurotomy. However, this procedure would still be practised in developing countries like ours due to financial constraints.

Adolescent↗

Hypoplastic right ventricle with mild pulmonary stenosis in an adult.

A rare cyanotic heart disease surviving to adulthood with minimal symptoms is presented. The final diagnosis was hypoplastic right ventricle with mild pulmonary stenosis, where the latter was not responsible for the right-to-left shunting across a large atrial septal defect. The differences from cases reported in the literature are highlighted.

Adult↗

Haemorheological factors in the pathophysiology of acute stroke.

Blood viscosity studies were carried out in fourteen patients with acute stroke, eight with cerebral infarction, six with cerebral haemorrhage and in thirteen controls. We observed a statistically significant higher values of plasma, red cell and whole viscosity in patients with acute stroke than in normal controls. Plasma fibrinogen levels were statistically higher (p less than 0.01) in patients than in normal controls. The platelet aggregation was increased in two young adults with acute stroke. The results suggest that the haemorheological factors play an important role in the pathophysiology of stroke patients.

Acute Disease↗

Mechanism of H2O2-induced modulation of airway smooth muscle.

We investigated the effects of H2O2 generated by glucose (G) and glucose oxidase (GO) on the isolated rabbit tracheal smooth muscle suspended in Krebs-Ringer solution. H2O2 generated by G+GO was measured with luminol-dependent chemiluminescence. G+GO in the concentrations of 1x (1.80 microM G, 0.075 U/ml GO) and 2, 4, and 8x generated 1.35, 3.2, 6.10, and 6.00 microM of H2O2, respectively. H2O2 produced relaxation of rabbit tracheal smooth muscle, relaxed acetylcholine (ACh)-precontracted muscle, and reduced muscle responsiveness to ACh. These effects were concentration dependent. H2O2, however, produced contraction of guinea pig tracheal smooth muscle. Catalase completely inhibited the H2O2-induced relaxation of ACh-precontracted tracheal smooth muscle. H2O2-induced relaxation was greater in preparations with intact epithelium (65%) than in those denuded of epithelium (40%). The relaxant effects of H2O2 in the presence of an inhibitor of nitric oxide synthesis (NG-monomethyl-L-arginine), an inhibitor of guanylate cyclase (methylene blue), an inhibitor of cyclooxygenase (indomethacin), and an ATP-sensitive K+ channel blocker (glipizide) were 44, 44, 39, and 48%, respectively. H2O2-induced relaxation in the presence of indomethacin in preparations with denuded epithelium was 29%. These results suggest that H2O2-induced relaxation of tracheal smooth muscle is partly epithelium dependent and is mediated by inhibitory arachidonic acid metabolites, epithelium-derived relaxing factor (nitric oxide), ATP-sensitive K+ channels, and the synthesis and release of prostaglandins from epithelium and the underlying smooth muscle.

Animals↗

Beneficial effects of methionine on myocardial hemodynamic and cellular functions in hemorrhagic shock.

Hypochlorous acid (HOCl), produced by activated polymorphonuclear (PMN) leukocytes, has been reported to depress cardiac function and contractility. Various mechanisms exist for activation of PMN leukocytes during hemorrhagic shock and reperfusion. In order to determine the role of HOCl in hemorrhagic shock and reinfusion, the authors studied the effects of shock and reinfusion on the cardiac function, contractility, blood lactate, blood gases, and creatine kinase (CK) and MB fraction of CK (MBCK) with and without methionine (quencher of HOCl) in anesthetized dogs. Dogs were divided into two groups: Group I, hemorrhagic shock (two hours) and reinfusion (two hours): Group II, hemorrhagic shock and reinfusion with methionine treatment. Cardiac index, mean arterial pressure, and index of cardiac contractility were similar in the two groups during shock. Postinfusion recovery of cardiac function and contractility was better in group II. Increases in blood lactate were similar in the two groups during shock. The rate of return of blood lactate to preshock values after reinfusion was greater in group II. The increases in serum CK and MBCK of the two groups during shock were similar but not significant. Following reinfusion the levels of these enzymes increased significantly, but the increases in group II were less. These results suggest that HOCl produced by activated PMN leukocytes may play a role in cardiac damage during hemorrhagic shock and reinfusion. Methionine may have beneficial effects in the hemodynamic and metabolic recovery and may reduce cellular damage during hemorrhage shock and reinfusion.

Animals↗

Methionine in protection of hemorrhagic shock: role of oxygen free radicals and hypochlorous acid.

Various mechanisms may exist for activation of polymorphonuclear (PMN) leukocytes during hemorrhagic shock and reinfusion. During activation of PMN leukocytes, hypochlorous acid (HOCl) is produced in addition to oxygen free radicals. We studied the effects of hemorrhagic shock and reinfusion on cardiac function and contractility, oxygen free radical producing activity of PMN leukocytes (PMN chemiluminescence), and serum and cardiac tissue malondialdehyde (MDA), a lipid peroxidation product, with and without methionine (quencher of hypochlorous acid) in anesthetized dogs, in order to assess the role of hypochlorous acid in depression of cardiac function and contractility in hemorrhagic shock. The dogs were divided into two groups: group I, hemorrhagic shock (2 hr) followed by reinfusion (2 hr); and group II, hemorrhagic shock and reinfusion similar to group I but methionine (30 mg/kg i.v.) was administered before bleeding, before reinfusion, and after 1 hr of reinfusion in this group. Mean arterial pressure (mAo), mean pulmonary arterial pressure (mPAP), index of myocardial contractility (dp/dtmax), and cardiac function (stroke volume index [SVI], left-ventricular work index [LVWI]) decreased significantly during shock and the decreases were similar in both groups. The indices of myocardial contractility which are independent of pre- and/or afterload ([dp/dt]/IIP and [dp/dt]/IIP/CPIP) were affected to a lesser degree than the other indices of myocardial contractility (dp/dtmax) during shock and reinfusion. However, the systemic and pulmonary vascular resistance increased significantly in both groups. Postinfusion recovery of cardiac function and contractility in group II was greater than in group I. Cardiac function and contractility after reinfusion returned to preshock levels initially followed by a decrease below the preshock values in group I. However, these parameters remained at or above preshock levels after reinfusion in group II. Cardiac tissue MDA levels were higher in group I, as compared to those in control dogs. The tissue levels of MDA in group II were lower than in group I but similar to those of control. The serum MDA did not change significantly during shock and reinfusion in either group. Although there were increases in the serum MDA after reinfusion in group I, they were not significant. While the chemiluminescent activity of PMN leukocyte increased significantly in group I, this activity decreased significantly in group II during shock and reinfusion. Methionine in in vitro studies did not affect the oxygen free radical producing activity of PMN leukocyte. These results suggest that hypochlorous acid is produced during shock and reinfusion. The decrease in the cardiac function and contractility after reinfusion may be due to hypochlorous acid.

Animals↗

Combination therapy of parkinsonism with deprenyl.

In view of the encouraging results in various trials with deprenyl as an added drug therapy for Parkinson's disease, a pilot study to study deprenyl's efficacy in the Indian population was undertaken. Eleven patients were recruited in this open trial and were objectively assessed by Unified Rating Scale for Parkinsonism of Columbia University, Modified Hoehn and Yahr Staging and Schwab and England activities of daily living. Side effects, mood changes, changes in dyskinesia percentage, early morning dystonia and off period percentage were also noted. This study suggests improvement in the above parameters with minimal side effects.

Adult↗

Interaction of assembly protein AP-2 and its isolated subunits with clathrin.

The clathrin assembly protein complex AP-2 is a multimeric subunit complex consisting of two 100-115-kDa subunits known as alpha and beta and 50- and 16-kDa subunits. The subunits have been dissociated and separated by ion-exchange chromatography in 7.5 M urea. Fractions highly enriched in either the alpha or beta subunit were obtained. The alpha fraction interacted with clathrin as evidenced by its ability to bind to preassembled clathrin cages. It also reacted with dissociated clathrin trimers under conditions that favor assembly of coat structures, but did not yield discrete clathrin polygonal lattices. The enriched beta fraction (containing small amounts of alpha) reacted with clathrin to yield intact coats with the incorporation of approximately equivalent amounts of alpha and beta subunits into the polymerized species; excess free beta subunit was unreactive. The AP-2 complex was also completely dissociated in a highly denaturing solvent, 6 M Gdn.HCl, and the constituent subunits of 100-115, 50, and 16 kDa were separated by gel filtration. In a coassembly assay with clathrin, the clathrin polymerizing activity was exclusively associated with the 100-kDa subunit fraction with stoichiometric incorporation of both alpha and beta subunits of 100 kDa into the polymerized coats, and with no requirement for 50- or 16-kDa subunits. These observations demonstrate that the assembly activity of the complex is associated with the alpha and beta subunits and suggest that both subunits, through independent interactions with clathrin, are required for expression of complete lattice assembly activity.

Animals↗

Oxygen-derived free radicals producing activity and survival of activated polymorphonuclear leukocytes.

Activation of polymorphonuclear (PMN) leukocytes is known to generate oxygen free radicals (OFR). However the fate of activated PMN leukocytes is not known. We investigated the OFR producing (chemiluminescence) activity and the survival of the activated PMN leukocytes. The study was divided into two groups. Group I, In vivo study (n = 7): zymosan (8.4 mg/kg) was administered intravenously in the anesthetized dogs and the blood samples were collected before and after 5, 15, 30, 60 and 120 min of zymosan administration. This group represents the in vivo pre-stimulated PMN leukocytes; Group II, In vitro study (n = 7): the blood were collected from dogs and further divided into two groups. Group A (n = 7): non-stimulated, without any added zymosan and group B (n = 7): zymosan was added to stimulate PMN leukocytes. Blood samples from group A and B were also collected at various time intervals similar to in vivo studies. Oxygen free radical producing activity of PMN leukocytes was monitored by measuring luminol-dependent chemiluminescence (CL). Opsonized zymosan was used to activate PMN leukocytes. The studies in which the PMN leukocytes were stimulated in in vivo, both oxygen derived free radicals and superoxide dismutase (SOD) inhibitable oxygen free radical CL decreased significantly for 60 min and tended to reach thereafter to the pre-stimulated values. The resting chemiluminescence (chemiluminescence without zymosan stimulation in the assay medium) increased significantly for 15 min reaching to pre-stimulated values at 30 min and thereafter. In in vitro studies, oxygen derived free radicals CL of pre-stimulated PMN leukocytes (Group B) was depressed for the whole duration of investigation while SOD inhibitable CL was depressed for only 60 min. There was approximately a two-fold increase in the resting CL within 5 min of PMN leukocyte activation and it remained high for the whole duration of study. The chemiluminescence of non-stimulated PMN leukocytes in vitro (group A) remained practically normal throughout the period of observation. In in vivo studies, total white blood cells (WBC) and PMN leukocyte counts decreased initially and tended to approach towards pre-stimulated values at the end of the protocol. There were no changes in these counts in in vitro studies. These results indicate that the capacity to generate OFR is decreased in the in vivo and in vitro pre-stimulated PMN leukocytes. However this activity recovers with time. This study also suggests that the activated PMN leukocytes are not destroyed.

Animals↗

Clathrin assembly protein AP-3. The identity of the 155K protein, AP 180, and NP185 and demonstration of a clathrin binding domain.

Three independently isolated clathrin-associated proteins have been reported that have molecular weights of approximately 155,000-185,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis: the 155K protein (Keen, J. H., and Black, M. M. (1986) J. Cell Biol. 102, 1325-1333), AP 180 (Ahle, S., and Ungewickell, E. (1986) EMBO J. 5, 3143-3149), and NP185 (Kohtz, D. S., and Puszkin, S. (1988) J. Biol. Chem. 263, 7418-7425). Using two-dimensional isoelectric focusing polyacrylamide gel electrophoresis and one- and two-dimensional immunoblots with two different monoclonal antibodies, we show that these three proteins are identical. The term AP-3 is used to denote this protein. A preliminary analysis of the domain structure of AP-3 was done by controlled proteolysis. Trypsin treatment of AP-3 yields two distinct classes of products. The larger fragments obtained (100,000-135,000 apparent Mr) are acidic and behave anomalously on gel electrophoresis, yielding aberrantly high Mr and exhibiting poor dye binding; these characteristics are shared with intact AP-3. Trypsin also generates a smaller neutral species of approximately 30,000 Da which migrates appropriately on sodium dodecyl sulfate-gel electrophoresis, binds dye comparatively strongly, and behaves as a monomeric globular species in solution. In addition, this species, which is also released by a variety of other proteases, binds specifically and reversibly to clathrin-Sepharose, identifying it as a clathrin recognition domain.

Adaptor Proteins, Vesicular Transport↗

Rapid diagnosis of tuberculous meningitis by polymerase chain reaction.

The polymerase chain reaction (PCR) in cerebrospinal fluid was compared with conventional bacteriology and an enzyme-linked immunosorbent assay (ELISA) for cerebrospinal fluid antibodies in the diagnosis of tuberculous meningitis (TBM). PCR was the most sensitive technique; it detected 15 (75%) of 20 cases of highly probable TBM (based on clinical features), 4 (57%) of 7 probable cases, and 3 (43%) of 7 possible cases. ELISA detected 11 (55%) of the highly probable cases and 2 each of the probable and possible cases. Culture was positive in only 4 of the highly probable cases. Among the controls (14 pyogenic meningitis, 3 aseptic meningitis, 34 other neurological disorders), 6 subjects tested early in the study (2 pyogenic meningitis, 4 other disorders) were PCR positive. Second DNA preparations from their stored cerebrospinal fluid samples were all PCR negative, suggesting that the false-positive results were due to cross-contamination. 18 PCR-positive TBM samples retested were all still PCR positive. The antibody ELISA was positive in 3 controls despite the use of a high cutoff value.

Bacteriological Techniques↗