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Biomedical subjects

S Puri

Publications and source records attributed to S Puri.

At least 55 records · Page 3Linked to original sources

Studies on the effects of monosodium glutamate on hepatic microsomal lipid peroxidation, calcium, ascorbic acid and glutathione and its dependent enzymes in adult male mice.

Daily administration of monosodium glutamate (MSG) to adult male mice subcutaneously, for 6 days, at dose levels of 4 and 8 mg/g body weight, significantly increased lipid peroxidation in the hepatic microsomes, as seen 31 days after the last injection. A highly significant increase was observed in the level of hepatic calcium and ascorbic acid. The glutathione (GSH) content was significantly decreased but the activities of glutathione dependent enzymes like GR, GPX, GSTs were found to be significantly increased. These observations suggested that MSG at dose levels above 4 mg/g body weight induced oxidative stress in hepatic microsomes. Attempts to maintain the redox state of the cell are suggested by increase in the ascorbic acid content and the activities of glutathione dependent enzymes.

Animals↗

A novel delivery system for continuous desferrioxamine infusion in transfusional iron overload.

Fifteen iron-overloaded thalassaemia major (TM) patients and two homozygous sickle cell patients (SCD) were treated continuously for 7d each week with the novel 48 h continuous subcutaneous (s.c.) desferrioxamine (DFX) delivery device (code C1083, Baxter) and 10 TM patients received the 24 h continuous intravenous (i.v.) DFX delivery device (code C1071). The 27 patients had previously received conventional s.c. DFX for 8-10h on 5 or more days each week. The serum non-transferrin bound iron (NTBI) levels fell significantly in both groups within 12h of commencing the continuous infusion. In the s.c. group the mean level fell from 4.2 to 2.0 mumol/l (P = 0.001), whereas in the i.v. group the mean level fell from 3.6 to 0.1 mumol/l (P = 0.006) the initial levels being measured 12h after stopping conventional s.c. DFX. After 4 weeks there was a significant fall in serum ferritin in both groups (P = 0.009). The new DFX delivery device is effective at removing toxicfree iron from plasma and reducing body iron. Moreover, it is preferred by patients with much improved compliance compared to the conventional s.c. DFX pump.

Adolescent↗

Reduced alveolar-capillary membrane diffusing capacity in chronic heart failure. Its pathophysiological relevance and relationship to exercise performance.

BACKGROUND: The pulmonary diffusing capacity for carbon monoxide (DLCO) is reduced in chronic heart failure (CHF) and is an independent predictor of peak exercise oxygen uptake. The pathophysiological basis for this remains unknown. The aim of this study was to partition DLCO into its membrane conductance (DM) and capillary blood volume components (Vc) and to assess if alveolar-capillary membrane function correlated with functional status, exercise capacity, and pulmonary vascular resistance. METHODS AND RESULTS: The classic Roughton and Forster method of measuring single-breath DLCO at varying alveolar oxygen concentrations was used to determine DM and Vc in 15 normal subjects and 50 patients with CHF. All performed symptom-limited maximal bicycle exercise tests with respiratory gas analysis; 15 CHF patients underwent right heart catheterization. DLCO was significantly reduced in CHF patients compared with normal subjects, predominantly because of a reduction in DM (7.0 +/- 2.6 versus 12.9 +/- 3.8 versus 20.0 +/- 6.1 mmol.min-1.kPa-1 in New York Heart Association class III, class II, and normal subjects, respectively, P < .0001), even when the reduction in lung volumes was accounted for by the division of DM by the effective alveolar volume. The Vc component of DLCO was not impaired. DM significantly correlated with maximal exercise oxygen uptake (r = .72, P < .0001) and inversely correlated with pulmonary vascular resistance (r = .65, P < .01) in CHF. CONCLUSIONS: Reduced alveolar-capillary membrane diffusing capacity is the major component of impaired pulmonary gas transfer in CHF, correlating with maximal exercise capacity and functional status. DM may be a useful marker for the alveolar-capillary barrier damage induced by raised pulmonary capillary pressure.

Blood-Air Barrier↗

Antioxidant effects of pyruvate in isolated rat hearts.

Sprague-Dawley rat hearts were perfused under constant flow conditions, and a balloon was inserted into the left ventricle to measure heart rate (HR) and left ventricular pressures. Left ventricular generated pressure (LVGP) was calculated as peak systolic minus end diastolic pressure. Three substrate groups, pyruvate (5 mM), glucose (15 mM) and octanoate (0.5 mM), were employed. Oxidative stress was induced by perfusion with tertiary-butyl hydroperoxide (tBHP, 0.35 mM, 12 min) followed by 25 min of perfusion with control buffer. Hearts perfused with pyruvate showed no significant decrease in contractile function following tBHP treatment (HR x LVGP = 17666 +/- 585 mmHg/min, initial: 16414 +/- 2083 post-tBHP treatment). Glucose-perfused hearts had an intermediate decrease in function (19174 +/- 828 mmHg/min, initial; 4379 +/- 2083 post-tBHP), while octanoate-perfused hearts recovered no contractile function. Peak release of LDH was lowest in hearts perfused with pyruvate (115 +/- 17 mU/g wet wt/min), intermediate in glucose-perfused hearts (1575 +/- 380) and highest in octanoate-perfused hearts (3074 +/- 499). Thiobarbituric acid reactive substances (TBARS) were unchanged in hearts perfused with pyruvate (16.2 +/- 5 nmoles/g wet wt), but increased significantly in glucose-perfused hearts (36.1 +/- 1) and in octanoate-perfused hearts (45.5 +/- 9). Total glutathione levels were unchanged in hearts perfused with pyruvate (753 +/- 68 nmoles/g wet wt), but significantly decreased in glucose-perfused hearts (594 +/- 68) and in octanoate-perfused hearts (445 +/- 38) following tBHP-treatment. Pyruvate significantly reduced oxidative injury. In contrast, glucose provided a small reduction in injury while octanoate-perfused hearts had the most severe injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Differences in hepatic drug metabolizing enzymes and their response to lindane in rat, rabbit and monkey.

Untreated rabbit liver microsomes demonstrated the highest content of cytochrome P450 and activity of NADPH cytochrome c reductase compared to rat and monkey. The sodium dodecyl sulfate polyacrylamide gel electrophoresis of microsomes from untreated rabbit demonstrated a greater quantity of 50 KDa polypeptide than in rat and monkey. The activity of glutathione-S-transferase towards 1-chloro-2,4-dinitrobenzene and the band intensity of 26 KDa polypeptide was found to be at maximum in untreated rabbits, while rat liver demonstrated the highest activity of glutathione-S-transferase towards ethacrynic acid. The extent of hepatic microsomal lipid peroxidation was at maximum in untreated rats. The activity of catalase was higher in untreated monkeys compared to untreated rats and rabbits. Lindane at a dose of 10 mg kg-1 body weight for a period of six days increased the hepatic content of cytochrome P450 and the activities of NADPH cytochrome c reductase, aminopyrine N-demethylase, glutathione-S-transferases, haem oxygenase and lipid peroxidation, decreased non-protein thiols and concomitantly intensified the 50 and 26 KDa polypeptides in the microsomes and 100,000 x g supernatants respectively, in the rat but not in the rabbit or monkey. The results demonstrate that lindane is a bifunctional inducer in the rat and non-functional in rabbit and monkey. It also increased the activities of hepatic drug metabolizing enzymes with concomitant production of oxidative stress in the rat, whereas in rabbit and monkey it did not alter the drug metabolizing enzymes nor produced any oxidative stress.

Aminopyrine N-Demethylase↗

A simple quantitative assay for ristocetin cofactor activity using microtiter plate and ELISA plate reader.

Ristocetin cofactor activity is the test of choice for diagnosing von Willebrand disease. There is however no simple and precise quantitative method for its rapid determination in the clinical laboratory. We describe here a new approach for measuring ristocetin cofactor activity using an ELISA plate reader. Paraformaldehyde-fixed platelets, diluted plasma samples and ristocetin were mixed and incubated in the wells of a microtiter plate. Platelet agglutination was measured by light absorbance at 405 nm. Measurements of platelet agglutination at 1x to 64x dilution of a normal pooled plasma were used to construct a standard curve. Further characterization showed a significant linear correlation between results determined by the new method and by an aggregometer assay (p < 0.0001), and that the intra- and inter-assay variations were 6% and 17%, respectively. Therefore, the newly developed assay provides a simple and rapid way for precise quantitation of plasma ristocetin cofactor activity.

Blood Proteins↗

Ancrod infusion for anticoagulation during and after PTCA in a patient with heparin-induced thrombocytopenia.

Ancrod is a rapid-acting defibrinogenating agent derived from the venom of the Malayan pit viper which has been used successfully as an alternative to heparin sulfate for anticoagulation during peripheral vascular procedures and coronary artery bypass surgery. We describe the first use of ancrod for anticoagulation before and during percutaneous transluminal coronary angioplasty (PTCA) in a patient with heparin-associated thrombocytopenia.

Ancrod↗

A differential dopamine receptor involvement during stress ulcer formation in rats.

The involvement of dopaminergic (DA) receptors and their possible interactions were evaluated during stress ulcer formation in rats. The DA1 antagonist SCH 23390 (0.025, 0.05, or 0.1 mg/kg) produced only marginal aggravations in gastric stress pathology when compared to vehicle controls. The DA2 antagonist sulpiride (10 or 50 mg/kg) had dose-related effects. The lower dose aggravated whereas the higher dose attenuated stress ulcerogenesis. The DA2 agonist bromocriptine (2.5 or 5.0 mg/kg), however, attenuated gastric stress ulcers. Pretreatment of rats with the DA depletor alpha-methyl-para-tyrosine or the DA1-antagonist SCH23390 clearly neutralized the stress ulcer-attenuating effects of bromocriptine. These results reaffirm a gastric cytoprotective role for DA and further suggest that DA1-DA2 receptor interactions are crucial during DAergic regulation of gastric mucosal integrity during stress.

Animals↗

Role of dopaminergic mechanisms in the regulation of stress responses in experimental animals.

The effects of some dopaminergic agents were evaluated on stress responses in normal and immunized experimental animals. Restraint stress (RS) consistently induced gastric mucosal lesions and elevated plasma corticosterone in rats. Pretreatment with alpha-methyltyrosine (alpha-MT), haloperidol, or sulpiride aggravated both responses, whereas bromocriptine attenuated them. In rats immunized with sheep red blood cells (SRBCs), RS prevented the booster-induced rise in anti-SRBC antibody titre. This response was further suppressed by alpha-MT, haloperidol, or sulpiride pretreatment, whereas bromocriptine potentiated the humoral immune response. In mice immunized with SRBCs, antigen challenge-induced increase in footpad thickness was inhibited by RS. Similar inhibitions in this response were also seen after alpha-MT or haloperidol treatment. The results are discussed in light of complex dopaminergic mechanisms in the regulation of visceral, endocrinological, and immune responses during stress.

Animals↗

Increased alveolar/capillary membrane resistance to gas transfer in patients with chronic heart failure.

OBJECTIVE: To investigate pulmonary diffusive resistance to gas exchange in patients with heart failure and healthy volunteers, assessing the relative contributions of the alveolar/capillary membrane and pulmonary capillary blood. SETTING: Hospital outpatient department and pulmonary function laboratory. PATIENTS: 38 patients (mean age 60) receiving treatment with loop diuretics and angiotensin converting enzyme inhibitors for stable symptomatic heart failure of > 6 months duration (New York Heart Association (NYHA) classes II and III). Results were compared with those of 17 healthy volunteers (mean age 52). METHODS: The alveolar/capillary membrane diffusive resistance and the pulmonary capillary blood volume available for physiological gas exchange were determined by the Roughton and Forster method, which measures the single breath pulmonary diffusing capacity for carbon monoxide at varying alveolar oxygen concentrations. RESULTS: Total pulmonary diffusive resistance was higher in patients than controls. Alveolar/capillary membrane resistance formed the main component of this increase, accounting for a mean (SD) of 63% (20%) and 86% (8%) of total pulmonary diffusive resistance in patients in NYHA II and III classes respectively, compared with 53% (10%) in controls. The pulmonary capillary blood volume was not significantly different between controls and patients in NYHA class II (66 (18) ml v 61 (18) ml), but was increased in those in NYHA class III (95(46) ml, P < 0.05). CONCLUSION: This study confirmed impairment of pulmonary diffusion at rest in patients with chronic heart failure and identified impaired alveolar/capillary membrane function as the main factor responsible.

Adult↗