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Biomedical subjects

J Kalra

Publications and source records attributed to J Kalra.

At least 73 records · Page 4Linked to original sources
PubMed1990

Effect of polymorphonuclear leukocyte-derived oxygen free radicals and hypochlorous acid on cardiac function and some biochemical parameters.

Polymorphonuclear (PMN) leukocyte activation is known to result in the production and release of oxygen free radicals and hypochlorous acid. Various clinical conditions are associated with PMN leukocyte stimulation. The present investigation deals with the effects of stimulated PMN leukocytes in the absence and in the presence of scavengers of oxygen free radicals (superoxide dismutase, catalase), hypochlorous acid quencher (methionine), and myeloperoxidase inhibitor (azide) on cardiac function and contractility; blood lactate, gases, and pH levels, blood and cardiac tissue malondialdehyde; and PMN leukocyte chemiluminescence activity in anesthetized dogs. Opsonised zymosan was used for stimulation of PMN leukocytes, and the effects were observed for 2 hours. The dogs were divided into four groups: group I, zymosan; group II, superoxide dismutase + catalase + zymosan; group III, methionine + zymosan; group IV, azide + methionine + zymosan. Zymosan produced a decrease in cardiac function and in indices of myocardial contractility and an increase in systemic and pulmonary vascular resistance. There was a decrease in blood pH and in PMN leukocyte chemiluminescense and an increase in the blood lactate and malondialdehyde. Superoxide dismutase plus catalase and methionine reduced the effect of zymosan on cardiac function and contractility and on blood malondialdehyde, lactate, and pH. The combination of azide and methionine did not prevent the deleterious effects of zymosan on cardiac function and contractility. Cardiac tissue malondialdehyde levels were lower in groups III and IV than in groups I and II which had values similar to each other. Methionine was superior to superoxide dismutase plus catalase in the prevention of the deleterious effects of PMN leukocyte stimulation on the various measured parameters. These results suggest that oxygen free radicals and hypochlorous acid are cardiac depressants and increase systemic and pulmonary vascular resistance in addition to causing tissue damage. Clinical situations with PMN stimulation may result in cardiac depression. The oxygen free radical scavenger and hypochlorous acid quencher may be beneficial in the counteraction of the deleterious effects of PMN leukocyte stimulation on the hemodynamic parameters and cellular integrity.

Animals↗
PubMed1990

A modification of the urine osmolal gap: an improved method for estimating urine ammonium.

A modification of the urine osmolal gap was evaluated as an estimate of urine [NH4+]. We proposed that: Urine [NH4+] = Urine osmolality - [2(Na+ + K+) + urea + glucose]/2 Spot urine samples were collected from normal volunteers and from individuals with ketonuria; the modified urine osmolal gap as well as two other previously described estimates of urine [NH4+] were compared with measured urine [NH4+]. There was a significant positive linear correlation between the urine [NH4+] and the modified urine osmolal gap in normal volunteers (r = 0.81; p less than 0.01) and in individuals with ketonuria (r = 0.93; p less than 0.001). The originally described urine osmolal gap greatly overestimated the urine [NH4+] but also showed a significant correlation. The urine anion gap was not a valid estimate of urine [NH4+] within the range of values measured in our subjects. The modified urine osmolal gap is an improvement over previously described estimates of urine [NH4+] and can be used as a single calculation in place of the other two.

Acid-Base Equilibrium↗
PubMed1989

Effect of oxygen free radicals on cardiovascular function at organ and cellular levels.

Oxygen free radicals (OFR) have been implicated as a causative factor of cell damage in several pathologic conditions. It is possible that OFR could have effects on cardiac function and contractility. The present investigation deals with the effects of OFR in the absence and in the presence of scavangers of OFR (superoxide dismutase and catalase) on cardiac function, index of cardiac contractility, serum creatine kinase (CK), and blood lactate, PO2 and pH in the anesthetized dogs. The hemodynamic measurements and collection of blood samples for measurement of CK, lactate, PO2 and pH were made before and at various intervals after administration of OFR for 1 hour. Xanthine and xanthine oxidase were used to generate OFR. OFR produced a decrease in cardiac function and indices of myocardial contractility and an increase in the serum CK. OFR produced an increase in the systemic and pulmonary vascular resistance. Although there was a tendency for an increase in the blood lactate, the increase was not significant. The blood PO2 and pH were not affected. Superoxide dismutase (SOD), alone or in combination with catalase, tended to protect cardiac function against the deleterious effects of OFR. Scavangers of OFR prevented the OFR-induced rise in serum CK. Although the protective effect of SOD plus catalase was slightly better than SOD alone, the results were not significantly different from each other. These results suggest that OFR are cardiac depressant and increase the peripheral vascular resistance besides causing cellular damage. Scavangers of OFR may be beneficial in counteracting the deleterious effects of OFR on hemodynamic parameters and cellular integrity.

Animals↗
PubMed1989

Role of oxygen free radicals and pH on the release of cardiac lysosomal enzymes.

We investigated the effect of exogenous oxygen free radicals and various pH on the release of lysosomal hydrolases from dog myocardial lysosomes. A lysosomal enriched fraction from the homogenate of dog heart was prepared, using differential centrifugation technique. Exogenous oxygen free radicals were generated using xanthine-xanthine oxidase system. The release of lysosomal hydrolases was measured from the lysosomal enriched fraction. There was about 3-fold increase in the release of cathepsin D and beta-N-acetylglucosaminidase activities in the preparations treated with xanthine-xanthine oxidase as compared to those without such treatment. The presence of superoxide dismutase, an oxygen free radical scavenger, prevented the release of cathepsin D and beta-N-acetylglucosaminidase from the lysosomes. Sonication and lubrol treatments, which are known to cause membrane disruption, also induced the release of these enzymes from lysosomal enriched fraction. However, this release was not prevented by superoxide dismutase. The changes in pH (4.5, 5.5, 6.0, 6.5, 7.4, 8.0) alone did not cause any increase in the enzyme release. The presence of oxygen free radicals at each pH resulted in a similar increase in the release of cathepsin D and beta-N-acetylglucosaminidase. These studies suggest that oxygen free radicals and not the alterations in pH are primarily responsible for the release of lysosomal hydrolases. Oxygen free radicals, in addition to their direct myocardial damaging effect, may also be responsible for the cardiac damage through the release of lysosomal enzymes.

Acetylglucosaminidase↗
PubMed1989

Increased production of oxygen free radicals by polymorphonuclear leukocytes in heart failure due to aortic stenosis.

Oxygen free radicals have been linked to a wide variety of cellular damage in biological systems. Polymorphonuclear (PMN) leukocytes stimulation is one of the known sources for oxygen free radicals. It has been suggested that oxygen free radicals depress the excitation-contraction coupling in cardiac muscle. It is possible that a decrease in the myocardial contractility in heart failure might be due to an increased oxygen-free-radical-producing activity of PMN leukocytes. The authors studied, therefore, the release of oxygen free radicals, as measured by luminol-dependent chemiluminescence activity, from the PMN leukocytes in dogs with heart failure due to aortic stenosis. Hemodynamics and phagocytic activity of PMN leukocytes were studied in 6 control dogs and 6 dogs with aortic stenosis of six to nine months' duration. There was a significant decrease in the index of myocardial contractility and an increase in the left ventricular end-diastolic pressure in dogs with aortic stenosis, suggesting left ventricular failure in these dogs. Although there was a tendency for a decrease in the cardiac index in dogs with aortic stenosis, the decrease was not significant. Phagocytic activity of PMN leukocytes in blood was studied in control dogs and dogs with aortic stenosis. Phagocytosis was initiated by addition of opsonized zymosan and chemiluminescence was monitored by use of a luminometer. The peak chemiluminescence activity of the PMN leukocytes in blood of dogs with heart failure was about threefold greater than that in the blood from control dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Experimental atherosclerosis and oxygen free radicals.

Oxygen free radicals are known to produce cellular injury by peroxidation of phospholipids in the cell membrane. These free radicals might damage the endothelial cell and thus set the stage for atherosclerosis. The authors studied the effect of high-cholesterol diets on the genesis of atherosclerosis and lipid peroxidation products, malondialdehyde (MDA) in rabbits. The animals were divided into four groups each comprising 5 rabbits, on the basis of their diets. Group I, control diet; group II, cholesterol; group III, coconut oil; group IV, a mixture of cholesterol, coconut oil, and cholic acid. Rabbits were sacrificed five months after being on the respective diets. Blood samples were obtained for the measurements of total cholesterol, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C), triglycerides, and MDA at the end of the protocol. The aortas were removed from different animals for the identification of atherosclerotic plaques. Plaques were detected in all the animals in group II and group IV. The serum total cholesterol, LDL-C, and VLDL-C were significantly higher in animals of group II and IV than in those of group I. The values for serum total cholesterol, HDL-C, LDL-C, and VLDL-C in group III were not significantly different from those in group I. The blood MDA and serum triglycerides were also higher in animals of group II and IV than in those of group I. There were, however, no significant differences in these parameters in group III as compared with those in group I.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Increased chemiluminescence of polymorphonuclear leucocytes in dogs with volume overload heart failure.

Polymorphonuclear leucocyte (PMN) stimulation is known to generate oxygen free radicals. Exogenous oxygen free radicals, generated by xanthine and xanthine oxidase, have been implicated in the decrease of cardiac contractility. It is possible that PMN have increased capacity to release oxygen free radicals in failing heart. It was, therefore, decided to investigate PMN chemiluminescence (oxygen free radicals) from blood in dogs with heart failure due to chronic volume overload. The dogs were divided into two groups: (A) normal, six dogs; (B) dogs with mitral insufficiency (MI) of 6-9 months' duration, six dogs. Haemodynamic parameters were recorded to assess cardiac failure. Mixed venous blood was collected to measure PMN chemiluminescence. Stimulation of PMN was initiated by addition of opsonized zymosan and chemiluminescence was monitored using a luminometer. The haemodynamic parameters in dogs with MI showed that these dogs had left ventricular failure. The peak chemiluminescent activity of PMN in blood of dogs with left ventricular failure was approximately four times that in the blood from normal dogs. This increase in chemiluminescence reflects an increase in the generation of oxygen free radicals from PMN in dogs with chronic heart failure. The decrease in the myocardial contractility in cardiac failure might be due to an increase in the oxygen free radicals produced by the PMN.

Animals↗
PubMed1988

Oxygen free radicals induced release of lysosomal enzymes in vitro.

The effect of oxygen free radicals, generated by xanthine and xanthine oxidase, was studied on the release of lysosomal hydrolase from rat liver lysosomes in vitro. A lysosomal enriched subcellular fraction was prepared, using differential centrifugation technique, from the homogenate of rat liver. The biochemical purity of the lysosomal fraction was established by using the markers of different cellular organelles. Oxygen free radicals were generated in vitro by the addition of xanthine and xanthine oxidase. The release of lysosomal hydrolase (beta-glucuronidase) from the lysosomal fraction was measured. There was a 3 to 4 fold increase in the release of beta-glucuronidase activity in the presence of xanthine and xanthine oxidase when compared to that in the absence of xanthine and xanthine oxidase. In the presence of superoxide dismutase (SOD), a scavenger of oxygen free radicals, the xanthine and xanthine oxidase system was unable to induce the release of beta-glucuronidase activity from the lysosomes. Sonication (2 bursts for 15 sec each) and Lubrol (2 mg/10 mg lysosomal protein) treatment, which are known to cause membrane disruption, also induced the release of beta-glucuronidase from lysosomal fraction. This release of beta-glucuronidase by sonication and lubrol treatment was not prevented by SOD. These data indicate that lysosomal disruption is a consequence of oxygen free radicals, generated by xanthine and xanthine oxidase.

Animals↗
PubMed1988

Regulation of carnosine metabolism: the subcellular localization of carnosinase in liver.

We studied the subcellular localization of carnosinase (EC 3.4.13.3) in rat liver. The liver homogenate was fractionated by differential centrifugation into a nuclear (N), a mitochondrial (M), a lysosomal (L), a microsomal (P) and a soluble (S) fraction. The purity of different subcellular fractions was established by using different markers. The carnosinase activity in different fractions was measured by fluorometric determination of L-histidine produced using carnosine as a substrate. The intracellular distribution of carnosinase was very similar to that of lactate dehydrogenase with the highest relative specific activity of enzyme being observed in the soluble fraction. These results indicate that carnosinase enzyme is primarily located in the soluble (cytoplasmic) fraction of rat liver.

Animals↗
PubMed1988

Oxygen free radicals and heart failure.

We hypothesize that oxygen free radicals are involved in the genesis and maintenance of volume and pressure overload heart failure. Pressure and volume overload would produce myocardial ischemia. During ischemia there will be an increase in xanthine and xanthine oxidase; and a decrease in the superoxide dismutase and glutathione peroxidase activity leading to an increase in the oxygen free radicals. A decrease in the cellular pH during ischemia would release phospholipase which would, in turn, release arachidonic acid from phospholipids. Leukotrienes and prostaglandins will be synthesized through arachidonic acid metabolism. During this synthesis not only oxygen free radicals will be produced but also there will be formation of leukotriene, LTB4, which is known to activate neutrophil and hence increased secretion of oxygen free radicals. Increased circulatory catecholamines due to compensatory mechanism would also lead to an increase in the oxygen free radicals. Oxygen free radicals are known to depress Ca++ binding and uptake of sarcoplasmic reticulum which would lead to a decrease in the myocardial contractility. We have shown that oxygen free radicals depress cardiac function and cardiac contractility. It is, therefore, suggested that oxygen free radicals might be involved in the development of heart failure. The use of agents that reduce the amount of oxygen free radicals would be of value in the prevention and treatment of heart failure.

Animals↗
PubMed1988

Acute hemorrhage and oxygen free radicals.

Oxygen free radicals are known to produce cellular injury. There are various mechanisms during hemorrhagic shock that can lead to an increase in the oxygen free radicals, which would produce a loss of membrane integrity and a decrease in cardiac function and cardiac contractility. The authors studied the effect of acute hemorrhage and reperfusion on the hemodynamics, blood lactate, and oxygen free radicals. Dogs were divided into two groups, group I, hemorrhagic shock and reinfusion; group II, hemorrhagic shock and reinfusion with superoxide dismutase (SOD) and catalase treatment. The dogs were bled (50% of the estimated blood volume) over a period of five to twelve minutes. After an hour of bleeding, the shed blood was transfused over twenty to twenty-five minutes. Group II received SOD (0.7 mg/kg, IV) and catalase (0.7 mg/kg, IV) within ten minutes of bleeding. The hemodynamic measurements and collection of blood samples for measurement of oxygen free radicals and lactate were made before hemorrhage and at fifteen, thirty, and sixty minutes of hemorrhage and at fifteen, thirty, and sixty minutes after reperfusion of shed blood. There was a decrease in the cardiac function and index of myocardial contractility associated with an increase in the blood lactate after hemorrhage in group I. Similar but less marked changes in these parameters were observed in group II. Recovery of hemodynamic parameters with reinfusion was better in group II as compared with that in group I. There was an increase in blood oxygen free radicals (superoxide anions) in group I, especially after reinfusion. No such changes were observed in group II.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1987

Hepatocellular carcinoma in a long-term survivor of acute lymphocytic leukemia.

Hepatocellular carcinoma (HCC) occurred in a 28-year-old woman treated for acute lymphocytic leukemia (ALL) with methotrexate (MTX) and 6-mercaptopurine (6-MP), off all therapy for 15 years, who was also heterozygous for alpha-1 antitrypsin (alpha-1 AT) deficiency. MTXD is responsible for the development of HCC in this patient. The literature concerning the incidence of HCC in patients treated with MTX and 6-MP and in alpha-1 antitrypsin deficiencies is reviewed.

Adult↗
PubMed1987

Simultaneous renal cell carcinoma and squamous cell carcinoma of kidney.

A unique case of a collision tumor of the kidney composed of a renal cell carcinoma and a squamous cell carcinoma is reported. Although a few cases of combined tumors of the kidney have been reported previously, we were unable to find any similar case in the literature. Squamous cell carcinoma of the kidney usually behaves aggressively. Early diagnosis and surgical treatment before the tumor has extended beyond the capsule offer the best hope of cure.

Aged↗
PubMed1987

Value of free thyroxine (FT4), free triiodothyronine (FT3), and sensitive thyrotropin (TSH) assay in the assessment of optimal thyroxine therapy.

We describe a sensitive thyrotropin (TSH) assay in the evaluation of thyroxine replacement therapy. Patients taking varying amounts of L-thyroxine replacement doses were studied using a thyrotropin-releasing hormone (TRH) test and a sensitive TSH assay as the indices of optimal replacement therapy. There were no differences in the mean thyroxine doses of those patients who had a normal TRH response and those who had a flat response. Similarly there were no significant differences in the serum free thyroxine (FT4), free triiodothyronine (FT3), or total triiodothyronine (TT3) levels between these two groups. The patients in both groups had normal basal serum TSH values as measured by a standard, HTSH RIABEAD (Abbott) method. However, serum TSH values, as measured by a sensitive TSH3 MAIACLONE (Serono) immunoradiometric method, were subnormal in all patients with flat TRH responses. The TSH (Serono) assay provided the best single blood test of optimal thyroxine replacement.

Adult↗
PubMed1987

Evaluation and assessment of high sensitivity thyrotropin methods as an index for thyroid function.

We report the evaluation of four new commercially available sensitive assay kits for determination of thyrotropin (TSH) and their clinical utility in normal subjects and patients with thyroidal and non-thyroidal illnesses. The sensitivity for the reliable detection of serum TSH by these methods ranged from 0.1-0.4 mU/L and their decreasing order was : NML greater than Serono greater than Abbott EIA greater than Hybritech. The coefficient of variation ranged from 2.0-5.8% for intra-assay and 2.3-8.6% for interassay at different concentration levels. Patients studied (n = 130) were assigned into four groups on the basis of the serum thyroxine value and their clinical findings. In total, there were 17 discrepancies (five with Hybritech, three with NML, five with Abbott EIA, and four with Serono) in making the correct diagnosis using these sensitive TSH methods as a single diagnostic test. These discrepancies were mainly in the same patients who were clinically euthyroid but had subnormal TSH values. There were no discrepancies in making the correct diagnosis for patients with hyperthyroidism or hypothyroidism using these sensitive TSH methods. Our observations indicate that the sensitive TSH methods are reliable in measuring subnormal levels and may be used to detect hyperthyroidism without affecting in any way their value in detecting hypothyroidism.

Adolescent↗
PubMed1987

Pharmacokinetic comparison of intranasal, oral, and intramuscular metoclopramide in healthy volunteers.

This was a randomized, crossover study of the bioavailability and pharmacokinetics of metoclopramide given by intranasal (IN), oral (PO), and intramuscular (IM) routes. The formulations tested were 5 and 10 mg of IN gel, 10 mg PO, and 5 mg IM. The findings showed that metoclopramide follows similar absorption and elimination characteristics when given via these three extravascular routes. There were no statistically significant differences in the area under the drug concentration versus time curve (AUC) or peak metoclopramide plasma concentration (Cmax) data following PO, IM, or 10-mg IN administration. However, the 5-mg IN doses achieved an AUC that was 39.5% the AUC of the 10-mg IN dose. These data show consistent and relatively predictable metoclopramide plasma concentrations following IN administration. Further, 10-mg doses of IN and PO metoclopramide appear to be bioequivalent.

Administration, Intranasal↗