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M Chopra

Publications and source records attributed to M Chopra.

At least 55 records · Page 3Linked to original sources
PubMed1994

Developmental temperature selectively regulates a voltage-activated potassium current in Drosophila.

Ionic currents are regulated by many conditions including disease states, aging, learning and memory, and chronic drug treatment. Here we describe a novel phenomenon of regulation of ionic currents by developmental temperature. Raising Drosophila larvae at 28 degrees C instead of 18 degrees C increased one of the two voltage-activated K(+)-currents, the delayed sustained IK, in their muscles by up to 3.5-fold, with little effect on the early transient current, IA. Consistent with this increase in IK, the amplitude and the duration of the action potentials were reduced. The major increase in IK occurred between a rather abrupt interval from 25 degrees to 28 degrees C. The activation curve of the increased current was shifted towards hyperpolarizing potentials. There was no change in activation kinetics. This phenomenon has mechanistic implications for activity-dependent neuronal plasticity, expression of ion channels in cultured cells and heterologous systems, phototransduction, and behavior. The specificity of the regulation suggests a discrete mechanism geared to affect excitability such that it can respond to altered external stimuli such as temperature.

Action Potentials↗
PubMed1994

The assessment of the HO. scavenging action of therapeutic agents.

A new method is reported for the assessment of the HO. scavenging action of therapeutic agents. It is based on the photolysis of zinc oxide and has a detection limit of 3.3%. The scavenging order of the compounds tested was penicillamine > rentiapril > ascorbic acid > cysteine > glutathione > thiomalic acid > N-acetylcysteine > myocrysin > methionine. None were as effective as DMSO. It is argued that these compounds can have an in vivo protective effect where HO. is produced from oxidant producing cells, thus limiting radical induced damage.

Azo Compounds↗
PubMed1993

Evidence of oxidative stress in chronic heart failure in humans.

Chronic heart failure (CHF) due to coronary artery disease (CAD) has been shown to be associated with increased plasma thiobarbituric reactive substances (TBARS) and reduced plasma thiol (PSH) concentrations, suggesting oxidative stress (OS). The aims of the present studies were (a) to determine whether OS is due to CAD or CHF per se and (b) to determine if a wider range of more specific markers of OS are abnormal in CHF. In the first study, two groups of patients (n = 15 each) were compared. Group 1 (11 male, mean age 56 years) had CHF due to CAD and group 2 (12 male, mean age 53 years) had non-CAD CHF. Median plasma TBARS in controls was 7.6 nmol.ml-1, 10.0 nmol.ml-1 in group 1 and 9.3 nmol.ml-1 in group 2 (P < 0.01 both groups vs control). Median PSH was 505 384 and 364 nmol.ml-1 (P < 0.05 and P < 0.01 vs control) respectively. Fifty-three patients with CHF were recruited in the second study. Malondialdehyde and PSH were 10.3 and 409 nmol.ml-1 respectively, compared to control values of 7.9 and 560 nmol.ml-1 (both P < 0.001). The median values for the following additional measures of OS in controls and patients were: erythrocyte superoxide dismutase 131 vs 114 U.l-1 (P = 0.005); caeruloplasmin oxidase 97 vs 197 U.l-1 (P < 0.01); erythrocyte glutathione 1.56 nmol.ml-1 vs 1.77 nmol.ml-1 (P < 0.02); plasma conjugated dienes 0.28 vs 0.33 optical density units (P = ns).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Antioxidant effects of angiotensin-converting enzyme (ACE) inhibitors: free radical and oxidant scavenging are sulfhydryl dependent, but lipid peroxidation is inhibited by both sulfhydryl- and nonsulfhydryl-containing ACE inhibitors.

With an assay that generates free radicals (FR) through photooxidation of dianisidine sensitized by riboflavin, 4 x 10(-5) M captopril, epicaptopril (SQ 14,534, captopril's stereoisomer), zofenopril, and fentiapril [all sulfhydryl (-SH)-containing angiotensin-converting enzyme (ACE) inhibitors] were shown effective scavengers of nonsuperoxide free radicals whereas non-SH ACE inhibitors were not. Captopril was a more effective FR scavenger at pH 5.0 than at pH 7.5. Captopril (2 x 10(-5) M) also scavenged the other toxic oxygen species hydrogen peroxide and singlet oxygen and inhibited microsomal lipid peroxidation. Finally, captopril reduced the amount of superoxide anion-radical detected after neutrophils in whole blood were activated with zymosan, probably by inhibiting leukocyte superoxide production.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

Evidence for oxidative stress in unstable angina.

OBJECTIVE: To determine whether unstable angina, which is characterised by recurring episodes of myocardial ischaemia and reperfusion, is associated with oxidative stress (that is, where there is an imbalance between oxidants, such as free radicals, which are in excess and antioxidants). DESIGN: Between group comparison of patients with unstable angina, stable angina, and healthy controls. SETTING: The coronary care unit and cardiac investigation ward of a regional cardiology centre. PATIENTS: Twenty five consecutive patients admitted to the coronary care unit with unstable angina. Twenty five consecutive patients admitted to the cardiac investigation ward (patients with stable angina undergoing coronary angiography) were used as controls for the presence of atherosclerosis, drug treatment, and smoking habit. Thirty eight healthy controls (hospital staff and patients admitted for minor surgical procedures who were otherwise healthy) were also studied. MAIN OUTCOME MEASURES: Thiobarbituric acid related substances (TBARS) in plasma and plasma reduced thiol (PSH) as indicators of oxidative damage to lipids and proteins respectively were measured. Coronary angiography was performed in all patients with stable angina and roughly half of those with unstable angina. RESULTS: Mean (SEM) plasma TBARS in unstable angina and stable angina were 9.95 (0.36) nmol/ml and 9.14 (0.28) nmol/ml respectively (p = 0.08). Mean plasma TBARS in healthy controls were 8.09 (0.21) nmol/ml (p < 0.05 compared with both angina groups). Mean (SEM) PSH concentration in unstable angina was 4.21 (9) nmol/ml and in stable angina was 4.85 (9) nmol/ml (p < 0.05). Mean PSH in healthy controls was 5.64 (8) nmol/ml (p < 0.001 compared with both angina groups). The extent of coronary artery disease, use of medication, and smoking habit were not significantly different between the angina groups. CONCLUSIONS: Biochemical indicators of oxidative stress are more abnormal in unstable than stable angina. This is in keeping with experimental evidence that episodes of ischaemia and reperfusion lead to generation of free radicals and toxic oxygen species and depression of endogenous antioxidant activity. The clinical significance of this finding remains to be determined, although, experimentally, free radicals and toxic oxygen species have adverse effects on myocardial contractile function, myocardial electrical stability, endothelial mediated vasodilatation, and coagulation.

Adult↗
PubMed1991

Influence of ACE inhibitors on free radicals and reperfusion injury: pharmacological curiosity or therapeutic hope?

1. The currently available evidence shows that thiol containing ACE inhibitors are free radical (FR) scavengers in vitro; in particular the OH. radical is effectively scavenged by these compounds. There is also good evidence that, in vivo, ACE inhibitors can preserve myocardial contractile function following a period of reversible ischaemia (by directly protecting myocytes and/or preserving coronary flow through protection of endothelial cells). These in vivo benefits are probably also due to FR scavening, mainly due to the presence of a thiol group but, also as a consequence of augmented prostanoid production. 2. Use of more relevant animal models and testing of a range of doses of ACE inhibitors might be undertaken before clinical investigation is considered. Because of its nature, however, the existence and importance of reperfusion injury in man will only be proven or disproven by pharmacological intervention. One option is to compare a thiol containing agent with absent or minimal haemodynamic effects with placebo as an adjunct to thrombolysis. This is the simplest approach. An alternative approach is to conduct a comparative study of a -SH containing ACE inhibitor and a non -SH containing ACE inhibitor given prior to thrombolysis. There are many problems with either approach. The lack of reliable measures of FR activity in man and difficulty in measuring accurately left ventricular function post-myocardial infarction means that mortality is likely to be the only reliable end-point in such a study.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1991

Oxygen free radicals and congestive heart failure.

Plasma lipid peroxides (malondialdehyde) and thiols were measured in 45 patients with congestive heart failure and 45 controls. Malondialdehyde concentrations were significantly higher in the patients with congestive heart failure (median 9.0 nmol/ml interquartile range (IQR) 7.9-10.2) than in the controls (median 7.7 nmol/ml (IQR 6.9-9.2)). Plasma thiols were significantly lower in congestive heart failure (median 420 mumol/l (IQR 379-480)) than in the controls (median 463 mumol/l (IQR 445-525)). There was a significant but weak negative correlation between malondialdehyde and left ventricular ejection fraction (r = -0.35) and a positive correlation between plasma thiols and left ventricular ejection fraction (r = 0.39). This study provides clinical support for experimental data indicating that free radicals may be important in heart failure. It also suggests that the degree of free radical production may be linked to the severity of the disease.

Adult↗
PubMed1990

Oxidative damage in chronic heart failure: protection by captopril through free radical scavenging?

The pathogenesis of heart failure is not yet fully understood. In animal models there is some evidence to suggest a role for free radicals (FRs). We have investigated malondialdehyde - LM in plasma of patients with heart failure and found it to be raised when compared to controls. We present data to show that Captopril, a drug with an ACE inhibitory effect is a FR scavenger both in vitro and ex-vivo in patients with heart failure.

Aged↗
PubMed1990

Free radical scavenging: a potentially beneficial action of thiol-containing angiotensin converting enzyme inhibitors.

Free radical (FR) scavenging may be a therapeutically useful adjunctive property of angiotensin converting enzyme (ACE) inhibitors. In this study we have shown that SH-containing ACE inhibitors (captopril, epicaptopril, zofenopril) are potent FR scavengers at a concentration of 4 x 10(-5) M whereas non-SH ACE inhibitors (enalaprilat, quinaprilat and perindoprilat) have no FR-scavenging activity at this concentration. Furthermore, the SH-containing agents preferentially scavenged general radicals rather than superoxide radicals, i.e. suggesting that these drugs would be effective in quenching the culprit FR in ischaemia/reperfusion injury.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1990

Lipid peroxidation during myocardial ischaemia induced by pacing.

Oxygen derived free radical generation can be shown in experimental models of myocardial ischaemia and reperfusion and may cause cellular damage by peroxidizing polyunsaturated membrane phospholipids. An attempt was made to quantify human intracardiac lipid peroxidation during transient myocardial ischaemia by measuring the aortic and coronary sinus concentrations of malondialdehyde (a marker of lipid peroxidation) before, during, and after incremental pacing. Twenty six patients were paced until they had severe chest pain or 2 mm ST segment depression or they reached a paced rate of 180 beats/min. They were divided into two groups according to whether or not lactate was produced during pacing. Twelve patients (group 1), all with coronary artery disease, produced myocardial lactate during pacing. None of the other 14 patients (group 2), half of whom had coronary disease, produced lactate during pacing. Concentrations of malondialdehyde in the aorta and coronary sinus were significantly higher in group 1 than in group 2. Five minutes after the end of pacing coronary sinus malondialdehyde concentrations in group 1 had increased significantly from baseline values. There were no changes with time in the coronary sinus concentration of malondialdehyde in group 2 or in the aorta in either group. The negative malondialdehyde extraction ratio in group 1 suggests that intracardiac lipid peroxidation occurs during transient human myocardial ischaemia.

Adult↗
PubMed1989

Free radical pathology in chronic arterial disease.

The generation of toxic oxygen metabolites is more usually associated with inflammation. However, pathological free radical reactions can cause tissue damage by adversely affecting prostacyclin (PGI2) synthesis allowing initiation of coagulation. We have assessed changes in the red cell defence to toxic oxygen metabolite generation, viz measurement of glutathione concentration (GSH) and superoxide dismutase activity (SOD). GSH and SOD were measured in 20 patients with peripheral arterial disease, 22 patients with vasculitis, and 11 patients with angina, and compared to 17 matched controls. The 53 subjects with arterial disease had significantly lower SOD levels: in contrast GSH levels were significantly higher. Extracellularly plasma thiol levels (PSH) were low and caeruloplasmin (Cp) levels were high. We suggest that free radical pathology exists not only in inflammatory vascular disease but also in atherosclerosis.

Angina Pectoris↗
PubMed1989

Captopril: a free radical scavenger.

The use of captopril in heart failure and hypertension is becoming increasingly accepted. Captopril has a sulphydryl group in its molecular structure. We wondered if this might confer free radical scavenging activity on the drug and have investigated this in an in vitro system. Results show that captopril is a free radical scavenger and we suggest that this action might be relevant in its use in heart failure and other vascular diseases.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1989

Free radicals and Graves' disease: the effects of therapy.

Plasma thiol (PSH), caeruloplasmin (CP), intracellular lysate thiol (LSH) and superoxide dismutase (SOD) activity were measured in 30 patients with newly diagnosed Graves' disease (GD). Compared to control subjects (C) PSH and SOD were significantly reduced (C vs GD, 507 vs 449 mumol/l, P less than 0.01; 2.1 vs 1.6 mumol/l, P less than 0.01 respectively) and LSH was significantly raised (C vs GD 181 vs 298 mumol/l). Treatment with carbimazole produced a significant rise in LSH and SOD. Propylthiouracil (PTU) treatment raised LSH levels but 131I treatment produced no significant change. All four parameters are involved in different ways in oxygen metabolism and together provide an indication of oxidative stress across the red-cell membrane. In addition LSH is a general radical scavenger and SOD a specific O2- scavenger. In Graves' disease the increased oxidative stress and increased general radical scavenging may result from raised free-radical activity. These changes, which have not previously been reported in Graves' patients, were modified by antithyroid drug therapy, but it is not clear whether this is a direct or indirect effect.

Adult↗