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Biomedical subjects

A Dubey

Publications and source records attributed to A Dubey.

27 records · Page 2Linked to original sources

Mitochondrial oxidative damage, hydrogen peroxide release, and aging.

The objective of this study was to elucidate the possible nature of the mechanism underlying the widely observed phenomenon that the rate of H2O2 production by mitochondria increases during the aging process, using flight muscle mitochondria of the male housefly as a model system. The protein carbonyl content of mitochondria increased linearly with age of the flies, and was also inversely associated with the life expectancy of flies. Exposure of flies to 100% oxygen caused a progressive increase in the level of mitochondrial carbonyl content. The rate of H2O2 release by such oxidatively damaged mitochondria was higher than the controls. Similarly, X-irradiation of submitochondrial particles simultaneously resulted in increased rate of H2O2 production and elevated level of carbonyl content. Results of this and previous studies indicate that oxidative damage to mitochondrial membranes may be responsible for the age-related increase in mitochondrial H2O2 generation.

Aging↗

Protein oxidative damage is associated with life expectancy of houseflies.

The objective of this study was to test some of the predictions of the oxidative-stress hypothesis of aging, which postulates that aging is causally associated with the molecular damage inflicted by reactive oxygen species. Protein carbonyl content was used as an index of molecular oxidative modifications. The carbonyl content was found to be associated with the physiological age or life expectancy of flies rather than with their chronological age. Exposure of flies to sublethal hyperoxia (100% oxygen) irreversibly enhanced the carbonyl content of the flies and decreased their rate of oxygen consumption. Results of this study indicate that protein carbonyl content may be a biomarker of aging and support the general concept that oxidative stress may be a causal factor in the aging process.

Animals↗

Diltiazem enhances potassium disposal in subjects with end-stage renal disease.

Seven subjects with end-stage renal disease (ESRD) who were anuric and dialysis-dependent were studied during a 28-hour interdialytic period to assess changes in plasma potassium. Plasma potassium, glucose, magnesium, aldosterone, and cortisol were measured every 4 hours. Eight normal subjects were similarly treated. Subjects with ESRD had a progressive increase in plasma potassium, in contrast to normal subjects who exhibited a characteristic diurnal variation. In ESRD, diltiazem significantly reduced the rate of increase in plasma potassium compared with placebo and resulted in a significantly lower net increase in potassium over the entire 28-hour period. Diltiazem did not affect plasma potassium in normal subjects. Diltiazem did not affect plasma aldosterone, cortisol, glucose, or magnesium. In conclusion, diltiazem reduced the rate of increase of plasma potassium during a 28-hour interdialytic period.

Adolescent↗

The diurnal rhythm of plasma potassium: relationship to diuretic therapy.

Plasma potassium levels have been implicated in the genesis of cardiac arrhythmias, particularly in patients receiving diuretic therapy. The present study was undertaken to evaluate the stability of plasma potassium levels throughout a 28-h period. Normal volunteers (n = 8) and subjects with essential hypertension (n = 10) were studied in a clinical research center while receiving controlled dietary intakes. Plasma potassium followed a diurnal rhythm in both groups, with a peak level at 12 h and a trough level at 24 h. The average peak-to-trough difference was 0.62 +/- 0.05 mmol/L. Urinary potassium excretion also followed a diurnal rhythm, with the lowest excretory rate during the evening hours, when plasma potassium reached its nadir. Subjects with essential hypertension were restudied after 4 weeks of hydrochlorothiazide (50 mg/day) and then after an additional 4 weeks of hydrochlorothiazide (50 mg/day) and amiloride (5 mg/day). Hydrochlorothiazide alone reduced plasma potassium at all times of measurement without altering the diurnal rhythm. The combination of hydrochlorothiazide and amiloride resulted in higher plasma potassium levels in the morning, but did not significantly affect evening plasma potassium levels. The frequency of hypokalemia (K less than or equal to 3.0 mmol/L) was related to the time at which the plasma potassium was measured. We conclude that plasma potassium undergoes a diurnal rhythm and that diuretics shift this rhythm to uniformly lower values. This rhythm must be considered when defining the frequency of hypokalemia.

Adult↗

Structure-activity studies on antihyperlipidemic N-benzoylsulfamates, N-benzylsulfamates, and benzylsulfonamides.

A series of aryl substituted N-benzoyl- and N-benzylsulfamic acid sodium salts and benzylsulfonamide sodium salts have been prepared and examined for antihyperlipidemic activity in male CF1 mice at a dose level of 20 mg/kg/d ip for 16 d. These substances were also subjected to toxicological evaluation and chemical stability studies. In general, both series of sulfamates and sulfonamides significantly lowered serum cholesterol and triglyceride levels in mice. The compounds were nonmutagenic, showed no acute toxicity or impaired liver or kidney function in male mice, and were chemically stable both as the monohydrates and in aqueous solution over a pH range of 3.5-7.4. While both series of sulfamates and sulfonamides lowered serum cholesterol and triglyceride levels, the sulfamates were relatively more potent with regard to decreasing cholesterol levels, while the sulfonamides were more effective in lowering serum triglyceride levels in mice.

Animals↗

Antihyperlipidemic activity of o-chlorobenzylsulfonamide in rodents.

o-Chlorobenzylsulfonamide was observed to be a potent hypolipidemic agent in rodents, reducing serum cholesterol levels 71% and triglyceride levels 49% at 60 mg/kg/d. The agent was effective both in normal and hyperlipidemic mice and was active both orally and intraperitoneally. o-Chlorobenzylsulfonamide significantly inhibited phosphatidate phosphohydrolase activity and marginally inhibited sn-glycerol-3-phosphate acyl transferase activity both in vitro and in vivo. The lowering of serum cholesterol levels appeared to be correlated with the accelerated excretion of cholesterol via the bile into the feces, with a marginal reduction of cholesterol absorption from the intestine. Reduced concentrations of lipids, e.g., cholesterol, triglycerides, and neutral lipids, were observed in the liver, small intestine, and blood lipoprotein fractions of rats.

Absorption↗

Acute encephalopathy associated with measles.

Thirty children presenting with acute encephalopathic illness within a month of measles were studied. A male preponderance was found and 83.3% of cases were below 5 years of age. The interval between onset of measles rash and that of encephalopathy ranged from 0 to 20 days. Fever (96.6%), convulsions (70%), and coma (90%) were found in a high percentage of cases, while focal neurological deficits and abnormal movements were found in a small number of patients (3.3% and 16.6% respectively). Signs of cerebellar or medullar involvement were not seen. Only 1 (3.3%) case had pleocytosis in the cerebrospinal fluid. Eleven (36.6%) patients died in hospital. The pathogenesis of acute encephalopathy following measles is discussed.

Brain Diseases↗