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Biomedical subjects

S D Varma

Publications and source records attributed to S D Varma.

At least 55 records · Page 3Linked to original sources
PubMed1993

Effect of metabolic inhibitors and anaerobiosis on rat lens.

The effect of the inhibitors of aerobic metabolism on the transport of rubidium and ATP content in rat lens has been studied under organ culture system. The inhibitors used were malonate, monofluoroacetate, cyanide, antimycin A, 2-heptyl-4-hydroxyquinoline-N-oxide (HQNO), 2,4-dinitrophenol (DNP) and dicumarol. All these compounds inhibited the transport of rubidium, reflecting a decrease in the ability of the lens to transport potassium. The levels of ATP also decreased. The results were similar to those obtained under anaerobic conditions where the lenses were incubated in a nitrogen atmosphere without the inhibitors. The degree of inhibition observed by the metabolic inhibitors as well as by anaerobiosis indicate that the rat lens depends substantially on aerobic oxidation for its energy needs, unlike bovine and rabbit lenses studied before.

Adenosine Triphosphate↗
PubMed1993

Transient disappearance of a symptomatic macular hyperfluorescent lesion following vitrectomy: a case report.

We have presented a case of symptomatic macular fluorescence of a presumed vascular etiology that transiently disappeared post vitrectomy. Laser photocoagulation to the involved area resulted in a good visual outcome. We propose that the transient improvement in the fluorescein leakage represented a temporary alteration of cellular metabolism, or vascular perfusion, attributable to the perfusion solution. We suggest that additional studies are indicated to further explore this phenomenon and its potential clinical applicability.

Fluorescein Angiography↗
PubMed1992

Prevention of galactose cataract by pyruvate.

The effect of pyruvate on the progress of galactose cataract has been studied. Pyruvate was administered topically in the form of eye drops. Such treatment was found to delay the onset of the cataractous changes. Cataract formation was studied by visual inspection with pen light, as well as with slit lamp biomicroscopy in the intact animal. The delay in the formation of cataract was associated with the preservation of the levels of lens ATP, soluble proteins and the decreased accumulation of galactitol. In vitro organ culture experiments yielded similar results.

Adenosine Triphosphate↗
PubMed1991

Prevention of selenite cataract by vitamin C.

Studies have been conducted to determine the efficacy of vitamin C in the prevention of cataracts induced by selenite. Administration of the latter to rat pups results in the development of advanced cataracts within 5 days. Treatment with ascorbate had a significant preventive effect. The observations indicate that selenite cataract is due to an oxidative stress to the lens. In addition, the findings are in conformity with our view that ascorbate functions as an anticataractogenic substance.

3,4-Methylenedioxyamphetamine↗
PubMed1991

Radio-isotopic determination of hydrogen peroxide in aqueous humor and urine.

The concentrations of hydrogen peroxide in the aqueous humor and urine of several animal species and humans have been determined. The determinations are based on peroxide-dependent decarboxylation of I-[14C]-alpha-ketoglutaric acid and measurement of the resulting 14CO2 by quantitating the radioactive disintegration. The levels of H2O2 in most animals varied between 5.0 and 41 microM for aqueous, and 115 and 187 microM for urine. The levels of peroxide in the urine of steer, cat and baboon were lower and fell out of the above range. In the aqueous of humans with cataracts, the levels ranged from 33 to 324 microM, the overall average being 189 +/- 88 microM. The source of such high levels in the aqueous of cataract patients is currently being studied.

Aged↗
PubMed1991

Scientific basis for medical therapy of cataracts by antioxidants.

Cataract is one of the major causes of age-dependent visual impairment and blindness. The geographic distribution of cataract is known to be associated with the intensity and duration of sunlight--especially of the ultraviolet frequency--at particular places. Exposure of animals and humans to oxygen has also been known to result in cataract formation. Studies described in this communication indicate that the ocular lens is physiologically damaged when exposed to an environment of active species of oxygen, commonly referred to as oxyradicals. Several photochemical and nonphotochemical models have been described. The results suggest that an intraocular generation of active oxygen may constitute a significant risk factor in the overall pathogenesis of senile cataracts. The cataractogenic effect of oxyradicals, however, can be thwarted by nutritional and metabolic antioxidants such as ascorbate, vitamin E, and pyruvate. These agents, therefore, may be useful for prophylaxis or therapy against cataracts.

Animals↗
PubMed1991

Hydrogen peroxide in the eye lens: radioisotopic determination.

Lenses from normal rabbits, mice, rats, cattle, guinea pigs, lambs, chicken, cats, baboons, blue acara (fish) and dogs were examined for the presence of H2O2. No previous reports exist on the presence and levels of H2O2 in normal eye lenses. Freshly isolated lenses of these animals were extracted with trichloroacetic acid and the extract neutralized with Tris. H2O2 was assayed in these extracts by reacting them with 1-14C-alpha-ketoglutarate and measuring the 14CO2 produced by peroxide-dependent decarboxylation. Peroxide of the order of 10(-4)M was detected in most of the lenses except in baboons wherein it exists between 10(-4) and 10(-5)M. Culture experiments with rat lenses demonstrated that GSH may make a major contribution to the formation of H2O2 in the intact lens in vivo.

Animals↗
PubMed1991

Hydrogen peroxide in human blood.

Blood and plasma of humans and rats were analyzed for hydrogen peroxide. The samples were analyzed after deproteinization with trichloroacetic acid, immediately after they were withdrawn from human volunteers or rats. A radio-isotopic technique based on peroxide-dependent decarboxylation of 1-14C-alpha-ketoacids and consequent liberation of 14CO2 was used. The results demonstrate the presence of micromolar levels of H2O2, both, in the plasma as well as in the whole blood. The values in the whole blood were substantially greater than the plasma. This was true for rats as well as humans. The presence of such significant quantities of H2O2 in the blood have been demonstrated for the first time. The investigation, therefore, opens a newer avenue of research on diseases purported to be related to the generation of oxygen radicals in vivo.

Animals↗
PubMed1990

Photoinduction of cataracts in rat lens in vitro. Preventive effect of pyruvate.

Intact rat lenses were incubated in riboflavin-containing Tyrode solution or medium-199, generating photochemically active species of oxygen and the oxidative stress measured in terms of the decrease in active accumulation of rubidium, and the fall in the levels of glutathione and ATP. Addition of pyruvate to the medium prevented the tissue against oxidative damage as evidenced by a greater accumulation of rubidium and higher levels of glutathione and ATP. Pyruvate was thus found to be effective against the toxicity of oxygen derivatives, particularly the hydrogen peroxide. In dark experiments also, conducted in glucose-free medium, the uptake of rubidium was substantially greater in the presence of pyruvate. The levels of ATP were also higher. These results, therefore, suggest that this ketoacid is beneficial to the tissue through its ability to decompose H2O2 as well through providing a metabolic support. The development of in vitro cataract under the photochemical effects of riboflavin and oxygen was also effectively thwarted by pyruvate. The results are thus potentially useful from the point of view of developing pyruvate and similar compounds as effective anticataract agents.

Adenosine Triphosphate↗
PubMed1990

Excretion of hydrogen peroxide in human urine.

The excretion of hydrogen peroxide in human urine has been demonstrated for the first time. This was accomplished by a new radioactive method developed on the basis of decarboxylation of alpha-ketoglutaric acid by H2O2. Urine samples were incubated with alpha ketoglutarate pulsed with iwts 1-14C-analogue, and CO2 formed by decarboxylation was determined by radioactivity measurements. Blanks were prepared by pre-incubation of the samples with catalase. Both male and female subjects were studied. On an average the concentration of H2O2 in urine was approximately 100 +/- 60 microM (10(-4) M). Peroxide excretion was found to be unexpectedly high and might thus be useful for clinical diagnosis and therapy in diseases purported to be related to oxidative stress.

Adult↗
PubMed1990

Copper catalyzed oxidation of ascorbate: chemical and ESR studies.

Cu-catalyzed oxidation of ascorbate has been studied in the absence and the presence of superoxide dismutase, catalase, mannitol, glycerol, ethanol, formate, and thiourea. None of these agents except thiourea inhibited the reaction. Therefore, the role of the Haber-Weiss reaction in the ascorbate oxidation could not be demonstrated. Electron spin resonance studies demonstrated that the preventive effect of the thiol is primarily due to the chelation of the reduced copper ions with the sulphur atom. The oxidation was also prevented by the chelation of copper with physiological levels of bovine serum albumin. These observations are consistent with the concept that a metal-oxygen complex is perhaps directly involved in the oxidative process. Measurements of the peroxide produced during oxidation indicated that significant amounts of this compound accumulates only at lower levels of ascorbate and in the absence of a protein or other chelating agents. At higher ascorbate levels no peroxide accumulation takes place. These results are, thus, useful in predicting the conditions under which the nutrient may act as a pro-oxidant or as an anti-oxidant. The observations suggest that under normal conditions low levels of ascorbate may act as a pro-oxidant through H2O2 production if the system has transition metal ions devoid of chelating agents. At higher concentrations ascorbate acts predominantly as an antioxidant.

Ascorbic Acid↗
PubMed1989

Radio-isotopic determination of subnanomolar amounts of peroxide.

A new radio-isotopic method for determination of peroxide in subnanomolar concentrations has been described. The method is based on the reactivity of peroxide with alpha-Ketoglutaric acid containing [I-14C]-alpha-Ketoglutaric acid, and measurement of the resulting 14CO2 by radioactivity. The recovery of standard peroxide, alone or mixed with some biologically derived samples, following this technique was found to be 97 +/- 2.7%. The method may therefore be useful for determination of peroxides in active biological samples.

Animals↗
PubMed1988

Ascorbic acid and the eye lens.

Exposure of mice to hyperbaric oxygen leads to an inhibition of the mitotic activity in the germinative epithelium of the lens. This is followed by an eventual development of cataracts. Cataracts have also been observed in human beings treated with hyperbaric oxygen for different afflictions. The lens damage and cataract formation appears to be due to in situ generation of active radicals and other active species of oxygen. These oxygen derivatives may also contribute to the multifactorial process of senile cataract formation in human beings. This hypothesis is based on in vitro experiments with rat lenses cultured in medium generating oxygen radicals, the generation of the radicals being accomplished either photochemically or enzymatically. The ability of the lens to transport rubidium and amino acids from such a medium is adversely affected. This is a recognized index of the damage to the tissue physiology. Scavengers of active oxygen species have been found to protect against this damage. Ascorbate, present in concentrations similar to that in the primate aqueous and lens, is also protective. The studies, therefore, point to an antioxidant and perhaps an anti-cataract effect of ascorbate. Pyruvate is another agent useful in this regard.

Animals↗
PubMed1988

Peroxide damage to the eye lens in vitro prevention by pyruvate.

The ability of pyruvate to protect the eye lens against physiological damage by hydrogen peroxide has been studied. The physiological damage was estimated in terms of a decrease in the ability of the lens to transport rubidium against an electrochemical gradient under organ culture conditions. Peroxide was either added directly to the culture medium or generated therein by incorporation of xanthine and xanthine oxidase. In both these cases, addition of pyruvate to the medium led to a greater accumulation of rubidium by the lens. The net accumulation of this cation in the presence of 1 to 5 mM pyruvate from the medium containing peroxide (0.2 to 0.45 mM) was very close to that observed in the absence of peroxide. The protective effect was thus substantial. The mechanism of the pyruvate effect has been discussed, and seems to be related to the scavenging of peroxide by pyruvate.

Animals↗
PubMed1987

In vitro damage to rat lens by lumazine and xanthine oxidase: prevention by superoxide dismutase.

Intact rat lenses incubated with lumazine and xanthine oxidase are physiologically damaged as evidenced by a decrease in the net accumulation of rubidium ions against a concentration gradient. Superoxide dismutase protected the tissue against this damage. These experiments, therefore, demonstrate the susceptibility of the lens tissue to O2- injury under ambient and nonphotochemical conditions, suggesting a possible implication of this radical in the tissue in vivo and eventual cataract formation. The lumazine/xanthine oxidase system which is known to cause oxygen reduction predominantly by the monovalent route, producing superoxide, appears quite suitable to evaluate the toxicity of O2- to the tissues in vitro.

Animals↗