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Biomedical subjects

A H Ali

Publications and source records attributed to A H Ali.

At least 19 recordsLinked to original sources
PubMed2000

Diabetes-induced biochemical changes in rat lens: attenuation of cataractogenesis by pyruvate.

AIM: Studies have been conducted to determine the effect of pyruvate administration on the biochemistry of rat lens and the status of its transparency as affected by diabetic conditions. METHODS: Sprague-Dawley rats were rendered diabetic by intravenous (i.v.) injection of streptozotocin (55 mg/kg body weight (b.w.)) and treated with sodium pyruvate (2%) in drinking water. The levels of glucose, fructose, sorbitol, ATP, GSH, MDA as well as glycated proteins in the lenses were determined at various intervals after the onset of diabetes and the values compared with untreated diabetic controls. The progress of cataract formation and associated histological changes in the tissue were also monitored. RESULTS: Studies show that the pyruvate treatment decreased the extent of several biochemical changes known to be associated with cataract formation, such as the elevation in the levels of glycated proteins, sorbitol, lipid peroxidation (MDA) and inhibition of the cation pump. The progress of cataract was also significantly delayed. CONCLUSION: Exogenous administration of this compound hence was found to exert an overall protective effect against cataract formation induced by the diabetic conditions.

Adenosine Triphosphate↗
PubMed1999

Attenuation of sugar cataract by ethyl pyruvate.

Studies describe an attenuation of sugar cataract formation by topical administration of ethyl pyruvate. Cataract formation was induced by feeding young rats a 30% galactose diet. Mature cataracts appeared in about thirty days. Instillation of the eye drops containing 5% ethyl pyruvate decelerated the process significantly. Biochemically, the effect was reflected by lowering in the contents of dulcitol and glycated proteins. The ATP levels were also higher in comparison to the placebo treated group. The effects are hence attributable to the effect of pyruvate in inhibiting dulcitol synthesis and protein glycation, in addition to its antioxidant properties and metabolic support. The use of esterified pyruvate instead of the unesterified pyruvate was preferred because of its greater penetration through the cornea and consequently a higher concentration attained in the aqueous humor.

Adenosine Triphosphate↗
PubMed1999

Non-enzymatic glycation of lens proteins and haemoglobin-inhibition by pyruvate: an in-vivo study.

AIM: Previous studies have demonstrated that pyruvate can prevent protein glycation and oxidative stress under in-vitro conditions. The aim of this study was to examine the in-vivo effectiveness of this metabolite against glycation of lens crystallins and haemoglobin in galactosemic rats. METHODS: Sprague-Dawley rats were maintained on a 30% or 50% galactose-containing diet in the absence or presence of 2% or 5% pyruvate in food and water, respectively. The animals were killed subsequently and the extent of glycation of lens crystallins and haemoglobin was determined using an affinity column chromatograpic technique. RESULTS: Maintenance of rats on the high galactose diet resulted in a significant increase in glycation of both the proteins. The increase was faster and more substantial in the animals maintained on the 50% galactose diet than that in the animals fed a 30% galactose diet. The increase in the latter was also very significant. Supplementation with pyruvate inhibited the process. CONCLUSION: The inhibition is attributable to a competitive binding of pyruvate to the protein NH2 groups as well as to the antioxidant effect of the compound. The studies therefore suggest that this and other alpha-keto-acids may be physiologically useful in minimizing glycation and oxidative stress induced tissue pathology by the hyperglycaemic conditions, such as diabetes and galactosemia. The results are also considered pharmacologically significant.

Animals↗
PubMed1999

Attenuation of galactose-induced cataract by pyruvate.

Data in the present paper demonstrate a significant inhibition in the progress of sugar cataract formation by systemic administration of pyruvate. The formation of the cataract was induced by feeding young rats a diet containing 30% galactose. All animals fed this diet developed nuclear lens opacity by the end of 30 days. This was delayed if the diet and water contained, in addition, 2% sodium pyruvate. The incidence of cataract in the latter group was 0% at day 30 and only 25% at day 55. Physiologically, the inhibition was associated with the prevention of lens membrane damage as reflected by its ability to maintain transport of rubidium ions against a concentration gradient; decreased tissue hydration as indexed by the lens wet weight; inhibition of protein glycation, and higher levels of ATP. Since pyruvate, being a normal tissue metabolite, is likely to be non-toxic, the findings are considered useful for further pharmacological studies with this and other similar metabolites, relevant to protection against various secondary complications of diabetes and galactosemia.

Adenosine Triphosphate↗
PubMed1998

Oxidative stress to rat lens in vitro: protection by taurine.

The concentration of taurine is high in the lens. However, its function therein remains unknown. Studies from other tissues suggest that in addition to several other modes of action, it acts as an antioxidant. We therefore hypothesize that taurine may be a part of the antioxidant defense mechanisms involved in protecting the lens against oxidative stress and consequent cataract formation. In these studies, the protective effect of taurine was examined using lens culture system with menadione as an oxidant. Inclusion of this compound in the incubation medium was found to have several adverse effects on the lens, such as a decrease in its ability to accumulate rubidium against a concentration gradient and fall in the levels of glutathione, ATP and an increase in water insoluble proteins. All these deleterious effects were attenuated significantly by addition of physiological amounts of taurine to the menadione-containing medium.

Adenosine Triphosphate↗
PubMed1998

Corneal damage by half mustard (2-chloroethyl ethyl sulfide, CEES) in vitro preventive studies: a histologic and electron microscopic evaluation.

The effect of half-mustard (2-chloroethyl ethyl sulfide, CEES) on the morphology and ultrastructure of the cornea has been studied in vitro. Extensive necrotic changes were observed histologically as well as electron microscopically. The outer layer of corneal epithelium was observed to undergo vacuolization and globulization prior to its denudation. The epithelium becomes separated from the Bowman's membrane. These necrotic changes are prevented from taking place in the presence of a mixture of taurine, pyruvic acid, alpha-keto glutaric acid and pantothenic acid suggesting the use of this mixture in the prevention of mustard damage.

Animals↗
PubMed1998

Half mustard (CEES) induced damage to rabbit cornea: attenuating effect of taurine-pyruvate-alpha-ketoglutarate-pantothenate mixture.

Studies have been conducted on the corneal damage by half mustard (2-chloroethyl-ethyl sulfide, CEES) and its possible prevention by a mixture of taurine, alpha-ketoglutarate, pyruvate and pantothenate. CEES has been found to damage the membrane permeability function of the corneal epithelium as evidenced by increased flux of the rubidium ion from the epithelial to the endothelial side. The cornea also loses its transparency. These damaging effects are preventable by the above mixture labeled as VM. It is conceived that use of such a mixed formulation may provide a pharmacological means of prophylactic and post-exposure treatment against the tissue damage caused by exposure to the mustards.

Animals↗
PubMed1998

Prevention of intracellular oxidative stress to lens by pyruvate and its ester.

Pyruvate is a well-known scavenger of hydrogen peroxide (H2O2). In addition, it scavenges superoxide radical (O2.-). However, evidence on its intracellular antioxidant function is meager at present. Hence, we have examined the effectiveness of this metabolite and its ethyl ester against intracellular oxidative damage to the lens under organ culture. Menadione, a redoxcycling quinone, was used to generate the reactive oxygen species (ROS). It was found to inhibit lens metabolism as evidenced by a decrease of ATP. Additionally, tissue oxidation was apparent by loss of glutathione (GSH), and increase in the level of oxidized glutathione (GSSG), coupled with increase of the urea soluble proteins (water insoluble). The overall physiological damage was apparent by the inhibition of the Na+-K+-ATPase dependent cation pump, as evidenced by a decreased rubidium transport. These deleterious effects were attenuated by pyruvate and ethyl-pyruvate. The later was found to be more effective.

Adenosine Triphosphate↗
PubMed1997

Formation of advanced glycation end (AGE) products in diabetes: prevention by pyruvate and alpha-keto glutarate.

Glycation of proteins and their subsequent structural and functional modifications have been ascribed to play a prominent role in the pathogenesis of several secondary complications of diabetes, such as cataract and retinopathy. In addition, it plays a role in the generalized ageing process as well. Investigations have been conducted to explore the possibility of preventing the above process by use of pyruvate and alpha-keto glutarate as representatives of physiologically compatible keto acids. The results demonstrate that both these compounds are effective in preventing the initial glycation reaction as well as the formation of AGE products. Both these compounds also inhibit the generation of high molecular weight aggregates associated with cataract formation. Mechanistically, the preventive effects appear to be due to (1) competitive inhibition of glycation by the keto acids and (2) the antioxidant (radical scavenging) properties of these compounds. The results are hence considered useful from the point of view of developing these and other keto acid derivatives as pharmacological agents useful in preventing glycation related protein changes and consequent tissue pathological manifestations.

Animals↗
PubMed1997

Prevention of lens protein glycation by taurine.

Modifications in lens protein structure and function due to nonenzymic glycosylation and oxidation have been suggested to play a significant role in the pathogenesis of sugar and senile cataracts. The glycation reaction involves an initial Schiff base formation between the protein NH2 groups and the carbonyl group of a reducing sugar. The Schiff base then undergoes several structural modifications, via some oxidative reactions involving oxygen free radicals. Hence certain endogenous tissue components that may inhibit the formation of protein-sugar adduct formation may have a sparing effect against the cataractogenic effects of sugars and reactive oxygen. The eye lens is endowed with significant concentration of taurine, a sulfonated amino acid, and its precursor hypotaurine. It is hypothesized that taurine and hypotaurine may have this purported function of protecting the lens proteins against glycation and subsequent denaturation, in addition to their other functions. The results presented herein suggest that these compounds are indeed capable of protecting glycation competitively by forming Schiff bases with sugar carbonyls, and thereby preventing the glycation of lens proteins per se. In addition, they appear to prevent oxidative damage by scavenging hydroxyl radicals. This was apparent by their preventive effect against the formation of the thiobarbituric acid reactive material generated from deoxy-ribose, when the later was exposed to hydroxyl radicals generated by the action of xanthine oxidase on hypoxanthine in presence of iron.

Animals↗
PubMed1997

Nitrite-induced photo-oxidation of thiol and its implications in smog toxicity to the eye: prevention by ascorbate.

Studies have been conducted on nitrite-induced oxidation of corneal thiols and reduced glutathione (GSH). Oxidation of GSH in the presence of nitrite (NaNO2) was minimal in the dark. Exposure of GSH to UV (365 nm) in the presence of nitrite substantially accelerated this oxidation; only < 10% of the original GSH remained at the end of 20 minutes. A similar Thiol depletion was observed in the case of corneal epithelial extracts irradiated with UV in the presence of the nitrite. Nitrite is therefore considered to be a potent phototoxicant with possible pathophysiological implications to the external eye tissues. Ascorbate was found to be effective in preventing thiol oxidation, suggesting the possibility of preventing nitrogen oxide-based smog irritation to the eye by this physiologically compatible antioxidant.

Animals↗
PubMed1995

Prevention of oxidative damage to rat lens by pyruvate in vitro: possible attenuation in vivo.

Studies have been conducted to assess the possible preventive effect of pyruvate against lens protein oxidation and consequent denaturation and insolubilization. Rat lens organ culture system was used for these studies. The content of water insoluble proteins (urea soluble) increased if the lenses were cultured in medium containing hydrogen peroxide. Incorporation of pyruvate in the medium prevented such insolubilization. The insolubilization was associated primarily with loss of gamma crystallin fraction of the soluble proteins. PAGE analysis demonstrated that insolubilization is related to -S-S- bond formation which was preventable by pyruvate. Since pyruvate is a normal tissue metabolite the findings are considered pathophysiologically significant against cataract formation. This was apparent by the prevention of selenite cataract in vivo by intraperitoneal administration of pyruvate.

Adenosine Triphosphate↗
PubMed1993

Affinities for the aryl hydrocarbon receptor, potencies as aryl hydrocarbon hydroxylase inducers and relative toxicities of polychlorinated biphenyls. A congener specific approach.

Polychlorinated biphenyls (PCBs) are nonplanar aromatic xenobiotics that are not structurally related to polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs), yet, some PCBs are potent ligands for the aryl hydrocarbon receptor (AhR), active inducers of aryl hydrocarbon hydroxylase (AHH) and 7-ethoxyresorufin O-deethylase (EROD), and elicit toxicological responses in animals similar to PCDDs and PCDFs. We report new methodologies for quantifying the affinities of PCBs for AhR and corresponding potencies as AHH and EROD inducers. The models show that lipophilicities, electron affinities, entropies and electronic energy gaps of PCBs are key physicochemical properties controlling their AhR, AHH and EROD activities. Using 3,3',4,4'-tetrachlorobiphenyl (TCB) as the reference compound, it is shown that PCBs having higher electron affinities, lower lipophilicities and entropies than TCB are potent ligands for rat hepatic AhR. In addition, the congeners having higher binding affinities to AhR and smaller energy gaps than TCB are potent AHH and EROD inducers in rat hepatoma cells in culture. The reported models qualitatively explain and quantify AhR, AHH and EROD activities of all 209-PCBs and related xenobiotics, e.g. PCDDs and PCDFs. Furthermore, we demonstrated that AhR and AHH activities of PCBs relative to 2,3,7,8-tetrachlorodibenzo-p-dioxin correlate with corresponding in vivo relative toxicities in animals as well as assigned toxic equivalency factors. The reported methodologies are likely to be useful for identifying potentially toxic aromatic xenobiotics in mammals, and minimizing the need for animal testing.

Aryl Hydrocarbon Hydroxylases↗
PubMed1993

Binding of polychlorinated biphenyls to the aryl hydrocarbon receptor.

A new thermodynamic model for calculating the dissociation constants of complexes formed between the aryl hydrocarbon receptor (AhR) and polychlorinated biphenyls (PCBs) is reported. The free energies of binding of PCBs to AhR are controlled by their lipophilicities, electron affinities, and entropies. The corresponding physicochemical properties of polychlorinated dibenzo-p-dioxins and dibenzofurans also control their interactions with AhR. We present evidence supporting the hypothesis that the majority of PCBs are likely to interact with AhR in their nonplanar conformations. In addition, we demonstrate that the affinities of PCBs for AhR relative to 2,3,7,8-tetrachlorodibenzo-p-dioxin correlate with corresponding toxic equivalency factors in animals. The reported methodology is likely to be applicable to other polyhalogenated and mixed polyhalogenated bi- and terphenyls and related xenobiotics; thus, it could minimize the number of in vivo studies in laboratory animals and facilitate the identification of potentially hazardous aromatic xenobiotics.

Animals↗
PubMed1989

Effect of different cryoprotectants and transfer temperatures on the survival rate of hemp (Cannabis sativa L.) cell suspension in deep freezing.

Adequate cell dehydration is the precipitating element in the successful cryopreservation of plant cells and organs. This could be achieved by using different cooling rates, transfer temperatures and cryoprotectants. Experiments were performed to determine these critical points in the freeze preservation procedure of Cannabis sativa (L.) suspension cultures. The explants were frozen at a cooling rate of 2 degrees C/min, while the transfer temperatures were -10 degrees C, -20 degrees C, -30 degrees C, -40 degrees C and -50 degrees C. The applied cryoprotectants were the DMSO, glycerol, proline and PEG in different concentration. The highest viability (58%) was obtained by using 10% DMSO and at -10 degrees C transfer temperature. The optimum transfer temperature varied remarkably by different cryoprotectant concentrations indicating the importance of their interactions.

Cannabis↗
PubMed1981

Pulmonary arterio-venous fistula in a child: a rare cause of congenital cyanosis.

A 12-year-old girl with a solitary pulmonary arterio-venous fistula (P.A.V.F.) affecting the R.L.L. is reported. The cyanosis was noted since birth and increased with age. The diagnosis was confirmed by right heart catheterization and pulmonary arteriography. Preoperatively, her hematocrit was 73%, paO2 36 mm Hg and no bruit was heard. The treatment consisted of a right lower lobectomy. One year postoperatively, the patient has normal activities, is asymptomatic and has no evidence of residual disease. A short review of the literature on the subject of P.A.V.F. is included and indicates the relative rarity of surgical treatment of this disease in childhood.

Arteriovenous Fistula↗