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Biomedical subjects

G M Wang

Publications and source records attributed to G M Wang.

At least 73 records · Page 4Linked to original sources
PubMed1987

An evaluation system for ranking chemicals with teratogenic potential.

An evaluation system has been developed which permits comparison of the relative toxicity of chemicals based on their potential to alter embryonal and early-stage fetal development. It was considered necessary, from a regulatory standpoint, to develop a system for ranking chemicals which possess teratogenic potential. A detailed discussion of the various parameters selected and their relative importance is provided.

Abnormalities, Drug-Induced↗
PubMed1987

Pro-oxidant activation of ocular reductants. 1. Copper and riboflavin stimulate ascorbate oxidation causing lens epithelial cytotoxicity in vitro.

Ascorbic acid may not only be involved as an antioxidant in the aqueous humour and lens but under certain conditions may also undergo 'pro-oxidant conversion' leading to the generation of oxidants. It is demonstrated that the bovine aqueous humour contains electron spin resonance (ESR) detectable levels of ascorbyl semiquinone free radical associated with the transition metal-catalysed oxidation of ascorbate. Cu2+ was found to be a more efficient catalyst of ascorbate oxidation than Fe2+ and was similarly more potent in inhibiting 86Rb uptake of lens epithelial cells in the presence of ascorbate. The metal-chelating agent diethylenetriaminepentaacetic acid (DETAPAC) inhibited metal-catalysed ascorbate oxidation and lens epithelial cytotoxicity. Riboflavin in the presence of light stimulates the formation of ESR-detectable ascorbyl semiquinone radicals and stimulates O2 consumption (oxidation) by ascorbate in a manner dependent upon the concentration of riboflavin. It is proposed that photoexcited riboflavin can perform a one-electron oxidation of ascorbate generating a riboflavin radical. This radical may then autoxidize generating superoxide anion. The riboflavin-mediated photoimpairment of 86Rb uptake of bovine lens epithelial cells was found to be dependent upon the presence of ascorbate. This 'pro-oxidant' activation of ascorbate by riboflavin is discussed in the context of previous studies on riboflavin phototoxicology.

Animals↗
PubMed1987

Does elevated glutathione protect the cell from H2O2 insult?

Utilizing glutathione ethyl ester (GSH-EE), the glutathione (GSH) level of lens epithelial cells can be increased as much as 1.9-fold. The epithelial cells maintain the additional GSH in the reduced form. This system was utilized to examine the relative effectiveness of cells with elevated GSH to withstand H2O2 insult. Three parameters were investigated, 86Rb accumulation, a measure of membrane function, ATP levels, an indication of overall metabolism and glyceraldehyde-3-phosphate dehydrogenase (GPD) activity, indicating intracellular enzyme susceptibility to oxidative insult. Under oxidative stress, much of the GSH is in the oxidized form but upon removal of the stress, rapidly returns to the reduced state. However, a loss of approximately 20% in GSH equilibrium levels has been consistently observed. Elevated GSH does not significantly increase the cells' ability to withstand or recover from oxidative stress. Indeed, elevated GSH was found to be somewhat deleterious, causing a decreased ability to recover from oxidative insult. However, in the case of GPD, a significant protection of activity was observed. The overall conclusion is that elevating intracellular GSH concentration does not increase the cells' overall ability to withstand oxidative damage.

Adenosine Triphosphate↗
PubMed1987

Stimulation of glucosylated lens epithelial Na,K-ATPase by an aldose reductase inhibitor.

In diabetes, glucosylation of the Na,K-ATPase of the lens epithelium makes the pump inefficient. K+ transport and ATP hydrolysis (at near saturating ATP concentrations) are inhibited and the kinetics of ATP hydrolysis become substrate inhibition type. The AR inhibitor (AL1576, Alcon Laboratories) stimulates K+ transport and ATP hydrolysis by glucosylated bovine lens Na,K-ATPase. This inhibitor has a slight stimulatory effect upon the unmodified enzyme function also. The AR inhibitor is not able to prevent glucosylation of the pump in high-glucose-containing medium.

Adenosine Triphosphate↗
PubMed1986

Mitigation of an anthracycline-induced cardiomyopathy by pretreatment with razoxane: a quantitative morphological assessment.

A quantitative evaluation of structural modifications was undertaken in the myocardium of daunorubicin (DNR)-treated and razoxane (RZ)-protected mice. BDF1 mice were injected with DNR, 15 mg/kg; a second group of mice was subjected to the same conditions but, in addition, received a pretreatment of RZ, 200 mg/kg. Representative cubes of myocardial tissue were processed for viewing with the electron microscope. Five hundred myocardial cells in each group were examined for the presence of lesions which had been categorized as early, moderate, or advanced. Contrasting the total number of demonstrable lesions in each group revealed a statistically significant reduction of 38% in abnormalities present in RZ-protected mice. By category, RZ-pretreated mice showed a mitigation in the appearance of early and moderate alterations and a striking reduction in the incidence of advanced, irreversible lesions. These results indicate that the cardiomyopathy associated with DNR administration can be ameliorated by pretreatment with RZ; this protective effect is markedly exerted by preventing the development of severe, irreversible lesions in the murine myocardium; the initial, non-transient structural alteration subsequent to DNR-exposure appears to affect the myocardial sarcoplasmic reticulum.

Animals↗
PubMed1986

A new HPLC method to determine glutathione-protein mixed disulfide.

A sensitive method for measuring glutathione-protein mixed disulfides is described. The method is based on cleavage of the protein disulfides with performic acid followed by reaction with dinitrofluorobenzene and HPLC analysis with a Bondapak-amine column. Samples containing 0.1 nmoles or more of glutathione-protein mixed disulfide can be detected. The method has been used to demonstrate (a) the presence of low levels of glutathione mixed disulfide in gamma crystallin isolated from bovine lenses, (b) a dramatic increase in such mixed disulfides after exposure of denatured gamma crystallin to O2 in the presence of glutathione, and (c) the formation of glutathione-protein mixed disulfide in lens epithelial cells exposed to 0.6 mM H2O2 for one hour.

Animals↗
PubMed1985

The effect of H2O2 on lens epithelial cell glutathione.

Investigation of lens epithelial cells indicates that under normal conditions, essentially all of the detectable cellular glutathione is in a reduced state. However, exposure to levels of H2O2 in the range found in the aqueous fluid of cataract patients causes rapid, very large changes in the glutathione redox ratios. Immediately following short-term exposure to 0.15-0.2 mM H2O2, reduced glutathione drops to 19% of its normal level and the remainder of the total glutathione is found in the oxidized form. Within the next few minutes, the redox ratio returns to normal. However, total glutathione levels remain approximately 20% below normal even one hour after exposure to H2O2. With exposure to a higher concentration of H2O2, a greater loss of glutathione is observed. The results suggest that the glutathione redox ratios change dramatically as a result of oxidative insult but quickly return to normal when the oxidative insult is removed. The formation of mixed glutathione-protein disulfide was also observed but only after long-term (1 hour) exposure to a high level (0.6 mM) of H2O2.

Animals↗
PubMed1984

Evaluation of pesticides which pose carcinogenicity potential in animal testing. I. Developing a tumor data evaluation system.

A modified-Squire carcinogen ranking system has been developed by the Worker Health and Safety Unit of the California Department of Food and Agriculture to deal with pesticides which pose carcinogenic potentials. For pesticide products that have been adequately tested with sufficient data for such evaluation, this system can provide an in-depth review which is necessary for the better understanding of a chemical under investigation. Only with such understanding can a product be placed in its proper perspective with respect to its carcinogenic potency. When applying this rather intensive tumor data evaluation system, a total scoring point and carcinogenicity categorization may be provided, which, in conjunction with human exposure information, may be adequate for regulatory decision making. Based upon the adequacy of tumor data, seven pesticides were investigated using the current tumor data evaluation system. These pesticides were chosen to demonstrate the stepwise evaluation procedure for carcinogenicity evaluation.

Animals↗
PubMed1984

Evaluation of pesticides which pose carcinogenicity potential in animal testing. II. Consideration of human exposure conditions for regulatory decision making.

In reaching a regulatory decision on the use of pesticides with carcinogenic potential, it is of great importance to investigate the extent of dermal exposure and absorption of a pesticide to users and field workers. By applying this information, along with the appropriate carcinogenicity categorization of a pesticide, a reasonably sound regulatory decision can be derived. Seven pesticides were selected, based on adequacy of tumor data, and were taken through the tumor evaluation system as reported in Part I 1984, Regul. Toxicol. Pharmacol. 4, 355-360). A step-by-step analysis on how a regulatory decision is reached on each pesticide by the EPA and CDFA was discussed.

Agricultural Workers' Diseases↗
PubMed1984

Evaluation of free flaps transferred by microvascular anastomosis in oral and maxillofacial surgery.

The authors discuss indications for the use of microvascular free flaps transferred to the oral and maxillofacial region. A series of 139 cases, involving 145 free flaps, is reported over a three year period. The overall success rate for all types of flaps was 89.3%. Advantages and disadvantages of the use of various flaps are presented and suggestions are offered to avoid complications.

Adolescent↗
PubMed1982

Mitigating effects of ICRF-159 (razoxane) on a daunomycin-induced cardiomyopathy in mice.

In an attempt to induce in mice the cardiomyopathy associated with daunomycin treatment and to ameliorate this disorder by a protective pretreatment with ICRF-159 (razoxane), young male BDF 1 mice were injected with daunomycin, 6 mg/kg, in multiple doses. A second group of mice were pretreated by injection with razoxane, 200 mg/kg, 24 hours before each daunomycin administration. Within three weeks of the third daunomycin injection one half of the unprotected mice were moribund and were sacrificed. Mice pretreated with razoxane survived the length of the experiment without exhibiting any disabilities. Myocardial tissue of all mice was processed for light and electron microscopic examination. The myocardial ultrastructure of daunomycin-toxic mice showed foci of incipient changes, characterized by sarcoplasmic translucency, vacuolation of membrane-limited components, degeneration of mitochondria and lysosomal aggregates. Evaluation of mice pretreated with razoxane either failed to reveal ultrastructural alterations or demonstrated only minimal changes in the myocardium.

Animals↗