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Biomedical subjects

M W Williams

Publications and source records attributed to M W Williams.

At least 19 recordsLinked to original sources
PubMed1992

Absorption and lymphatic transport of peroxidized lipids by rat small intestine in vivo: role of mucosal GSH.

The absorption and lymphatic transport of peroxidized MaxEPA fish oil was studied using the lymph fistula rat to determine the role of mucosal glutathione (GSH) in intestinal metabolism of luminal lipid hydroperoxides. Decreasing intestinal GSH concentrations with buthionine sulfoximine (BSO, 1.15 +/- 0.20 nmol/g), diethyl maleate (DEM, 0.93 +/- 0.26 nmol/g), phorone (1.46 +/- 0.14 nmol/g), or 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU, 1.54 +/- 0.18 nmol/g) compared with control (2.60 +/- 0.38 nmol/g) resulted in higher luminal recovery of the infused lipid hydroperoxide (% of infused dose): BSO (87.8 +/- 4.8%), DEM (86.1 +/- 1.3%), phorone (78.1 +/- 2.1%), and BCNU (71.7 +/- 4.8%) compared with control (52.8 +/- 4.3%). These results suggest that decreased elimination of luminal peroxidized lipids is associated with decreased tissue GSH. Treatment of rats with BSO, DEM, phorone, or BCNU resulted in dramatic increases in appearance of peroxidized lipids in lymph over 6-h lipid infusion (54.7 +/- 3.7, 57.7 +/- 4.6, 46.4 +/- 2.7, and 42.1 +/- 3.9 nmol, respectively) compared with control (20.5 +/- 3.4 nmol). The results are consistent with decreased intracellular metabolism of absorbed hydroperoxides and enhanced transport into lymph under GSH-deficient conditions. The current findings suggest that the function of the mucosal GSH peroxidase/oxidized glutathione (GSSG) reductase system may play an important role in intestinal handling of luminal lipid hydroperoxides. A compromised function of this detoxication mechanism in GSH-deficient states can significantly alter the metabolic fate of dietary peroxidized lipids.

Absorption↗
PubMed1992

Intestinal absorption and lymphatic transport of peroxidized lipids in rats: effect of exogenous GSH.

We previously found that mucosal glutathione (GSH) plays an important role in the intestinal metabolism of luminal peroxidized lipids [T. Y. Aw, M. W. Williams, and L. Gray. Am. J. Physiol. 262 (Gastrointest. Liver Physiol. 25): G99-G106, 1992]. To determine the effects of exogenous GSH on lipid hydroperoxide elimination under conditions in which mucosal GSH was initially depleted with buthionine sulfoximine (BSO), we infused peroxidized lipid solutions without or with GSH into the proximal intestine of rats and monitored the steady-state output of hydroperoxides in lymph and recovery of luminal hydroperoxides. GSH supplementation in BSO-treated rats resulted in a concentration-dependent attenuation of lymphatic output of peroxidized lipids that was correlated with increases in mucosal GSH. Compared with BSO control, the luminal lipid hydroperoxide contents were significantly lower in GSH-supplemented rats, consistent with enhanced elimination of peroxidized lipids by exogenous GSH. The effect of GSH was ameliorated by the inhibitors of GSH uptake, suggesting that the uptake of GSH is required for promotion of intestinal removal of luminal hydroperoxides. Other thiols, either at comparable or higher concentrations than GSH, were without significant effects on lymphatic transport or luminal recovery of lipid hydroperoxides, indicating that these thiols are poor substitutes for GSH. Overall, the data are consistent with exogenous GSH being a source for cellular reduction of peroxidized lipids. Results from these studies could directly impact on future consideration of therapeutic means to increase cellular antioxidant systems to promote intestinal hydroperoxide detoxication.

Animals↗
PubMed1988

Phallic reinnervation via the pudendal nerve.

Total phallic reconstruction presents the genitourinary reconstructive surgeon with one of the most difficult surgical challenges. The development of microsurgical techniques and free tissue transfers have advanced phallic reconstruction by reducing the number of surgical procedures and by allowing more selectivity in choosing the best innervated donor tissue. During the last 5 years 16 patients underwent total phallic reconstruction using free tissue transfers from distant donor sites. The pudendal nerve was coapted routinely to the major sensory nerves of the donor free flap. The most accurate objective baseline parameters of penile sensibility are pressure and vibratory thresholds, and electrically evoked potentials. We examined 30 normal subjects and 7 patients at least 1 year postoperatively for penile (phallic) sensibility. A pressure aesthesiometer, a biothesiometer and electrodiagnostic studies were used for testing. The 7 postoperative patients (in all of whom the pudendal nerve was incorporated into the reconstruction) had an encouraging return of tactile and erogenous sensibility compared to normal subjects. This is a promising advance in phallic reconstruction.

Adolescent↗
PubMed1987

Cadmium resistance in Drosophila: a small cadmium binding substance.

A small cadmium-binding substance (CdBS) has been observed in adult Drosophila melanogaster that were raised for their entire growth cycle on a diet that contained 0.15 mM CdCl2. Induction of CdBS was observed in strains that differed widely in their sensitivity to CdCl2. This report describes the induction of CdBS and some of its characteristics.

Animals↗
PubMed1985

Genetic and physiological parameters associated with cadmium toxicity in Drosophila melanogaster.

Two strains of Drosophila melanogaster represent the extremes in resistance and sensitivity to the lethal effects of CdCl2. The strain containing the mutations vermilion and brown (v; bw) and the strain Austin had LC50's of 3.3 and 1.3 mM CdCl2, respectively. The three major chromosomes from these two strains were assorted genetically into the six possible combinations. The measured LC50's for CdCl2 for these six genotypes fell into two groups according to the X chromosome; those containing the X chromosome from v; bw had LC50's 0.5-1.0 mM greater than those in which the X chromosome was from Austin. Since the parent strains differed by 2 mM, we suggest that the X chromosome is a major, but not the sole, site of genes to produce resistance to CdCl2. When 109Cd was in the diet the uptake by v; bw and Austin over 2 days was the same. After 4 days of uptake, the Austin strain excreted the 109Cd five times faster than v; bw but the six genotypes did not differ appreciably in excretion rate from one another and resembled the sensitive parent Austin more than the resistant one. Thus a second process is indicated that distinguishes resistance to CdCl2 that apparently is not associated with the X chromosome.

Animals↗
PubMed1975

Toxic effects of a new boron containing heterocycle: 4,4,8,8-tetraethyl-3,3a,4,8-tetrahydro 3a,4a,4-diazabora-S-indacene.

LD50 values in mice for 4,4,8,8-tetraethyl-3,3a,4,8-tetrahydro-3a,4a,4-diazabora-S-indacene (Myborin) were determined by the ip, po, and sc routes. The LD50 value for ip was 69.5 mg/kg found by the method of Litchfield and Wilcoxon, with upper and lower confidence limits of 77.8 and 62.1 mg/kg. Oral and sc LD50's were approximated after the method of Deichmann and LeBlanc and were found to be 180 mg/kg (po) and 420 mg/kg (sc). Each of these values has a confidence range of +/- 30%. Myborin induced convulsions, hyperreflexia, and death accompanied by tetany when given by either the ip or oral routes. Moreover, Myborin induced porphyria in animals surviving for 24 hr after these routes of administration and in virtually all animals dosed sc. Death by the sc route is probably a result of acute porphyria. Hepatomegaly and skin photosensitivity were demonstrated to be profound. Boron levels in the livers of mice were determined colorimetrically 24 hr after ip injections of Myborin and in untreated control mice. The quantity of boron found in the experimental group was 15.46 mug/g wet liver as compared to 8.11 mug/g wet liver for controls (P less than 0.01). The difference corresponds to 23% of the injected quantity of boron.

Animals↗