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Biomedical subjects

M E Davis

Publications and source records attributed to M E Davis.

At least 127 records · Page 7Linked to original sources

Effect of chloroacetic acids on the kidneys.

The effects of dichloroacetate (DCA) and trichloroacetate (TCA) administered in drinking water were studied. At high concentrations of either compound, weight loss, or failure to gain weight, was observed. Food consumption was also decreased; both effects were attributed to decreased water consumption. Renal phosphate-dependent glutaminase activity was increased at the highest concentration, and urinary ammonia was also increased. These changes indicated renal adaptation to an acid load. DCA, in pharmacological doses, impairs glucoenogenesis from lactate in part by decreasing lactate availability. Similar tendencies were observed in the present studies; however, female rats showed a biphasic response. At lower DCA concentrations, tissue lactate and plasma glucose concentrations were increased, whereas at higher concentrations of DCA, the expected decreases were observed.

Acetates↗

Dental health status of an aging VA population: implications for a preventive dental health care program.

The purpose of this study was to describe the sociodemographic characteristics and dental health status of the largest eligible class of veterans (Class IV) within the Greater Miami catchment area. Only 43 percent of 4,882 Class IV patients within this area have sought VA dental care. Sociodemographic data were obtained from a randomized sample of both the VA-treated and non-VA-treated groups. The prevalence and incidence of dental diseases and actual dental treatment procedures completed for the VA-treated sample were determined from clinical records. Results indicated that periodontal disease and dental caries are substantial problems; small groups of patients account for the majority of treatment needs and associated costs; 71 percent of these patients are over 55 years of age; and the "average" Class IV patient is lower middle-class and retired. Study implications suggest that the best strategy for developing an effective VA dental health program would be one in which each patient would have a preventive regimen tailored to meet his needs and the ability to comply with the preventive program. The VA needs to determine the cost-effectiveness and dental health advantages of providing preventive dental health care services to eligible veterans.

Adult↗

Changes of hexachlorobutadiene nephrotoxicity after piperonyl butoxide treatment.

The effects of piperonyl butoxide on hexachlorobutadiene (HCBD) nephrotoxicity were measured. The time course and severity of toxicity were affected. Five hours after either piperonyl butoxide or HCBD glomerular filtration rate (GFR) was decreased; at 24 h GFR had recovered for the piperonyl butoxide group but continued to fall in the HCBD group. The group treated with piperonyl butoxide and HCBD had the same GFR as the group treated with just HCBD. At 24 h after HCBD the piperonyl butoxide pretreated group was not different from the oil pretreated controls. At 48 h after HCBD, reabsorbtion of water and glucose was more severely impaired in the group pretreated with piperonyl butoxide. These results support the hypothesis that HCBD metabolites are involved in renal tubular dysfunction.

Animals↗

The lactose synthase acceptor site: a structural map derived from acceptor studies.

A pictorial map of the lactose synthase (galactosyl transferase) acceptor binding site has been formulated from this and published studies on substrate analogs and inhibitors. The basic requirements are a pyranose, thiopyranose or inositol ring structure and equatorial substituents (if any) at C-2, C-3, C-4, and C-5. The aglycone (at C-1) may be either alpha or beta-, but alpha- is somewhat preferred. In the absence of alpha-lactalbumin galactosyl transferase will accept long chain 2-N-acyl substituents on the glucosamine (GlcNH2) structure. An equatorial amino or N-acetyl substituent (e.g. mannosamine, N-acetylmannosamine) is also a suitable acceptor in the absence of alpha-lactalbumin since both N-acetylglucosamine and N-acetylmannosamine have complementary binding loci for the N-acyl moiety. The aglycone moiety must be equatorial (beta-configuration). However, upon alpha-lactalbumin binding the aglycone specificity allows for axial (alpha-configuration) as well as equatorial substituents. Furthermore, the 2-N-acyl substituent binding locus is blocked beyond a 2-N-hexanoyl group. It is suggested that alpha-lactalbumin binds to a hydrophobic site some distance from the C-2 group.

Acetylglucosamine↗

Perfluorocarbon emulsions in cancer therapy: preliminary observations on presently available formulations.

Perfluorocarbon (PFC) emulsions, due to their favorable oxygen transporting properties, have been proposed as tumor sensitizers for application in both radiotherapy and chemotherapy. While this application is a very promising one it is by no means simple, and presently available formulations are inadequate. Intravenous administration of these emulsions can produce a severe hemodilution which tends to offset the desired effect; these emulsions can alter the pharmacokinetics of simultaneously administered drugs. Unless these variables are taken into account the risk of false negative and false positive results will be excessive. Of more serious concern are the profound disturbances produced by these emulsions in the reticuloendothelial system. Using two of the more popular PFC, Fluosol-DA and DMA/NONANE, we have shown that daily administration of these emulsions can produce 9-fold increases in liver size and 27-fold increases in spleen size. This problem appears to involve the surfactant used in both emulsions, pluronic F-68. It will be necessary to circumvent this problem before further study of their potential application can proceed.

Animals↗

Life cycle efficiency of beef production: I. Cow efficiency ratios for progeny weaned.

Weights and individual feed consumption collected on 160 beef, dairy and beef X dairy dams and their progeny were used to estimate several measures of lifetime cow efficiency. Dams were fed either a high or a low energy diet. Efficiency was expressed as the ratio of outputs to inputs. Outputs included progeny weaning weights plus cow salvage weight, and inputs were progeny creep feed consumption plus the dam's lifetime feed consumption. In the first approach, life cycle cow efficiency was estimated by expressing weight output as a ratio to feed inputs when weights and feed consumptions were weighted by their probabilities; probabilities were a function of age distribution and percentage calf crop in a theoretical herd consisting of 100 cows and 20 yearling replacement heifers. In the second approach, actual lifetime cow efficiency was estimated by expressing weight outputs as a ratio to feed inputs when all components were weighted equally. Both approaches included efficiency estimates calculated with and without cow salvage value. Dams receiving low energy diets generally had lifetime efficiencies equal or superior to those fed high energy diets in spite of older ages at calving. Dams on the high energy diet had greater salvage value, but did not wean calves of sufficient additional size to offset their own increased metabolizable energy (ME) intake. Dam breeds and breed crosses of smaller size tended to be more efficient than those of large size, demonstrating the effectiveness of mating small dams to large sire breeds for improving cow efficiency. Breeds calving at later ages were less efficient. Efficiency ratios improved as number of progeny weaned increased.

Age Factors↗

Life cycle efficiency of beef production: II. Relationship of cow efficiency ratios to traits of the dam and progeny weaned.

Several measures of life cycle cow efficiency were calculated using weights and individual feed consumptions recorded on 160 dams of beef, dairy and beef X dairy breeding and their progeny. Ratios of output to input were used to estimate efficiency, where outputs included weaning weights of progeny plus salvage value of the dam and inputs included creep feed consumed by progeny plus feed consumed by the dam over her entire lifetime. In one approach to estimating efficiency, inputs and outputs were weighted by probabilities that were a function of the cow herd age distribution and percentage calf crop in a theoretical herd. The second approach to estimating cow efficiency involved dividing the sum of the weights by the sum of the feed consumption values, with all pieces of information being given equal weighting. Relationships among efficiency estimates and various traits of dams and progeny were examined. Weights, heights, and weight:height ratios of dams at 240 d of age were not correlated significantly with subsequent efficiency of calf production, indicating that indirect selection for lifetime cow efficiency at an early age based on these traits would be ineffective. However, females exhibiting more efficient weight gains from 240 d to first calving tended to become more efficient dams. Correlations of efficiency with weight of dam at calving and at weaning were negative and generally highly significant. Height at withers was negatively related to efficiency. Ratio of weight to height indicated that fatter dams generally were less efficient. The effect of milk production on efficiency depended upon the breed combinations involved. Dams calving for the first time at an early age and continuing to calve at short intervals were superior in efficiency. Weaning rate was closely related to life cycle efficiency. Large negative correlations between efficiency and feed consumption of dams were observed, while correlations of efficiency with progeny weights and feed consumptions in individual parities tended to be positive though nonsignificant. However, correlations of efficiency with accumulative progeny weights and feed consumptions generally were significant.

Animals↗

Functional and biochemical correlates of chlordecone exposure and its enhancement of CCl4 hepatotoxicity.

Animals pretreated with chlordecone exhibit a greatly increased hepatotoxic response to CCl4 challenge. Possible mechanisms underlying this interaction were examined. A single p.o. administration of chlordecone (5 mg/kg) was followed by CCl4 (200 microliter/kg) administered i.p. 48 h later. Twenty-four hours later, animals treated with chlordecone mccl4 had decreased hepatic excretory function (20% of controls) and elevated plasma transaminase activities and bilirubin. Hepatic mixed function oxidase activity was assessed as pentobarbital sleeping time and was not affected by chlordecone pretreatment. Irreversible binding of label from 14CCl4 to hepatic protein or lipid was not different in the chlordecone group compared to vehicle controls. Hepatic and renal glutathione concentrations were not affected by chlordecone alone (at 6 h, 1, 2, 3, 5 and 7 days) or by a combination of chlordecone (48 h) and CCl4 (24 h). CCl4-induced lipid peroxidation of liver tissue, measured in vitro or in vivo, was not increased by chlordecone treatment. Thus, while the mechanism for the enhanced toxicity remains to be elucidated, these results suggest that the interaction between chlordecone and CCl4 is a subtle one, not causally involving increased covalent binding of the toxin, increased susceptibility of tissue lipids to peroxidative damage or decreased hepatic GSH.

Animals↗

Disposition and nephrotoxicity of hexachloro-1,3-butadiene.

Hexachloro-1,3-butadiene (HCBD) administration to rats results in impaired kidney function. The time course of nephrotoxicity and disposition of HCBD were examined. Within 4 h after HCBD (300 mg/kg, i.p.) compromised kidney function was found as decreased urine osmolality, glomerular filtration rate (GFR) and drug excretion. At 24 h elevated blood urea nitrogen (BUN) was found. However, no definitive signs of hepatotoxicity were observed up to 48 h after HCBD. Control ralts excreted 40% of tracer dose (0.1 mg/kg, i.p.) of [14C]HCBD in feces and 30% in urine in 48 h. Rats with HCBD-induced nephrotoxicity excreted much less, 7% in feces and 6% in urine. Aliquots of these samples were extracted with hexane. All of 14C in bile and 87% of that in urine was water soluble, indicating that HCBD was biotransformed into polar metabolites.

Animals↗

Alterations of xenobiotic excretory function induced by potassium dichromate or carbon tetrachloride pretreatment.

Biliary and urinary excretory functions were determined in animals pretreated with a hepatotoxin (CCl4) or a nephrotoxin (K2Cr2O7), using polar metabolites of imipramine (PMIMP) and digoxin as models for anionic and neutral transport systems. Biliary excretion of PMIMP was decreased in CCl4-treated rats; urinary excretion was increased. Urinary and biliary excretion of digoxin were both unaffected by CCl4 treatment, but accumulation of digoxin by liver was impaired. K2Cr2O7 treatment resulted in severe nephrotoxicity accompanied by decreased urinary excretion of both model compounds. Hepatic excretion of digoxin, but not PMIMP, was increased in these animals. With minimal nephrotoxicity, urinary excretion of both compounds was unaffected. Thus the effect of toxicity on hepatic or renal excretion depends on the properties of the compounds used for excretion studies. In addition, for compounds excreted by both routes, impaired excretion by one route may be accompanied by increased excretion by the other. The extent of this compensatory mechanism may depend on several factors including the physiochemical properties of the compounds and the degree to which they are excreted by each route normally. In addition, specific cellular transport mechanisms may be important factors if involved in the excretory events.

Animals↗

Reduction of opiate binding to brainstem slices associated with the development of tolerance to morphine in rats.

Previous studies revealed that the characteristics of opiate binding sites are different in brainstem slices and homogenates. In the present study, the binding of opiate agonists, morphine and etorphine, and that of the antagonist, naloxone, to thin slices of rat brain stem was studied. Sodium ion inhibits agonist binding and enhances antagonist binding in brainstem slices. Development of the analgesic tolerance to morphine is accompanied by a reduction of opiate binding. The opiate binding recovers partially toward control values during morphine withdrawal. Kinetic analyses indicate that sodium-induced changes in opiate binding sites are different from those caused by chronic morphine treatment. These results provide evidence that analgesic tolerance is associated with changes in opiate receptors.

Analgesics↗

Opiate receptor: cooperativity of binding observed in brain slices.

Kinetic constants for binding of 3H-labeled morphine and naloxone were determined from Hill plot analyses and from experiments in which the concentration of tritiated drug was constant and that of nonlabeled drug varied. With brain slices, the binding of either drug exhibited strong positive cooperativity (Hill slope greater than 3); this was not observed in brain homogenates. Thus, in slices the relationship between opiate binding site and ligand may be more relevant physiologically and pharmacologically.

Animals↗