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Biomedical subjects

G C Tremblay

Publications and source records attributed to G C Tremblay.

At least 19 recordsLinked to original sources
PubMed2001

The Zipper: a method for using personal identifiers to link data while preserving confidentiality.

OBJECTIVE: This report describes a method for linking separate confidential data sets that contain personal identifying information while preserving required anonymity. METHODS: Research data were linked with child abuse and neglect (CAN) report data by an independent "safe" analyst using an identical set of unique identifier codes assigned to each case in both data sets after all personal identifiers had been removed. RESULTS: The research team never learned CAN report status of individuals, the state agency never saw the research data, and the desired analyses were completed using the merged data set. CONCLUSIONS: The method was successfully used to merge data from separate sources without divulging confidential information.

Abstracting and Indexing↗
PubMed2001

Insulin-like effects of a physiologic concentration of carnitine on cardiac metabolism.

Pharmacologic (millimolar) levels of carnitine have been reported to increase myocardial glucose oxidation, but whether physiologically relevant concentrations of carnitine affect cardiac metabolism is not known. We employed the isolated, perfused rat heart to compare the effects of physiologic levels of carnitine (50 microM) and insulin (75 mU/l [0.5 nM]) on the following metabolic processes: (1) glycolysis (release of 3H2O from 5-3H-glucose); (2) oxidation of glucose and pyruvate (production of 14CO2 from U-14C-glucose, 1-14C-glucose, 3,4-14C-glucose, 1-14C-pyruvate, and 2-14C-pyruvate); and (3) oxidation of palmitate (release of 3H2O from 9,10-3H-palmitate). We found that addition of carnitine (50 microM) to a perfusate containing both glucose (10 mM) and palmitate (0.5 mM) stimulated glycolytic flux by 20%, nearly doubled the rate of glucose oxidation, and inhibited palmitate oxidation by 20%. These actions of carnitine were uniformly similar to those of insulin. When carnitine and insulin were administered together, their effects on the oxidation of glucose and palmitate, but not on glycolysis, were additive. When pyruvate (1 mM) was substituted for glucose, neither carnitine nor insulin influenced the rate of oxidation of pyruvate or palmitate. In combination, however, carnitine and insulin sharply suppressed pyruvate oxidation (75%) and doubled the rate of palmitate oxidation. None of the responses to carnitine or insulin was affected by varying the isotopic labeling of glucose or pyruvate. The results show that carnitine, at normal blood levels, exerts insulin-like effects on myocardial fuel utilization. They also suggest that plasma carnitine in vivo may interact with insulin both additively and permissively on the metabolism of carbohydrates and fatty acids.

Animals↗
PubMed2001

Dietary L-carnitine suppresses mitochondrial branched-chain keto acid dehydrogenase activity and enhances protein accretion and carcass characteristics of swine.

A trial was conducted to biochemically explain the decreased lipid deposition and increased protein accretion observed in pigs fed carnitine. Our hypothesis was that an increase in the ratio of acetyl CoA:CoA-SH produced by stimulation of fatty acid oxidation by supplemental L-carnitine may decrease branched-chain alpha-keto acid dehydrogenase activity and increase pyruvate carboxylase activity. Such changes could reduce oxidative loss of branched-chain amino acids and provide more carbons for amino acid biosynthesis. Yorkshire gilts (n = 36; 12 per treatment) were fed a control diet or diets containing either 50 or 125 ppm of added L-carnitine during growth from 56 to 120 kg. After slaughter, the semitendinosus muscle and liver were collected for isolation of mitochondria and hepatocytes. Increasing dietary L-carnitine did not influence growth performance (P > 0.10) but linearly decreased (P < 0.05) 10th rib backfat thickness and increased (linear, P < 0.05) percentages of lean and muscle. The rates of [1-(14)G]palmitate oxidation in isolated hepatocytes and isolated mitochondria, and incorporation of [35S]methionine into the acid insoluble fraction of isolated hepatocytes were increased (linear, P < 0.01) in pigs fed L-carnitine. Flux through branched-chain alpha-keto acid dehydrogenase linearly decreased (P < 0.01) in isolated liver and muscle mitochondria with increasing dietary carnitine. Flux through pyruvate carboxylase was increased (linear, P < 0.01) in isolated mitochondria from liver of pigs fed carnitine, and assays with particle-free extracts indicated that the amount of mitochondrial pyruvate carboxylase was tripled by feeding carnitine (linear, P < 0.01). The association of increased protein accretion and reduced backfat thickness with greater rates of palmitate oxidation, more rapid flux through pyruvate carboxylase, and reduced flux through branched-chain alpha-keto acid dehydrogenase suggests pigs fed carnitine are more able to use fat for energy, divert carbon toward synthesis of amino acids, and spare branched-chain amino acids for protein synthesis.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed2000

Cloning and characterization of salmon hsp90 cDNA: upregulation by thermal and hyperosmotic stress.

Accumulating evidence suggests that glucocorticoids are essential for development of hypoosmoregulatory capacity in salmon during adaptation to seawater. Heat shock protein (hsp)90 has been reported to function in signal transduction and the maturation and affinity of glucocorticoid receptors. We sought to determine whether this hsp might be upregulated by thermal and hyperosmotic stress in salmon, a species that migrates between the freshwater and marine environments. A 2625-bp cDNA cloned from a salmon cDNA library was found to code for a protein of 722 amino acids exhibiting a high degree of identity with zebra fish (92%) and human (89%) hsp90beta. Accumulation of hsp90 mRNA was observed in isolated branchial lamellae incubated under hyperosmotic conditions and in branchial lamellae of salmon exposed to hyperosmotic stress in vivo. In contrast, exposure of kidney to hyperosmotic stress in vitro and in vivo failed to elicit an increase in the quantity of hsp90 mRNA. By way of comparison, accumulation of hsp90 mRNA was observed in both branchial lamellae and kidney tissue subjected to thermal stress in vitro and in vivo. Western blot analyses of proteins isolated from tissues under identical conditions in vitro revealed that the pool of hsp90 increased with thermal stress but not with osmotic stress. The results suggest that accumulation of hsp90 mRNA in response to osmotic stress is unrelated to cellular protein denaturation and that synthesis of hsp90 may be regulated at both the level of transcription and translation.

Amino Acid Sequence↗
PubMed2000

Linking childhood sexual abuse and abusive parenting: the mediating role of maternal anger.

OBJECTIVE: This study had two primary objectives: First, to examine the association between childhood sexual abuse (CSA) and later parenting characteristics, particularly physical abuse potential, and second, to explore maternal anger as a mediator of the relationship between CSA and adult physical abuse potential. METHOD: Utilized a community sample of low SES participants that included 138 mothers classified as having experienced CSA, and a comparison group of 152 non-sexually abused mothers. Parenting variables examined included the mothers' physical abuse potential, nurturance toward their children, unrealistic developmental expectations of children, as well as frequencies of spanking and general punishment. Data was collected via interview and other self-report measures. RESULTS: Even after controlling for mothers' childhood experience of Physical abuse, CSA significantly predicted adult risk of physically abusing one's own children. Further, maternal anger was confirmed as a mediator of the relationship between having been sexually abused as a child and the potential for physically abusing one's own children. CONCLUSIONS: CSA may be a risk factor for subsequent physically abusive parenting, while anger appears to play a significant role in mediating this relationship. Findings are discussed in the context of current knowledge concerning the impact of child sexual abuse and the processes contributing to abusive parenting.

Adult↗
PubMed1999

Hsp70 and a 54 kDa protein (Osp54) are induced in salmon (Salmo salar) in response to hyperosmotic stress.

Hsp70 and a 54 kDa osmotic stress protein (osp54) were induced in isolated tissues of anadromous Atlantic salmon (Salmo salar) upon exposure to hyperosmotic conditions. Incubation of branchial lamellae, hepatic tissue, and erythrocytes in medium supplemented with 200-600 mM NaCl dramatically reduced protein synthesis. Although general protein synthesis remained depressed following transfer of tissues from 450 mM supplemental NaCl to iso-osmotic medium, hsp70 was prominently induced in branchial lamellae and hepatic tissue. Accumulation of hsp70 mRNA and a decrease in actin mRNA suggest preferential upregulation of the hsp70 gene. Induction of osp54 was observed in branchial lamellae and erythrocytes, but not in hepatic tissue, during exposure to 75-125 mM supplemental NaCl. Use of glycerol in place of NaCl to create hyperosmotic conditions stimulated induction of hsp70 in branchial lamellae. Substitution with mannitol resulted in induction of osp54 in both branchial lamellae and erythrocytes. The solute-specific and temporal patterns of response suggest that hsp70 and osp54 might function in concert to restore osmotic homeostasis and renature proteins destabilized or denatured during the early stages of osmotic shock.

Animals↗
PubMed1999

Prevention of childhood injury: clinical and public policy challenges.

Injuries are the leading killer of children in the United States, at a rate significantly higher than in other industrialized countries. In this article, we outline how a behaviorally and developmentally based model of prevention may assist in determining effective interventions for various injury risks. Two conclusions emerge: (a) the strength of perceived costs and consequences for taking effective safety actions greatly influences the probability that they will be implemented; and (b) intervening at the most developmentally appropriate time is likely to result in more effective outcomes. Further, clinical psychologists are uniquely suited to assess contingencies that maintain unsafe practices, but we need to enlist the participation of citizens and other professionals to mount persuasive intervention campaigns. Despite strong demonstration projects, childhood injury reduction has lagged behind other public health endeavors. Obstacles to injury prevention include (a) the diffusion of injury threats, complicating the identification of effective targets for intervention; (b) the tendency of parents and even some health professionals to regard injuries as products of fate, which fosters complacency; (c) the failure of U.S. social service policy to support preventive strategies; and (d) an American cultural tradition of opposing regulation. Suggestions for improved public policy and intervention procedures are advanced.

Caregivers↗
PubMed1996

Atlantic salmon (Salmo salar) fed L-carnitine exhibit altered intermediary metabolism and reduced tissue lipid, but no change in growth rate.

Metabolic evidence was sought to explain the reduced body fat and increased body protein observed in Atlantic salmon fed diets supplemented with L-carnitine. By stimulating fatty acid oxidation, dietary carnitine might increase flux through pyruvate carboxylase and decrease flux through the branched-chain alpha-keto acid dehydrogenase complex, by increasing regulatory ratios of acetyl CoA:free enzyme A (CoA-SH) and ATP:ADP. Such changes could conserve nitrogen by providing more carbon for amino acid biosynthesis and by blocking oxidative loss of the branched-chain amino acids. Consistent with this hypothesis, salmon fed carnitine (23 mmol/kg diet) for 9 wk exhibited greater metabolic rates than cohorts fed a carnitine-free diet (P < 0.05) for the following: 1) 1-[14C] palmitate oxidation by liver cubes (48%) and by isolated hepatocytes (151%), 2) pyruvate-dependent [14 CO2]-fixation by isolated mitochondria (81%), 3) incorporation of 1-[14C] lactate into glucose by liver cubes (120%) and by isolated hepatocytes (210%), and 4) incorporation of [35S]-methionine into the acid-insoluble fraction of liver cubes (59%) and isolated hepatocytes (89%). Hepatic concentrations of seven amino acids, including the branched-chain amino acids, were greater (7-112%), as were the plasma concentrations of three of these (45-130%). However, 230% more enzyme in the mitochondria of carnitine-fed fish, and not a difference in the ratios of acetyl CoA:CoA-SH or ATP:ADP, appeared to account for accelerated flux through pyruvate carboxylase; flux through the dehydrogenase complex was unchanged. These results implicate induction of pyruvate carboxylase (or a reduction in turnover) and enhanced protein synthesis in the mechanism for carnitine-induced changes in gluconeogenesis and nitrogen metabolism.

Amino Acids↗
PubMed1993

The biochemistry and toxicology of benzoic acid metabolism and its relationship to the elimination of waste nitrogen.

Detoxification of sodium benzoate by elimination as a conjugate with glycine, a nonessential amino acid, provides a pathway for the disposal of waste nitrogen. Since 1979, sodium benzoate has been widely used in the therapeutic regimen to combat ammonia toxicity in patients born with genetic defects in the urea cycle. Although the clinical use of benzoate is associated with improved outcome, the search for biochemical evidence in support of the rationale for benzoate therapy has produced conflicting results. This review begins with an historical account leading to elucidation of the biochemistry of benzoate detoxification and early work indicating the potential utility of the pathway for elimination of waste nitrogen. An introduction to contemporary efforts at employing benzoate to treat hyperammonemia is followed by a detailed review of studies on benzoate metabolism and resultant toxic interactions with other major metabolic pathways. With this background, the several metabolic routes by which benzoate is thought to promote the disposal of waste nitrogen are then examined, followed by a consideration of alternative mechanisms by which benzoate might combat ammonia toxicity.

Ammonia↗
PubMed1992

L-carnitine protects fish against acute ammonia toxicity.

1. Juvenile chinook salmon (Oncorhynchus tshawytscha) were injected intraperitoneally (i.p.) with 0.25 M mannitol followed 1 hr later by an i.p. challenge of ammonium acetate. 2. At 10.75 mmol ammonium acetate/kg body weight, 98% of the fish showed signs of ammonium toxicity and 69% died. 3. Substitution of L-carnitine (10-16 mmol/kg) for mannitol afforded striking protection from the subsequent challenge with ammonium acetate; 67% showed no signs of ammonia toxicity and only 4% died. 4. Of other quaternary amines tested, trimethylamine oxide also afforded protection, but betaine and choline did not.

Acetates↗
PubMed1991

Reversible inhibition of the urea cycle and gluconeogenesis by N,N-diethyl-m-toluamide.

Addition of DEET to suspensions of rat hepatocytes completely abolished synthesis of urea from ammonia and production of glucose from lactate. Both activities were fully restored after cells were washed and resuspended in DEET-free medium. These results suggest the DEET-induced impairment is a reversible biochemical defect at a site common to both pathways.

Ammonia↗
PubMed1991

On the mechanism of inhibition of gluconeogenesis and ureagenesis by sodium benzoate.

Synthesis of glucose from lactate and generation of urea from ammonia were inhibited when sodium benzoate was added to suspensions of rat hepatocytes. Assays with isolated mitochondria suggested pyruvate carboxylase and the N-acetyl-L-glutamate (NAG)-dependent carbamoylphosphate synthetase (CPS-I) as potential sites of inhibition for both pathways, owing to a shared dependency on aspartate efflux from the mitochondria and its subsequent conversion to oxaloacetate in the cytosol. Assays with isolated hepatocytes indicated inhibition to be initiated by accumulation of benzoyl CoA with a resultant depletion of free CoA and acetyl CoA. Measurements of adenine nucleotides showed that benzoate metabolism did not sufficiently alter energy status to account for the observed inhibition. Consistent with these interpretations, acceleration of the conversion of benzoyl CoA to hippurate by the addition of glycine restored the levels of free CoA and acetyl CoA and the rates of gluconeogenesis and ureagenesis. Reduction of the levels of aspartate and glutamate, presumably by interference with the anapleurotic function of pyruvate carboxylase, most likely accounted for inhibition of gluconeogenesis by benzoate. Whether reduced flux through the urea cycle also contributed to inhibition of gluconeogenesis (by diminishing cytosolic conversion of aspartate to oxaloacetate) requires further study. Depression of glutamate and acetyl CoA to levels at or below the Km for NAG synthetase probably accounted for the observed inhibition of ureagenesis. Rates of urea production were observed to vary with changes in the levels of NAG, suggesting NAG-dependent CPS-I to be the primary site of inhibition of ureagenesis by benzoate.

Acetyl Coenzyme A↗
PubMed1989

Potentiation of benzoate toxicity by glyoxylate. Inhibition of pyruvate carboxylase and the urea cycle.

It has been proposed that administration of non-nitrogenous precursors to glycine is necessary to realize the full potential of benzoate metabolism as a pathway for disposal of waste nitrogen during ammonia intoxication (Coude et al., Clin Chim Acta 136: 211-217, 1984). However, when glyoxylate, a keto acid precursor to glycine, was administered with benzoate 1 hr prior to a challenge of ammonia, protection against ammonia toxicity was less successful than with benzoate alone. At the cellular and subcellular levels, glyoxylate and benzoate each inhibited the urea cycle in isolated hepatocytes and pyruvate carboxylase in isolated mitochondria. The action of each drug was associated with depletion of aspartate content in isolated hepatocytes and reduction of pyruvate-dependent incorporation of CO2 into aspartate in assays with isolated mitochondria. Depression of aspartate regeneration by inhibition of pyruvate carboxylase is a likely mechanism for impairment of urea cycle activity by both drugs. In whole animals, inhibition of pyruvate carboxylase may contribute to benzoate toxicity and the adverse influence of glyoxylate on benzoate therapy.

Animals↗
PubMed1989

Inhibition of pyruvate carboxylase by sequestration of coenzyme A with sodium benzoate.

Pyruvate-dependent CO2 fixation by isolated mitochondria was strongly inhibited by sodium benzoate. Pyruvate carboxylase was identified as a site of inhibition by limiting flux measurements to assays of pyruvate carboxylase coupled with malate dehydrogenase. Benzoate reduced pyruvate-dependent incorporation of [14C]KHCO3 into malate and pyruvate-dependent malate accumulation by 74 and 72%, respectively. Aspartate-dependent malate accumulation was insensitive to benzoate, ruling out malate dehydrogenase as a site of action. Inhibition by benzoate was antagonized by glycine, which sharply accelerated conversion of benzoate to hippurate. Assays of coenzyme A and its acyl derivatives revealed inhibition to correlate with depletion of acetyl CoA and accumulation of benzoyl CoA. Depletion of acetyl CoA was sufficient to account for greater than 50% reduction in pyruvate carboxylase activity. Competition between acetyl CoA and benzoyl CoA for the activator site on pyruvate carboxylase was insignificant. Results support the interpretation that the observed inhibition of pyruvate carboxylase occurred primarily by depletion of the activator, acetyl CoA, through sequestration of coenzyme A during benzoate metabolism.

Acetyl Coenzyme A↗
PubMed1989

Determination of isocitrate lyase and malate synthase activities in a marine bivalve mollusk by a new method of assay.

1. A new method for the assay of isocitrate lyase (EC 4.1.3.1) was developed, based on the isolation of 14C-glyoxylate semicarbazone by co-crystallization with authentic carrier. The method was easily adapted to measure malate synthase (EC 4.1.3.2). 2. Interfering reactions were avoided with this method, and isocitrate dehydrogenase (ID) was easily distinguished from isocitrate lyase (IL). Assay of IL in germinating pumpkin seeds gave rates proportional to the amount of extract, with greater sensitivity and less variability than the spectrophotometric method. 3. Six species of marine bivalve mollusks were tested for IL activity, and two species produced glyoxylate: Crassostrea virginica at 0.10 mumol/hr/g tissue, and Petricola pholadiformis at 0.85 mumol/hr/g. The other four species, and four other marine invertebrates from other phyla, lacked detectable IL activity. 4. The rate of disappearance of glyoxylate in the malate synthase (MS) reaction indicated that Petricola had an activity of 0.60 mumol/hr/g: this is the first demonstration of activities of both IL and MS in a marine invertebrate.

Animals↗
PubMed1989

Biosynthesis of hippurate, urea and pyrimidines in the fatty liver: studies with rats fed orotic acid or a diet deficient in choline and inositol, and with genetically obese (Zucker) rats.

The activities of pathways for the biosynthesis of hippurate, urea and pyrimidines in hepatocytes isolated from lean livers were compared with those from three sources of fatty liver: a) the genetically obese Zucker rat, b) Sprague-Dawley rats fed a diet deficient in choline and inositol, and c) Sprague-Dawley rats fed a diet supplemented with orotic acid. The capacity for hippurate synthesis was not significantly affected by fat accumulation, but ureagenesis from saturating ammonia and ornithine was diminished about 50% in all models when fat content rose above 12% wet wt of liver. Pyrimidine biosynthesis under these conditions was similarly diminished with fat accumulation. Ureagenesis was inhibited by sodium benzoate in hepatocytes from lean livers, but not in hepatocytes from fatty livers. Other results suggest that higher rates of ureagenesis than could be achieved with the fatty liver are required in order to demonstrate inhibition by benzoate. Incorporation of [14C]NaHCO3 into orotate was also inhibited by sodium benzoate, but in hepatocytes from fatty as well as lean livers. The metabolic basis for impairment of ureagenesis and pyrimidine biosynthesis in the fatty liver requires further study. That the capacity for hippurate synthesis was not significantly affected suggests a pathway-specific mechanism.

Ammonium Chloride↗
PubMed1986

The effect of sodium benzoate on ammonia toxicity in rats.

At 9.5 mmoles/kg body weight, sodium benzoate sharply increased mortality in rats subsequently challenged with ammonia. Fasted animals were less sensitive to potentiation of ammonia toxicity by benzoate than were fed animals. At 2.5 mmoles/kg body weight, benzoate was observed to protect fasted animals against ammonia toxicity. Measurements of ammonia disappearance, urea formation, and hippurate synthesis in suspensions of isolated hepatocytes indicate that benzoate potentiates ammonia toxicity by inhibiting the urea cycle.

Acetates↗