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Biomedical subjects

J E Fischer

Publications and source records attributed to J E Fischer.

At least 325 records · Page 18Linked to original sources
PubMed1983

Albumin turnover in sarcoma-bearing rats in relation to cancer anorexia.

Hypoalbuminemia, a frequent finding in cancer patients, can be demonstrated in the tumor-bearing rat. In actuality, the circulating amount of albumin is maintained in tumor-bearing rats, although total body water and plasma volume are increased. The fractional degradation rate of newly synthesized albumin labelled by the injection of carbon-14-carbonate was significantly increased in tumor-bearing rats (half-life 55 hours) as compared with control rats (half-life 85 hours). These findings indicate maintained synthesis of albumin in the tumor-bearing rats, a finding consistent with an increased ratio of specific activity in albumin to that in plasma urea after the injection of carbon-14-carbonate. Hypoalbuminemia in cancer seems to be the net result of an increased turnover rate of albumin and dilution of the maintained albumin mass. Despite the presence of cancer anorexia, the flux of substrates from the degradation of peripheral tissues is sufficient to supply the liver and, in turn, to enable an increased protein synthesis with maintenance of the synthetic rate of albumin.

Albumins↗
PubMed1983

Increased blood-brain transport of tryptophan after portacaval anastomoses in germ-free rats.

Portal-systemic shunting in rats results in altered plasma concentrations of the large neutral amino acids (NAA), and increased blood-brain barrier NAA transport. Bacterial ammonia production in the bowel, especially the colon, is thought to play a major role in the etiology of portal-systemic encephalopathy (PSE). In order to isolate the role of bacteria in PSE, plasma and brain amino acids and ammonia (NH3) were studied in germ-free (GF) rats with portacaval shunts (PCS). Germ-free rats underwent end-to-side portacaval shunt or sham operation under germ-free conditions and were kept in a germ-free isolator under careful bacteriologic control. Similar operations were carried out on conventional animals. Two weeks post-operatively blood-brain transport of the neutral amino acid tryptophan was studied and the animals sacrificed. Plasma NH3 rose after PCS both in GF and in conventional rats. In germ-free and conventional rats with PCS, there was a significant elevation in plasma of the aromatic amino acids and decreased concentrations of the branched-chain amino acids. In the brain, both groups had elevated aromatic amino acids, while the branched-chain amino acids remained normal. The blood-brain transport of tryptophan was elevated in portacaval shunted rats, whether germ-free or conventional. These studies suggest the elevated plasma levels of ammonia and disturbances in plasma and brain amino acids seen after portacaval shunt are not dependent on the presence of gut bacteria.

Amino Acids↗
PubMed1983

Serotonin depletion by 5,7-dihydroxytryptamine or para-chloroamphetamine does not affect cancer anorexia.

Anorectic tumor-bearing rats exhibited increased brain levels of the 5-HT precursor, tryptophan, and metabolite, 5-hydroxyindoleacetic acid (5-HIAA). In an effort to determine whether indoleamine systems had any role in the etiology of cancer anorexia the anorectic effects of cancer (Walker 256 carcinosarcoma) were investigated in immature female rats that had been depleted of brain serotonin (5-HT) by the intracisternal injection of 5,7-dihydroxytryptamine (5,7-DHT) or the systemic injection of para-chloramphetamine (PCA). Although both 5,7-DHT and PCA significantly reduced brain concentrations of 5-HT and 5-HIAA by approximately 50%, no effects on the onset or severity of the anorectic response to cancer were observed. Similarly, neither drug affected eating in non-tumor-bearing control animals. Therefore, these data do not support increased brain 5-HT activity as a primary mediator of cancer anorexia.

5,7-Dihydroxytryptamine↗
PubMed1983

Changes in brain amines associated with cancer anorexia.

Analysis of indole amine metabolism within acute (Walker 256 carcinosarcoma) and chronic (methycholanthrene-induced sarcoma) animal models of cancer anorexia demonstrated elevated levels of plasma free tryptophan, whole brain tryptophan, serotonin and 5-hydroxyindoleacetic acid in anorectic tumor-bearing rats. Whole brain levels of catecholamines were not changed within either tumor line. Regional central nervous system determination of tryptophan metabolism in rats bearing Walker 256 tumors revealed elevated tryptophan in the hypothalamus, corpus striatum, mesencephalon, diencephalon, cerebellum and cortex, increased serotonin in the diencephalon and cerebellum and elevated 5-hydroxyindoleacetic acid in the diencephalon, hippocampus, pons-medulla, cerebellum and cortex. Although tryptophan was significantly increased only in the corpus striatum and diencephalon of the more chronic methycholanthrene tumor model, serotonin concentration was elevated in the corpus striatum, diencephalon, hippocampus, pons-medulla, cerebellum and cortex, while levels of 5-hydroxyindoleacetic acid were significantly increased in all these areas as well as in the mesencephalon. Since similar changes in indole activity were not observed in pair-fed control rats, it is concluded that the elevated serotonin and 5-hydroxyindoleacetic acid levels in tumor-bearing rats did not result from undernutrition alone. Assay of regional catecholamines revealed few food-relevant changes, with norepinephrine being elevated in the corpus striatum and decreased in the pons-medulla of tumor-bearing rats. Therefore, these experiments suggest that the increased serotonin metabolism observed in tumor-bearing rats may be involved in the etiology of the anorexia of cancer.

Amino Acids↗
PubMed1983

Influence of age on protein and energy utilization in adult rats.

Male, Sprague-Dawley rats at 15 and 25 months of age were fed for 21 days diets containing 2, 3, or 4% casein supplemented with 0.078 g methionine/g casein at three levels of intake. Metabolizable energy intakes (MEI) required to maintain energy of total carcass and carcass protein were predicted from regression equations relating change in energy of total carcass and carcass protein to MEI. Mean MEI required to maintain energy of total carcass for 15- and 25-month-old rats, respectively, were 112 versus 88, 99 versus 76 and 94 versus 74 kcal/(kg0.75 X day) for 2, 3 and 4% casein, respectively. Mean MEI required to maintain energy of carcass protein for 2, 3 and 4% casein were 103, 98 and 85 kcal/(kg0.75 X day) for the 15-month-old animals and 93, 90 and 62 kcal/(kg0.75 X day) for the 25-month-old animals. Confidence intervals for mean maintenance energy intakes were wide and overlapped as age and casein concentration were varied. However, trends were evident. For both ages, as casein concentration increased, mean requirements decreased, and at each casein concentration, the 25-month-old animals had lower mean requirements than the 15-month-old animals.

Aging↗
PubMed1983

Effect of total hepatectomy and administration of branched-chain amino acids on regional norepinephrine, dopamine, and amino acids in rat brain.

In rats after total hepatectomy, the effect of infusing glucose alone or combined with branched-chain amino acids on amino acid concentrations in plasma and cerebral cortex and on catecholamine levels in eight different regions of the brain was studied. Infusion of branched-chain amino acids reduced the accumulation of tryptophan, phenylalanine, and tyrosine in plasma, while in cerebral cortex, the concentrations of phenylalanine and tyrosine were normalized and that of tryptophan was reduced greatly. In rats with hepatectomy and glucose infusion alone, norepinephrine levels were decreased in seven of eight brain regions with the exception of striatum, while dopamine was reduced significantly in striatum only. Infusion of branched-chain amino acids resulted in higher norepinephrine in cortex, mesencephalon, and hypothalamus and higher striatal dopamine 18 hours after hepatectomy. Thus, infusing branched-chain amino acids and reducing the accumulation of various neutral amino acids in brain may partially prevent the loss of norepinephrine from brain after total hepatectomy.

Amino Acids, Branched-Chain↗
PubMed1983

Increased lithogenicity of the bile after jejunoileal bypass in the rat.

Increased formation of biliary calculi is a complication of jejunoileal bypass (JIB) in man. We investigated the biliary lipid composition and bile flow rate in the rat 42 days after a JIB or sham operation. In the bile of the bypassed rats, the percentage cholesterol saturation and the concentration of phospholipids were significantly increased, while the concentration of bile acids and the lithogenic index (bile acids + phospholipids/cholesterol) were markedly decreased. The concentrations of cholesterol in the bile and in the liver were unchanged. These results suggest an increase in lithogenicity of the bile with decreased bile flow after JIB in the rat.

Animals↗
PubMed1982

Effect of infusing the branched-chain amino acids on concentrations of amino acids in plasma and brain and on brain catecholamines after total hepatectomy in the rat.

In totally hepatectomized rats supported by infusion of glucose, the concentrations of many amino acids in plasma and brain rose progressively over time, while the brain levels of norepinephrine decreased. Infusion of a solution containing glucose, leucine, isoleucine, and valine after hepatectomy greatly reduced the accumulation of other essential amino acids in plasma and brain. However, the decrease in brain norepinephrine content was not significantly affected by this infusion, suggesting that high brain concentrations of monoamine precursor amino acids are not the primary cause of norepinephrine depletion after hepatectomy.

Amino Acids↗
PubMed1982

Correlation of changes in brain indoleamine metabolism with onset of anorexia in rats.

The association of elevated brain serotonergic activity with cancer anorexia was investigated in three experiments. Significant increases in whole brain tryptophan, serotonin and 5-hydroxyindoleacetic acid in anorectic rats bearing methylcholanthrene sarcomas demonstrated the general nature of this phenomenon. In the Walker 256 sarcoma model, significant increases in whole brain serotonin and 5-hydroxyindoleacetic acid immediately preceded the onset of anorexia, suggesting that these changes in serotonin activity were not caused by decreased food intake. Investigations of regional brain changes in serotonin activity of rats bearing Walker 256 tumors revealed widespread increases in tryptophan, while serotonin was increased in the diencephalon and cerebellum and 5-hydroxyindoleacetic acid was increased in the cortex, hippocampus, diencephalon, pons-medulla and cerebellum. Therefore, these experiments demonstrate that increased brain serotonin activity is a general phenomenon, being observed in two lines of anorexia-producing tumors, that it precedes the onset of anorexia and that selective increases in serotonin activity occur within different regions of the brain.

Animals↗
PubMed1982

Analysis of the interaction of naltrexone with eating following adrenergic and cholinergic stimulation of the hypothalamus.

The anoretic potency of the narcotic antagonist drug nalthrexone, was investigated against eating elicited by the perifornical hypothalamic injection of 24.0 nmol of norepinephrine or 6.0 nmol of carbachol. Although eating following administration of norepinephrine was not significantly affected by pretreatment with naltrexone, carbachol-induced eating and drinking were dramatically attenuated by doses of naltrexone as small as 0.25 mg/kg. These data suggest the existence of an opiate link in these cholinergically-mediated behaviors.

Animals↗
PubMed1982

Brain serotonergic activity and plasma amino acid levels in genetically obese Zucker rats.

In order to test the hypothesis that serotonergic activity is abnormal in the brains of genetically obese Zucker rats, levels of serotonin (5-HT); its amino acid precursor, tryptophan (Trp), and its major metabolite, 5-hydroxyindoleacetic acid (5-HIAA) were measured in eight brain regions in groups of obese and non-obese male rats. Plasma albumin levels as well as levels of amino acids and related compounds in plasma and in a cortical sample were also determined in the same animals. While Trp was lower in several brain regions of the obese animals, the only region showing a depressed level of 5-HT in the obese group was the mesencephalon. Obese animals also had a lower amount of 5-HIAA in the diencephalon, but no other differences were significant. Both elevations and depressions were observed in cortical amino acid levels in obese animals. The level of plasma albumin was increased in the obese group. Free Trp was decreased in the plasma of obese rats while levels of other amino acids (methionine, leucine, isoleucine, valine and phenylalanine) which compete with Trp for transport across the blood-brain barrier were elevated. Thus the combination of lower plasma free Trp and increased levels of competitive amino acids appears to contribute to decreased levels of Trp in the brain of genetically obese rats.

Amino Acids↗