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Biomedical subjects

W T Chance

Publications and source records attributed to W T Chance.

At least 73 records · Page 4Linked to original sources
PubMed1988

Influence of total nitrogen, asparagine, and glutamine on MCA tumor growth in the Fischer 344 rat.

Previous studies from this laboratory have demonstrated that growth of the methylcholanthrene (MCA) sarcoma is dependent on total nitrogen substrate availability in vivo and on the specific amino acids asparagine and glutamine in vitro. This experiment determines whether these two phenomena can be used to selectively depress tumor growth and maintain host carcass. Sixty-two rats were inoculated with sarcoma and were infused for 10 days with isocaloric (60 kcal/day) TPN solutions at 100%, 16%, 10%, and 5% of normal nitrogen levels, either with (W) or isonitrogenously without (WO) the amino acids asparagine, glutamine, aspartic acid, and glutamic acid. W solutions contained 33% of these amino acids. Mean weights of 100 W tumors were significantly greater (p = 0.002) than all other groups. Total body weights minus tumor weights were similar in W versus WO animals at each rate of nitrogen infusion. Mean venous plasma concentrations of asparagine, aspartic acid, glutamine, and glutamic acid were similar in all eight groups. These data indicate that the same degree of tumor depression produced by nitrogen deprivation can also be produced by removal of asparagine, glutamine, and their precursors from nutrient solutions without adverse effects on carcass mass. The mechanisms involved are not readily explained by analysis of venous plasma amino acid concentrations.

Amino Acids↗
PubMed1987

Neurotransmitter alterations associated with feeding and satiety.

Chronically malnourished rats were sacrificed in a food-deprived state, following eating a small amount of food, or following feeding to satiation. Regional analysis of brain neurotransmitter, neurotransmitter precursor and metabolite concentrations revealed significantly elevated levels of dopamine metabolites in the corpus striatum and nucleus accumbens of the satiated rats. Food-deprived and both refed groups exhibited elevated concentrations of the serotonin metabolite, 5-hydroxyindoleacetic acid, in most brain areas examined. These results suggest increased metabolism of dopamine to be associated with satiety rather than with the act of feeding alone. Increased serotonin metabolism appears to reflect overall nutritional status rather than the onset of satiety.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1987

Resting energy expenditure of host and tumor is similar in rats with methylcholanthrene-induced sarcoma.

In the present study we assessed the resting energy expenditure of 30 free-feeding control and methylcholanthrene-induced sarcoma-bearing rats prior to and following surgical removal of the tumor. Tumor-bearing rats demonstrated carcass wasting and massive tumor growth. The resting energy expenditure data in our model suggest that neither the presence and growth of a tumor nor its removal significantly change resting energy expenditure beyond the normal range for non-tumor-bearing rats. We suggest that in the partition of energy costs between host and tumor, both carry a similar input, proportional to their relative weight, into the total combined resting energy expenditure of host and tumor.

Animals↗
PubMed1987

Burn-induced alterations in feeding, energy expenditure, and brain amine neurotransmitters in rats.

A 30% body surface area, open-flame, full-thickness burn of adult rats induced a 4-day period of anorexia that was followed by hyperphagia beginning on postburn day 10. The hyperphagic burned rats also exhibited increased resting energy expenditure and no gain in body weight, suggesting hypermetabolism. Plasma levels of immunoreactive insulin and albumin were decreased in both groups of burned rats; immunoreactive pancreatic glucagon concentrations were elevated only in the anorectic burned rats. Plasma levels of epinephrine were elevated in the hyperphagic burned rats. In the brain, dopamine metabolism appeared to be increased in the corpus striatum, nucleus accumbens, and amygdala of anorectic burned rats; norepinephrine levels were elevated in the hypothalamus and nucleus accumbens of the hyperphagic-hypermetabolic rats. These data indicate that this animal model of major burn trauma exhibits anorexia, hyperphagia, catabolism, and hypermetabolism. Furthermore, elevated dopamine metabolism appears to be associated with the anorexia, while the hyperphagia-hypermetabolism may be mediated by norepinephrine.

Animals↗
PubMed1987

Acivicin reduces tumor growth during total parenteral nutrition (TPN).

Glutamine appears to be an important substrate for tumor growth. Since tumor growth rate may be stimulated by total parenteral nutrition (TPN), we investigated the effect of the glutamine antimetabolite, acivicin, on methylcholanthrene sarcoma growth in rats maintained on TPN or on rat chow. Acivicin treatment significantly reduced tumor growth by 67% in rats receiving TPN and by 71% in rats maintained on chow. Carcass weights were significantly increased by TPN in both acivicin-treated and saline solution-treated tumor-bearing rats. Tumor-carcass ratios were significantly decreased in both groups of acivicin-treated tumor-bearing rats. Acivicin treatment or a similar approach may therefore be useful for stabilizing tumor growth in patients receiving TPN.

Animals↗
PubMed1986

Antagonism of stress-induced analgesia by quaternary naloxone.

Both naloxone hydrochloride and the quaternary compound, naloxone methylbromide, significantly reduced antinociception elicited by 90 s of continuous footshock. Peripheral specificity of quaternary naloxone was demonstrated by its lack of antagonism of morphine analgesia. These results suggest that a significant portion of the antinociception elicited by these parameters of footshock and assessed by tail-flick procedures in rats is due to the activation of peripheral endorphins.

Analgesia↗
PubMed1986

Reversal of tumor-induced biochemical abnormalities by insulin treatment in rats.

In F344 rats bearing transplantable 3-methylcholanthrene (CAS: 56-49-5)-induced sarcomas, plasma concentrations of immunoreactive insulin were decreased following the development of mild or severe anorexia. Plasma levels of immunoreactive glucagon and lactate were elevated in severely anorectic tumor-bearing (TB) rats, while plasma glucose concentrations remained normal. Both groups of TB rats exhibited decreased plasma levels of serine, glutamine, citrulline, and tryptophan and increased concentrations of alanine. Plasma levels of proline and phenylalanine were also elevated in the severely anorectic TB rats. In a second experiment, 7 daily treatments with insulin corrected the anorexia for 6 days and increased body weights of TB rats. Plasma concentrations of lactate and immunoreactive glucagon were decreased, and the abnormal plasma concentrations of glutamine, proline, analine, and phenylalanine were altered toward normal following the insulin treatments. Therefore, these data are consistent with insulin treatments benefiting the TB host by increasing feeding, increasing body weight, reducing tumor glycolysis and metabolism, reducing gluconeogenesis, and reducing host catabolism, while not stimulating tumor growth. Thus insulin therapy may have potential benefits in cancer treatment by shifting glucose metabolism toward the host and away from the tumor.

Amino Acids↗
PubMed1985

Behavioral depression after intraventricular infusion of octopamine in rats.

The behavioral and neurochemical effects of four intraventricular infusions of octopamine (3,200 micrograms), tryptophan (800 micrograms), and octopamine plus tryptophan delivered over 6 hours was studied in rats after performing a portacaval anastomosis or a sham operation. After each infusion, each animal was rated for neurologic depression with a 17 point test battery. Although overt coma was not induced, octopamine infusions severely depressed neurologic function. Concentrations of norepinephrine, dopamine, and serotonin in the brain were significantly decreased after the infusion of octopamine. Levels of norepinephrine in the brain were significantly correlated with neurologic status and greater depletion of norepinephrine was associated with greater neurologic depression. These studies demonstrate that infusing large amounts of the trace amine octopamine depresses behavior in the rat and this depression is most closely associated with depletion of stores of norepinephrine in the brain.

Animals↗
PubMed1985

Effects of jejunoileal bypass on food intake, amino acid levels, and indoleamine metabolism in rats.

Adult rats were subjected to either a 90 to 95 percent jejunoileal bypass or a sham operation and were sacrificed 35 days after surgery. Rats with jejunoileal bypass lost 33 percent of their original weight, whereas the sham operated rats gained 14 percent. Food intake per 100 g body weight was significantly increased between postoperative days 14 and 35 in the jejunoileal bypass rats. Levels of tryptophan were significantly reduced in the cortex, hypothalamus, striatum, hippocampus, mesencephalon, diencephalon, pons-oblongata, and cerebellum, whereas serotonin concentrations were lowered in the diencephalon, pons-medulla, and cerebellum in jejunoileal rats compared with control rats. Levels of 5-HIAA were reduced in the hypothalamus, cortex, mesencephalon, and diencephalon. In the plasma of bypassed rats, concentrations of valine, leucine, isoleucine, tryptophan, methionine, threonine, and tyrosine were significantly lower than in the control rats. In the cerebral cortex, levels of phenylalanine, tyrosine, histidine, and glutamine were increased. The results suggest involvement of indoleamine metabolism in disrupted eating after jejunoileal bypass. The elevated brain levels of glutamine, phenylalanine, tyrosine, and histidine resemble similar changes seen after portosystemic shunting in rats.

Amino Acids↗
PubMed1985

Burn trauma induces anorexia and aberrations in CNS amine neurotransmitters.

A 30% surface area, full-thickness, open-flame burn of guinea pigs induced significant anorexia and rapid loss of body weight. Analysis of regional brain concentrations of amine neurotransmitters suggested burn-specific elevation of serotonergic neurotransmission, reduction of dopamine metabolism, and elevation of norepinephrine concentrations in brain areas thought to control feeding. These data suggest that specific regional aberrations in each of these amine neurotransmitters may contribute to the anorexia associated with major thermal injury.

Animals↗
PubMed1984

Plasma and brain cholecystokinin levels in cancer anorexia.

The syndrome of cancer anorexia includes early satiety in man and a reduction in the duration of feeding in experimental animals. These aberrations suggest dysfunction of peripheral and/or central nervous system satiety mechanisms in tumor-bearing individuals. Since the gut peptide, cholecystokinin (CCK), has been implicated as a potent satiety cue in man and animals, plasma and brain concentrations of CCK were measured by radioimmunoassay in anorectic tumor-bearing rats. Plasma concentrations of immunoreactive CCK were not significantly altered in either an acute Walker 256 carcinosarcoma or more chronic methylcholanthrene-induced sarcoma animal model of cancer anorexia. However, levels of immunoreactive CCK were significantly reduced in the hypothalamus and cerebral cortex of animals bearing the methylcholanthrene sarcoma during both mild and severe anorexia. These data demonstrate that elevations in immunoreactive CCK are not a major factor in the etiology of cancer anorexia. If brain CCK is involved in satiety, tumor-bearing rats may be attempting to compensate for their anorexia by down-regulating CCK production.

Animals↗
PubMed1983

Clonidine analgesia: tolerance and cross-tolerance to autoanalgesia.

Clonidine induced significant antinociception in rats, as assessed by radiant-heat tail-flick procedures. Continued administration of 0 5 mg/kg and 1.0 mg/kg of the drug for 7 days induced significant analgesic tolerance in a dose-dependent manner. Significant cross-tolerance to antinociception elicited by acute footshock or classical conditioning procedures was observed, with the greatest cross-tolerance being exhibited by the 1.0 mg/kg group. These data suggest similar noradrenergic mechanisms may subserve clonidine antinociception and autoanalgesia.

Analgesia↗
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↗
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↗