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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Panhypopituitarism may be associated with spontaneous hypoglycemia and marked insulin sensitivity. Five children with both growth hormone (GH) and adrenocorticotrophin (ACTH) insufficiency were studied in three periods: a) on no therapy; b) during cortisone acetate; and c) during GH and cortisone acetate replacement. With total caloric restriction prior to therapy, all patients became hypoglycemic (109 +/- 18 leads to 37 +/- 3.5 mg/dl, mean +/- SEM) and ketonemic (beta-hydroxybutyrate 0.10 +/- 0.02 leads to 3.04 +/- 0.63 mM and acetoacetate 0.05 +/- .01 leads to 0.80 +/- 0.15 mM) within 30 hours. Glutamine and alanine concentrations fell with fasting (511 +/- 13 leads to 293 +/- 26 muM and 394 +/- 58 leads to 137 +/- 12 muM, respectively) but to levels lower than in normal children. However, only alanine was significantly lower (P less than 0.05). With cortisone plus GH therapy, fasting glycemia was improved (73 +/- 6 mg/dl) at 30 hours fasting and was associated with increased alanine and glutamine concentrations (206 +/- 28 muM and 448 +/- 40 muM, respectively) and less ketonemia (beta-hydroxybutyrate 1.13 +/- 0.39 mM). Cortisone therapy alone resulted in intermediate improvement of these values. Only combined therapy resulted in increased lactate and pyruvate concentrations, which fell to normal with fasting. Fasting urinary ammonia excretion was unchanged whereas urea nitrogen excretion decreased significantly with therapy. The responses to alanine infusions following each study period in one patient were normal. The glycemic response to iv glucose was similar during each study period; however, post-prandial and glucose-stimulated insulin responses were increased with cortisone and cortisone plus GH therapy. We suggest that the hypoglycemia observed in hypopituitary patients is a substrate-mediated phenomenon, and that cortisone and growth hormone replacement therapy improve fasting glucose homeostasis, increase circulating alanine and glutamine concentrations, and decrease hepatic gluconeogenesis. These effects may be mediated through an increase in fat catabolism.
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PMID:The role of growth hormone and cortisone on glucose and gluconeogenic substrate regulation in fasted hypopituitary children. 17 83

An original method which uses in vitro anaerobic incubation at 37 degrees C followed by centrifugation, ultrafiltration, and ion exchange chromatography is described; it shows that faecal material suspended in physiological saline can destroy added creatinine. The rate of breakdown by suspensions from uraemic subjects (mean 780 mumol h-1kg-1 SEM 70) was slightly faster than in normal subjects (mean 550 mumol h-1kg-1 SEM 80). Methylamine concentration increased over eight hours as creatinine was metabolised and sarcosine appeared as an intermediate. The rates of these reactions varied within and between individuals and were inhibited by oxygen and centrifugation but not by oxytetracycline. Concentrations of free amino acids did not change significantly despite the formation of ammonia. This approach should be useful in studying the metabolic inter-relationships between intestinal contents and the host organism in health and disease.
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PMID:In vitro metabolism of creatinine, methylamine and amino acids by intestinal contents of normal and uraemic subjects. 48 52

The effects of chronic hyperammonemia on cerebral metabolism were studied in rats four and eight weeks after the construction of a portacaval shunt. Compared to sham-operated controls, shunted animals had increased arterial concentrations of ammonia and glutamine and decreased glutamate. Cerebral blood flow, measured by xenon 133 washout in animals lightly anesthetized with nitrous oxide, increased from a control of 91 +/- 5 (mean +/- SEM) to 139 +/- 20 ml per 100 gm tissue per minute after shunting for eight weeks; however, the cerebral metabolic rate for oxygen was not different from control four or eight weeks after the shunting procedure. Following intraperitoneal administration of a small ammonium acetate load (2.6 mmol/kg), eight-week portacaval animals consistently underwent a fall in cerebral blood flow and cerebral oxygen consumption and developed high-voltage slow waves in the electroencephalogram. Glutamine was produced by the brains of all groups of animals; the cerebral metabolic rate for glutamine was greater than control in eight-week portacaval rats, the only animals to show a net uptake of ammonia into brain. The findings suggest that increased cerebral sensitivity to ammonia, along with nonspecific effects of chronic portal-systemic shunting, may lead to uncoupling of cerebral blood flow and oxidative metabolism.
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PMID:Cerebral blood flow and metabolism in chronically hyperammonemic rats: effect of an acute ammonia challenge. 66 74

Chloramines, compounds made up of chlorine and ammonia, when present in tap water used for dialysis cause methemoglobinemia and hemolysis. Ascorbic acid addition has been reported to effectively neutralize chloramines in vitro and in patients dialyzed with the single batch dialysis delivery system. We extended these observations to patients dialyzed with the proportioning dialysis delivery system where exposure time of ascorbic acid to chloramines is shorter. This may be important since we found that the half time of the reaction between ascorbic acid and chloramines is 4 minutes. Red cell oxidant sensitivity in 15 patients was assessed by incubating red cells with ascorbate-cyanide and measuring methemoglobin which averaged 2.17 +/- 0.42 g/100 ml (SEM) before dialysis and 2.87 +/- 0.52 g/100 ml after dialysis (NS). Reduced glutathione (GSH) levels were also measured as an index of red cell oxidant damage. GSH decreased from a mean of 7.40 +/- 0.59 micromoles/g Hb before dialysis to 6.98 +/- 0.52 micronmoles/g Hb after dialysis (P less than 0.01). In 2 patients there was no change in 51Cr red cell survival when dialyzed on either the proportioning system or other chloramine free systems. We conclude that addition of ascorbic acid to neutralize chloramines in tap water is also effective when using the proportioning dialysis delivery system.
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PMID:Prevention of chloramine-induced hemolysis in dialyzed patients. 69 6

Hyperammonemia increases brain glutamine levels, causes astrocytic swelling, and depresses cerebral blood flow (CBF) responsivity to CO2. Methionine sulfoximine (MSO) inhibition of glutamine synthetase activity, known to be enriched in astrocytes, prevents ammonia-induced increases in brain glutamine and water content. We tested the hypothesis that inhibition of glutamine accumulation restores CBF responsivity to CO2 during acute hyperammonemia. Pentobarbital-anesthetized rats treated with either vehicle or MSO (150 mg/kg i.p.) received a 6-hour intravenous infusion of either sodium or ammonium acetate. With subsequent induction of hypercapnia, CBF increased from 113 +/- 14 (mean +/- SEM) to 194 +/- 9 ml/min per 100 g in control rats but was unchanged from 107 +/- 13 to 79 +/- 10 ml/min per 100 g in hyperammonemic rats. Treatment with MSO in hyperammonemic rats restored the CBF response to hypercapnia (from 73 +/- 8 to 141 +/- 14 ml/min per 100 g). With induction of hypocapnia, CBF decreased from 114 +/- 11 to 88 +/- 11 ml/min per 100 g in control rats but increased from 112 +/- 13 to 142 +/- 19 ml/min per 100 g in hyperammonemic rats. Treatment with MSO in hyperammonemic rats did not fully restore the response to hypocapnia but prevented the paradoxical increase in CBF (from 80 +/- 8 to 80 +/- 8 ml/min per 100 g). In control rats, MSO did not affect CO2 responsivity. Treatment with MSO prevented ammonia-induced increases in intracranial pressure. Hyposmotic-induced increases in brain water content and intracranial pressure attenuated the CBF response to hypercapnia but, unlike hyperammonemia, did not attenuate the response to hypocapnia. In contrast to hypercapnia, vasodilation in response to arterial hypotension was intact in hyperammonemic rats. We conclude that the grossly abnormal CBF responsivity to CO2 alterations during hyperammonemia is linked to glutamine accumulation rather than ammonia per se. Cerebral edema secondary to glutamine accumulation may contribute in part to abnormal CBF responses, although other aspects of astrocyte dysfunction are likely to be important.
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PMID:Restoration of cerebrovascular CO2 responsivity by glutamine synthesis inhibition in hyperammonemic rats. 139 82

beta-Oxidation of [1-14C]palmitic acid was examined in homogenates of astrocytes cultured from neonatal mouse brain. Under optimal reaction conditions (< or = 50 micrograms protein, 10 min at 37 degrees C), oxidation increased as a function of palmitate concentration (15 microM to 2 mM) and reached a maximum rate of 1.98 +/- 0.29 nmol/min/mg protein (mean +/- SEM) at 0.2 mM substrate. Eadie-Hofstee analysis of data from four experiments yielded apparent values for Vmax of 1.87 nmol/min/mg protein, and for Km, 35-40 microM. There were no dramatic changes in the oxidation rate in cells between 10 and 36 days in culture. During the 10-min assays, less than 0.05% of the radioactivity was converted to 14CO2 by the astrocytes; water-soluble products accounted for 1-2% of the total substrate added. Studies with KCN indicated that 60-70% of the total activity occurred in the mitochondria. We have been studying the structural and functional changes associated with the cerebral encephalopathy of Reye's syndrome (RS). Three-week-old astrocytes exposed to serum from RS children for the final 7 days of culture exhibited minor mitochondrial pleomorphism and had increased numbers of other intracellular organelles. Examination of the effects of agents implicated in RS indicated that oxidation of [1-14C]palmitate was not altered by Na+ salicylate (1-3 mM), but was inhibited by the industrial surfactant, Toximul MP-8 (> or = 10 micrograms/ml), 4-pentenoic acid (> or = 0.1 microM), or with 4 days' exposure to ammonia (10 nM). The latter treatment also resulted in an increase in protein synthesis, cell volume, and malondialdehyde formation. These results suggest that some of the "toxins" implicated in RS inhibit fatty-acid oxidation in the astrocytes and produce other lipid-related abnormalities that could be related to encephalopathy.
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PMID:Beta-oxidation of [1-14C]palmitic acid by mouse astrocytes in primary culture: effects of agents implicated in the encephalopathy of Reye's syndrome. 146 46

Grey seal pups (Halichoerus grypus) were collected at the time of weaning (mid-October) and fasted for 52 days at thermoneutrality in separate cages. Body weight decreased exponentially, while metabolic rate dropped 45% from an average of 2.95 +/- 0.15 (SEM) W kg-1 at day 2 of fasting to a stable level of 1.62 +/- 0.06 (SEM) W kg-1 from day 10 to day 47 of fasting. Respiratory quotient was low, indicating extensive catabolism of triglycerides, while plasma cortisol was fairly stable at 110 +/- 8 (SEM) nmol l-1 throughout the fasting period. Daily urinary output decreased from 236 +/- 20 (SEM) ml day-1 at day 2 to a stable value of 87 +/- 6 (SEM) ml day-1 between days 8 and 50 of fasting. The urine was analysed for urea, uric acid, creatinine, ammonia, total nitrogen and osmolality. Urea was always the principal excretory end-product, amounting to between 70 and 80% of the total excreted nitrogen. The urine was moderately concentrated (range 770-1300 mosmol kg-1). Total excreted urinary nitrogen decreased by 68% from 3.7 +/- 0.7 (SEM) g day-1 to 1.2 +/- 0.4 (SEM) g day-1 between days 2 and 50. The urinary nitrogen was used to calculate the daily amount of protein being oxidized and its energy content was compared with the measured basal metabolic rate of individual animals. Approximately 6% of the energy expended by grey seal pups during the post-weaning fast is derived from oxidation of protein. It is concluded that a rapid depression of basal metabolic rate and extensive blubber catabolism enable grey seal pups to endure prolonged periods of fasting without any apparent signs of discomfort or stress.
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PMID:Depressed metabolism and low protein catabolism in fasting grey seal pups. 236 22

1. Melanophores and xanthophores are pigment cell derivatives of the NC. In amphibian embryos they migrate from their original position on the neural tube dorsally (into the dorsal fin) as well as laterally (between somites and epidermis) and arrange themselves into typical pigment patterns of the skin. We investigated pigment pattern formation in two species of tailed amphibians, Triturus alpestris (alpine newt) and Ambystoma mexicanum (Mexican axolotl). In larvae of T. alpestris alternating longitudinal stripes or bands of melanophores and xanthophores develop, whereas in larvae of A. mexicanum a barred pattern with alternating transverse bands of melanophores and xanthophores is formed. Iridophores, a third type of pigment cell, are present later in both species and therefore play no role during early larval pigment pattern development. Visibly differentiated melanophores and xanthophores can be distinguished from each other under the light microscope by their contents of black melanins and yellow pterins respectively. With the dopa reaction (indicates tyrosinase in melanophores), and ammonia treatment (stimulates pterin fluorescence in xanthophores), the pigment cell phenotypes can be visualized even before their normal visible differentiation. In the TEM, melanophores and xanthophores can be distinguished from each other by their morphologically distinct pigment organelles and in the SEM by their different surface structure. 2. Because of the NC origin of melanophores and xanthophores and the ease with which these cells can be demonstrated even before they are visible from outside, their different arrangements in Triturus and axolotl embryos offer suitable model systems for studying the migration, interaction and localization of NC derivatives in relation to specific environmental influences. The environment of NC cells are the neural tube, epidermis, somites and lateral plate mesoderm, and the subepidermal ECM, a network of collagen fibrils associated with glycosaminoglycans, proteoglycans and glycoproteins. 3. Development of the pigment pattern in T. alpestris: Melanophores and xanthophores start to leave the NC at stage 28, melanophores slightly earlier than xanthophores. Both cell types become scattered in the dorsolateral trunk. In contrast to melanophores in the axolotl, melanophores in T. alpestris cannot be demonstrated with the dopa reaction before they become visibly black. From stage 29+ onwards, melanophores start to accumulate in zones alongside the dorsal and lateral somite edges, where they form compact stripes later. Xanthophores can be demonstrated from stage 28+ onwards only with the SEM (by means of their specific surface structures) or with the fluorescence microscope (by means of their fluorescing pterins). At state 34, xanthophores become visible externally as yellow cells.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The development of the larval pigment patterns in Triturus alpestris and Ambystoma mexicanum. 236 40

Ammonia is a bacterial metabolite which is commonly used to alter cytoplasmic and lysosomal pH of eukaryotic cells. Here we examine its effect on external N-formyl peptide receptors of human neutrophils. Ammonia does not affect the number of N-formyl peptide receptors on the cell surface, nor the association of the ligand-receptor complex with the cytoskeleton. However, ammonia causes a marked decrease in the affinity of the chemotactic peptide receptor for its ligand. The Kd of untreated cell for the chemotactic peptide was 0.65 +/- 0.06 nM, whereas that of ammonia treated cells was 1.02 +/- 0.10 nM (Mean +/- SEM, N = 6). These results suggest that ammonia can affect external as well as internal cellular components. Since ammonia is used to alter lysosomal and cytoplasmic pH, and is a metabolite of common bacterial pathogens, these results bear directly on its use in cell biology and on its potential as a virulence factor.
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PMID:Effects of ammonia on human neutrophil N-formyl chemotactic peptide receptor-ligand interaction and cytoskeletal association. 259 Feb 35

The main adduct of cis-diamminedichloroplatinum(II) (cis-Pt) with DNA, cis-[Pt(NH3)2(dGpdG)], was administered i.p. to rats. Urine was collected daily for 4 days. The adduct was purified by a weak cation exchanger and quantitated by HPLC with UV detection. The recovery of the adduct was 30.0 +/- 7.0% (mean +/- SEM). The main reason for the low recovery was the chemical instability of cis-[Pt(NH3)2 (dGpdG)] in urine as shown in an in vitro incubation. Adjusted for this instability the recovery in urine was greater than 70% of the dose. When cis-Pt-DNA (the molar ratio of cis-Pt to nucleotide = 1:50) was administered i.p. to rats only 1.25 +/- 0.23% of platinum was excreted in urine in the form of cis-[Pt(NH3)2(dGpdG)] and cis-[Pt(NH3)2(dApdG)] during the first 4 days. If the removal of the cis-Pt-DNA adducts from human tissues is to be followed, their possible slow excretion and chemical instability in urine needs to be considered.
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PMID:Excretion kinetics of the DNA adducts of cis-diamminedichloroplatinum(II) formed in vitro in rat urine. 316 53


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