Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The objective was to assess the association of fetal liver function tests in various (noninfectious) abnormal fetal conditions. Liver function tests and complete blood counts were evaluated in 72 consecutive fetal blood specimens obtained by cordocentesis. The indications for cordocentesis included: fetal malformation (24), red blood cell alloimmunization (23), possible fetal infection (17), oligohydramnios (5), and immunologic thrombocytopenic purpura (3). Statistical analysis included analysis of variance and linear regression analysis. Liver function tests including total protein, albumin, total bilirubin, alanine and aspartate aminotransferase were all within the range of previously published normal values. However, fetal gamma-glutamyltransferase levels (mean +/- SEM) were 157.1 +/- 15.1 IU/l (norm: 24.4 +/- 1.2 IU/l; p < 0.001). There were no statistically significant differences in the gamma-glutamyltransferase levels between the various groups of fetal abnormalities. Mean fetal gamma-glutamyltransferase levels in 8 normal fetuses were 106.2 +/- 17.5 IU/l. In conclusion, fetal gamma-glutamyltransferase levels are significantly elevated in several abnormal fetal conditions.
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PMID:Fetal liver function tests: umbilical cord gamma-glutamyltransferase as a marker for fetal abnormality. 791 28

The aim of this study was to investigate whether, when muscle glycogen is reduced, a pre-exercise infusion of branched-chain amino acids (BCAA) modifies exercise performance or the metabolic and respiratory responses to incremental exercise. Six moderately trained volunteers took part in the following protocol on two occasions. On day 1, at 9 a.m. in the postabsorptive state, they performed a graded incremental exercise (increases of 35 W every 4 min) to exhaustion (Ex-1). A meal of 1,000 kcal (4,200 kJ; 60% protein, 40% fat) was consumed at 12 p.m. No food was then allowed until the end of the experiment (20-21 h later). A 90-min period of exercise at alternating high and moderate intensities, designed to deplete muscle glycogen, was performed between 6 p.m. and 7.30 p.m. The morning after (day 2), the subjects randomly received either a mixed solution of BCAA (260 mg x kg-1 x h-1 for 70 min), or saline. They then repeated the graded incremental exercise to exhaustion (Ex-2). Metabolic and respiratory measurements suggested a muscle glycogen-depleted state had been achieved. No significant differences were observed in total work performed, maximal oxygen uptake or plasma ammonia, alanine, and blood pyruvate concentrations in the two treatments. After BCAA infusion, higher blood lactate concentrations were observed at maximal power output in comparison with those during saline [BCAA 4.97 (SEM 0.41) mmol x l-1, Saline 3.88 (SEM 0.47) mmol x l-1, P < 0.05].(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of infusing branched-chain amino acid during incremental exercise with reduced muscle glycogen content. 795 52

rt-PA-K, a variant of recombinant tissue-type plasminogen activator (rt-PA) with substitution of amino acids 296 to 299 with alanine (KHRR296-299AAAA) has increased fibrin-specificity and reduced sensitivity to plasminogen activator inhibitor-1; rt-PA-T, with threonine 103 replaced by asparagine has an additional glycosylation site and a reduced clearance; and rt-PA-N, with asparagine 117 mutagenized to glutamine lacks the high mannose carbohydrate side chain. We have investigated whether combination of these properties in a single molecule might yield an improved thrombolytic agent. The thrombolytic potency and fibrin-specificity of the combination mutant rt-PA-TNK was compared with that of rt-PA in a combined venous whole blood clot model and platelet-rich arterial eversion graft thrombosis model in dogs given intravenous heparin and aspirin. Infusion of 0.125 to 1.0 mg/kg over 60 min in groups of 4 to 5 dogs produced dose-dependent fibrin-specific venous clot lysis. The thrombolytic potency (percent lysis per mg compound administered per kg body weight) of rt-PA-TNK was significantly higher than that of rt-PA as evidenced by a higher maximal rate of lysis of 480 +/- 100% versus 140 +/- 40% within the 2 h observation period per mg of compound administered per kg body weight (mean +/- SEM, p = 0.004) and a significantly lower dose of 0.08 +/- 0.01 versus 0.21 +/- 0.04 mg/kg body weight at which the maximal rate of lysis was obtained (p = 0.004).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparative thrombolytic properties of tissue-type plasminogen activator and of a plasminogen activator inhibitor-1-resistant glycosylation variant, in a combined arterial and venous thrombosis model in the dog. 797 84

Using electrophysiological and radiotracer studies in parallel, we have investigated the characteristics of the endogenous Na(+)-dependent amino acid transporter (system B0,+) in Xenopus oocytes with regard to ion dependence, voltage dependence and transport stoichiometry. In voltage-clamped oocytes (-60 mV) superfusion with saturating concentrations of amino acids (1 mM) in 100 mM NaCl resulted in reversible, inward currents (mean +/- SEM): alanine, 1.83 +/- 0.09 nA (n = 21); arginine, 2.54 +/- 0.18 nA (n = 17); glutamine, 1.73 +/- 0.10 nA (n = 19). Only arginine evoked a current in choline medium (0.50 +/- 0.13 nA, n = 10), whereas Cl- replacement had no effect on evoked currents. The glutamine-evoked current was saturable (Imax = 1.73 nA, glutamine Km = 0.12 mM) and linearly dependent upon voltage between -90 and -30 mV. Using direct and indirect (activation) methods, we found that transport can proceed with Na+/amino acid coupling stoichiometry of either 1:1 or 2:1, but coupling was the same for each amino acid tested (alanine, arginine and glutamine) within a batch of oocytes (i.e. from a single toad). Despite the net single positive charge on arginine, the magnitude of the net transmembrane charge movement during Na(+)-coupled arginine transport was identical to that for the zwitterionic neutral amino acids glutamine and alanine; this may be explained by a concomitant stimulation of K+ efflux during arginine transport with a putative coupling of 1 K+:1 arginine.
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PMID:Na+/amino acid coupling stoichiometry of rheogenic system B0,+ transport in Xenopus oocytes is variable. 814 15

Metabolic activity of a gel-entrapment, hollow fiber, bioartificial liver was evaluated in vitro and during extracorporeal hemoperfusion in an anhepatic rabbit model. The bioartificial liver contained either 100 million rat hepatocytes (n = 12), fibroblasts (n = 3), or no cells (n = 7) during hemoperfusion of anhepatic rabbits. Eight other anhepatic rabbits were studied without hemoperfusion as anhepatic controls, and three sham rabbits served as normal controls. Albumin production rates (mean +/- SEM) were similar during in vitro (17.0 +/- 2.8 micrograms/h) and extracorporeal (18.0 +/- 4.0 micrograms/h) application of the hepatocyte bioartificial liver. Exogenous glucose requirements were reduced (p < 0.01) and euglycemia was prolonged (p < 0.001) in anhepatic rabbits treated with the hepatocyte bioartificial liver. The maximum rate of glucose production by the hepatocyte bioartificial liver ranged from 50-80 micrograms/h. Plasma concentrations of aromatic amino acids, proline, alanine, and ammonia were normalized in anhepatic rabbits during hepatocyte hemoperfusion. Gel-entrapped hepatocytes in the bioartifical liver performed sulfation and glucuronidation of 4-methylumbelliferone. P450 activity was demonstrated during both in vitro and extracorporeal application of the BAL device by the formation of 3-hydroxy-lidocaine, the major metabolite of lidocaine biotransformation by gel-entrapped rat hepatocytes. In summary, a gel-entrapment, bioartificial liver performed multiple hepatocyte-specific functions without adverse side effects during extracorporeal application in an anhepatic, small animal model. With its potential for short term support of acute liver failure, scale-up of the current bioartificial liver device is indicated for further investigations in large animal, preclinical trials.
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PMID:Extracorporeal application of a gel-entrapment, bioartificial liver: demonstration of drug metabolism and other biochemical functions. 816 29

It has been hypothesized that the beneficial effect on hepatic encephalopathy of lactulose or neomycin might be exerted by their effect on intermediary glutamine metabolism and ammonia generation within enterocytes. We examined glutamine consumption and the production of alanine and ammonia (net substrate exchange in nmol min-1 g-1) in isolated vascularly and luminally perfused small intestine from rats with and without pretreatment with lactulose (2.0 g/kg) or paromomycin (60 mg/kg). Without pretreatment, 50 mM lactulose or 1 mM paromomycin were equally ineffective to significantly reduce the consumption of arterial glutamine (-92 +/- 5 vs. -80 +/- 6 vs. -71 +/- 6 for controls, lactulose, or paromomycin; mean +/- SEM, n = 6 each, n.s. by analysis of variance), and the production of alanine (41 +/- 3 vs. 44 +/- 3 vs. 61 +/- 7, n.s.) or ammonia (42 +/- 6 vs. 42 +/- 6 vs. 38 +/- 6, n.s.). Similarly, glutamine utilisation, and the release of alanine and ammonia were not different after pretreatment for 10 days. Also, both agents did not reduce glutamine absorption from the lumen (-170 +/- 9 vs. -171 +/- 6 vs. -219 +/- 25, n = 5 each) or the concomitant vascular release of metabolic products alanine (92 +/- 7 vs. 78 +/- 10 vs. 77 +/- 10 vs. 77 +/- 7, n.s.) and ammonia (73 +/- 6 vs. 69 +/- 7 vs. 65 +/- 8, n.s.). Our results do not support the hypothesis, that lactulose or paromomycin reduce ammonia generation by small intestinal mucosa through a specific effect on intermediary glutamine metabolism.
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PMID:Lactulose or paromomycin do not affect ammonia generation in the isolated perfused rat small intestine. 819 8

Ten amniotic fluid samples (36-38 weeks gestation) are analysed by NMR spectroscopy. Of the species identified in the spectra, valine (mean 198 microM: SEM 57 microM), lactate (9.73 mM; 2.05 mM), alanine (689 microM: 115 microM), acetate (6.87 mM: 1.54 mM), citrate (363 microM: 59 microM), glucose (4.54 mM: 1.28 mM) indoxyl-sulphate (n = 4,270 microM), histidine (n = 6, 125 microM: 31 microM) and formate (n = 4, 92 microM) are quantified using standard addition. The factors governing the detection limits and lowest quantifiable amounts are discussed as are the extension of the work into in vivo magnetic resonance spectroscopy (MRS) in the clinic.
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PMID:Quantitative 1H-NMR analysis of amniotic fluid. 825 26

The uptake, release, and metabolism of alanine were studied in primary cultures of cerebral cortical neurons or astrocytes and cerebellar granule neurons. All three cell types exhibited a saturable, sodium-dependent uptake of alanine with Km values (microM) of 256 +/- 30, 463 +/- 39, and 292 +/- 39, respectively, and Vmax values (nmol/min/mg) of 15.9 +/- 0.7, 7.9 +/- 0.01, and 17.4 +/- 0.8, respectively. The corresponding values (nmol/min/mg) for the specific activity of alanine aminotransferase were 4.7 +/- 0.4, 17.1 +/- 2.5, and 4.5 +/- 0.9 (all values represent the mean +/- SEM). Release of alanine from the cells was rectilinear with time over a 10 hr period in case of astrocytes (40 nmol/hr/mg) and cerebellar granule neurons (21 nmol/hr/mg). In cortical neurons the release rate declined from an initial value of 19 nmol/hr/mg during the first 3 hr to a value of less than 3 nmol/hr/mg during the subsequent 7 hr of incubation. Metabolism of [14C]alanine to 14CO2 was found to have a lag period of 15 min and subsequently the rate of CO2 production was constant over a 45 min period with a value of 0.5 nmol/min/mg in granule neurons and about 0.3 nmol/min/mg in the other two cell types. Altogether the results show that alanine is preferentially produced in and released from astrocytes and accumulated into both GABAergic cortical neurons and glutamatergic cerebellar granule neurons.
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PMID:Uptake, release, and metabolism of alanine in neurons and astrocytes in primary cultures. 837 25

His-DTrp-Ala-Trp-DPhe-Lys-NH2 (GHRP-6) is a synthetic compound that releases GH in a dose-related and specific manner in several species, including man. To further characterize the effects and mechanism of action of GHRP-6 on GH secretion, we assessed in normal man plasma GH responses to that hexapeptide 1) alone and in combination with exogenous GH-releasing hormone (GHRH) administration, 2) in a state of high endogenous somatostatinergic tone after atropine administration, and 3) in a state of low endogenous somatostatinergic tone induced by the cholinergic receptor agonist drug pyridostigmine or after insulin-induced hypoglycemia. We found a similar increase in plasma GH levels after the administration of either GHRP-6 (1 microgram/kg) or GHRH (1 microgram/kg); the areas under the curve (AUC) were (mean +/- SEM) 973 +/- 181 and 821 +/- 139, respectively. After combined GHRP-6 and GHRH administration, GH responses were considerably greater than those after either compound alone (4412 +/- 842; P < 0.01). Administration of the cholinergic receptor antagonist atropine (1 mg, im) completely prevented the GH responses to GHRP-6 (area under the curve, 103 +/- 14 vs. 815 +/- 156, respectively). On the other hand, pyridostigmine, a cholinergic agonist, slightly increased GH responses to GHRP-6 (P < 0.01 when comparing the AUC after pyridostigmine administration of 1571 +/- 151 and the AUC after administration of GHRP-6 alone of 815 +/- 156). Finally, combined GHRP-6 and insulin administration induced a much greater increase in plasma GH levels (AUC, 4047 +/- 327) than insulin alone (1747 +/- 229; P < 0.05) or GHRP-6 alone (1248 +/- 376; P < 0.05). Our results lend support to the view that GHRP-6-induced GH secretion is exerted through a non-GHRH-dependent mechanism. Furthermore, the fact that enhancement of somatostatinergic tone with atropine completely prevented the GH responses to GHRP-6, while pyridostigmine and insulin-induced hypoglycemia, which increased plasma GH levels by inhibiting hypothalamic somatostatin release, increased the same response suggest that although GHRP-6-induced GH secretion is dependent on the endogenous somatostatinergic tone, the stimulatory effect of GHRP-6 on plasma GH levels is not mediated by a change in hypothalamic somatostatinergic tone.
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PMID:Effect of growth hormone (GH)-releasing hormone (GHRH), atropine, pyridostigmine, or hypoglycemia on GHRP-6-induced GH secretion in man. 842 Oct 84

GH secretion in response to all provocative stimuli is decreased in patients with obesity. However, the precise mechanism causing this impairment in GH release is unknown. His-DTrp-Ala-Trp-DPhe-Lys-NH2 (GHRP-6) is a synthetic compound that releases GH in a dose-related and specific manner in several species, including man. To gain further insight into disrupted GH secretion in obesity, GHRP-6 and GH-releasing hormone (GHRH) at a dose of 100 micrograms, i.v., were administered either alone or in combination in a group of 19 obese subjects. In a group of obese patients, GHRP-6 induced GH secretion, with a GH peak (mean +/- SEM) of 15.7 +/- 4.4 micrograms/L and an area under the curve (AUC) of 674 +/- 187, which were larger than those after GHRH stimulation (6.8 +/- 1.1 and 412 +/- 71, respectively). Enhancement of the endogenous cholinergic tone was obtained in another group of obese subjects by means of pyridostigmine (120 mg, orally). Pyridostigmine administered 60 min before GHRP-6, increased both the mean GH peak (32.2 +/- 6.9) and the AUC (1413 +/- 537) after GHRP-6 administration. In a separate group of subjects, the combined administration of GHRP-6 and GHRH induced a massive discharge of GH, with individual responses ranging from 14-86 micrograms/L. GHRP-6 plus GHRH induced a mean GH peak of 42.2 +/- 10.9 and an AUC of 1894 +/- 784 (P < 0.05), clearly indicating a potentiating (synergic) action when the two compounds were administered together. These data show that GH responses to GHRP-6 were almost twice those to GHRH in obese patients. The stimulatory effect exerted by pyridostigmine on GHRP-6-induced GH secretion supported the view of increased somatostatinergic tone in obesity. Finally, the massive GH discharge that followed the administration of GHRH plus GHRP-6 was not observed after any stimulus in obesity, clearly indicating that the impaired GH secretion is a functional and potentially reversible state.
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PMID:Massive growth hormone (GH) discharge in obese subjects after the combined administration of GH-releasing hormone and GHRP-6: evidence for a marked somatotroph secretory capability in obesity. 847 88


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