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Four experiments were conducted to characterize the interactions between fumaric (FA), malic (MA), or citric acid (CA) and NaHCO3. In two experiments, seven diets were formulated containing 2.5% FA, MA, and CA, with or without 2.3, 1.9, or 1.4% NaHCO3, respectively, as well as a control diet (no addition of organic acids or NaHCO3) for 28-d-old pigs (Exp. 1, corn-soy protein concentrate-based diet) and 1-wk-old chicks (Exp. 4, corn-soy-based diet). In Exp. 1, at 2 and 4 wk, the FA+NaHCO3 treatment resulted in greater average daily gain (ADG) and feed intake (ADFI) compared with the control (P < .05). In Exp. 2, 28-d-old pigs were fed corn-soy diets with .9, 1.6, and 2.3% NaHCO3 in addition to 2.5% FA. After wk 2, there was a quadratic response in ADG (P < .08) and ADFI (P < .05) when increasing levels of NaHCO3 were added to the diet. This was true at wk 4 for both ADG and ADFI (P < .05). In Exp. 3, finishing pigs were fed corn-soy diets containing 2.5% FA or 2.5% FA + 2.3% NaHCO3 added to a control diet. No effect (P < .05) of FA or NaHCO3 was observed. In Exp. 4, the combination of CA+NaHCO3 or MA+NaHCO3 was superior to FA+NaHCO3 for ADG (P < .08) and ADFI (P < .05) when fed to young chicks.
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PMID:Characterization of the nutritional interactions between organic acids and inorganic bases in the pig and chick. 805 72

1. Fifty-seven taste neurons were isolated in the nucleus solitary tract (NST) and tested with 15 sapid chemicals. On average, NST neurons responded well to NaCl, sucrose, monosodium L-glutamate (MSG), NaNO3, and glycine (mean = 8.2-11.0 spikes/s). Mean responses to KCl, NH4Cl, HCl, malic acid, and quinine HCl (QHCl) were low (mean = 0.7-2.9). The average responses to the other stimuli (citric acid, MgCl2, fructose, maltose, and polycose) fell between these extremes (mean = 4.3-5.1). 2. On the basis of the largest response to the four standard stimuli, the neurons were classified as follows: 15 NaCl-best, 23 sucrose-best, 17 citric acid-best, and 2 QHCl-best. 3. The NaCl-best neurons responded robustly and nearly equally to the three sodium salts (mean = 15.7-20.8) but much less so and more variably to the nonsodium, chloride salts (mean = -0.1-4.6). Sucrose-best neurons responded strongly to sucrose, glycine, and MSG (mean = 13.7-17.8), but only moderately to the other sugars (fructose and maltose) and to polycose (mean = 8.4, 9.8, and 8.8, respectively). 4. Citric acid-best neurons responded moderately to citric and malic acid (mean = 9.4 and 4.7), but less so to HCl (mean = 3.1). The two QHCl-best neurons responded moderately to QHCl and MgCl2 (mean = 12.0 and 9.5), but weakly or not at all to the other stimuli (mean = -1.1-3.1). 5. Unlike parabrachial taste neurons, none of the medullary taste cells responded specifically to Cl(-)-containing chemicals. The responses that did occur to nonsodium salts were weak and variable and often occurred in either citric acid-best or QHCl-best neurons, rather than in those that responded vigorously to sodium salts. Similar relationships have been observed in anesthetized preparations. 6. A hierarchical cluster analysis for 57 neurons across 15 stimuli produced four second-order clusters that consisted primarily of NaCl-best, sucrose-best, citric acid-best, and QHCl-best neurons, respectively. Although the analysis for neurons produced only four such clusters, a similar analysis for the 15 stimuli separated the sodium salts (NaCl and NaNO3), nonsodium salts (KCL, NH4Cl, and MGCl2, sweeteners (sucrose, maltose, fructose, and glycine), acids (citric acid and malic acid), and QHCl. 7. Monosodium glutamate activated both NaCl-best and sucrose-best neurons, but the stimulus analysis clumped it with the sodium salts.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Taste responses of neurons in the nucleus of the solitary tract of awake rats: an extended stimulus array. 822 76

Methods of cryopreservation for spermatozoa from domestic cat epididymides and vasa deferentia were compared as models for posthumous gamete salvage from non-domestic felids. Spermatozoa were collected either immediately after castration (Fresh, n = 37) or after being cooled (5 degrees C) in tissue overnight (Cool, n = 37) and released into one of three extenders containing 20% egg yolk and 3% glycerol for cryopreservation: (1) TE: Tris buffer, citric acid and fructose; (2) TC: Tris buffer, citric acid and glucose, or (3) CP: lactose, and frozen over lipid nitrogen. Before and after freezing, each sperm cell sample was evaluated for motility and percentage morphologically normal cells. Samples were also evaluated for their ability to initiate fertilization using a zona attachment assay. Neither percentage morphologically normal spermatozoa nor percentage motility differed among the three diluents for prefreeze and post-thaw samples, regardless of the collection treatment. However, CP tended to provide lower post-thaw status than did the TE and TC cryoextenders. Before freezing, there was no difference in percentage motility between the Fresh and Cool groups (mean: 76 versus 72%, respectively); however, progressive status and normal morphology were lower (P < 0.05) in Cool (3.0 and 57%) than in Fresh (3.4 and 64%) samples. After thawing there was a greater decline (P < 0.05) in percentage motility in the Cool than in the Fresh group (34 versus 24%) and the number of intact acrosomes dropped from prefreeze values of 66.7 +/- 6.3 and 56.4 +/- 4.8% to 17.8 +/- 3.9 and 20.9 +/- 4.6% after thawing in the Fresh and Cool groups, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparative cryopreservation and capacitation of spermatozoa from epididymides and vasa deferentia of the domestic cat. 822 40

Penicillium simplicissimum excreted more than 100 mmol citric acid l-1 [2.9 mmol (g dry wt)-1; 9 d] if an industrial filter dust (> 50% ZnO) providing a high extracellular buffering capacity was present in the medium. A similar specific [2 mmol (g dry wt)-1], but lower absolute (26 mmol l-1), citric acid excretion occurred in the absence of an extracellular buffer and if amino acids or urea were used as nitrogen source. P. simplicissimum excreted no citric acid under conditions where Aspergillus niger produces citric acid (deficiency of trace elements, low pH and reduced biomass formation). Citric acid excretion by P. simplicissimum always paralleled biomass formation and occurred in a pH range between 4 and 7. This indicated that different imbalances of metabolism were responsible for citric acid excretion in A. niger and P. simplicissimum. However, provided a high extracellular buffering capacity was present, the response of the Penicillium system to different carbon and nitrogen sources was similar to the Aspergillus system. In contrast, the metals iron and copper had virtually no effect on citric acid excretion compared with A. niger. Estimation of intracellular citric acid, as well as the effects of the uncoupler 2,4-dinitrophenol, and the H(+)-ATPase inhibitor sodium orthovanadate, led to the conclusion that the buffer-stimulated citric acid efflux was dependent on metabolic energy and an energized plasma membrane, respectively. Despite similarities to the Aspergillus system, a different mechanism for buffer-stimulated citric acid excretion by P. simplicissimum seems probable.
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PMID:Influence of medium components and metabolic inhibitors on citric acid production by Penicillium simplicissimum. 824 37

Three patients with primary myoadenylate deaminase deficiency were subjected to exercise on a bicycle ergometer at 125 W for 30 minutes. Blood samples prior to, during, and at the end of exercise were analyzed for lactate, ammonia, and hypoxanthine. In addition, urinary hypoxanthine excretion was measured. In these patients the serum lactate level increased to concentrations between 7.9 and 9.0 mmol/l at the end of exercise whereas the mean lactate level in nine control subjects at the end of exercise was 3.3 mmol/l (range 1.1-8.1 mmol/l). There was no difference to control subjects in the exercise-induced increase in plasma levels of ammonia and hypoxanthine or in the increase in urinary hypoxanthine excretion. The findings support the hypothesis of a reduced substrate supply to the citric acid cycle in myoadenylate deaminase deficiency. The normal formation of ammonia and hypoxanthine excludes a marked loss of adenine nucleotides in working muscles in these patients.
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PMID:Ergometer exercise in myoadenylate deaminase deficient patients. 835 5

Pancreatic islets were cultured for 24 h in the presence of 1 mM glucose, which renders islets incapable of responding to glucose with insulin release. These islets were compared to islets maintained at 20 mM glucose for 24 h. Detritiation of [2-3H]glucose and [5-3H]glucose in 1 mM glucose islets was normal, suggesting that glucose transport and phosphorylation and all enzymes of glycolysis were not down-regulated in the incapacitated islets. 14CO2 formation from [U-14C]glucose and [6-14C]glucose was inhibited up to 80% and 14CO2 from methyl succinate was inhibited up to 60%, indicating that down-regulation at (a) mitochondrial site(s) might explain the incapacitated insulin release. 14CO2 formation from [3,4-14C]glucose (which becomes [1-14C]pyruvate) was decreased, indicating that the reaction catalyzed by pyruvate dehydrogenase was down-regulated. This decrease, however, was not as large as the decreases in 14CO2 formation from [U-14C]glucose, [2-14C]glucose (which becomes [2-14C]pyruvate), or [6-14C]glucose (which becomes [3-14C]pyruvate), indicating that other reactions were also down-regulated. 14CO2 formation from [1-14C]glucose was inhibited less than that from [6-14C]glucose in the incapacitated islets (34 vs 54%) and these rates indicated that flux of glucose through the pentose phosphate pathway was increased in the incapacitated islet, such that 29% (0.4 nmol of 1.4 glucose/100 islets/90 min) was metabolized via this pathway in the incapacitated islet but only 3.4% (0.1 of 2.9 nmol glucose/100 islets/90 min) was metabolized via the pentose pathway in the 20 mM glucose islets. With rates of 14CO2 evolved from glucose labeled at C2 and C6 and from methyl succinate labeled at C1 + C4 and C2 + C3 the 14CO2 ratio formula was used to calculate the ratios of carboxylated and decarboxylated pyruvate. Roughly equal amounts of pyruvate entered the citric acid cycle by each route in islets maintained for 24 h at 1, 5, or 20 mM glucose. The results indicate that decarboxylation and carboxylation of pyruvate were about equally suppressed in incapacitated islets and that direct inhibition of reactions of the cycle was unlikely. This is consistent with evidence which indicates that down-regulation of both pyruvate carboxylase and pyruvate dehydrogenase occurs in incapacitated islets, i.e., under long-term conditions that modify amounts of enzymes (MacDonald et al., 1991, J. Biol. Chem. 266, 22392-22397).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Estimates of glycolysis, pyruvate (de)carboxylation, pentose phosphate pathway, and methyl succinate metabolism in incapacitated pancreatic islets. 837 57

Previous work demonstrated that methyl esters of succinate are potent insulin secretagogues in pancreatic islets, while unesterified succinate is not. This can be explained by studies reported here, which show that 14C-labeled dimethyl succinate is metabolized to 14CO2 by pancreatic islets, but that 14C-labeled succinic acid is not metabolized. Islets maintained at 1 mM glucose in tissue culture medium for 1 day lose the ability to release insulin in response to glucose and glucose metabolism is decreased 50-80%. The metabolism of dimethyl [1,4-14C]succinate and dimethyl [2,3-14C]succinate is decreased 50-60% in these incapacitated islets relative to islets maintained at 20 mM glucose. From the ratio of 14CO2 formed from dimethyl [1,4-14C]succinate, relative to that from dimethyl [2,3-14C]succinate, "acetate" ratios of 4.9-6.2 were calculated and from the ratio of 14CO2 formed from [2-14C]glucose, relative to that from [6-14C]glucose, "pyruvate ratios" of 1.6-1.7 were calculated. According to the 14CO2 ratios method, these ratios indicate that 53-66% of pyruvate derived from glucose enters the citric acid cycle via carboxylation and 34-47% enters via decarboxylation. Malic enzyme, which carboxylates pyruvate in the cytosol, was normal in islets maintained at 1 mM glucose. Previous work indicated that inhibition of glucose metabolism in islets maintained at low glucose is due to decreased net synthesis of the mitochondrial enzymes pyruvate dehydrogenase and pyruvate carboxylase [J. Biol. Chem. (1991) 266, 22392-22397], which decarboxylate and carboxylate pyruvate, respectively. Acetate (1 mM) but not pyruvate, when added to islets maintained at low glucose, increased dimethyl succinate metabolism to almost that of islets maintained at high glucose. This is consistent with a low amount of pyruvate dehydrogenase being unable to supply acetyl-CoA for condensation with oxalacetate (derived from succinate) and that the rate of the citric acid cycle could be enhanced by adding acetate which can bypass the reaction catalyzed by pyruvate dehydrogenase.
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PMID:Metabolism of the insulin secretagogue methyl succinate by pancreatic islets. 842 53

Rhenium-186 has been determined to be a leading radionuclide for radioimmunotherapy. However, the use of 186Re has been limited due to the lack of a convenient and efficient method by which the radionuclide can be bound to monoclonal antibodies. We have developed a simple technique to label IgM, IgG, fragmented antibodies and tumor necrosis factor-alpha with 186Re. This technique uses ascorbic acid (AA) for controlled reduction of antibody disulfide groups to sulfhydryls and SnCl2 in citric acid for the reduction of 186ReO4-. The labeling yields as determined by instant thin-layer chromatography, molecular filtration and gel filtration were greater than 95% and the colloid formation was less than 5%. The labeled antibodies were stable when challenged with 100 and 250 molar excess of DTPA and HSA for 24 hr at 37 degrees C. SDS-PAGE analysis and autoradiography of labeled IgM, IgG and F(ab')2 monoclonal antibodies indicated uniform labeling and that no fragmentation of the monoclonal antibodies had taken place during the labeling procedure. Immunospecificity of 186Re-labeled human neutrophil specific IgM, as determined by in vitro antigen excess assay, was comparable to that of indium-111-labeled c-DTPA-IgM and technetium-99m-labeled-IgM. A nuclear histone specific 186Re-TNT-1-F(ab')2 was evaluated in mice bearing experimental tumors. The tumor/muscle ratios at 4 and 24 hr were 5.9 +/- 0.21 and 13.8 +/- 6.7, respectively compared to that of 2.4 +/- 0.3 at 4 hr p.i. with a nonspecific protein. The labeling technique is simple, reliable and has already been adapted to a single-vial kit preparation.
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PMID:Rhenium-186-labeled monoclonal antibodies for radioimmunotherapy: preparation and evaluation. 842 45

1. Kallidin (5-500 nmol), hypertonic saline (0.9-20% NaCl) or low pH medium (citric acid: pH 2.5-1) applied (50 microliters) to the human nasal mucosa produced a pain response (evaluated by a visual analogue scale) that was related to the concentration of the peptide, NaCl or hydrogen ions, respectively. 2. Application (50 microliters) of capsaicin (50 nmol) to the human nasal mucosa produced overt pain. After repeated administrations (once a day for 5-7 days) to one nostril this effect underwent almost complete desensitization, while in the contralateral nostril, treated with the vehicle, the response to capsaicin was unaffected. 3. The pain response produced in the human nasal mucosa by topical application (50 microliters) or kallidin (50-500 nmol), NaCl (10-20%) or citric acid (pH 1.5-1) solutions was then studied before and after local capsaicin desensitization. 4. The pain response to pH 1.5 or 1 citric acid was markedly reduced (by 60% and 75%, respectively) in the capsaicin-treated nostril. However, the pain response to 10% or 20% NaCl or the mild pain response to 50 or 500 nmol kallidin were unaffected by capsaicin pre-treatment. 5. The present results suggest that prolonged topical capsaicin treatment to the human nasal mucosa may lead to selective desensitization to certain algesic stimuli such as capsaicin itself and hydrogen ions.
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PMID:Capsaicin-desensitization to the human nasal mucosa selectively reduces pain evoked by citric acid. 844 36

A gradient reversed-phase HPLC method for potency determination of N-0923 (10 mg) from a transdermal delivery system (TDS), was developed and validated with single point calibration using internal standard quantitation. N-0923 and the internal standard, N-0434, are eluted from a reversed-phase C18 column using a gradient which contains 0.1 M triethylamine-0.04 M citrate buffer, pH 5.9, water, and acetonitrile with UV detection at 272 nm. N-0923 is isolated from the transdermal delivery system by extraction with n-heptane followed by extraction of the resulting organic phase with 0.1 M citric acid containing the internal standard. The method was free from matrix interferences in both untreated and forced degraded placebo delivery systems. Acceptable linearity and quantitative recovery from spiked placebo delivery systems over the range 50-150% of nominal label claim were demonstrated. Within-day assay precision from individual samples of active transdermal delivery systems (n = 10) was 5.6% R.S.D. The detection limit was at least 0.1 microgram/ml which is equivalent to 0.05% of the working standard concentration. Replicate injection precision at this level was 0.08% R.S.D. (n = 4). Analysis of thermally stressed active and placebo delivery systems with this HPLC method and photodiode-array detection showed that the chromatography was stability-indicating as demonstrated by the absence of measurable interferences from principal degradation products of either the n-0923 or the delivery system excipients.
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PMID:Development and validation of a gradient reversed-phase high-performance liquid chromatographic assay for S(-)-2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin (N-0923) from a transdermal delivery system. 854 20


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