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1.
Abstract. To test if different leucine tracers behave in an indistinguishable manner and, by implication, that their metabolism is identical to that of natural leucine, we measured whole body leucine turnover in dogs and humans and fibrinogen synthesis in dogs by simultaneously infusing either [1–14C]leucine or [4,5–3H]leucine or [I-14C]α-ketoisocaproate (KIC) and [4,5–3H]KIC. Whole body leucine fluxes calculated from the plasma specific activity of the transaminated product of the infused tracer (reciprocal pool model) were lower (dogs by 5.7%; humans by 6.4%, both P<0.02) when the plasma 'H specific activity compared to 14C specific activity were used with leucine tracers and were also lower (dogs by 4.4%, P<0.02; humans by 86%, P<0.06 ) using the KIC tracers. Using leucine or KIC tracers in dogs, the fractional rate of fibrinogen synthesis was 6.7% or 9.4% lower, respectively, (P<0.02) using the 3H versus the 14C tracer. The apparently lower incorporation of 3H into protein was only in part accounted for by detritiation (2.1%, P = 0.05) of [3H]leucine during acid hydrolysis of proteins. These results suggest that in vivo and/or in vitro differential isotope effects are small (˜5%), but should be considered when dual isotopes infusions are employed to partition amino acid metabolism.  相似文献   

2.
Summary— This study aims to evaluate whether or not the kinetics of L-dopa, its main metabolites (3-O-methyldopa, 3-OMD, homovanilic acid, HVA and 3,4-dihydroxyphenylacetic acid, DOPAC) and carbidopa, vary according to the 24-hour scale in rats. Four groups of seven adult male Wistar AF EOPS rats were used for these experiments; each group received L-dopa (200 mg·kg−1 ip) and carbidopa (20 mg·kg−1 ip) at 1000, 1600, 2200 or 0400 hours. L-dopa, 3-OMD, DOPAC, HVA and carbidopa were simultaneously determined by specific ion-pair reversed-phase high performance liquid chromatography with electrochemical detection. A temporal variation of the kinetics of both L-dopa and carbidopa was demonstrated with higher plasma clearance and lower area under concentration curve after the administration at 2200 hours. Moreover, a temporal variation of the metabolism of L-dopa was indirectly documented by temporal variation in kinetics of 3-OMD, DOPAC and HVA.  相似文献   

3.
Abstract. The turnover of ketone bodies and acetate was evaluated as well from the disappearance rate of (3-14C)acetoacetate or (1-14C)acetate respectively as from the conversion of FFA into these metabolites in normal weight and obese overnight-fasted and in obese long-term starved patients. The disappearance rate of (1-14C)oleate was the same in all three groups.
Long-term starvation enhanced ketone body turnover almost 10-fold, whereas the disappearance rate for ketone bodies decreased from 0·035 to 0·015 min-1. Under the same circumstances the turnover of acetate was about 1 μmol g-1 min-1 accounting for about 5% of FFA turnover.
Long-term starvation decreased the conversion of (1-14C)oleate into triglycerides by almost 50% and increased the (2-C)-(4-C)/(1-C) ratio of radioactivity in ketone bodies. The reincorporation of radioactivity from the (1-C)position of (1-14C)oleate into the ((2-C)-( n -C)) position of FFA, which is a measure of the reutilization of acetyl-CoA for FFA synthesis decreased significantly during long-term starvation.  相似文献   

4.
Red wine-induced release of [14C]5-hydroxytryptamine (5HT) from platelets of red wine-sensitive migraine patients, migraine patients not sensitive to red wine and controls, was determined in vitro . No significant differences in platelet [14C]5HT release were found between any of the groups investigated.  相似文献   

5.
Abstract. Lactate is the predominant gluconeogenic precursor in man. To determine the dose-response relationships between plasma lactate concentration and rates of lactate incorporation in plasma glucose (lactate gluconeogenesis, LGN), we infused 17 normal volunteers with sodium lactate for 180 min at rates ranging from 6 to 40 γmol kg-1 min-1 and measured [U-14C]lactate incorporation into plasma glucose, as well as rates of lactate and glucose appearance in plasma. With the highest lactate infusions, plasma lactate increased up to 7 mM (compared to 1.1±0.13 mM during control sodium bicarbonate infusions, n=10) and LGN averaged 4.73 ± 0.23 μmol kg-1 min-1 (compared to 1.57 ± 0.26 μmol kg-1 min-l in bicarbonate control experiments, P< 0.001). The data relating plasma lactate concentration to LGN best fit a sigmoidal curve which plateaued at plasma lactate concentrations of approximately 6 mM and yielded an ED50 of 2.04 ± 0.20 (SD) mM and a Vmax (6.25±1.2) (SD) (mUmol kg-1 min-1). The sum of the basal rate of lactate appearance and the rate of lactate infusion was not significantly different from the overall rates of lactate appearance during the lactate infusions (35.8±2.2 vs. 34.8±2.9 μmol kg-1 min-1, P = 0.23). Thus, our results support the view that infusion of exogenous lactate does not suppress endogenous lactate appearance in plasma.  相似文献   

6.
Abstract The effect of infusions of recombinant insulin-like growth factor-I (IGF-I) (34, 103 or 688 pmol min-1 kg-1), insulin (3·4, 10·3 or 68·8 pmol min-1 kg-1) or combined infusions (34 pmol IGF-I+ 3·4 pmol min-1 kg-1 insulin or 103 pmol IGF-I+ 3·4 pmol min-1 kg-1 insulin) on protein metabolism, using an infusion of [1-14C] leucine was investigated in anaesthetized fasted dogs. Leucine concentration, production rate (measure of protein degradation), oxidation rate and non-oxidative disappearance rate (measure of protein synthesis) were decreased in a similar dose dependent manner by the IGF-I and insulin infusions (P <0·01). The decrease in these measurements of leucine metabolism were greater following 34 pmol IGF-I + 3·4 pmol insulin than with either component infused alone (P <0·05). Free fatty acid concentrations were decreased by all insulin doses (P < 0·01) but only by 103 and 688 pmol min-1 kg-1 insulin-like growth factor (P < 0·05, P < 0·01). These data demonstrate that IGF-I, like insulin, has a dose dependent effect on protein metabolism and that combined insulin and IGF-I infusions have additive effects on protein metabolism.  相似文献   

7.
Transdermal permeation of two types of NSAIDs, [3H] flurbiprofen and [14C] indomethacin, was examined by use of the Ussing-type chamber method. We found that the transdermal permeability in the absorptive direction (Pabs) of [3H] flurbiprofen was significantly higher than that of [14C] indomethacin. A lower pH (5.0) on the epidermal side increased the accumulation and the Pabs of [3H] flurbiprofen (18-fold and 50-fold, respectively) and [14C] indomethacin (18-fold and 22-fold, respectively), compared with pH 7.4. Coadministration of unlabeled flurbiprofen and indomethacin increased Pabs of [3H] flurbiprofen and [14C] indomethacin, respectively, in a concentration-dependent manner. Similar high-affinity transport was also observed in the uptake of [3H] flurbiprofen by human epidermal keratinocytes (HEK001 cells). RT-PCR analysis revealed the expression of mRNA of numerous transporters including MRP, OATP, MCT and OCTN family members in hairless mouse skin, human skin and HEK001 cells. These findings support the novel hypothesis that transdermal permeation of NSAIDs is mediated by saturable transport mechanisms, which may be candidates as targets for transdermal delivery of drugs.  相似文献   

8.
Phosphatidylcholine (PC) is the major phospholipid of the hydrophobic gastric mucosal barrier and is chiefly released from mucous cells into the gastric mucus. Whereas the mucosa contains highly unsaturated PC, gastric mucus predominantly contains palmitoyl-oleoyl-PC and palmitoyl-linoleoyl-PC, indicating a selective release of these PC species into the gastric lumen. In order to understand gastric PC metabolism, we investigated synthesis and release of PC in cultivated porcine gastric mucous cells, using dual labelling with [methyl-3H]-choline and [1-14C]-palmitate, in the presence of 12- O -tetradecanoylphorbol-13-acetate (TPA), indomethacin and prostaglandin E2 (PGE2). Linear incorporation of [methyl-3H]-choline and [1-14C]-palmitate into PC was achieved for at least 8 h. In contrast to type II pneumocytes TPA increased PC synthesis in gastric mucous cells but not its release. Indomethacin did not influence PC synthesis, but it decreased the release of newly synthesized PC. PGE2 antagonized the effect of indomethacin on PC release. We conclude that PC release by isolated porcine gastric mucous cells is regulated in a manner different from type II pneumocytes. PC release is impaired by indomethacin and this impairment is restored by PGE2.  相似文献   

9.
There is evidence that low-density lipoprotein (LDL) plays a crucial role in atherogenesis. On the cellular level, LDL has been shown to activate a number of mechanisms involved in atherogenesis and vasoconstriction. Local immoderate vasoconstriction is physiologically antagonized by nitric oxide, which is released from the endothelium. To find out whether LDL also influences the synthesis of nitric oxide in vascular smooth muscle cells, both the conversion of arginine to citrulline and the production of nitrite were determined as a measure of nitric oxide formation. After incubation of rat vascular smooth muscle cells with native LDL (25 μg mL−1) for 24 h, the production of both l -[14C]-citrulline [39 600 (3600) cpm mg−1 cell protein] and nitric oxide [2.95 (0.56) μmol L−1] were about twice and 1.5-fold the amount of the corresonding values in untreated cells (mean ± SD, P  < 0.05, n  = 4). Oxidized LDL was less effective than the native form. The presence of the arginine analogue N G-methyl- l -arginine reduced citrulline production dose-dependently but augmented DNA synthesis, both induced by LDL. In addition, the lipoprotein caused a 1.6-fold increase in cyclic GMP production following a 24-h incubation [control = 10.9 (3.8) pmol mg−1 cell protein, P  = 0.016]. The results suggest that native LDL might partly impair its atherogenic potential on the vasculature by stimulating the production by smooth muscle cells of both nitric oxide and cyclic GMP.  相似文献   

10.
Absorption and Metabolism of L-Dopa by the Human Stomach   总被引:1,自引:0,他引:1  
Abstract. The absorption and gastric metabolism of L-dopa (L-dihydroxyphenylalanine) were studied in 14 Parkinsonian patients. Patients were given p. o. 25 μCi (500 mg) 14C L-dopa labelled at the β-carbon mixed with 2 g polyethylene glycol as a dilution marker. Absorption was evaluated by determining the gastric rate of absorption, gastric clearance, serum levels, and urinary excretion of 14C. L-dopa and its metabolites in the gastric juice and serum were fractionated by column chromatography. Patients with gastric juice pH of 1.2-2.1 had a gastric rate of absorption of 62.6±4.7 mg/h with a gastric clearance of 31.7.4.1 ml/h. The gastric emptying time was 228±96min. 17.2–26.4% of total radioactivity in the gastric juice were dopa metabolites. Patients with gastric pH of 6.9-7.2 had a very rapid emptying time (an average of 22 min.) with no gastric absorption. The amount of metabolites in their gastric juice was insignificant. Gastric absorption and emptying time were reduced in patients when the gastric pH was raised to 3.5-4.5 with antacids. Serum peak concentrations were higher and more rapidly achieved in patients with high gastric pH than in those with low pH.
The most rapidly achieved and highest serum peak levels were observed in patients with partial gastrectomy and in those who were given the drug by duodenal infusion. It appears that direct absorption of L-dopa by the stomach may be limited by gastric metabolism of the drug, a possibility supported by the study in vitro of human stomach tissue obtained at surgery. The inverse relationship between the gastric emptying time and serum levels suggests that the intestine is the major site of L-dopa absorption. Thus factors that prolong gastric emptying time may lower serum levels of L-dopa by delaying access of the drug to the site of absorption and by increasing metabolism before absorption.  相似文献   

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