The effect of oral inorganic sulphate on the metabolism of 4-hydroxyphenethylamine (tyramine) in man: tyramine O-sulphate measurement in human urine.
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SUBMITTER: Smith I
PROVIDER: S-EPMC1168225 | biostudies-other | 1974 Jul
REPOSITORIES: biostudies-other
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Project description:1. The metabolism of inorganic [(35)S]sulphate (Na(2) (35)SO(4)) was studied in the isolated perfused rat liver at three initial concentrations of inorganic sulphate in the perfusion medium (0, 0.65 and 1.30mm), in relation to sulphation and glucuronidation of a phenolic drug, harmol (7-hydroxy-1-methyl-9H-pyrido[3,4-b]indole). 2. [(35)S]Sulphate rapidly equilibrated with endogenous sulphate in the liver. It was excreted in bile and reached, at the lowest concentration in the perfusion medium, concentrations in bile that were much higher than those in the perfusion medium; at the higher sulphate concentrations, these concentrations were equal. The physiological concentration of inorganic sulphate in the liver, available for sulphation of drugs, is similar to the plasma concentration. 3. At zero initial inorganic sulphate in the perfusion medium, the rate of sulphation was very low and harmol was mainly glucuronidated. At 0.65mm-sulphate glucuronidation was much decreased and considerable sulphation took place, indicating efficient competition of conjugation by sulphation. At 1.30mm-sulphate the sulphation increased still further. 4. The results suggest that an important factor in sulphation is the relatively high K(m) of synthesis of adenosine 3'-phosphate 5'-sulphatophosphate (the co-substrate of sulphation) for inorganic sulphate, which is of the order of the plasma concentration of inorganic sulphate. The steady-state adenosine 3'-phosphate 5'-sulphatophosphate concentration may determine the rate of sulphate conjugation of drugs in the rat in vivo.
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Project description:In chronic kidney disease (CKD) patients, it would be desirable to reduce the intake of inorganic phosphate (P) rather than limit the intake of P contained in proteins. Urinary excretion of P should reflect intestinal absorption of P(inorganic plus protein-derived). The aim of the present study is to determine whether the ratio of urinary P to urinary urea nitrogen (P/UUN ratio) helps identify patients with a high intake of inorganic P.A cross-sectional study was performed in 71 patients affected by metabolic syndrome with CKD (stages 2-3) with normal serum P concentration. A 3-day dietary survey was performed to estimate the average daily amount and the source of P ingested. The daily intake ofPwas1086.5 ± 361.3mg/day; 64% contained in animal proteins, 22% in vegetable proteins, and 14% as inorganic P. The total amount of P ingested did not correlate with daily phosphaturia, but it did correlate with the P/UUN ratio (p < 0.018). Patients with the highest tertile of the P/UUN ratio >71.1 mg/g presented more abundant inorganic P intake (p < 0.038).The P/UUN ratio is suggested to be a marker of inorganic P intake. This finding might be useful in clinical practices to identify the source of dietary P and to make personalized dietary recommendations directed to reduce inorganic P intake.
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Project description:In response to kidney damage, osteocytes increase the production of several hormones critically involved in mineral metabolism. Recent studies suggest that osteocyte function is altered very early in the course of chronic kidney disease. In the present study, to clarify the role of osteocytes and the canalicular network in mineral homeostasis, we performed four experiments. In Experiment 1, we investigated renal and intestinal Pi handling in osteocyte-less (OCL) model mice [transgenic mice with the dentin matrix protein-1 promoter-driven diphtheria toxin (DT)-receptor that were injected with DT]. In Experiment 2, we administered granulocyte colony-stimulating factor to mice to disrupt the osteocyte canalicular network. In Experiment 3, we investigated the role of osteocytes in dietary Pi signaling. In Experiment 4, we analyzed gene expression level fluctuations in the intestine and liver by comparing mice fed a high Pi diet and OCL mice. Together, the findings of these experiments indicate that osteocyte ablation caused rapid renal Pi excretion (P?<?0.01) before the plasma fibroblast growth factor 23 (FGF23) and parathyroid hormone (PTH) levels increased. At the same time, we observed a rapid suppression of renal Klotho (P?<?0.01), type II sodium phosphate transporters Npt2a (P?<?0.01) and Npt2c (P?<?0.05), and an increase in intestinal Npt2b (P?<?0.01) protein. In OCL mice, Pi excretion in feces was markedly reduced (P?<?0.01). Together, these effects of osteocyte ablation are predicted to markedly increase intestinal Pi absorption (P?<?0.01), thus suggesting that increased intestinal Pi absorption stimulates renal Pi excretion in OCL mice. In addition, the ablation of osteocytes and feeding of a high Pi diet affected FGF15/bile acid metabolism and controlled Npt2b expression. In conclusion, OCL mice exhibited increased renal Pi excretion due to enhanced intestinal Pi absorption. We discuss the role of FGF23-Klotho on renal and intestinal Pi metabolism in OCL mice.
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Project description:ImportanceSeveral methods have been established in recent decades that allow use of spot urine to estimate dietary sodium intake. However, their accuracies have been controversial in children.ObjectiveTo validate the performance of three commonly used methods-the Kawasaki, Tanaka, and International Cooperative Study on Salt, Other Factors, and Blood Pressure (INTERSALT) methods. Additionally, this study explored the accuracies of the Tanaka and INTERSALT methods by using spot urine samples taken at four separate times.MethodForty-one adolescents aged 14 to 16 years completed two non-consecutive 24-hour urine collections and their mean values were used as reference data. The second-morning urine was used for assessment with the Kawasaki method; a casual spot urine and spot urine samples taken at four separate times (morning, afternoon, evening, and overnight) were used for assessment with the Tanaka and INTERSALT methods.ResultsThe mean differences were 1801 mg, 542 mg, 47 mg, and -31 mg for the Kawasaki, Tanaka, INTERSALT1 (with potassium), and INTERSALT2 (without potassium) methods with their required spot urine, respectively. The proportions of relative difference levels within ± 10% were 4.9% for the Kawasaki method, 19.5% for the Tanaka method, 36.6% for the INTERSALT1 method, and 36.6% for the INTERSALT2 method.InterpretationThe INTERSALT method seemed to provide minimally biased estimations of mean population sodium intake with casual spot urine. However, there is a need to be cautious regarding inconsistencies in estimation among different levels of sodium intake. The methods assessed in this study were unable to accurately estimate sodium intake at the individual level.
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Project description:Tyramine was conjugated with sulphate by extracts of monkey intestine and livers of monkey, rat, mouse, guinea pig and man. The activity measured in monkey intestine was almost three times that of monkey liver. Labelled tyramine sulphate synthesized from [14C] tyramine, [3H] tyramine or Na235SO4, on acid hydrolysis, released its radioactive precursor. Liver extracts of monkey, rat, mouse and guinea pig synthesized respectively 145,66,21 and 6 pmol of [14C] tyramine sulphate/min per mg of protein. Except with the monkey, intestine exhibited very low activity. trans-2-Phenylcyclopropylamine, a monoamine oxidase inhibitor, was added as a routine to the enzyme preparation, as its omission resulted in the production of p-hydroxyphenylacetic acid in appreciable amounts. This oxidative deamination of tyramine, however, did not decrease the sulpho-conjugation of tyramine. The low Km (9.1 muM) of sulphotransferase for tyramine is probably responsible.
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Project description:This paper uses newly available data from Web of Science on publications matched to researchers in Survey of Doctorate Recipients to compare the quality of scientific publication data collected by surveys versus algorithmic approaches. We illustrate the different types of measurement errors in self-reported and machine-generated data by estimating how publication measures from the two approaches are related to career outcomes (e.g., salaries and faculty rankings). We find that the potential biases in the self-reports are smaller relative to the algorithmic data. Moreover, the errors in the two approaches are quite intuitive: the measurement errors in algorithmic data are mainly due to the accuracy of matching, which primarily depends on the frequency of names and the data that was available to make matches, while the noise in self reports increases over the career as researchers' publication records become more complex, harder to recall, and less immediately relevant for career progress. At a methodological level, we show how the approaches can be evaluated using accepted statistical methods without gold standard data. We also provide guidance on how to use the new linked data.
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