对苯二甲酸接触工人尿酶及微球蛋白的变化

选择１２７名ＴＰＡ作业工人进行动式个体采样,并留取１２７名ＴＰＡ作业工人当日工前工后尿样和７０名对照工人的工前尿。对尿样中γ谷氨酰转肽酶（ＧＧＴ）、碱性磷酸酶（ＡＬＰ）、乳酸脱氢酶（ＬＤＨ）、Ｎ乙酰βＤ氨基葡糖苷酶（ＮＡＧ）活性以及尿ＴＰＡ、α１微球蛋白（α１ＭＧ）、β２微球蛋白（β２ＭＧ）水平进行分析。结果显示,ＴＰＡ接触组尿ＧＧＴ、ＡＬＰ、ＬＤＨ、ＮＡＧ活性以及尿α１ＭＧ、β２ＭＧ水平与对照组相比无显著差别,而５～ｍｍｏｌ／ｍｏｌ．Ｃｒ尿ＴＰＡ负荷组工人尿β２ＭＧ与对照组相比有明显升高（Ｐ＜００５）,尿β２ＭＧ与尿ＴＰＡ负荷量呈现一定的剂量依赖关系。尿ＴＰＡ水平对尿酶活性、α１ＭＧ均未产生明显影响。不同累积接尘量和不同工龄的工人尿酶和微球蛋白无明显差异。提示ＴＰＡ对肾实质可造成一过性可逆性影响,尚不能说明肾实质受到器质性损伤。     

Iodine deficiency disorders in Bangladesh

An extensive iodine deficiency disorders survery was conducted in Bangladesh in 1993 to assess the latest iodine nutriture status of the country. The clinical variables of the survey were goitre and cretinism, and the biochemical variable was urinary iodine. The “EPI-30 cluster” sampling methodology was followed for selecting the survey sites. In each survey site, the study population consisted of boys and girls, aged 5–11 years, and men and women, aged 15–44 years, in about equal populations. the total number of survey sites was 78 and the total number of respondents was 30 072. The total number of urine samples was 4512 (15% sub-sample). The current total goitre rate (grade 1+grade 2) in Bangladesh is 47.1% (hilly, 44.4%; flood-prone, 50.7%; and plains, 45.6%). The prevalence of cretinism in the country is 0.5% (hilly, 0.8%; flood-prone, 0.5%; and plains, 0.3%). Nearly 69% of Bangladeshi population have biochemical iodine deficiency (urinary iodine excretion [UIE]<10 mg/dl) (hilly, 84.4; flood-prone, 67.1%; and plains 60.4%). Women and children are more affected than men, in terms of both goitre prevalence and UIE. The widespread severe iodine deficiency in all ecological zones indicates that the country as a whole is an iodine-deficient region. Important recommendations of global interest are made from the experience of the survey. An erratum to this article is available at .     

Contractile and cytoskeletal proteins in urinary bladder smooth muscle from rats treated with epidermal growth factor

Systemic treatment with epidermal growth factor (EGF) induces growth of all wall layers in the urinary tract of pigs and rats. The present study was initiated to describe morphological and biochemical changes in the bladder smooth muscle from rats treated with EGF for 4 weeks. Eight-week-old female Wistar rats were treated with subcutaneous injections of vehicle (n=16) or EGF (n=8, 150 g/kg per day) for 4 weeks. After EGF treatment the bladders were increased in weight [74.4±0.4 vs 122.1±0.5 mg, P<0.001 (mean ± SEM)]. Sodium dedecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) analyses of six bladders from each group revealed that the total amounts of actin, myosin and desmin were statistically significantly increased by 62%, 61% and 154%, respectively. The relative amounts of actin and myosin were unchanged whereas the desmin to actin ratio was significantly increased — as previously described in rat bladder smooth muscle hypertrophy. Light and electron microscopy of two bladders from each group revealed increased wall thickness involving all wall layers. The smooth muscle fibres at a midventral bladder location seemed only slightly hypertrophic — some degree of hyperplasia was therefore suspected. In conclusion, EGF treatment for 4 weeks induced a net synthesis of contractile and cytoskeletal proteins in the urinary bladder smooth muscle.     

Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on the in vivo and in vitro dechlorination of pentachlorophenol

The metabolism of pentachlorophenol has been studied in the rat after pretreatments with phenobarbital, 3-methyl-cholanthrene or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). In addition to the previously identified metabolite, tetrachloro-p-hydroquinone, trichloro-p-hydroquinone has been identified in urine as a metabolite. The formation of the latter represents a type of dechlorination different from that of the formation of tetrachlorohydroquinone. The inducing agents, 3-methylcholanthrene and TCDD have similar effects on the dechlorination and increase the formation of tetrachloro-p-hydroquinone more pronounced than does phenobarbital. In contrast to phenobarbital they also increase the formation of trichloro-p-hydroquinone and the total elimination of pentachlorophenol and its metabolites. The in vivo findings are supported by in vitro studies with microsomes from rats pretreated with phenobarbital or TCDD. Use of the inhibitor -diethylaminoethyl-diphenyl propylacetate (SKF 525-A) in vitro showed a more pronounced inhibition on microsomes from phenobarbital-treated rats than on microsomes from untreated or TCDD-treated rats.Gas chromatography-mass spectrometry have been used for the identification and quantification of pentachlorophenol and its metabolites.

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Zusammenfassung Der Metabolismus von Pentachlorphenol nach Vorbehandlung der Versuchstiere (Ratten) mit phenobarbital, 3-Methylcholantren oder 2,3,7,8-Tetrachlordibenzo-p-Dioxin (TCDD) ist untersucht worden. Zu dem schon früher nachgewiesenen Metaboliten Tetrachlor-p-Hydrochinon wurde nun auch Trichlor-p-Hydrochinon als Harnmetabolit festgestellt. Die Bildung des letzteren stellt eine andere Art von Dechlorierung dar als diejenige die bei der Entstehung von Tetrachlor-p-Hydrochinon vorliegt. 3-Methylcholantren und TCDD haben ähnlichen Einfluß auf die Dechlorierung und steigern die Bildung von Tetrachlor-p-Hydrochinon mehr ausgeprägt als es bei phenobarbital der Fall ist. Im Gegensatz zu phenobarbital steigern sie auch die Bildung von Tri-chlor-p-Hydrochinon sowie die totale Eliminierung von Pentachlorphenol und von Metaboliten. Die in vivo-Befunde werden von in vitro-Studien mit Mikrosomen von mit phenobarbital oder TCDD vorbehandelten Ratten gestützt. Anwendung des Inhibitors -Diethylaminoethyl-Diphenyl-Propylacetat (SKF 525-A) zeigte in vitro eine ausgeprägtere Inhibition der Mikrosomen von mit phenobarbital behandelten Ratten als der Mikrosomen von unbehandelten oder TCDD-behandelten Ratten. Nachweis und Bestimmung von Pentachlorphenol und seinen Metaboliten wurden gaschromatographisch-massenspektrometrisch durchgeführt.

     

Increased kallikrein excretion in spontaneously hypertensive rats and its inhibition by 6-hydroxydopamine

Summary Urinary kallikrein excretion was studied in young, stroke-prone, spontaneously hypertensive rats (spSHR). Seven-week-old spSHR were found to excrete more kallikrein into the urine than normotensive Wistar Kyoto control rats (WKR). Chemical sympathectomy, induced by 6-hydroxydopamine (6-OHDA) immediately after birth, resulted in normotensive blood-pressure levels and in a reduction of kallikrein in spSHR. In normotensive WKR, blood pressure and urinary kallikrein excretion were only slightly diminished by 6-OHDA. The results suggest a relationship between sympathetic activity and kallikrein excretion, being especially pronounced in spSHR, which have an elevated sympathetic activity.Supported by the Deutsche Forschungsgemeinschaft, Sonderforschungsbereich 90-Cardiovaskuläres System     

Determination of tetrahydrophtalimide and 2-thiothiazolidine-4-carboxylic acid,urinary metabolites of the fungicide captan,in rats and humans

Summary Capillary gas chromatographic (GC) methods using sulphur and mass selective detection for the qualitative and quantitative determination of tetrahydrophtalimide (THPI) and 2-thiothiazolidine-4-carboxylic acid (TTCA), urinary metabolites of the fungicide captan in rat and humans, were developed. Urinary detection limits were 2.7 g/l for THPI and 110 g/l for TTCA. Intraperitoneal and oral administration of captan to rats resulted in a 48-h cumulative urinary excretion of THPI of 1%–2% and 3%–9% of the dose, respectively. Cumulative urinary excretion of TTCA over 48 h ranged from 2% to 5% of the captan dose for the respective routes of administration. In urine of non-exposed human subjects, neither THPI nor TTCA could be detected. In urine of fruit-growers who were occupationally exposed to captan, both THPI and TTCA could be detected. Based on these results, THPI and TTCA are proposed as promising parameters for the biological monitoring of occupational exposure to captan.     

Effect of deltamethrin on antipyrine pharmacokinetics and metabolism in rat

The effect of deltamethrin pretreatment on the pharmacokinetics and metabolism of antipyrine was studied in male rats. The total plasma clearance of antipyrine was significantly decreased by deltamethrin pretreatment (20 mg/kg and 40 mg/kg daily for 6 days prior to antipyrine administration), while the elimination half-life at phase, the area under the concentration-time curve and the mean residence time of antipyrine were significantly increased. The magnitude of the observed changes was dose dependent. The urinary excretion of norantipyrine, 4-hydroxyantipyrine and 3-hydroxymethylantipyrine was decreased by 39%, 32% and 26%, respectively (p<0.001) in the presence of deltamethrin. In addition, the rate constants for formation of each of these metabolites were significantly decreased by an average of approximately 71%. These results suggest that deltamethrin is capable of inhibiting oxidative metabolism, a finding which could be of clinical and toxicological significance.     

Prediction of survival and recurrence in bladder carcinoma

Summary We have followed a large population of patients receiving radiation treatment for bladder carcinoma with respect to survival and recurrence-free survival. Bivariate and multivariate life table analyses have been performed using a set of independent variables. The most important were T class, grade (G), urinary carcinoembryonic antigen (U-CEA) taken before treatment and cytological analysis 4 months after treatment. We compared the usual way of classifying a patient (T+G) with the combination of U-CEA and cytology since the latter two variables seemed to have great prognostic importance. The analyses show that T+G gives the best significance for survival (P=0.0003) while U-CEA and cytology is better for recurrence-free survival (=0.0002). 0.0002).     

Action of the competitive angiotensin II antagonist saralasin during the initial phase of glycerol-induced acute renal failure of the rat

Summary The effects of the competitive angiotensin II antagonist saralasin (1-sarcosine-8-alanine-5-isoleucine-angiotensin II) on renal function in healthy rats and in rats with myohemoglobinuric acute renal failure were studied. Acute renal failure was induced by an intramuscular injection of 50% glycerol (10 ml ·kg^–1). Functional impairment of the glycerol treated animals consisted in a decrease of renal blood flow (electromagnetic flowmeter) and GFR and in an increase of urine volume and arterial blood pressure.In healthy rats saralasin (6 g·kg^–1·min^–1 i.v.) had no renal effects by itself but antagonized the angiotensin II (200 ng·kg^–1·min i.v.) induced fall of renal blood flow and GFR and the increase of arterial blood pressure. Given to glycerol treated animals saralasin did not induce any change of arterial blood pressure, renal blood flow, GFR or the urinary excretion of fluid and sodium.Supported by Deutsche Forschungsgemeinschaft     

Pharmacokinetics of spironolactone in man

Summary Five healthy male volunteers received 500 mg Aldactone^® orally together with 100 Ci ³H-20-21-spironolactone; one elderly patient received 1 mCi ³H-spironolactone without additional cold drug. For 6 days the disposition kinetics of the drug were studied in plasma, urine and feces. The tritium concentrations in plasma reached a peak between 25–40 min after administration amounting to 2–3% of the dose/1. Up to the 12th h, they fell rapidly and showed a monoexponential decline (t _1/2 : 2.57±0.27 days) between the 36th and 96th h. Later, a striking increase in the speed of elimination of radioactivity from plasma (t _1/2 : 1.66±0.21 days) was observed. The biological half-life of labeled material in plasma was longer than that of fluorigenic compounds. 47–57% of the dose were excreted in urine and the remaining amount culd be detected in feces (total recovery 90%). The half-life of the urinary excretion rate was distinctly shorter (t _1/2 : 0.9±0.11 days) than that of total radioactivity in plasma. This, together with an observed increase of the polar fraction in urine from 35 up to 85%, which was accompanied by a decrease in plasma from 55 to 35%, suggests either tubular reabsorption or enterohepatic recirculation of lipophilic compounds. TLC-separation of the lipophilic fraction in urine revealed two previously unknown compounds of which the main congener was identified as 3-(3-oxo-7-methylsulfonyl-6, 17-dihydroxy-4-androsten-17-yl) propionic acid -lactone, as well as canrenone and the metabolites which have already been described (Karim and Brown, 1972; Karim et al., 1975). This metabolite represents the main lipophilic degradation product in urine within the first hours, whereas the 6-OH-7-methylsulfinylspirolactone leveled off and seemed to be an endexcretion product. For further characterisation, the polar fraction was subjected to acidic hydrolysis. The known metabolic pathways of spironolactone degradation are discussed.The paper includes parts of the thesis of G. Luszpinski