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B Zimmerli

Publications and source records attributed to B Zimmerli.

28 records · Page 2Linked to original sources

Rat hepatocytes exhibit basolateral Na+/HCO3- cotransport.

Primary cultures and plasma membrane vesicles were used to characterize Na+ and HCO3- transport by rat hepatocytes. Na+ uptake into hepatocytes was stimulated approximately 10-fold by 25 mM extracellular HCO3-.HCO3--stimulated Na+ uptake was saturable, abolished by 4-acetamido-4'-isothiocyano-2,2'-disulfonic acid stilbene (SITS), and unaffected by amiloride or Cl- removal. Neither propionate nor acetate reproduced this effect of HCO3-. 22Na efflux from preloaded hepatocytes was similarly increased approximately 10-fold by an in greater than out HCO3- concentration gradient. 22Na efflux was also increased by valinomycin and an in greater than out K+ concentration gradient in the presence but not absence of HCO3-. Intracellular pH (pHi) measured with the pH-sensitive fluorochrome 2',7'-bis-(2-carboxyethyl)-5-(and 6-)carboxyfluorescein (BCECF) decreased at a rate of 0.227 (+/- 0.074 SEM) pH units/min when extracellular HCO3- concentration was lowered from 25 to 5 mM at constant PCO2. This intracellular acidification rate was decreased 50-60% in the absence of Na+ or presence of SITS, and was unaffected by amiloride or Cl- removal. Membrane hyperpolarization produced by valinomycin and an in greater than out K+ concentration gradient caused pHi to fall; the rate of fall was decreased 50-70% by Na+ removal or SITS, but not amiloride. An inside positive K+ diffusion potential and a simultaneous out greater than in HCO3- gradient produced a transient 4,4'-diisothiocyano-2,2' disulfonic acid stilbene (DIDS) sensitive, amiloride-insensitive 22Na accumulation in basolateral but not canalicular membrane vesicles. Rat hepatocytes thus exhibit electrogenic basolateral Na+/HCO3- cotransport.

Animals↗

Multispecificity of Na+-dependent taurocholate uptake in basolateral (sinusoidal) rat liver plasma membrane vesicles.

To test the hypothesis of broad specificity of the hepatocellular bile acid uptake system(s) we investigated the kinetics and substrate specificity of Na+-dependent taurocholate uptake in basolateral (sinusoidal) rat liver plasma membrane vesicles in the presence and absence of bovine serum albumin. Bovine serum albumin selectively stimulated the Na+-dependent portion of taurocholate uptake and decreased its apparent Km from 46 +/- 6 to 17 +/- 3 microM, whereas it had no effect on Vmax (4.2 +/- 0.2 nmol.mg-1.min-1). Based on complementary analysis by Dixon- and Cornish-Bowden-plots the following compounds were identified as competitive inhibitors of Na+-dependent taurocholate uptake: cholate (Ki = 140 +/- 30 microM); taurochenodeoxycholate (Ki = 9 +/- 3 microM); chenodeoxycholate (Ki = 53 +/- 6 microM); progesterone (Ki = 110 +/- 30 microM); 17-beta-estradiol-3-sulfate (Ki = 28 +/- 4 microM); bumetanide (Ki = 440 +/- 85 microns); furosemide (Ki = 460 +/- 140 microM); verapamil (Ki = 65 +/- 35 microM); and phalloidin (Ki = 850 +/- 350 microM). In contrast, noncompetitive inhibition was found with bromosulfophthalein (Ki = 12 +/- 2 microM), cyclosporin A (Ki = 3 +/- 1 microM) and 4,4'-diisothiocyano-2,2'-disulfonic acid stilbene (Ki = 45 +/- 7 microM). These results support the concept of multispecificity of the Na+-dependent basolateral bile acid uptake system with respect to different bile acids and drugs. In addition, the findings provide further evidence for bile acids and bromosulfophthalein being taken up into rat hepatocytes by different transport systems, thus supporting the assumption of multiple basolateral organic anion "carriers" with distinct, yet partially overlapping substrate specificities.

Animals↗

[Modelling the transfer of pollutants from painted surfaces to the surrounding air].

As dried paintings may emit pollutants into indoor air by evaporation or sublimation processes, men living in such rooms my incorporate a certain amount of these substances via the respiratory tract or via the skin according to the pollutant concentration. Furthermore, foodstuff and feeds may as well absorb such substances. The chronic toxicity of the single compound and its daily up- take by man determine the risk of a possible danger to human health. For the toxicological evaluation of pollutants emanating from paints it is necessary that procedures are available to estimate the maximum indoor air concentration of these pollutants. Model experiments are described and equations are given for the calculation of the equilibrium concentration of pollutants occurring in indoor air after the application of paints. The validity of the equations has been ascertained taking as examples different fungicides and pesticides. The concentration values from model experiments were in good agreement with the results of field measurements.

Air Pollutants↗

Ethyl carbamate: analytical methodology, occurrence, formation, biological activity and risk assessment.

Ethyl carbamate (EC) is a genotoxic compound in vitro and in vivo, it binds covalently to DNA and is an animal carcinogen. Today, EC is mainly found as a natural trace constituent in different alcoholic beverages and in fermented food items. Data on analytical methodology and the levels of EC in different food items are summarized and the daily burden of humans is estimated. Under normal dietary habits excluding alcoholic beverages, the unavoidable daily intake is 10-20 ng/kg b.w. On the basis of the evaluation of all toxicity data and its mode of action a conventional risk assessment of EC indicates that this level represents a negligible lifetime cancer risk (less than 0.0001%). Individual habits may greatly enhance the risk. Regular drinking of table wine (500 ml/day) would increase the risk up to 5 times, regular drinking of stone-fruit distillates (20-40 ml/day) would raise the calculated hypothetical tumor risk to near 0.01%. Human exposure to carcinogenic compounds should be as low as reasonably achievable. In order to take reliable measures to reduce EC levels in beverages and foods, it is crucial to know the mode of its formation. For its natural formation the presence of ethanol is absolutely required. In stone-fruit distillates hydrogen cyanide together with photochemically active substances are crucial to form EC. The main part of EC is formed after the distillation involving photochemical reactions. In wine (and probably bread) significant EC formation seems to depend on heat treatment. While in distillates hydrogen cyanide is the most important single precursor, in wine different carbamyl compounds, mainly urea, seem to be involved in EC formation. Despite this apparent difference a common EC formation pathway is discussed for all alcoholic beverages by assuming cyanic-/isocyanic acid as an important ultimate reactant with ethanol. Some ideas are presented as to the possible course of future work.

Carcinogens↗

Ochratoxin A in table wine and grape-juice: occurrence and risk assessment.

The concentrations of ochratoxin A (OA) and C (ethyl ester of OA, OC) have been measured in table wine from the Swiss retail market. The overall median concentrations of OA in white, rose and red table wine were (number of samples; range) < 3 pg/ml (24; < 3-178 pg/ml), 19 pg/ml (15; < 3-123 pg/ml) and 13 pg/ml (79; < 3-388 pg/ml)), respectively. For dessert wines (Malaga, Marsala) a median of 337 pg/ml (5; 44-451 pg/ml) resulted. Concentrations of OC were about 10% of those of OA. OA has been detected in red grape-juices for the first time with median concentrations amounting to 235 pg/ml (8; < 3-311 pg/ml). White grape-juices (3) as well as other fruit juices (2 apple, 6 orange, 2 others) did not contain OA (< 5 pg/ml). The analytical method used was not appropriate for grapefruit-juices because of an interfering substance. The results indicate that OA is formed prior to the alcoholic fermentation. It also appears that the more southerly in Europe is the origin of the samples the higher is the frequency of occurrence and the concentration of OA in red wines and red grape-juices. Although the estimated mean daily OA intake of 0-7 ng/kg body mass (men) can easily be more than doubled by moderate wine consumption, an additional health risk by OA is not to be expected. On the other hand the consumption of red grape-juices among infants and children may result in intakes high enough to justify a reduction of the OA concentrations in these juices to less than 100 pg/ml.

Beverages↗