Seroprevalence of viral hepatitis in Tanzanian adults.

In a cross-sectional study in Dar es Salaam, Tanzania, we determined the seroprevalence of markers for hepatitis A, B, C and E viruses and examined associated risk markers. Among 403 healthy adults, the seroprevalence of antibodies to hepatitis A virus was 99.0% (95% confidence interval: 97.5-99.7). Prior exposure to hepatitis C and E viruses was rare (hepatitis C: 0.7% (0.2-2.1); hepatitis E: 0.2% (< 0.1-1.4)). The prevalence of all markers of hepatitis B was 70.7% (66.0-75.1). Hepatitis B surface antigen was identified in 6.0% (3.9-8.7) of subjects. Independent predictors of hepatitis B infection identified by logistic regression included older age, male gender, Muslim religion and type of abode. Given the high prevalence of hepatitis B and the low prevalence of hepatitis C, the majority of chronic viral hepatitis is likely to be associated with hepatitis B. Control efforts should focus primarily on hepatitis B.

Assessment of water use for estimating exposure to tap water contaminants.

Epidemiological studies examining the association between exposure to tap water contaminants (such as chlorination by-products) and disease outcomes (such as cancer and adverse reproductive outcomes) have been limited by inaccurate exposure assessment. Failure to take into account the variation in beverage and tap water consumption and exposure to volatile contaminants through inhalation and dermal absorption can introduce misclassification in assessing the association between exposure to tap water contaminants and health. To refine exposure assessment of tap water contaminants, we describe in detail the tap water consumption, showering, and bathing habits of pregnant women and their male partners as assessed by a questionnaire and a 3-day water diary. We found good agreement between questionnaire and 3-day water diary values for drinking water intake (Pearson's r = 0.78) and for time spent showering(r = 0.68) and bathing (r = 0.78). Half of the participants consumed tap water on a regular basis with an overall mean +/- 1 standard deviation (SD) of 0. 78 +/- 0.51 l/day. Our results further suggest that full-time employees, compared to women working part-time or less, have more heterogeneous consumption patterns over time. Seventy-nine percent of women and 94% of men took showers for an average of 11.6 +/-4.0 min and 10.4 +/- 4.8 min, respectively. Baths were taken more frequently by women than men (21% vs. 3%) for an average of 22.9 +/-10.1 min and 21.3 +/- 12.4 min, respectively. Thus, these patterns of tap water use should be considered in the design and interpretation of environmental epidemiology studies.

Adenosine nucleotides in bile.

Activation of purinergic receptors by ATP stimulates Cl- efflux in biliary epithelial cells. To determine whether purinergic agonists are present under physiological conditions, we have assayed mammalian bile for nucleotides and assessed whether hepatoma and cholangiocarcinoma cell lines are capable of nucleotide release. Bile samples were collected from human, rat, and pig donors and assayed for nucleotide concentrations by luminometry. ATP, ADP, and AMP were present in bile from each species, and the average total nucleotide concentration in human bile was 5.21 +/- 0.91 microM (n = 16). In an in vitro model of HTC rat hepatoma cells or Mz-ChA-1 cholangiocarcinoma cells on a superfused column, nucleotides were present in the effluent from each cell type. Addition of alpha, beta-methyleneadenosine 5'-diphosphate (50 microM) to inhibit 5'-nucleotidase activity increased AMP concentrations two- to threefold. Exposure to forskolin (100 microM) or ionomycin (2 microM) stimulated nucleotide release from cholangiocarcinoma but not hepatoma cells. These studies indicate that adenosine nucleotides are present in bile in concentrations sufficient to activate purinergic receptors. Purinergic receptor activation by local nucleotide release might constitute an autocrine and/or paracrine mechanism for modulation of biliary secretion.

Ursodeoxycholate increases cytosolic calcium concentration and activates Cl- currents in a biliary cell line.

BACKGROUND & AIMS: Ursodeoxycholate (UDC) stimulates a bicarbonate-rich choleresis, but the cellular mechanisms involved are not fully established. Because ductular secretion also increases biliary HCO3-concentration, the purpose of this study was to evaluate whether UDC has direct effects on duct cells by measuring intracellular calcium concentration ([Ca2+]i) and membrane Cl- permeability in Mz-ChA-1 human cholangiocarcinoma cells. METHODS: Intracellular calcium levels were measured using fura-2 fluorescence. Membrane Cl- permeability was assessed in subconfluent monolayers using 125I efflux and in individuals cells using whole-cell patch clamp techniques. RESULTS: Exposure to UDC (2.5 mmol/L) increased [Ca2+]i from 180 +/- 25 to 639 +/- 84 nmol/L due to release of Ca2+ from intracellular stores and stimulated 125I efflux approximately threefold above basal levels. Exposure to extracellular (1.25 mmol/L) or intracellular (100 mumol/L) UDC activated currents carried by Cl- ions; intracellular UDC increased current density from 4.7 +/- 1.3 to 32.5 +/- 8.8 pA/pF. UDC-stimulated currents were inhibited by chelation of intracellular calcium. CONCLUSIONS: UDC in pharmacological concentrations increases [Ca2+]i and stimulates Cl- efflux through opening of Cl- channels in biliary cells. We speculate that UDC could increase bile flow by direct stimulation of ductular secretion and may be of therapeutic benefit to patients with cystic fibrosis who have impaired adenosine 3',5'-cyclic monophosphate-dependent biliary secretion.

Adenosine triphosphate activates ion permeabilities in biliary epithelial cells.

BACKGROUND/AIMS: The biliary epithelium contributes to bile formation through absorption and secretion of fluid and electrolytes. The effects of extracellular nucleotides on membrane ion transport were assessed in isolated bile duct cells from rats and Mz-ChA-1 cells from a human cholangiocarcinoma. METHODS: The rates of efflux of 125I and 86Rb were used to assess membrane Cl- and K+ permeabilities, respectively. Patch clamp recordings of whole cell currents were used to evaluate the properties of adenosine triphosphate (ATP)-activated currents. RESULTS: Purinergic receptor agonists ATP and uridine triphosphate stimulated 125I and 86Rb efflux about twofold above basal levels. The effects were reproduced by a nonhydrolyzable analogue of ATP (adenosine 5'-O-[3-thiophosphate]) and were unaffected by an adenosine receptor blocker xanthine amine congener. 125I efflux was also stimulated by adenosine and its receptor agonists 5'-N-ethylcarboxamidoadenosine, N6-(2-phenylisopropyl)adenosine; these effects were inhibited by xanthine amine congener, suggesting a separate adenosine receptor. ATP, adenosine 5'-O-(3-thiophosphate), and uridine triphosphate each stimulated release of Ca2+ from intracellular stores, whereas adenosine had no effect. In whole cell recordings of Mz-ChA-1 cells, ATP activated an early transient outward current consistent with a K+ conductance and a later, sustained inward current consistent with a Cl- conductance. CONCLUSIONS: Biliary cells possess at least two classes of nucleotide receptors that modulate membrane ion permeability through Ca(2+)-dependent and -independent pathways, and ATP may be involved in the regulation of biliary secretion.