Health gains from solar water disinfection (SODIS): evaluation of a water quality intervention in Yaoundé, Cameroon.

In developing countries, the burden of diarrhoea is still enormous. One way to reduce transmission of pathogens is by water quality interventions. Solar water disinfection (SODIS) is a low-cost and simple method to improve drinking water quality on household level. This paper evaluates the implementation of SODIS in slum areas of Yaoundé, Cameroon. Promoters trained 2,911 households in the use of SODIS. Two surveys with randomly selected households were conducted before (N=2,193) and after (N=783) the intervention. Using a questionnaire, interviewers collected information on the health status of children under five, on liquid consumption, hygiene and other issues. Prior to the intervention, diarrhoea prevalence amounted to 34.3% among children. After the intervention, it remained stable in the control group (31.8%) but dropped to 22.8% in the intervention group. Households fully complying with the intervention exhibited even less diarrhoea prevalence (18.3%) and diarrhoea risk could be reduced by 42.5%. Multivariate analyses revealed that the intervention effects are also observed when other diarrhoea risk factors, such as hygiene and cleanliness of household surroundings, are considered. According to the data, adoption of the method was associated with marital status. Findings suggest health benefits from SODIS use. Further promotional activities in low-income settings are recommended.

Transcellular water transport in hepatobiliary secretion and role of aquaporins in liver.

In the context of the osmotic model of bile formation, we used isolated rat hepatocyte couplets and performed volume measurements by video image analysis to analyze the transport of water between the bile canalicular lumen, liver cells and the surrounding bathing medium. Increasing bath osmolarity by the addition of sucrose led to shrinkage of cells that preceded shrinkage of the canalicular lumen by approx. 1 sec. Thermodynamic modeling of water transport across the basolateral and apical cell membranes and across a paracellular pathway (tight junctions) revealed high hydraulic water permeabilities of both cell membranes of approx. 3*10(-4) cm*sec(-1)*(osmol/kg)(-1) indicating transcellular water flux between bathing medium and bile. Tight junctions exhibited low water permeability but allowed for electrolyte permeation that enables canalicular spaces to shrink below van't Hoff equilibrium during the osmotic maneuver. The results are discussed with respect to the role of different types of membrane aquaporins being expressed in hepatocytes.

Reactive oxygen species facilitate the insulin-dependent inhibition of glucagon-induced glucose production in the isolated perfused rat liver.

Recent studies indicate that intracellular insulin signalling involves the formation of reactive oxygen species (ROS) by NADPH oxidases (NOX). ROS inhibit intracellular protein tyrosin phosphatases whereby phosphoprotein signalling is enhanced and prolonged. We used the isolated perfused rat liver and detected ROS formation by measuring the surface fluorescence at wavelengths specific for the intracellular ROS sensor carboxydihydrodichlorofluorescein. Insulin (2, 5, 20 nM) induced low level ROS formation that was abolished by the NOX inhibitor diphenyleneiodonium chloride (4 microM). Studying insulin-dependent inhibition of glucagon-activated glucose production showed that melatonin (50 microM), used as ROS scavenger, inhibited ROS formation and blunted the effect of insulin on glucose production. The data support the general notion that hormone-dependent ROS formation modifies intracellular signal transduction.

Water disinfection and hygiene behaviour in an urban slum in Kenya: impact on childhood diarrhoea and influence of beliefs.

In this research project, we studied factors that presumably affect the incidence of diarrhoea among young children in urban slums in developing countries: consumption of safe drinks, hygiene behaviour, cleanliness of household surroundings and the quality of raw water. Beliefs concerning the causes of diarrhoea were also related to health-improving behaviour, namely the application of the water-treatment method SODIS (solar water disinfection) and hygiene behaviour. We conducted a survey in a shanty town in Nairobi, Kenya. Field workers interviewed 500 households. Analysis with regression models revealed that two out of the four postulated factors were significant: children have a lower risk of contracting diarrhoea when they consume high percentages of safe drinks and live in households with good hygiene. As regards beliefs, we found that biomedical knowledge of children's diarrhoea as well as the perceived social norm for treating water was associated with the use of SODIS and good hygiene.

Melatonin modulates acid/base transport in human pancreatic carcinoma cells.

Melatonin was found to improve pancreatic organ function in diseased animals. To study whether pancreatic bicarbonate secretion is stimulated by melatonin, investigations were done in two human ductal pancreatic adenocarcinoma cell lines MIA PaCa-2 (MIA) and PANC-1 (PANC). Using the fluorescence pH-sensor BCECF-AM, we monitored melatonin effects on basal intracellular pH (pH(i)), and on pH(i) recovery after intracellular alkalinization produced by the removal of extracellular HCO(3) (-)/CO(2). Exposure to 1 microM melatonin for 24 hrs and presence of the indoleamine during the experiment increases the basal pH(i). Moreover, pHi recovery and HCO(3) (-) secretion are facilitated after the alkaline load. These findings are in line with the observed increase in mRNA expression of the Na(+)/HCO(3) (-)-cotransporter SLC4A4b for the uptake and the Cl(-)/HCO(3) (-)-exchanger SLC26A6 for the secretion of HCO(3) (-). The reduction in Na(+)/H(+)- exchanger SLC9A1 mRNA would favor pH(i) recovery after alkalinization, but it does not explain the initial increase in pHi. This controversial effect and the requirement for continuous presence of melatonin throughout the experiment suggest that nontranscriptional signalling may contribute to the effects of melatonin on acid/base movements. In summary, we show a stimulatory effect of melatonin on bicarbonate secretion in the pancreatic cancer cell lines which may help to prevent duodenal damage.

The effects of local anesthetics on bile flow, potassium equilibrium and oxygen consumption in the perfused rat liver.

Amide local anesthetics mainly undergo hepatic metabolism. Specific applications, such as catheter application for long-term pain therapy, may result in large plasma concentrations. As it is unknown whether local anesthetics influence liver function, we examined the influence of lidocaine, bupivacaine, and ropivacaine in concentrations of 1 and 10 microg/mL on the metabolic activity of the perfused rat liver. At the large concentrations, all three local anesthetics caused an immediate increase of oxygen consumption. Bupivacaine and ropivacaine also transiently reduced potassium release. All drugs increased bile flow; this choleretic effect was also significant for bupivacaine and lidocaine in smaller concentrations. In the smaller concentration, only lidocaine significantly increased oxygen consumption. No significant changes in hepatic venous pH were observed. The results show that acute administration of all three local anesthetics results in significant changes of functional variables of the liver. The observed effects appear to result from mitochondrial uncoupling, uptake of the drugs, biliary secretion of their metabolites, and from inhibition of potassium channels. The data provide no evidence that these acute changes may result in enduring postoperative disturbances of liver function, such as cholestasis or jaundice.

Correction of CFTR malfunction and stimulation of Ca-activated Cl channels restore HCO3- secretion in cystic fibrosis bile ductular cells.

In view of the occurrence of hepatobiliary disorders in cystic fibrosis (CF) this study addresses the role of the cystic fibrosis transmembrane conductance regulator (CFTR) and of Ca(2+)-activated Cl(-) channels in promoting HCO3- secretion in bile ductular cells. Human cholangiocytes were isolated from control livers and from 1 patient with CF (DeltaF508/G542X mutations). Single channel and whole cell currents were analyzed by patch clamp techniques, and HCO3- secretion was determined by fluorometric analysis of the rate of recovery of intracellular pH following alkaline loading. In control cholangiocytes, both cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) catalytic subunit, activated CFTR Cl(-) channels that exhibited a nonrectifying conductance of 8 pS and appeared in clusters. Activation of Cl(-) current by cAMP was associated with an increase in the rate of HCO3- secretion. The basal rate of HCO3- secretion was lower in CF than in control cholangiocytes. In both control and CF cholangiocytes, raising intracellular Ca(2+) concentrations with ionomycin led to a parallel activation of Cl(-) current and HCO3- secretion. Consistent with reports that premature stop codon mutations (class I; e.g., G542X) can be read over by treatment with aminoglycoside antibiotics, exposure of CF cholangiocytes to gentamicin restored activation by cAMP of Cl(-) current and HCO3- secretion. The observation that activation of Ca(2+)-dependent Cl(-) channels can substitute for cystic fibrosis transmembrane conductance regulator (CFTR) in supporting HCO3- secretion and the efficacy of gentamicin in restoring CFTR function and HCO3- secretion in class I mutations are of potential clinical interest.

Bile Formation: a Concerted Action of Membrane Transporters in Hepatocytes and Cholangiocytes.

A large number of membrane transport mechanisms in hepatocytes and cholangiocytes serves for the secretion of bile acids, various other organic anions, organic cations, lipids, and electrolytes. After their functional characterization, some of these mechanisms' individual transport molecules are now identified, allowing better understanding of inherited and acquired disorders of bile formation.