Epidemiological and laboratory investigations of outbreaks of diarrhoea in rural South India: implications for control of disease

Two epidemics of acute, watery diarrhoea in villages in North Arcot district, India, were investigated. The attack rates were 10.03 and 15.53 per 100 population, the median duration was 5 days and enteric pathogens were present in 56.8% and 60.3% of specimens from the two villages, but no predominant pathogen was identified. Examination of stools from a 20% age-stratified random sample of the population of one of the villages after the epidemic found 22.9% of asymptomatic subjects excreted bacterial enteric pathogens. Despite the high background of enteric pathogen carriage, the isolation rates for shigellae, enteropathogenic Escherichia coli and Shiga-toxin producing E. coli were significantly higher (P < 0.001, P < 0.02, P < 0.05) during the epidemic. The epidemics may have been caused by faecal contamination of well water following rain. Point-of-use techniques for water disinfection may be most effective for preventing such outbreaks, but further research into the development of appropriate technology is required

Interactions of linear dicationic molecules with lipid A: structural requisites for optimal binding affinity

The structural determinants of the binding affinity of linear dicationic molecules toward lipid A have been examined with respect to the distance between the terminal cationic functions, the basicity, and the type of cationic moieties using a series of spermidine derivatives and pentamidine analogs by fluorescence spectroscopic methods. The presence of two terminal cationic groups corresponds to enhanced affinity. A distinct sigmoidal relationship between the intercationic distance and affinity was observed with a sharp increase at 11 Å, levelling off at about 13 Å. The basicity (pK) and nature of the cationic functions are poor correlates of binding potency, since molecules bearing primary amino, imidazolino, or guanido termini are equipotent. The interaction of pentamidine, a bisamidine drug, with lipid A, characterized in considerable detail employing the putative intermolecular excimerization of the drug, suggests a stoichiometry of 1:1 in the resultant complex. The binding is driven almost exclusively by electrostatic forces, and is dependent on the ionization states of both lipid A and the drug. Under conditions when lipid A is highly disaggregated, pentamidine binds specifically to bis-phosphoryl- but not to monophosphoryl-lipid A indicating that both phosphate groups of lipid A are necessary for electrostatic interactions by the terminal amidininium groups of the drug. Based on these data, a structural model is proposed for the pentamidine-lipid A complex, which may be of value in designing endotoxin antagonists from first principles

Competing orders in PZN-xPT and PMN-xPT relaxor ferroelectrics

Neutron and x-ray scattering studies on relaxor ferroelectric systems Pb(Zn$_{1/3}$Nb$_{2/3}$)O$_3$ (PZN), Pb(Mg$_{1/3}$Nb$_{2/3}$)O$_3$ (PMN), and their solid solutions with PbTiO$_3$ (PT) have shown that inhomogeneities and disorder play important roles in the materials properties. Although a long-range polar order can be established at low temperature - sometimes with the help of an external electric field; short-range local structures called the ``polar nano-regions'' (PNR) still persist. Both the bulk structure and the PNR have been studied in details. The coexistence and competition of long- and short-range polar orders and how they affect the structural and dynamical properties of relaxor materials are discussed.Comment: Article submitted for JPSJ Special Topics (Novel States of Matter Induced by Frustration

Gadd45α activity is the principal effector of Shigella mitochondria-dependent epithelial cell death in vitro and ex vivo

Modulation of death is a pathogen strategy to establish residence and promote survival in host cells and tissues. Shigella spp. are human pathogens that invade colonic mucosa, where they provoke lesions caused by their ability to manipulate the host cell responses. Shigella spp. induce various types of cell death in different cell populations. However, they are equally able to protect host cells from death. Here, we have investigated on the molecular mechanisms and cell effectors governing the balance between survival and death in epithelial cells infected with Shigella. To explore these aspects, we have exploited both, the HeLa cell invasion assay and a novel ex vivo human colon organ culture model of infection that mimics natural conditions of shigellosis. Our results definitely show that Shigella induces a rapid intrinsic apoptosis of infected cells, via mitochondrial depolarization and the ensuing caspase-9 activation. Moreover, for the first time we identify the eukaryotic stress-response factor growth arrest and DNA damage 45α as a key player in the induction of the apoptotic process elicited by Shigella in epithelial cells, revealing an unexplored role of this molecule in the course of infections sustained by invasive pathogens

Alteration of colonic absorption by long-chain unsaturated fatty acids: influence of hydroxylation and degree of unsaturation

Unabsorbed dietary unsaturated fatty acids may cause diarrhea in patients with steatorrhea, but their ability to cause colonic fluid secretion is not known. The present study investigated the effect of several dietary long-chain unsaturated fatty acids on colonic absorption and morphology in the rat colon in vivo. The fatty acids tested induced concentration-dependent net water secretion. The ability of these fatty acids to induce net water secretion varied as follows: linolenic acid (18:3) > linoleic acid (18:2), ricinoleic acid (18:1 OH) > oleic acid (18:1), palmitoleic acid (16:1). Net absorption of sodium and chloride were decreased in fatty acid perfusions. Mucosal activity of sodium potassium adenosine triphosphate and adenyl cyclase were not significantly altered by fatty acids. Epithelial cell damage was noted and correlated with the ability of the fatty acid to induce fluid secretion. Unsaturated fatty acids induce epithelial cell damage and fluid secretion in the colon, their effect being related to the degree of unsaturation