Equity implications for sanitation from recent health and nutrition evidence.

Recent evidence points to the possible underestimation of the health and nutrition impact of sanitation. Community sanitation coverage may first need to reach thresholds in the order of 60% or higher, to optimize health and nutrition gains. Increasing coverage of sanitation to levels below 60% of community coverage may not result in substantial gains. For example, moving Indonesia from 60% to 100% improved sanitation coverage could significantly reduce diarrhoea in children under 5 years old (by an estimated 24% reduction in odds ratio for child diarrhoea morbidity) with gains split equally by reaching underserved communities and the unserved within communities. We review the implications of these results across three levels of program implementation - from micro level approaches (that support communities to achieve open defecation-free status), to meso level (sub-national implementation) to macro level approaches for the national enabling environment and the global push to the Sustainable Development Goals. We found significant equity implications and recommend that future studies focus more extensively on community coverage levels and verified community open defecation free status rather than household access alone. Sanitation practitioners may consider developing phased approaches to improving water, sanitation and hygiene in communities while prioritizing the unserved or underserved.

RGS8 protein is distributed in dendrites and cell body of cerebellar Purkinje cell.

RGS8 was originally identified as an RGS protein specifically expressed in neuronally differentiated P19 cells. We generated a polyclonal antibody specific to rat RGS8 using a synthetic peptide. When nonneural cells (DDT1MF2, CHO, and NIH3T3) transfected with rat RGS8 cDNA were immuno-stained with this antibody, the RGS8 protein was mainly detected in the nuclei. Since RGS8 mRNA was exclusively expressed in Purkinje cells of the cerebellum in the rat brain, we further examined the cellular distribution of the RGS8 protein in Purkinje cells using cultured cerebellar cells and tissue sections of the cerebellum. The RGS8 protein was excluded from the nuclei and distributed in the cell body and dendrites, but not in the axons of Purkinje cells. These results demonstrate the presence of a mechanism controlling the distribution of RGS8 protein in cerebellar Purkinje cells.

Molecular cloning and characterization of Xenopus RGS5.

We identified six genes that encode putative RGS proteins (XRGSI-VI) in developing Xenopus embryos using PCR amplification with degenerate primers corresponding to the conserved region (RGS domain) of known RGS proteins. RT-PCR analysis revealed that mRNAs of these XRGSs are differentially expressed during embryogenesis. At stage 1, only XRGSII mRNA was detected. On the other hand, expression of XRGSVI mRNA increased apparently at stage 14 and expression of three of other XRGS (III, IV, V) elevated between stage 25 and 40. To further characterize XRGS proteins expressed in Xenopus embryos, we isolated a cDNA clone for XRGSIII. Based on determined nucleotide sequence, XRGSIII was considered as a Xenopus homologue of mammalian RGS5 (XRGS5). Genetic analysis using the pheromone response halo assay showed that expression of XRGS5 inhibits yeast response to alpha-factor, suggesting that XRGS5 negatively regulates the G-protein-mediated signaling pathway in developing Xenopus embryos.

RGS7 and RGS8 differentially accelerate G protein-mediated modulation of K+ currents.

The recently discovered family of RGS (regulators of G protein signaling) proteins acts as GTPase activating proteins which bind to alpha subunits of heterotrimeric G proteins. We previously showed that a brain-specific RGS, RGS8 speeds up the activation and deactivation kinetics of the G protein-coupled inward rectifier K+ channel (GIRK) upon receptor stimulation (Saitoh, O., Kubo, Y., Miyatani, Y., Asano, T., and Nakata, H. (1997) Nature 390, 525-529). Here we report the isolation of a full-length rat cDNA of another brain-specific RGS, RGS7. In situ hybridization study revealed that RGS7 mRNA is predominantly expressed in Golgi cells within granule cell layer of cerebellar cortex. We observed that RGS7 recombinant protein binds preferentially to Galphao, Galphai3, and Galphaz. When co-expressed with GIRK1/2 in Xenopus oocytes, RGS7 and RGS8 differentially accelerate G protein-mediated modulation of GIRK. RGS7 clearly accelerated activation of GIRK current similarly with RGS8 but the acceleration effect of deactivation was significantly weaker than that of RGS8. These acceleration properties of RGS proteins may play important roles in the rapid regulation of neuronal excitability and the cellular responses to short-lived stimulations.

Protective effect of a vasopressin-1 selective antagonist, OPC-21268, against ethanol-induced damage of the rat gastric wall.

Since endogenous vasopressin has been reported to be an aggressor in the gastric mucosa and a vasoconstrictor in the gastric circulation, we investigated the gastric cytoprotective effects of OPC-21268, a newly developed, nonpeptide, orally active vasopressin-1 receptor antagonist, on ethanol-induced gastric injury in rats. The rats were treated with OPC-21268 or placebo 2 hr before ethanol administration, and the gastric mucosa was evaluated macroscopically for ulcer damage, and histologically for gastric mucosal injury. Gastric mucosal blood flow, erythrocyte volume, and erythrocyte velocity were also measured in groups given saline, ethanol alone, and ethanol after OPC-21268. To investigate the role of systemic or locally secreted vasopressin, we measured plasma and tissue (gastric mucosa) vasopressin concentrations after ethanol or vehicle administration. Prophylactic OPC-21268 treatment improved the gastric ulcer score in a dose-dependent manner, and histological examination demonstrated that the drug significantly ameliorated the gastric injury induced by ethanol. The hemodynamic values obtained in the OPC-21268-treated and ethanol-treated group were similar to those in the saline control group, but values were significantly (P < 0.05) higher for gastric mucosal blood flow and erythrocyte velocity and lower for erythrocyte volume compared to the group given ethanol alone. Plasma vasopressin concentrations were not significantly different in the control group and at 15, 30, and 60 min after administration of ethanol. However, ethanol administration caused a threefold increase in gastric tissue vasopressin level (P < 0.05) compared to the control group. These results suggested that OPC-21268 relieved congestive hyperemia in the gastric mucosa and ameliorated the mucosal injury caused by ethanol, probably as a result of inhibition of vasopressin-mediated actions on the stomach. The vasopressin involved was probably generated locally in the gastric mucosa after ethanol administration.

Renal and hormonal responses to repeated treatment with enalapril in non-azotemic cirrhosis with ascites.

Since a single dose of the angiotensin-converting enzyme inhibitor enalapril was shown to cause natriuresis in cirrhosis in a previous study, we investigated whether repeated doses of this substance would sustain a favorable renal effect in cirrhosis. Ten milligrams of enalapril maleate were administered once a day for 8 days to ten patients with non-azotemic cirrhosis and ascites. Enalapril reduced blood pressure significantly at 4 to 12 h (systolic blood pressure) and 2, 6, and 8 h (diastolic blood pressure) on day 2, compared to pretreatment (day 0) values, but this depressor effect decreased on day 8. No change in heart rate could be detected. Enalapril significantly suppressed serum angiotensin-converting enzyme activity and plasma aldosterone concentration (p < 0.001 to 0.01), which were elevated prior to treatment, with pretreatment values of 25.8 +/- 1.8 IU/l for serum angiotensin-converting enzyme activity and 241 +/- 67 pg/ml for plasma aldosterone concentration. This drug caused a 12 to 24% increase (p < 0.05 to 0.01) in mean daily urinary volume and a 40 to 54% increase (p < 0.001 to 0.01) in mean daily urinary sodium excretion from the respective pretreatment baselines during the 8-day period. Creatinine clearance was improved (p < 0.05) by the treatment, with mean improvement values from 24 to 34% above the pretreatment value of 47.4 +/- 4.3 ml/min.(ABSTRACT TRUNCATED AT 250 WORDS)

Discharge pattern differences between cat interpositus and dentate neurons during isometric lever pressing.

Single-cell recordings in the cat during isometric muscle contraction with stepwise force development revealed that interpositus neurons tended to fire tonically with a maintained force level, whereas dentate neurons tended to fire rather phasically according to the rate of force transition.