Colocalization of GLUT2 glucose transporter, sodium/glucose cotransporter, and gamma-glutamyl transpeptidase in rat kidney with double-peroxidase immunocytochemistry.

Glucose is reabsorbed from the glomerular filtrate in the proximal segment of the renal tubule in two stages. The first stage is uphill transport across the brush border membrane by Na(+)-glucose cotransport and the second stage is downhill transport across the basolateral membrane by facilitated diffusion. Genes for both a renal Na(+)-glucose cotransporter (SGLT1) and a renal facilitated glucose transporter (GLUT2) have been cloned and sequenced. To examine whether SGLT1 and GLUT2 colocalize to the same tubular epithelial cells in rat kidney, double-immunoperoxidase studies with dual chromogens and paraformaldehyde perfusion-fixed frozen sections of rat kidney were performed. Antipeptide antisera were prepared against rat GLUT2 (amino acids 510-522) and rabbit SGLT1 (amino acids 402-420). Proximal tubules were identified immunocytochemically with an antiserum raised against a synthetic peptide corresponding to the 21 amino acids at the COOH-terminal of the heavy chain of rat gamma-glutamyl transpeptidase, which is a proximal tubule-specific enzyme. The anti-GLUT2 antiserum strongly stained the basolateral membrane of 46% of cortical tubules, whereas the SGLT1 antiserum stained the brush border of 56% of the cortical tubules. The gamma-glutamyl transpeptidase antiserum also stained the brush border of 51% of the cortical tubules. GLUT2 and SGLT1 colocalized to 40% of cortical epithelium, but 16% of cortical epithelial cells were immunopositive for brush border SGLT1 and immunonegative for basolateral GLUT2. These gamma-glutamyl transpeptidase staining results suggest that at least 50% of the tubules in the cortex are proximal tubules and that SGLT1 and GLUT2 colocalize to most proximal tubules. The fact that SGLT1 antiserum immunoreacted with tubules unreactive to the GLUT2 antiserum suggests that either the SGLT1 epitope is conserved on a related brush border protein or that there is another GLUT transporter responsible for the exit of sugar from these proximal tubule cells

Progress in Eddy Current Modeling via the Boundary Element Method

For the past several years, we have been developing an eddy current model, using the boundary element method (BEM). Last year, in particular, a BEM algorithm based on the Hertz potential approach was found and shown to be effective in dealing with complex part geometry, while keeping the computational resource requirement to a minimum [1–3]. This paper concerns a further extension of the model to include cracks

Puerperal Superior Sagittal Sinus Thrombosis and Pulmonary Embolism: A Case Report and Review of Literature

Superior sagittal sinus thrombosis is a rare and often misdiagnosed disorder. Its occurrence with pulmonary embolism (PE) is much rarer, more so when it occurs in the setting of puerperium. Although cerebral sagittal sinus thrombosis can occur at any time during life, women are particularly vulnerable before delivery and during the puerperal period due to the hypercoagulable state of pregnancy. We report a case which describes the challenging clinical course of a young woman who developed superior sagittal sinus thrombosis and PE during puerperium.Keywords: Embolism, puerperium, pulmonary, sagittal sinus, thrombosi

Multiple sclerosis susceptibility alleles in African Americans.

Multiple sclerosis (MS) is an autoimmune demyelinating disease characterized by complex genetics and multifaceted gene-environment interactions. Compared to whites, African Americans have a lower risk for developing MS, but African Americans with MS have a greater risk of disability. These differences between African Americans and whites may represent differences in genetic susceptibility and/or environmental factors. SNPs from 12 candidate genes have recently been identified and validated with MS risk in white populations. We performed a replication study using 918 cases and 656 unrelated controls to test whether these candidate genes are also associated with MS risk in African Americans. CD6, CLEC16a, EVI5, GPC5, and TYK2 contained SNPs that are associated with MS risk in the African American data set. EVI5 showed the strongest association outside the major histocompatibility complex (rs10735781, OR=1.233, 95% CI=1.06-1.43, P-value=0.006). In addition, RGS1 seems to affect age of onset whereas TNFRSF1A seems to be associated with disease progression. None of the tested variants showed results that were statistically inconsistent with the effects established in whites. The results are consistent with shared disease genetic mechanisms among individuals of European and African ancestry

Linking the oceans to public health: current efforts and future directions

This is the final version of the article. Available from BioMed Central via the DOI in this recordWe review the major linkages between the oceans and public health, focusing on exposures and potential health effects due to anthropogenic and natural factors including: harmful algal blooms, microbes, and chemical pollutants in the oceans; consumption of seafood; and flooding events. We summarize briefly the current state of knowledge about public health effects and their economic consequences; and we discuss priorities for future research.We find that:* There are numerous connections between the oceans, human activities, and human health that result in both positive and negative exposures and health effects (risks and benefits); and the study of these connections comprises a new interdisciplinary area, "oceans and human health."* The state of present knowledge about the linkages between oceans and public health varies. Some risks, such as the acute health effects caused by toxins associated with shellfish poisoning and red tide, are relatively well understood. Other risks, such as those posed by chronic exposure to many anthropogenic chemicals, pathogens, and naturally occurring toxins in coastal waters, are less well quantified. Even where there is a good understanding of the mechanism for health effects, good epidemiological data are often lacking. Solid data on economic and social consequences of these linkages are also lacking in most cases.* The design of management measures to address these risks must take into account the complexities of human response to warnings and other guidance, and the economic tradeoffs among different risks and benefits. Future research in oceans and human health to address public health risks associated with marine pathogens and toxins, and with marine dimensions of global change, should include epidemiological, behavioral, and economic components to ensure that resulting management measures incorporate effective economic and risk/benefit tradeoffs.Funding was provided in part by the NSF-NIEHS Oceans Centers at Woods Hole, University of Hawaii, University of Miami, and University of Washington, and the NOAA Oceans and Human Health Initiative Centers of Excellent in Charleston, Seattle and Milwaukee, the National Center for Environmental Health (NCEH) of the Centers for Disease Control and Prevention (CDC), and the WHOI Marine Policy Center. Grant numbers are: NIEHS P50 ES012742 and NSF OCE-043072 (HLKP, RJG, PH); NSF OCE-0432368 and NIEHS P50 ES12736 (LEF); NIEHS P50 ES012762 and NSF OCE-0434087 (EMF, AT, LRY); NSF OCE04-32479 and NIEHS P50 ES012740 (BAW

Survival rights for children: What are the national and global barriers?

Most children die in low and middle-income countries as a result of structural injustice, and while it may not be possible to prove causality between economic policies and breaches of rights, it is possible to audit policy and practices through the lens of human rights. Child health advocates need to highlight the fact that technical interventions, in the absence of action on structural injustice, cannot address the fundamental causes of poor health. It could even be said that we collude in the fallacy that injustices can be solved with technical solutions. The determinants of health, water, food, shelter, primary education and health care are minimum core human rights, are the rights required for survival and today should be available to every child (and their families) in all countries. However, there are national and global limitations on the ability of countries to determine policy and generate the revenue required for core human rights. The authors conducted a review of the literature on the main leakages from government revenues in low and middle-income countries to identify obstacles to children enjoying their right to survival. Based on the review the authors suggest a framework for an upstream audit that can be carried out, country by country, to identify barriers in terms of policies and the generation, allocation and utilisation of revenues. This audit involves systematically screening the policies and practices of the main actors: national governments, high-income country partners, multinational enterprises, and international organisations, for possible influence on the realisation of human rights. Human rights advocates and child health associations could lead or commission an upstream audit on behalf of children in their countries in order to identify the fundamental causes and real remedies

Variation in antibiotic treatment for diabetic patients with serious foot infections: A retrospective observational study

<p>Abstract</p> <p>Background</p> <p>Diabetic foot infections are common, serious, and diverse. There is uncertainty about optimal antibiotic treatment, and probably substantial variation in practice. Our aim was to document whether this is the case: A finding that would raise questions about the comparative cost-effectiveness of different regimens and also open the possibility of examining costs and outcomes to determine which should be preferred.</p> <p>Methods</p> <p>We used the Veterans Health Administration (VA) Diabetes Epidemiology Cohorts (DEpiC) database to conduct a retrospective observational study of hospitalized patients with diabetic foot infections. DEpiC contains computerized VA and Medicare patient-level data for VA patients with diabetes since 1998, including demographics, ICD-9-CM diagnostic codes, antibiotics prescribed, and VA facility. We identified all patients with ICD-9-CM codes for cellulitis/abscess of the foot and then sub-grouped them according to whether they had cellulitis/abscess plus codes for gangrene, osteomyelitis, skin ulcer, or none of these. For each facility, we determined: 1) The proportion of patients treated with an antibiotic and the initial route of administration; 2) The first antibiotic regimen prescribed for each patient, defined as treatment with the same antibiotic, or combination of antibiotics, for at least 5 continuous days; and 3) The antibacterial spectrum of the first regimen.</p> <p>Results</p> <p>We identified 3,792 patients with cellulitis/abscess of the foot either alone (16.4%), or with ulcer (32.6%), osteomyelitis (19.0%) or gangrene (32.0%). Antibiotics were prescribed for 98.9%. At least 5 continuous days of treatment with an unchanged regimen of one or more antibiotics was prescribed for 59.3%. The means and (ranges) across facilities of the three most common regimens were: 16.4%, (22.8%); 15.7%, (36.1%); and 10.8%, (50.5%). The range of variation across facilities proved substantially greater than that across the different categories of foot infection. We found similar variation in the spectrum of the antibiotic regimen.</p> <p>Conclusions</p> <p>The large variations in regimen appear to reflect differences in facility practice styles rather than case mix. It is unlikely that all regimens are equally cost-effective. Our methods make possible evaluation of many regimens across many facilities, and can be applied in further studies to determine which antibiotic regimens should be preferred.</p