Pericytes modulate endothelial inflammatory response during bacterial infection.

Pericytes are located around blood vessels, in close contact with endothelial cells. We discovered that pericytes dampen pro-inflammatory endothelial cell responses. Endothelial cells co-cultured with pericytes had markedly reduced expression of adhesion molecules (PECAM-1 and ICAM-1) and proinflammatory cytokines (CCL-2 and IL-6) in response to bacterial stimuli (Brucella ovis, Listeria monocytogenes, or Escherichia coli lipopolysaccharide). Pericyte-depleted mice intraperitoneally inoculated with either B. ovis, a stealthy pathogen that does not trigger detectable inflammation, or Listeria monocytogenes, developed peritonitis. Further, during Citrobacter rodentium infection, pericyte-depleted mice developed severe intestinal inflammation, which was not evident in control mice. The anti-inflammatory effect of pericytes required connexin 43, as either chemical inhibition or silencing of connexin 43 abrogated pericyte-mediated suppression of endothelial inflammatory responses. Our results define a mechanism by which pericytes modulate inflammation during infection, which shifts our understanding of pericyte biology: from a structural cell to a pro-active player in modulating inflammation. IMPORTANCE: A previously unknown mechanism by which pericytes modulate inflammation was discovered. The absence of pericytes or blocking interaction between pericytes and endothelium through connexin 43 results in stronger inflammation, which shifts our understanding of pericyte biology, from a structural cell to a player in controlling inflammation.

Parasitic profiling of Japanese quails (Coturnix japonica) on two farms with conventional production system in the Amazon region / Perfil parasitário de codornas (Coturnix japonica) em duas granjas com sistema convencional de produção na Amazônia

The health monitoring and management systems of coturniculture can be deemed to be in a developmental phase when compared to the poultry industry. Studies regarding taxonomy and parasitic biology in quails (Coturnix japonica) has not been well conducted in Brazil. Most of the information is available from the autopsy case reports, in many ways the parasitic fauna of quails is still unknown. The aim of this study was to conduct a parasitological research in quails in order to contribute to ameliorate this situation. 31 quails, which were 12 months old, were used for the study. Their carcasses and viscera were sent to the Laboratory of Entomology and Tropical Diseases, INPA, Manaus/AM. The circulatory, nervous, respiratory, digestive and reproductive systems of these were studied separately. No blood parasites were found, however, nine species of endoparasites were registered which were distributed among the classes Cestoda, Nematoda and Protozoa. The helminths were distributed in the duodenum, jejunum, ileum, cecum and oviduct. The cecum was found to be the most parasitized organ and contained a wide range of parasites having three species of protozoa and three species of nematodes. Six morphotypes of Eutrichomastix globosus were recorded, and some morphotypes were hyperparasitized with sporangia Sphaerita sp. in the cytoplasm. A large number of parasites were recorded in this study, as well as the protozoan Blastocystis hominis was first being observed for quail.(AU)

A coturnicultura conta com um monitoramento sanitário e sistemas de manejo ainda em desenvolvimento quando comparado à avicultura industrial. Pesquisas de taxonomia e biologia parasitárias em codornas (Coturnix japonica) são pouco realizadas no Brasil, sendo a maioria das informações disponíveis referentes a relatos de caso em achados de necropsia, portanto, em muitos aspectos a fauna parasitária de codornas é ainda desconhecida. Este trabalho teve por objetivo realizar uma pesquisa parasitológica em codornas em fim de postura. Para pesquisa foram disponibilizadas 31 codornas com idades de 12 meses. As carcaças e suas vísceras foram encaminhadas ao Laboratório de Entomologia e Doenças Tropicais INPA, Manaus/AM. Foram estudados separadamente os sistemas circulatórios, nervoso, respiratório, digestivo e reprodutivo. Das 31 codornas examinadas nenhuma apresentou hemoparasitos, contudo, foram registradas nove espécies de endoparasitos distribuídas entre as classes Cestoda, Nematoda e protozoários. Os helmintos distribuíam-se pelo duodeno, jejuno, íleo, cecos e oviduto. O ceco foi o órgão mais parasitado e com maior diversidade de parasitas, sendo três espécies de protozoários e três de nematóides. Foram registrados seis morfotipos de Eutrichomastix globosus, sendo que, alguns morfótipos estavam hiperparasitados com esporângio Sphaerita sp. no citoplasma. Uma grande variedade de parasitos foi registrada nesta pesquisa, bem como, o protozoário Blastocystis hominis pela primeira vez sendo descrito para codornas.(AU)

A vital role for voltage-dependent potassium channels in dopamine transporter-mediated 6-hydroxydopamine neurotoxicity.

6-Hydroxydopamine (6-OHDA), a neurotoxic substrate of the dopamine transporter (DAT), is widely used in Parkinson's disease models. However, the molecular mechanisms underlying 6-OHDA's selectivity for dopamine neurons and the injurious sequelae that it triggers are not well understood. We tested whether ectopic expression of DAT induces sensitivity to 6-OHDA in non-dopaminergic rat cortical neurons and evaluated the contribution of voltage-dependent potassium channel (Kv)-dependent apoptosis to the toxicity of this compound in rat cortical and midbrain dopamine neurons. Cortical neurons expressing DAT accumulated dopamine and were highly vulnerable to 6-OHDA. Pharmacological inhibition of DAT completely blocked this toxicity. We also observed a p38-dependent Kv current surge in DAT-expressing cortical neurons exposed to 6-OHDA, and p38 antagonists and Kv channel blockers were neuroprotective in this model. Thus, DAT-mediated uptake of 6-OHDA recruited the oxidant-induced Kv channel dependent cell death pathway present in cortical neurons. Finally, we report that 6-OHDA also increased Kv currents in cultured midbrain dopamine neurons and this toxicity was blocked with Kv channel antagonists. We conclude that native DAT expression accounts for the dopamine neuron specific toxicity of 6-OHDA. Following uptake, 6-OHDA triggers the oxidant-associated Kv channel-dependent cell death pathway that is conserved in non-dopaminergic cortical neurons and midbrain dopamine neurons.

Metabolic effects of fructose supplementation in diabetic individuals.

With new diabetes diet guidelines recommending high carbohydrate intake, questions arise regarding acceptable intake of simple sugars. Whereas several short-term studies report flattened glycemic and insulin response to fructose consumption, some also report increased serum triglyceride levels. Few studies examine the effects of long-term fructose consumption. We evaluated the long-term safety of fructose consumption in 14 middle-aged men with diabetes. Subjects followed an ambulatory high-fiber high-carbohydrate control diet at home for 8 wk, entered the hospital for 5 days on this diet, and spent the next 7 days on a similar diet supplemented with 50-60 g fructose. They continued the fructose diet at home for 23 wk, then resumed a postcontrol diet for an additional 16 wk. In the hospital, glycemic control improved significantly on the fructose-supplemented diet compared with the hospital control diet. In the ambulatory setting, no significant differences in plasma glucose, glycohemoglobin, serum cholesterol, triglycerides, lactate, or urate occurred between precontrol, fructose, or postcontrol periods. Fasting serum lactate was higher by 0.5 meq/L during the ambulatory fructose period than during the precontrol period. Body weight also increased during the ambulatory fructose period due to higher calorie intake. Adherence to fructose consumption was excellent and improved adherence to carbohydrate and fat recommendations. If total calorie intake is controlled to promote desirable body weight, crystalline fructose used with a high-carbohydrate high-fiber low-fat diet appears to be safe and acceptable for diabetic individuals.