Hemopressin, a hemoglobin fragment, dilates the rat systemic vascular bed through release of nitric oxide

The present study was undertaken to investigate the effects of intravenous (i.v.) administration of rat hemopressin (rHP), 30-1000 microg/kg, on systemic arterial pressure (SAP), cardiac output (CO) and systemic vascular resistance (SVR) in the anesthetized rat. Bolus i.v. injections of rHP produced mild decreases in SAP that were dose-dependent. Since CO was not altered, the decreases in SAP reflect reductions in SVR. The systemic vasodilator response to rHP was not subject to tachyphylaxis. The systemic vasodilator response to rHP was abolished by L-nitro-arginine methylester (L-NAME) but was not altered by meclofenamate. In addition, rHP lacked direct contractile and relaxant activity on isolated rat aortic rings (AA) and pulmonary arterial rings (PA). The present data suggest rHP dilates the rat systemic vascular bed through the endogenous release of nitric oxide (NO) independent of the formation of cyclooxygenase products including prostacyclin. It is possible rHP acts as an endogenous vasodilator substance to regulate local blood flow during clinical states of altered red cell turnover, microvascular disease and hemolysis.     

Rethinking leptin and insulin action: therapeutic opportunities for diabetes

Leptin is an adipocyte-derived hormone that primarily acts in the hypothalamus and plays a key role in the regulation of food intake, body weight, energy expenditure and neuroendocrine function. Leptin has direct peripheral effects on several tissues, and it may be independently involved in insulin secretion and action besides its effects on body weight regulation. Basal plasma leptin and insulin concentrations correlate with each other. Insulin and glucose appear to increase leptin secretion. In turn, leptin increases peripheral insulin sensitivity while decreasing insulin secretion from pancreatic beta cells. Leptin increases skeletal muscle glucose uptake and oxidation, and suppresses hepatic glucose output. Effects of leptin on lipid metabolism might reduce lipotoxicity and therefore contribute to the improvement of hepatic, skeletal and whole body insulin sensitivity. Leptin is the first adipokine used in the treatment of hypoleptinemic clinical disorders. Although leptin therapy has limited success in common obesity, it has impressive effects in congenital leptin deficiency, lipoatrophic diabetes and syndromes of severe insulin resistance. Leptin has been reported to ameliorate hyperinsulinemia and diabetes in the clinical setting of congenital leptin deficiency. It also improves hyperglycemia, insulin resistance, hyperinsulinemia, dyslipidemia and hepatic steatosis in lipoatrophic diabetes. These promising results warrant clinical trials to test the hypothesis that leptin alone or with classical antidiabetic agents may potentially be beneficial in the treatment of hypoleptinemic non-obese individuals with glucose intolerance and diabetes. This review summarizes the clinical applications of leptin, particularly emphasizing the effects of leptin on glucose homeostasis.     

Conformational Transition of Membrane-Associated Terminally Acylated HIV-1 Nef

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Sand fly (Diptera: Psychodidae) distribution in the endemic and non‐endemic foci of visceral leishmaniasis in northwestern Iran

An entomological study was conducted from June to September, 2010 in rural regions of Azarbayjan‐e‐sharqi, Azarbayjan‐e‐qarbi, and Ardabil provinces in northwestern Iran to determine sand fly fauna, diversity, and distribution in different habitats and altitudes using both sticky papers and light traps. Geographical distribution of sand flies and the similarity of populations in different locations were analyzed ecologically based on the Shannon‐Wiener Index and Jacard Coefficient, respectively. A total of 3,982 specimens was collected and sixteen species recorded. They belonged to the genera Phlebotomus [subgenus Phlebotomus (P. papatasi), Paraphlebotomus (P. sergenti, P. mongolensis, P. caucasicus, P. jacusieli), Larroussius (P. major s.l., P. tobbi, P. perfiliewi transcaucasicus, P. kandelakii) and Adlerius (P. halepensis, P. brevis, P. longiductus, P. balcanicus)], and Sergentomyia [subgenus Sergentomyia (S. sintoni, S. dentata and S. theodori)]. P. papatasi was the predominant species in all the locations except Bileh Savar, Macu, and Meshkin Shahr, followed by P. perfiliewi transcaucasicus and P. kandelakii. The latter species were caught from different habitats and altitudes with higher frequency than other species of the subgenus Larroussius. The lowest abundance belonged to P. jacusieli. The predominant species of subgenus Adlerius was P. halepensis. Data analysis showed that Meshkin Shahr and Bileh Savar had high and low diversities of sand fly distribution, respectively. Meshkin Shahr and Sarab districts had the highest similarity. Both are located in the foothills of Sabalan Mountain, with high diversity and richness.     

Neutron reflectometry and QCM-D study of the interaction of cellulases with films of amorphous cellulose

Improving the efficiency of enzymatic hydrolysis of cellulose is one of the key technological hurdles to reduce the cost of producing ethanol and other transportation fuels from lignocellulosic material. A better understanding of how soluble enzymes interact with insoluble cellulose will aid in the design of more efficient enzyme systems. We report a study involving neutron reflectometry (NR) and quartz crystal microbalance with dissipation monitoring (QCM-D) of the interaction of a fungal enzyme extract ( T. viride ) and an endoglucanse from A. niger with amorphous cellulose films. The use of amorphous cellulose is motivated by that the fact that several biomass pretreatments currently under investigation disrupt the native crystalline structure of cellulose and increase the amorphous content. NR reveals the profile of water through the film at nanometer resolution and is highly sensitive to interfacial roughness, whereas QCM-D provides changes in mass and film stiffness. NR can be performed using either H(2)O- or D(2)O-based aqueous reservoirs. NR measurement of swelling of a cellulose film in D(2)O and in H(2)O revealed that D/H exchange on the cellulose chains must be taken into account when a D(2)O-based reservoir is used. The results also show that cellulose films swell slightly more in D(2)O than in H(2)O. Regarding enzymatic digestion, at 20 °C in H(2)O buffer the T. viride cocktail rapidly digested the entire film, initially roughening the surface, followed by penetration and activity throughout the bulk of the film. In contrast, over the same time period, the endoglucanase was active mainly at the surface of the film and did not increase the surface roughness.     

Protein profiling of anastomosed facial nerve treated with mesenchymal stromal cells

Background aimsThe types of proteins released from mesenchymal stromal cells (MSC) are still unclear. Our aim was to compare apoptosis scores and the expression of myelin-associated glycoprotein (MAG), myelin basic protein (MBP), neural cell adhesion molecule (NCAM)-1,matrix metalloproteinase (MMP)-1A, tissue inhibitor of metalloproteinase (TIMP)-1, TIMP-1/MMP-1A ratio, nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), neurotrophin (NT)-3, NT-4, glial cell-derived neurotropic factor (GDNF), leukemia inhibitory factor (LIF), basic fibroblast growth factor (FGF)-2, insulin-like growth factor (IGF)-1, platelet-derived growth factor (PDGF)-α and transforming growth factor (TGF)-β1 in anastomosed facial nerves that had been treated with or without MSC.MethodsIn seven rats, the buccal branch of the right facial nerve was transected, anastomosed and treated with MSC (anastomosed + MSC group). The left buccal branch was anastomosed only (anastomosed-only group). The left mandibular branch served as an intact nerve group. On days 18–20, the distal segments of the branches were examined in terms of expression of the mentioned proteins and apoptosis scores using polymerase chain reaction (PCR) and terminal deoxynucleotidyl transferase-mediated digoxigenin-UTP nick end labeling (TUNEL) assays.ResultsMSC application significantly increased CNTF, PDGF-α, LIF, TGF-β1, BDNF and NT-3 expression (P < 0.05). MAG expression slightly decreased whereas NCAM-1, MMP-1A and FGF-2 slightly increased(P > 0.05). Changes in other proteins and apoptosis scores were not significant.ConclusionsThese results suggest that MSC increases expression of CNTF, PDGF-α, LIF,TGF-β1, BDNF and NT-3. MAG, NCAM-1, MMP-1A and FGF-2 expressions were slightly changed in this stage of nerve regeneration. The comparison of apoptotic activity was not conclusive. Overall, it appears that MSC might have differential effects on the mentioned tissue-related proteins and trophic/growth factors.     

A summary of the evidence for the change in European distribution of phlebotomine sand flies (Diptera: Psychodidae) of public health importance

The phlebotomine sand flies (Diptera: Psychodidae, Phlebotominae) are vectors of several infectious pathogens. The presence of a sand fly vector is considered to be a risk factor for the emergence of leishmaniasis in temperate Europe. Hence, the occurrence of phlebotomine sand flies and any changes in their distribution is important in determining the potential change in distribution of leishmaniasis in Europe. Therefore, published evidence for a changing distribution of the important phlebotomine sand fly vectors of leishmaniasis and phlebovirus infection in Europe is reviewed. This paper presents evidence of an increasing risk of establishment by sand fly species, especially for the Atlantic Coast and inland parts of Germany, Switzerland, and Austria. In addition to detection in potentially appropriate areas, the findings show areas of potential future establishment of the species. The most important and urgent necessity within the community of entomologists working on phlebotomines is the need to record the extremes of distribution of each species and obtain data on their regional presence/absence along with increased sharing of the data throughout European projects.