Interleukin-6 potentiates FcεRI-induced PGD2 biosynthesis and induces VEGF from human in situ-matured skin mast cells

Background

Interleukin-6 is a gp130 utilizing cytokine that is consistently associated with allergic diseases like asthma and urticaria in humans where mast cells are known to play a critical role. However, the role of IL-6 in allergic disease in not known. IL-6 was reported to enhance degranulation of in vitro-derived mast cells, but the effect of IL-6 on mediator release from human in situ-matured tissue-isolated mast cells had not been reported.

Chemical Evidence for the Separation of Gγ and Aγ Globin Chains by Polyacrylamide Gel Electrophoresis in Urea and Triton X-100

Polyacrylamide gel electrophoresis in urea and Triton X-100 of a hemolysate from human fetal red blood cells produces four major protein bands: α, β, and 2 γ globin chains. We have verified that the latter two are the ^Gγ and ^Aγ globin chains which have respectively glycine or alanine at position 136. After incorporation of either [³H] alanine or [³H] glycine into newly synthesized globin each y chain was isolated by preparative electrophoresis. The chains were cleaved with cyanogen bromide at methionines 55 and 133, then subjected to automated sequencing, and the residues from each sequencer turn counted. Glycine incorporation was detected for the third turn (position 136) of the ^Gγ chain and alanine for the ^Aγ Substantial metabolic conversion of [³H] glycine to serine and proline was also noted.     

Immunological Mechanisms Mediating Hantavirus Persistence in Rodent Reservoirs

Hantaviruses, similar to several emerging zoonotic viruses, persistently infect their natural reservoir hosts, without causing overt signs of disease. Spillover to incidental human hosts results in morbidity and mortality mediated by excessive proinflammatory and cellular immune responses. The mechanisms mediating the persistence of hantaviruses and the absence of clinical symptoms in rodent reservoirs are only starting to be uncovered. Recent studies indicate that during hantavirus infection, proinflammatory and antiviral responses are reduced and regulatory responses are elevated at sites of increased virus replication in rodents. The recent discovery of structural and non-structural proteins that suppress type I interferon responses in humans suggests that immune responses in rodent hosts could be mediated directly by the virus. Alternatively, several host factors, including sex steroids, glucocorticoids, and genetic factors, are reported to alter host susceptibility and may contribute to persistence of hantaviruses in rodents. Humans and reservoir hosts differ in infection outcomes and in immune responses to hantavirus infection; thus, understanding the mechanisms mediating viral persistence and the absence of disease in rodents may provide insight into the prevention and treatment of disease in humans. Consideration of the coevolutionary mechanisms mediating hantaviral persistence and rodent host survival is providing insight into the mechanisms by which zoonotic viruses have remained in the environment for millions of years and continue to be transmitted to humans.Hantaviruses are negative sense, enveloped RNA viruses (family: Bunyaviridae) that are comprised of three RNA segments, designated small (S), medium (M), and large (L), which encode the viral nucleocapsid (N), envelope glycoproteins (G_N and G_C), and an RNA polymerase (Pol), respectively. More than 50 hantaviruses have been found worldwide [1]. Each hantavirus appears to have coevolved with a specific rodent or insectivore host as similar phylogenetic trees are produced from virus and host mitochondrial gene sequences [2]. Spillover to humans causes hemorrhagic fever with renal syndrome (HFRS) or hantavirus cardiopulmonary syndrome (HCPS), depending on the virus [3]–[5]. Although symptoms vary, a common feature of both HFRS and HCPS is increased permeability of the vasculature and mononuclear infiltration [4]. Pathogenesis of HRFS and HCPS in humans is hypothesized to be mediated by excessive proinflammatory and CD8+ T cell responses (​).

Table 1

Summary of Immune Responses in Humans during Hantavirus Infection.

Chemical Evidence for the Separation of Gy and AY Globin Chains by Polyacrylamide Gel Electrophoresis in Urea and Triton X-100

Polyacrylamide gel electrophoresis in urea and Triton X-100 of a hemolysate from human fetal red blood cells produces four major protein bands: α, β, and 2 γ globin chains. We have verified that the latter two are the ^Gγ and ^Aγ globin chains which have respectively glycine or alanine at position 136. After incorporation of either [³H] alanine or [³H] glycine into newly synthesized globin each y chain was isolated by preparative electrophoresis. The chains were cleaved with cyanogen bromide at methionines 55 and 133, then subjected to automated sequencing, and the residues from each sequencer turn counted. Glycine incor-poration was detected for the third turn (position 136) of the ^Gγ chain and alanine for the ^Aγ. Substantial metabolic conversion of [³H] glycine to serine and proline was also noted.     

Effect of isotretinoin (Netlook) on the testis of adult male albino rats and the role of omega 3 supplementation: A histological and biochemical study

Isotretinoin is an oral retinoid which used across the world in the treatment of patients especially adolescents complaining of acne. In spite of the prevalent clinical use of isotretinoin, the generation of oxidative stress with the affection of several organs leads to the limitation and restriction of its use. Omega‐3 (N‐3) is an essential polyunsaturated fatty acid (PUFAs) with powerful antioxidant properties. The aim of this study was to investigate the histological and biochemical changes occurring in the rat testis following isotretinoin intake and to evaluate the role of omega 3 supplementation in ameliorating testicular damage. Thirty adult male albino rats were divided equally into three groups. Group I is the control group, group II received isotretinoin (1.0 mg/kg/day) dissolved in distilled water and group III received isotretinoin (1.0 mg/kg/day) and omega 3 (400 mg/kg/day). Testis samples were collected and processed for light and electron microscopic examination. The blood samples were collected for biochemical assessments. Results indicated that isotretinoin caused histological changes in all stages of spermatogenesis and alterations of the hormonal assay. These changes in the rat testis which were corrected by omega 3 use.     

Deciphering the enzymatic target of a new family of antischistosomal agents bearing a quinazoline scaffold using complementary computational tools

Abstract

A previous phenotypic screening campaign led to the identification of a quinazoline derivative with promising in vitro activity against Schistosoma mansoni. Follow-up studies of the antischistosomal potential of this candidate are presented here. The in vivo studies in a S. mansoni mouse model show a significant reduction of total worms and a complete disappearance of immature eggs when administered concomitantly with praziquantel in comparison with the administration of praziquantel alone. This fact is of utmost importance because eggs are responsible for the pathology and transmission of the disease. Subsequently, the chemical optimisation of the structure in order to improve the metabolic stability of the parent compound was carried out leading to derivatives with improved drug-like properties. Additionally, the putative target of this new class of antischistosomal compounds was envisaged by using computational tools and the binding mode to the target enzyme, aldose reductase, was proposed.     

Comparative physiological study of the wild type and the small colony variant of Pseudomonas aeruginosa 20265 under controlled growth conditions

Small-colony variants (SCVs) of Pseudomonas aeruginosa are often found in chronically infected airways of patients suffering from cystic fibrosis. These slow-growing morphological variants have been associated with persistent and antibiotic-resistant infections. Nevertheless, the behavior of SCVs under varied availability of O₂ and iron, two key variables relevant to the lung environment of CF patients and pathogenicity of P. aeruginosa, has not been systematically studied so far. In this work, the effects of O₂ and iron were comparatively studied for a CF P. aeruginosa wild type (WT) strain and its SCV phenotype in a real-time controlled cultivation system. Significant differences in the behavior of these strains were observed and quantified. In general, SCV exhibited a higher fitness than the WT toward aerobic conditions. Under iron rich condition, and despite less release of total extracellular proteins, absence of flagellin and lower siderophore production, the SCV cells grown at fully aerobic conditions showed a higher specific growth rate and a significantly higher cytotoxicity in comparison with the WT cells. The strains behaved also differently towards iron limitation. The phenomena of limited O₂ transfer from the gas to the liquid phase and enhancement of formation of virulence factors under conditions of iron limitation were much more profound in the SCV culture than in the WT culture. These results have important implications for better understanding the pathogenicity of P. aeruginosa and its small-colony variants.     

Bioreactor controlled by PI algorithm and operated with a perfusion chamber to support endothelial cell survival and proliferation

This paper reports the optimization of a perfusion bioreactor system previously reported by us (Chouinard et al., 2009). The implementation of a proportional-integral (PI) controller algorithm to control oxygen concentration and pH is presented and discussed. P and I values used by the controller were first estimated using a First-Order-Plus-Dead-Time (FOPDT, Matlab Simulink) and then tuned manually. A new gas exchanger design compatible with the PI controller was introduced and validated to decrease interaction between the injected gases and overall inertia of the system. The gas exchanger was used to adjust both pH and dissolved oxygen (DO) concentration. This new bioreactor system allowed real-time PI control over pH and DO concentration at different flow rates (from 2 to 70 mL min(-1)). Cell viability and proliferation were investigated to validate the updated bioreactor design and performance.