Co-administration of rIpaB domain of Shigella with rGroEL of S. Typhi enhances the immune responses and protective efficacy against Shigella infection

Shigella species cause severe bacillary dysentery in humans and are associated with high morbidity and mortality. The Invasion plasmid antigen (IpaB) protein, which is conserved across all Shigella spp., induces macrophage cell death and is required to invade host cells. The present study evaluates the immunogenicity and protective efficacy of the recombinant (r) domain region of IpaB (rIpaB) of S. flexneri. rIpaB was administered either alone or was co-administered with the rGroEL (heat shock protein 60) protein from S. Typhi as an adjuvant in a mouse model of intranasal immunization. The IpaB domain region (37 kDa) of S. flexneri was amplified from an invasion plasmid, cloned, expressed in BL21 Escherichia coli cells and purified. Immunization with the rIpaB domain alone stimulated both humoral and cell-mediated immune responses. Furthermore, robust antibody (IgG, IgA) and T-cell responses were induced when the rIpaB domain was co-administered with rGroEL. Antibody isotyping revealed higher IgG1 and IgG2a antibody titers and increased interferon-gamma (IFN-γ) secretion in the co-administered group. Immunization of mice with the rIpaB domain alone protected 60%–70% of the mice from lethal infection by S. flexneri, S. boydii and S. sonnei, whereas co-administration with rGroEL increased the protective efficacy to 80%–85%. Organ burden and histopathological studies also revealed a significant reduction in lung infection in the co-immunized mice compared with mice immunized with the rIpaB domain alone. This study emphasizes that the co-administration of the rIpaB domain and rGroEL protein improves immune responses in mice and increases protective efficacy against Shigella infection. This is also the first report to evaluate the potential of the GroEL (Hsp 60) protein of S. Typhi as an adjuvant molecule, thereby overcoming the need for commercial adjuvants.     

Surface Structure Characterization of Aspergillus fumigatus Conidia Mutated in the Melanin Synthesis Pathway and Their Human Cellular Immune Response

In Aspergillus fumigatus, the conidial surface contains dihydroxynaphthalene (DHN)-melanin. Six-clustered gene products have been identified that mediate sequential catalysis of DHN-melanin biosynthesis. Melanin thus produced is known to be a virulence factor, protecting the fungus from the host defense mechanisms. In the present study, individual deletion of the genes involved in the initial three steps of melanin biosynthesis resulted in an altered conidial surface with masked surface rodlet layer, leaky cell wall allowing the deposition of proteins on the cell surface and exposing the otherwise-masked cell wall polysaccharides at the surface. Melanin as such was immunologically inert; however, deletion mutant conidia with modified surfaces could activate human dendritic cells and the subsequent cytokine production in contrast to the wild-type conidia. Cell surface defects were rectified in the conidia mutated in downstream melanin biosynthetic pathway, and maximum immune inertness was observed upon synthesis of vermelone onward. These observations suggest that although melanin as such is an immunologically inert material, it confers virulence by facilitating proper formation of the A. fumigatus conidial surface.     

Common Hematological Disorders in Children

It is common for primary care physicians to be faced with children with hematological disorders in everyday practice. The article seeks to provide realistic information for the first-contact physician in handling common hematological diseases in children. Practical step-wise approach to understanding and investigating anemia and bleeding disorders is illustrated. Requirement of iron in normal children and management of iron deficiency anemia (IDA) and thalassemia is explained. The gold standard for IDA continues to be ferrous sulphate which has good bioavailability and is inexpensive. There is emerging concept of delayed clamping of umbilical cord at birth, particularly in regions with widespread IDA, to augment iron stores in infancy. Typical case scenarios of children with immune thrombocytopenia (ITP) and hemophilia are provided to facilitate the understanding of management in day to day practice. The vital role of the medical practitioner in shared care of patients with acute lymphoblastic leukemia and febrile neutropenia is emphasized. A risk based treatment algorithm for febrile neutropenia is provided.     

Imaging-based algorithmic approach to gallbladder wall thickening

Gallbladder(GB) wall thickening is a frequent finding caused by a spectrum of conditions. It is observed in many extracholecystic as well as intrinsic GB conditions. GB wall thickening can either be diffuse or focal. Diffuse wall thickening is a secondary occurrence in both extrinsic and intrinsic pathologies of GB, whereas, focal wall thickening is mostly associated with intrinsic GB pathologies. In the absence of specific clinical features, accurate etiological diagnosis can be challenging. The survival rate in GB carcinoma(GBC) can be improved if it is diagnosed at an early stage, especially when the tumor is confined to the wall. The pattern of wall thickening in GBC is often confused with benign diseases, especially chronic cholecystitis, xanthogranulomatous cholecystitis, and adenomyomatosis. Early recognition and differentiation of these conditions can improve the prognosis. In this minireview, the authors describe the patterns of abnormalities on various imaging modalities(conventional as well as advanced) for the diagnosis of GB wall thickening. This paper also illustrates an algorithmic approach for the etiological diagnosis of GB wall thickening and suggests a formatted reporting for GB wall abnormalities.     

Pharmacist involvement to improve patient outcomes in lower gastrointestinal surgery: a prospective before and after study

International Journal of Clinical Pharmacy - Background Enhanced recovery pathways were first introduced in the UK in 2002 (Enhanced Recovery Partnership Programme in Delivering enhanced...