Measurement of the Bovine Pancreatic Trypsin Inhibitors by Radioimmunoassay

Bovine pancreas contains two polypeptide trypsin inhibitors that are not homologous and differ in their inhibitory activity towards chymotrypsin, kallikrein, elastase, and other serine proteinases. The Kunitz inhibitor and the Kazal inhibitor are present in approximately equimolar concentrations in bovine pancreatic tissue, yet only the Kazal inhibitor is detectable in the pancreatic juice. The Kazal inhibitor has been named the pancreatic secretory trypsin inhibitor, PSTI because its concentration in the pancreatic juice parallels that of the exocrine secretory proteins. The Kunitz inhibitor is considered the intracellular inhibitor, however, no direct information is available concerning the intracellular localization of these inhibitors in the pancreas. The preparation of /sup 125/I-labeled derivatives of Kazal and Kunitz inhibitors by the lactoperoxidase method and a radioimmunoassay for each inhibitor are described. (auth

Multivariable regression analysis in Schistosoma mansoni-infected individuals in the Sudan reveals unique immunoepidemiological profiles in uninfected, egg+ and non-egg+ infected individuals

Background: In the Sudan, Schistosoma mansoni infections are a major cause of morbidity in schoolaged children and infection rates are associated with available clean water sources. During infection, immune responses pass through a Th1 followed by Th2 and Treg phases and patterns can relate to different stages of infection or immunity. Methodology: This retrospective study evaluated immunoepidemiological aspects in 234 individuals(range 4–85 years old) from Kassala and Khartoum states in 2011. Systemic immune profiles(cytokines and immunoglobulins) and epidemiological parameters were surveyed in n = 110 persons presenting patent S. mansoni infections (egg+), n = 63 individuals positive for S. mansoni via PCR in sera but egg negative (SmPCR+) and n = 61 people who were infection-free (Sm uninf). Immunoepidemiological findings were further investigated using two binary multivariable regression analysis. Principal Findings: Nearly all egg+ individuals had no access to latrines and over 90% obtained water via the canal stemming from the Atbara River. With regards to age, infection and an egg+ status was linked to young and adolescent groups. In terms of immunology, S. mansoni infection per se was strongly associated with increased SEA-specific IgG4 but not IgE levels. IL-6, IL-13 and IL-10 were significantly elevated in patently-infected individuals and positively correlated with egg load. In contrast, IL-2 and IL-1β were significantly lower in SmPCR+ individuals when compared to Sm uninf and egg+ groups which was further confirmed during multivariate regression analysis. Conclusions/Significance: Schistosomiasis remains an important public health problem in the Sudan with a high number of patent individuals. In addition, SmPCR diagnostics revealed another cohort of infected individuals with a unique immunological profile and provides an avenue for future studies on non-patent infection states. Future studies should investigate the downstream signalling pathways/mechanisms of IL-2 and IL-1β as potential diagnostic markers in order to distinguish patent from non-patent individuals

Hyperreactive onchocerciasis is characterized by a combination of Th17-Th2 immune responses and reduced regulatory T cells

<div><p>Clinical manifestations in onchocerciasis range from generalized onchocerciasis (GEO) to the rare but severe hyperreactive (HO)/sowda form. Since disease pathogenesis is associated with host inflammatory reactions, we investigated whether Th17 responses could be related to aggravated pathology in HO. Using flow cytometry, filarial-specific cytokine responses and PCR arrays, we compared the immune cell profiles, including Th subsets, in individuals presenting the two polar forms of infection and endemic normals (EN). In addition to elevated frequencies of memory CD4⁺ T cells, individuals with HO showed accentuated Th17 and Th2 profiles but decreased CD4⁺CD25^hiFoxp3⁺ regulatory T cells. These profiles included increased IL-17A⁺, IL-4⁺, RORC2⁺ and GATA3⁺CD4⁺ T cell populations. Flow cytometry data was further confirmed using a PCR array since Th17-related genes (IL-17 family members, IL-6, IL-1β and IL-22) and Th2-related (IL-4, IL-13, STAT6) genes were all significantly up-regulated in HO individuals. In addition, stronger <i>Onchocerca volvulus</i>-specific Th2 responses, especially IL-13, were observed <i>in vitro</i> in hyperreactive individuals when compared to GEO or EN groups. This study provides initial evidence that elevated frequencies of Th17 and Th2 cells form part of the immune network instigating the development of severe onchocerciasis.</p></div

Experimental investigation of possible cardiotoxic effects on the offspring of rats treated with high doses of fenoterol.

Peer Reviewe