217 research outputs found

    Glomerular thrombosis in pregnancy: Role of the L-arginine-nitric oxide pathway

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    Glomerular thrombosis in pregnancy: Role of the L-arginine-nitric oxide pathway. E. coli endotoxin (LPS) and certain cytokines induce synthesis of nitric oxide (NO) from L-arginine, but also promote endothelial injury and intravascular coagulation. NO has vasodilator and antithrombogenic properties. We investigated the relationship between the L-arginine-NO pathway and the susceptibility to LPS-induced glomerular thrombosis in pregnancy. Pregnant rats were given either 0.15 or 0.75 mg/kg/body wt of LPS intraperitoneally. In rats given 0.15 mg/kg/body wt of LPS urinary NO2−/NO3− (end products of NO) increased 200% (P < 0.05), plasma L-arginine did not change, and glomerular thrombosis was minimal. Pregnant rats given 0.75 mg/kg/body wt of LPS developed glomerular thrombosis in 75% of glomeruli (P < 0.05). In these rats plasma L-arginine fell 98%, from 53 ± 4 to 1.4 ± 0.9 mmol/liter (P < 0.05) but the urinary NO2−/NO3− did not increase. Oral administration of L-arginine but not D-arginine increased urinary NO2−/NO3− by 250% and averted glomerular thrombosis in these rats (P < 0.05). Virgin rats given 0.75 mg/kg/body wt of LPS did not contract glomerular thrombosis. In these rats plasma L-arginine decreased only 40% while urinary NO2−/NO3− concomitantly increased over 200% (P < 0.05). Plasma endothelin-1 increased only in rats exhibiting glomerular thrombosis. Thus, limited maternal reserve capability for NO synthesis may underlie, at least in part, the susceptibility for glomerular thrombosis in pregnancy

    The Rose Bengal Test in Human Brucellosis: A Neglected Test for the Diagnosis of a Neglected Disease

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    Brucellosis is a highly contagious zoonosis affecting livestock and human beings. The human disease lacks pathognomonic symptoms and laboratory tests are essential for its diagnosis. However, most tests are difficult to implement in the areas and countries were brucellosis is endemic. Here, we compared the simple and cheap Rose Bengal Test (RBT) with serum agglutination, Coombs, competitive ELISA, Brucellacapt, lateral flow immunochromatography for IgM and IgG detection and immunoprecipitation with Brucella proteins. We tested 208 sera from patients with brucellosis proved by bacteriological isolation, 20 contacts with no brucellosis, and 1559 sera of persons with no recent contact or brucellosis symptoms. RBT was highly sensitive in acute and long evolution brucellosis cases and this related to its ability to detect IgM, IgG and IgA, to the absence of prozones, and to the agglutinating activity of blocking IgA at the pH of the test. RBT was also highly specific in the sera of persons with no contact with Brucella. No test in this study outperformed RBT, and none was fully satisfactory in distinguishing contacts from infected patients. When modified to test serum dilutions, a diagnostic titer >4 in RBT resulted in 87.4% sensitivity (infected patients) and 100% specificity (contacts). We discuss the limitations of serological tests in the diagnosis of human brucellosis, particularly in the more chronic forms, and conclude that simplicity and affordability of RBT make it close to the ideal test for small and understaffed hospitals and laboratories

    Selective IgA Deficiency

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    Immunoglobulin A (IgA) deficiency is the most common primary immunodeficiency defined as decreased serum level of IgA in the presence of normal levels of other immunoglobulin isotypes. Most individuals with IgA deficiency are asymptomatic and identified coincidentally. However, some patients may present with recurrent infections of the respiratory and gastrointestinal tracts, allergic disorders, and autoimmune manifestations. Although IgA is the most abundant antibody isotype produced in the body, its functions are not clearly understood. Subclass IgA1 in monomeric form is mainly found in the blood circulation, whereas subclass IgA2 in dimeric form is the dominant immunoglobulin in mucosal secretions. Secretory IgA appears to have prime importance in immune exclusion of pathogenic microorganisms and maintenance of intestinal homeostasis. Despite this critical role, there may be some compensatory mechanisms that would prevent disease manifestations in some IgA-deficient individuals. In IgA deficiency, a maturation defect in B cells to produce IgA is commonly observed. Alterations in transmembrane activator and calcium modulator and cyclophilin ligand interactor gene appear to act as disease-modifying mutations in both IgA deficiency and common variable immunodeficiency, two diseases which probably lie in the same spectrum. Certain major histocompatibility complex haplotypes have been associated with susceptibility to IgA deficiency. The genetic basis of IgA deficiency remains to be clarified. Better understanding of the production and function of IgA is essential in elucidating the disease mechanism in IgA deficiency
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