Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0338671 (Steroids)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The glycoprotein corticosteroid-binding globulin (CBG) migrates as doublet bands in PAGE and SDS-PAGE, and as numerous bands in isoelectric focusing (IEF). This study deals with the origin of this heterogeneity. Desialation of rat CBG with neuraminidase does not abolish the doublet in either PAGE or SDS-PAGE, indicating that the doublet does not arise as a result of differences in sialic acid residues. Treatment of the separated upper and lower variants of native CBG with N-glycosidase F (PNGase-F) shows a differential pattern of deglycosylation over time indicating either differences in the number, type, or location of sugars attached to each of the variants. Rate of deglycosylation is quicker and more extensive for the upper variant when compared to the lower variant. PNGase-F treatment of 1% SDS-denatured CBG does not abolish the CBG doublet seen in SDS-PAGE, indicating that there is variation in the protein moiety. Sugars could not be detected on PNGase-F treated CBG using either wheat germ aglutinin horse radish peroxidase conjugate, concavilin-A HRP conjugate, or the digoxigenin glycan detection system. While the results clearly show differences in glycosylation between the CBG variants, differences in the protein moiety may also occur to give rise to the heterogeneity seen in CBG. The latter is supported by the fact that desialated CBG migrates as two bands in IEF. Migration in IEF is based solely on charge, and since only sialic acid residues are charged in N-linked glycosylation, any heterogeneity seen for the desialated glycoprotein must reside within the protein moiety itself. The presence of O-glycosylation containing an N-acetylgalactosamine with a beta 1-3 linkage to galactose could not be demonstrated using O-glycosidase. N-terminal blockage could not account for the variation, as both the upper and lower variants were able to be sequenced resulting in identical sequences for the first 13 amino acids. The data presented supports the hypothesis that the differences in the sugar as well as the protein moiety are responsible for the heterogeneity seen for CBG.
Steroids 1995 Nov
PMID:Studies on the role of glycosylation in the origin of the electrophoretic variants for rat corticosteroid-binding globulin. 858 98

Acute hypercytokinaemia represents an imbalance of pro-inflammatory and anti-inflammatory cytokines, and is believed to be responsible for the development of acute respiratory distress syndrome and multiple organ failure in severe cases of avian (H5N1) influenza. Although neuraminidase inhibitors are effective in treating avian influenza, especially if given within 48 h of infection, it is harder to prevent the resultant hypercytokinaemia from developing if the patient does not seek timely medical assistance. Steroids have been used for many decades in a wide variety of inflammatory conditions in which hypercytokinaemia plays a role, such as sepsis and viral infections, including severe acquired respiratory syndromes and avian influenza. However, to date, the results have been mixed. Part of the reason for the discrepancies might be the lack of understanding that low doses are required to prevent mortality in cases of adrenal insufficiency. Adrenal insufficiency, as defined in the sepsis/shock literature, is a plasma cortisol rise of at least 9 microg dl(-1) following a 250 microg dose of adrenocorticotropin hormone (ACTH), or reaching a plasma cortisol concentration of >25 microg dl(-1) following a 1-2 microg dose of ACTH. In addition, in the case of hypercytokinaemia induced by potent viruses, such as H5N1, systemic inflammation-induced, acquired glucocorticoid resistance is likely to be present. Adrenal insufficiency can be overcome, however, with prolonged (7-10 or more days) supraphysiological steroid treatment at a sufficiently high dose to address the excess activation of NF-kappaB, but low enough to avoid immune suppression. This is a much lower dose than has been typically used to treat avian influenza patients. Although steroids cannot be used as a monotherapy in the treatment of avian influenza, there might be a potential role for their use as an adjunct treatment to antiviral therapy if appropriate dosages can be determined. In this paper, likely mechanisms of adrenal insufficiency are discussed, drawing from a broad background of literature sources.
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PMID:A rationale for using steroids in the treatment of severe cases of H5N1 avian influenza. 1757 50

Laninamivir, a neuraminidase inhibitor (NAI), has been used for the treatment and prophylaxis of influenza A/B. To date, pneumonia has not been reported as an adverse effect of NAIs. Here, we report the first 2 cases of drug-induced pneumonitis after the administration of laninamivir octanoate (LO), a pro-drug of laninamivir. Case 1 reports a 20-year-old healthy woman presenting with LO-induced pneumonitis so severe that it was necessary for endotracheal intubation and administration of mechanical ventilator support. Steroids were used for the treatment of pneumonitis and rapid improvement was observed. Case 2 reports a 35-year-old healthy woman presenting with less severe LO-induced pneumonitis that improved without any treatment. In both cases, drug-induced lymphocyte stimulation tests (DLSTs) were positive. In the bronchoalveolar lavage (BAL) fluid, the proportion of eosinophils to lymphocytes was higher in Case 1. Conversely, the proportion of lymphocytes to eosinophils was higher in Case 2. Collectively, we determined 3 clinical issues: (1) LO could cause pneumonia; (2) BAL and DLST could be helpful in the diagnosis of LO-induced pneumonitis; and (3) LO-induced pneumonia could become severe, though steroids were effective in improving it.
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PMID:Drug-induced pneumonitis following the administration of laninamivir octanoate: The first two reported cases. 3117 81