PubMed · 10148447
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I Ziment, H Flaster. 1993. Using bronchodilators effectively.. https://pubmed.ncbi.nlm.nih.gov/10148447/
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Activation of the respiratory burst of granulocytes and macrophages by invading microorganisms is a key first line cellular defence against infection. Failure to generate this response leads to persistent life-threatening infection unless appropriate antibiotic treatment is given. The respiratory burst of neutrophils is usually measured spectrophotometrically by following ferricytochrome c reduction, and histologically by using the tetrazolium salt, nitroblue tetrazolium, which is reduced intracellularly to an insoluble formazan. In both assays, reduction is mediated by superoxide generated via NADPH oxidase. Because ferricytochrome c has a high molecular mass and high background absorbance at 550 nm, the assay lacks sensitivity and is not ideally suited to microplate measurement. We have circumvented these limitations by using the cell-impermeable, sulfonated tetrazolium salt, WST-1, which exhibits very low background absorbance and is efficiently reduced by superoxide to a stable water-soluble formazan with high molar absorptivity. This has permitted adaptation of the WST-1 assay to microplate format while retaining sensitivity. Reduction of WST-1 by activated human peripheral blood neutrophils correlated closely with ferricytochrome c reduction across a range of PMA concentrations and with time of activation by PMA and fMLP. Reduction of WST-1 was inhibited by 98% by superoxide dismutase (20 microg/ml) and by 88% by the NADPH oxidase inhibitor, diphenyleneiodinium (10 microM) but was resistant to catalase, azide and the NADH oxidase inhibitor, resiniferatoxin. WST-1 and ferricytochrome c reduction were also compared using xanthine/xanthine oxidase to generate superoxide. Under optimised assay conditions, both WST-1 and ferricytochrome c reduction were directly proportional to added xanthine. WST-1 generated approximately 2-fold greater increase in absorbance than ferricytochrome c at their respective wavelengths, and this translated into increased assay sensitivity. Addition of the intermediate electron acceptor, 1-methoxy phenazine methosulfate, increased the background of the neutrophil assay but did not affect the overall magnitude of the response. We have used the WST-1 assay to assess human neutrophil dysfunction and to compare anti-inflammatory activity.
BACKGROUND: Livedo reticularis generalisata (LR) in combination with affection of CNS is referred to as Sneddon's syndrome (SNS). Latest data suggest chronic progressive systemic disorder with occlusion of small and medium sized vessels (e.g., cutis, brain, kidneys, heart, eyes). No conclusive etiology is known, though there are correlations to the antiphospholipid syndrome, systemic secondary vasculitis and coagulopathies. Hereditary and toxic factors seem to play a role in pathogenesis in some cases. CASE REPORT: Diagnostic procedure and clinical course of a 56-year-old woman with dementia and hemiparesis proceeded by LR is reported. MRI-, SPECT- and TCD-findings were congruent with diffuse ischemic lesions of the brain due to affection of small- and medium-sized vessels. Histopathological specimens of the brain, meninges and cutis were non diagnostic. Some laboratory findings suggested vasculitis as an underlying cause. LR improved under immunosuppressive therapy with prednisolone and azathioprin. CONCLUSION: SNS does not seem to be a nosological entity. A differentiation between primary (idiopathic) and secondary SNS is useful for different therapeutical approaches.
Many rheumatic diseases affect women of childbearing age, and the medications used to treat these diseases may affect conception, pregnancy, fetal development, and lactation. Physicians who care for these women need to be aware of the potential adverse effects of these medications, and which medications can be used safely prior to conception and during pregnancy and lactation. Although reviews of individual classes of medications are available, there is no practical and comprehensive review that summarizes all of this information, and includes anticoagulant drugs and 2 recently approved drugs for rheumatoid arthritis. Women who take cytotoxic drugs should be informed of the risks of impaired fertility and congenital malformations, and must use effective methods of contraception. During pregnancy, nonsteroidal anti-inflammatory agents may be used until the last 6 weeks, and low to moderate doses of corticosteroids are safe throughout pregnancy. Among the disease-modifying agents, sulfasalazine and hydroxychloroquine treatment may be maintained. Cytotoxic drugs may be used after the first trimester to treat life-threatening disease. During lactation, prednisone, sulfasalazine, and hydroxychloroquine may be used cautiously. Women using heparin for treatment of antiphospholipid antibody syndrome should take measures to prevent bone loss. Men taking methotrexate, sulfasalazine, cyclosporine, azathioprine, or leflunomide should be apprised of the possibilities of infertility and teratogenicity.