There is shortage of extensive clinicopathologic studies of cellular senescence because the most reliable senescence biomarker, the detection of Senescence-Associated-beta-galactosidase activity (SA-β-gal), is inapplicable in archival material and requires snap-frozen tissues. We validated the histochemical Sudan-Black-B (SBB) specific stain of lipofuscin, an aggregate of oxidized proteins, lipids and metals, known to accumulate in aged tissues, as an additional reliable approach to detect senescent cells independently of sample preparation. We analyzed cellular systems in which senescence was triggered by replicative exhaustion or stressful stimuli, conditional knock-in mice producing precancerous lesions exhibiting senescence, and human preneoplastic lesions known to contain senescent cells. In the above settings we demonstrated co-localization of lipofuscin and SA-β-gal in senescent cells in vitro and in vivo (cryo-preserved tissue), strongly supporting the candidacy of lipofuscin for a biomarker of cellular senescence. Furthermore, cryo-preserved tissues positive for SA-β-gal were formalin-fixed, paraffin-embedded, and stained with SBB. The corresponding SA-β-gal positive tissue areas stained specifically for lipofuscin by SBB, whereas tissues negative for SA-β-gal were lipofuscin negative, validating the sensitivity and specificity of the SBB staining to visualize senescent cells in archival material. The latter unique property of SBB could be exploited in research on widely available retrospective tissue material.
Systemic non-biologic agents have long been in clinical use in medicine -often with considerable efficacy, albeit with some adverse effects -as with all medications. With the advent of biologic agents, all of which currently are restricted to systemic use, there is a growing need to ensure which agents have the better therapeutic ratio. The non-biologic agents (NBAs) include a range of agents, most especially the corticosteroids (corticosteroids). This study reviews the corticosteroids in systemic use in management of orofacial mucocutaneous diseases; subsequent studies discuss corticosteroid-sparing agents used in the management of orofacial diseases, such as calcineurin inhibitors used to produce immunosuppression; purine synthetase inhibitors; and cytotoxic and other immunomodulatory agents. Oral Diseases (2014) 20, 127-135
Systemic non-biologic agents have long been in clinical use in medicine -often with considerable efficacy, albeit with some adverse effects -as with all medications. With the advent of biologic agents, all of which currently are restricted to systemic use, there is a growing need to ensure which agents have the better therapeutic ratio. The non-biologic agents (NBAs) include a range of agents, most importantly the corticosteroids (steroids). Previous articles by us in this series have discussed systemic use of corticosteroids and purine synthesis inhibitors; the other immunomodulating agents (calcineurin inhibitors, thalidomide, dapsone, colchicine and cyclophosphamide) are reviewed in this final article.
The clinical presentation of oral lichen planus and oral lichenoid lesions is diverse. A special category of patients presents with lichenoid lesions affecting only the mucosa of their upper lip and the anterior upper gingiva. This is a concise review summarizing the specific characteristics of these patients.
Systemic non‐biological agents (NBAs) have been extensively used for immunosuppression in clinical medicine, often with considerable efficacy, although sometimes accompanied with adverse effects as with all medicines. With the advent of biological agents, all of which currently are restricted to systemic use, there is a rising need to identify which agents have the better therapeutic ratio. The NBAs include a range of agents, most especially the corticosteroids (corticosteroids). This article reviews the purine synthesis inhibitors (azathioprine and mycophenolate), which are currently the most commonly used systemically immunosuppressive agents in the management of orofacial mucocutaneous diseases. Subsequent articles discuss other corticosteroid‐sparing agents used in the management of orofacial disease, such as calcineurin inhibitors, and the cytotoxic and other immunomodulatory agents.
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