Resumo: FUNDAMENTOS: A coccidioidomicose é micose sistêmica usualmente manifesta como infecção benigna de resolução espontânea; porém, uma pequena proporção dos infectados desenvolve quadros progressivos potencialmente fatais, podendo atingir a pele com lesões pleomórficas disseminadas. OBJETIVOS: Identificar e descrever as manifestações cutâneo-mucosas da coccidioidomicose, as ocupações de risco relacionadas à doença e o quadro clínico associado. MÉTODOS: Estudo realizado entre os anos 2003 e 2006 em 30 pacientes portadores de coccidioidomicose provenientes dos estados do Piauí e Maranhão e diagnosticados por exame microscópico direto, cultivo do escarro ou sorologia de triagem de imunodifusão dupla em gel de ágar, aliados à anamnese e exame físico. RESULTADOS: Identificaram-se lesões extrapulmonares em 13 casos (43,3%), com predomínio de manifestações dermatológicas de hipersensibilidade: eritema nodoso (26,6%), exantema com lesões eritemato-escamosas (26,6%) e eritema multiforme (23,3%), além de úlceras de língua (13,3%) e lábio (6,6%) e abscesso subcutâneo (3,3%). Tais manifestações foram observadas na fase aguda da doença. CONCLUSÕES: As manifestações cutâneas associadas à infecção respiratória aguda fortalecem a hipótese diagnóstica desta doença, especialmente, em caçadores de tatus ou pessoas expostas à escavação do solo. Palavras-chave: Coccidioidomicose; Diagnóstico; Epidemiologia; Eritema multiforme; Eritema nodoso; Exantema Abstract: BACKGROUND: Coccidioidomycosis is a systemic mycosis that usually presents as a benign infection. Patients generally recover spontaneously; however, a small proportion of infected individuals develop progressive complications that may affect the skin in the form of disseminated pleomorphic lesions and may become fatal. OBJECTIVES: To identify and describe skin and mucous membrane manifestations of coccidioidomycosis, to identify occupational hazards associated with the disease and to determine its associated clinical presentation. METHODS: A study conducted between 2003 and 2006 involving 30 patients from the Brazilian states of Piauí and Maranhão with coccidioidomycosis diagnosed by direct microscopy, sputum culture or screening serology using agar gel double immunodiffusion, in association with anamnesis and physical examination. RESULTS: Extrapulmonary lesions were found in 13 cases (43.3%), consisting predominantly of dermatological manifestations of hypersensitivity: erythema nodosum (26.6%), exanthema with erythematosquamous lesions (26.6%) and erythema multiforme (23.3%), as well as ulcerations of the tongue (13.3%), lip ulcers (6.6%) and subcutaneous abscess (3.3%). These manifestations were seen during the acute phase of the disease. CONCLUSIONS: Skin manifestations associated with an acute respiratory infection reinforce the hypothesis of a diagnosis of coccidioidomycosis, particularly in individuals who hunt armadillos or in those exposed to soil excavation.

Epidemiological studies demonstrate the role of early and intensive glycemic control in the prevention of micro and macrovascular disease in both type 1 and type 2 diabetes mellitus (DM). Hyperglycemia elicits several pathways related to the etiopathogenesis of cardiovascular disease (CVD), including the generation of advanced glycation end products (AGEs). In this review, we revisit the role played by AGEs in CVD based in clinical trials and experimental evidence. Mechanistic aspects concerning the recognition of AGEs by the advanced glycosylation end product-specific receptor (AGER) and its counterpart, the dolichyl-diphosphooligosaccharide-protein glycosyltransferase (DDOST) and soluble AGER are discussed. A special focus is offered to the AGE-elicited pathways that promote cholesterol accumulation in the arterial wall by enhanced oxidative stress, inflammation, endoplasmic reticulum stress and impairment in the reverse cholesterol transport (RCT).

Advanced glycated albumin (AGE-albumin) impairs cholesterol efflux and contributes to inflammation in macrophages. The current study evaluated: (1) the persistence of the deleterious effect of AGE-albumin in cholesterol efflux and in inflammation, and (2) how metabolic control in diabetes mellitus (DM) contributes to attenuate the deleterious role of AGE-albumin in macrophage cholesterol homeostasis. Methods: AGE-albumin was produced in vitro or isolated from uncontrolled DM subjects’ serum before (bGC) and after improved glycemic control (aGC). Albumin samples were incubated with bone marrow-derived macrophages and 14C-cholesterol efflux or LPS- induced cytokine secretion were determined immediately, or after cell resting in culture media alone. The ABCA-1 degradation rate was determined after cell incubation with cycloheximide, and ABCA1 protein level by immunoblot. Oil Red O staining was used to assess intracellular lipid accumulation. Results: A persistent effect of AGE-albumin was observed in macrophages in terms of the secretion of inflammatory cytokines and reduced cholesterol efflux. HDL-mediated 14C-cholesterol efflux was at least two times higher in macrophages treated with aCG-albumin as compared to bGC-albumin, and intracellular lipid content was significantly reduced in aGC-albumin-treated cells. As compared to bGC-albumin, the ABCA-1 protein content in whole cell bulk was 94% higher in aCG-albumin. A 20% increased ABCA-1 decay rate was observed in macrophages treated with albumin from poorly controlled DM. AGE-albumin has a persistent deleterious effect on macrophage lipid homeostasis and inflammation. The reduction of AGEs in albumin ameliorates cholesterol efflux.

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