Bruton's tyrosine kinase inhibition—An emerging therapeutic strategy in immune‐mediated dermatological conditions

Bruton's tyrosine kinase (BTK), a member of the Tec kinase family, is critically involved in a range of immunological pathways. The clinical application of BTK inhibitors for B-cell malignancies has proven successful, and there is strong rationale for the potential benefits of BTK inhibitors in some autoimmune and allergic conditions, including immune-mediated dermatological diseases. However, the established risk-to-benefit profile of "first-generation" BTK inhibitors cannot be extrapolated to these emerging, non-oncological, indications. "Next-generation" BTK inhibitors such as remibrutinib and fenebrutinib entered clinical development for chronic spontaneous urticaria (CSU); rilzabrutinib and tirabrutinib are being studied as potential treatments for pemphigus. Promising data from early-phase clinical trials in CSU suggest potential for these agents to achieve strong pathway inhibition, which may translate into measurable clinical benefits, as well as other effects such as the disruption of autoantibody production. BTK inhibitors may help to overcome some of the shortcomings of monoclonal antibody treatments for immune-mediated dermatological conditions such as CSU, pemphigus, and systemic lupus erythematosus. In addition, the use of BTK inhibitors may improve understanding of the pathophysiological roles of mast cells, basophils, and B cells in such conditions.info:eu-repo/semantics/publishedVersio

Hibridização genômica in situ em triticeae: um enfoque metodológico.

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Rhodolith bed structure along a depth gradient on the northern coast of bahia state, brazil

O objetivo deste estudo foi determinar a estrutura de um banco de rodolitos ao longo de um gradiente de profundidade na plataforma em frente à cidade de Salvador, nordeste brasileiro. Foram analisadas as dimensões, a forma e composição das algas calcárias dos rodolitos, bem como a vitalidade, densidade e flora associada ao banco, em três profundidades: 5, 15 e 25 m. As amostras foram obtidas por meio de mergulho autônomo no verão de 2007. Cinco espécies de algas calcárias formadoras de rodolito foram identificadas: Sporolithon episporum, Lithothamnion brasiliense, Lithothamnion superpositum, Mesophyllum erubescens e Lithophyllum sp. A forma de crescimento incrustante e a forma esférica foram predominantes em todas as profundidades. Houve uma redução da dimensão e vitalidade dos rodolitos e um aumento da densidade com a profundidade. Cinqüenta e seis espécies de macroalgas foram encontradas como flora associada aos rodolitos. A profundidade mais rasa apresentou os maiores valores de biomassa e número de espécies de macroalgas. Esses resultados, associados com outras descrições recentes de bancos de rodolitos, indicam que o padrão estrutural desses bancos no Brasil, ao longo de gradientes de profundidade, pode estar relacionado a uma combinação da extensão e da inclinação da plataforma continental.The aim of this study was to determine the structure of a rhodolith bed along a depth gradient of 5 to 25 m in the shelf in front of Salvador City, a region of northeastern Brazil. The dimensions, morphology and coralline algae composition of the rhodoliths were analyzed, as well as the vitality, density, and associated flora of the bed at three depths: 5, 15 and 25 m. Samples were obtained by SCUBA divers in summer 2007. Five rhodolith-forming taxa were identified: Sporolithon episporum, Lithothamnion brasiliense, Lithothamnion superpositum, Mesophyllum erubescens, and Lithophyllum sp. The encrusting growth form and the spherical shape were predominant at all depths. Rhodolith dimensions and vitality decreased and the density increased from the shallow to the deepest zones. Fifty-six macroalgal species were found as rhodolith-associated flora. The shallower depth presented higher values for macroalgal biomass and number of species. These results associated with other recent rhodolith bed descriptions indicate that the pattern of Brazilian rhodolith bed structure along depth gradients may be related to a combination of the extent and slope of the continental shelf

Phenotypic eff ects of allotetraploidization of wild Arachis and their implications for peanut domestication.

Made available in DSpace on 2018-08-07T00:49:37Z (GMT). No. of bitstreams: 1 LealBertiolietal2017AmericanJournalofBotany.pdf: 2849247 bytes, checksum: d9dcbf4228792935ed1562886734aae6 (MD5) Previous issue date: 2017-06-14bitstream/item/180956/1/Leal-Bertioli-et-al-2017-American-Journal-of-Botany.pd

Recalcitrant Leg Ulcers as the Only Manifestation of Essential Type 2 Cryoglobulinemia

Chronic leg ulcers are persistent conditions that might be a diagnostic and therapeutic challenge, with great impact in health care costs and patients’ quality of life. We report a case of a 60-year-old woman, with long-lasting recalcitrant leg ulcers, which led to left leg amputation 10 years ago. Several attempts to heal the right leg were made, including skin grafting in three different occasions and several surgical debridements, all with unsatisfactory outcome. Some months before the ulcers began, the patient had been diagnosed with undifferentiated connective tissue disease because of arthralgia and positive antinuclear antibodies, therefore low dose systemic corticosteroids and azathioprine were prescribed. For the last 4 years she has been followed in our department and since then no evidence of clinical or laboratorial criteria for autoimmune diseases was found, thus the immunosuppressive therapy was stopped. She maintained ever since a high rheumatoid factor but without other evidence of autoimmune disease. Medical history was otherwise irrelevant. Several cutaneous biopsies were performed, with no evidence of malignancy or vasculitis. Recently, cryoglobulins became positive, with type 2b cryoglobulin identification on immunofluorescence. Serology for Hepatitis C virus was consistently negative, hence an Essential type 2 Cryoglobulinemia diagnosis was established. No renal impairment, vascular purpura, arthralgia or arthritis was found. The authors emphasize the importance of considering less common etiologies for chronic leg wounds, even in the absence of other suggestive symptomatology, as well as the pertinence of reconsidering diagnosis in highly suspect cases