17 research outputs found
Efficacy of Light-Activated Sealant on Enamel Demineralization in Orthodontic Patients: An Atomic Force Microscope Evaluation
Corticosteroids in ophthalmology : drug delivery innovations, pharmacology, clinical applications, and future perspectives
Spectroscopic and thermal investigations of charge-transfer complexes formed between cefotaxime sodium drug and various acceptors
ExercĂcio fĂsico, receptores β-adrenĂ©rgicos e resposta vascular Physical exercise, β-adrenergic receptors, and vascular response
O exercĂcio aerĂłbio promove efeitos benĂ©ficos na prevenção e tratamento de doenças como hipertensĂŁo arterial, aterosclerose, insuficiĂŞncia venosa e doença arterial perifĂ©rica. Os receptores β-adrenĂ©rgicos estĂŁo presentes em várias cĂ©lulas. No sistema cardiovascular, promovem inotropismo e cronotropismo positivo cardĂaco e relaxamento vascular. Embora os efeitos do exercĂcio tenham sido investigados em receptores cardĂacos, estudos focados nos vasos sĂŁo escassos e controversos. Esta revisĂŁo abordará os efeitos do exercĂcio fĂsico sobre os receptores β-adrenĂ©rgicos vasculares em modelos animais e humanos e os mecanismos celulares envolvidos na resposta relaxante. Em geral, os estudos mostram resultantes conflitantes, onde observam diminuição, aumento ou nenhum efeito do exercĂcio fĂsico sobre a resposta relaxante. Assim, os efeitos do exercĂcio na sensibilidade β-adrenĂ©rgica vascular merecem maior atenção, e os resultados mostram que a área de fisiopatologia vascular Ă© um campo aberto para a descoberta de novos compostos e avanços na prática clĂnica.<br>Aerobic exercise promotes beneficial effects on the prevention and treatment of diseases such as arterial hypertension, atherosclerosis, venous insufficiency, and peripheral arterial disease. β-adrenergic receptors are present in a variety of cells. In the cardiovascular system, β-adrenergic receptors promote positive inotropic and chronotropic response and vasorelaxation. Although the effect of exercise training has been largely studied in the cardiac tissue, studies focused on the vascular tissue are rare and controversial. This review examines the data from studies using animal and human models to determine the effect of physical exercise on the relaxing response mediated by β-adrenergic receptors as well as the cellular mechanisms involved in this response. Studies have shown reduction, increase, or no effect of physical exercise on the relaxing response mediated by β-adrenergic receptors. Thus, the effects of exercise on the vascular β-adrenergic sensitivity should be more deeply investigated. Furthermore, the physiopathology of the vascular system is an open field for the discovery of new compounds and advances in the clinical practice
Management of relapsed and refractory multiple myeloma: novel agents, antibodies, immunotherapies and beyond
Despite enormous advances, management of multiple myeloma (MM) remains challenging. Multiple factors impact the decision to treat or which regimen to use at MM relapse/progression. Recent major randomized controlled trials (RCTs) showed widely varying progression-free survivals (PFS), ranging from a median of 4 months (MM-003) to 23.6 months (ASPIRE). Based on these RCTs, next-generation proteasome inhibitors (carfilzomib and ixazomib), next-generation immunomodulatory agent (pomalidomide), and monoclonal antibodies (elotuzumab and daratumumab) were approved for relapsed and refractory MM. Daratumumab, targeting CD38, has multiple mechanisms of action including modulation of the immunosuppressive bone marrow micro-environment. In addition to the remarkable single agent activity in refractory MM, daratumumab produced deep responses and superior PFS in MM when combined with lenalidomide/dexamethasone, or bortezomib/dexamethasone. Other anti-CD38 antibodies, such as isatuximab and MOR202, are undergoing assessment. Elotuzumab, targeting SLAMF7, yielded superior response rates and PFS when combined with lenalidomide/dexamethasone. New combinations of these next generation novel agents and/or antibodies are undergoing clinical trials. Venetoclax, an oral BH3 mimetic inhibiting BCL2, showed single agent activity in MM with t(11;14), and is being studied in combination with bortezomib/dexamethasone. Selinexor, an Exportin-1 inhibitor, yielded promising results in quad- or penta-refractory MM including patients resistant to daratumumab. Pembrolizumab, an anti-PD1 check-point inhibitor, is being tested in combination with lenalidomide/dexamethasone or pomalidomide/dexamethasone. Chimeric antigen receptor-T cells targeting B-cell maturation antigen have yielded deep responses in RRMM. Finally, salvage autologous stem cell transplantation (ASCT) remains an important treatment in MM relapsing/progressing after a first ASCT. Herein, the clinical trial data of these agents are summarized, cautious interpretation of RCTs highlighted, and algorithm for salvage treatment of relapse/refractory MM proposed