Perfil de pacientes com artrite reumatoide em uso de inibidores do Fator de Necrose Tumoral alfa (TNF-alfa), cadastrados no Componente Especializado da Assistência Farmacêutica de Pernambuco, Brasil / Profile of patients with rheumatoid arthritis under treatment with inhibitors of tumor necrosis factor alpha (TNF-alfa) enrolled in the Specialized Program for Pharmaceutical Services of Pernambuco State (Brazil)

In Pernambuco, with federal funding from the Brazilian Ministry of Health, the State Department of Health provides the anti-TNF-α drugs (adalimumab, etanerceptand infliximab) for the treatment of rheumatoid arthritis (RA), as set out in a Clinical Protocol of Therapeutic Guidelines. The aim of the study was to describe the demographic and clinical profile of RA patients treated with anti-TNF-α drugs enrolled in the Specialized Programfor Pharmaceutical Services (CEAF) in Pernambuco. A cross-sectional study was performed by collecting patient data recorded in the Computerized System for Management and Monitoring of Drugs of the CEAF, for the base month and year, September 2012. The data analyzed were age, gender, International Classification of Diagnosed Disease, anti-TNF-α dispensed and city of residence. Out of 525 RA patients taking anti-TNF-α, 384 (73%) were women. Etanercept (57%) was in the highest number of prescriptions, followed by adalimumab (37%) and infliximab (11%). According to their home addresses, Health Management Region I had the highest prevalence of patients with RA in Pernambuco. The study enabled the profile of patients treated for RA with anti-TNF-α to be described. This information may help decision making and contribute to improving the management of Pharmaceutical Services and public health policies...

Em Pernambuco, por meio de financiamento federal do Ministério da Saúde, a Secretaria Estadual de Saúde, provê, ao tratamento da Artrite Reumatóide (AR), os medicamentos anti-TNF-α (adalimumabe, etanercepte e infliximabe), cujas linhas de cuidados estão definidas em Protocolos Clínicos de Diretrizes Terapêuticas. O estudo objetivou descrever o perfil demográfico e clínico dos pacientes com AR em uso de anti-TNF-α cadastrados no Componente Especializado da Assistência Farmacêutica (CEAF) em Pernambuco. Realizou-se um estudo transversal com a coleta de dados de pacientes cadastrados no Sistema Informatizado de Gerenciamento e Acompanhamento de Medicamentos do CEAF. Com mês e ano base em setembro de 2012, foram consideradas para análise a idade, gênero, Classificação Internacional da Doença diagnosticada, anti-TNF-α dispensado e município de residência. Considerando 525 pacientes com AR que utilizam anti-TNF-α, 384 (73%) eram mulheres. O Etanercepte (57%) apresentou maior número de prescrições, seguido do Adalimumabe (37%) e Infliximabe (11%). Segundo o local de residência, a I Gerência Regional de Saúde apresentou maior prevalência de pacientes com AR. O estudo possibilitou descrever o perfil dos pacientes que utilizam anti-TNF-α no tratamento da AR. Essas informações podem subsidiar tomadas de decisões, contribuir na melhoria da gestão da Assistência Farmacêutica e de políticas públicas em saúde...

Anti-inflammatory and antioxidant properties of a new arylidene-thiazolidinedione in macrophages.

Thiazolidinediones (TZDs) are a class of drugs used for treatment of type 2 diabetes. However, the therapy with currently available TDZs (e.g. rosiglitazone) is associated with important side effects, such as edema and weight gain, suggesting that the investigation of alternative TZDs with better pharmacological properties is warranted. In this study, we investigated both anti-inflammatory and antioxidant properties of a new chemically modified TZD, the arylidene-thiazolidinedione 5-(4-methanesulfonyl-benzylidene)-3-(4-nitrobenzyl)-thiazolidine-2,4-dione (SF23), and compared the results to those obtained with rosiglitazone. We found that our SF23 displays a weaker affinity for PPARγ, up-regulating in a lower magnitude the expression of both PPARγ and CD36 compared to rosiglitazone. In lipopolysaccharide (LPS)-stimulated macrophages, SF23 decreased nitrite production and attenuated the mRNA expression of both iNOS and COX-2. These anti-inflammatory effects were comparable to those obtained with rosiglitazone. Interestingly, SF23, but not rosiglitazone, prevented LPS-induced mitochondrial membrane hyperpolarization, apoptosis, reactive oxygen species (ROS) generation, and the expression of NADPH oxidase subunits, Nox1 and Nox2. In addition, in macrophages from Nrf2⁻/⁻ mice, SF23 protected against LPSinduced cellular death and ROS production, whereas rosiglitazone was only able to protect normal Nrf2⁺/⁺ cells against oxidative injury, suggesting that, unlike rosiglitazone, the antioxidant activity of SF23 might be Nrf2-independent. Finally, in macrophages exposed to high concentrations of glucose, SF23 induced significant increases in the mRNA expression of glucose transporters, insulin receptor substrate and mitoNEET. Altogether, our data indicate that our new chemically modified TDZ displays similar anti-inflammatory properties, but superior antioxidant effects on the LPS-stimulated macrophages compared to rosiglitazone.

Immunological studies and in vitro schistosomicide action of new imidazolidine derivatives

Schistosomiasis is a major public health problem with 207 million people infected and more than 779 million at risk. The drug of choice for treating schistosomiasis is praziquantel (PZQ); however, it is inefficient against immature forms of schistosomes. The aim of this study was to test new imidazolidine derivatives LPSF/PT09 and LPSF/PT10 against adult Schistosoma mansoni worms. IC50, cytotoxicity, immune response and cell viability assays were also available for these imidazolidines. Different concentrations of imidazolidine, from 32 to 320 »M, promoted motor abnormalities in breeding and unpaired worms, and death in 24 hours at higher concentrations. Although LPSF/PT09 and LPSF/PT10 did not affect IFN-³ and IL-10 production, they induced nitric oxide production and showed a similar behavior to praziquantel on cell death test. Thus, these new imidazolidine derivatives should undergo further study to develop schistosomiasis drugs.

[Substituted imidazolidinediones and thiazolidinediones: synthesis, structure and cytotoxic activity]. / Imidazolidinediones et thiazolidinediones substituées: synthèse, étude structurale et activité cytotoxique.

Synthesis and physico-chemical properties of nine 3-(4-fluoro or chlorobenzyl)-5-arylidène-imidazolidine-2,4-diones, four 3-(4-fluoro or bromobenzyl)-5-arylidène-thiazolidine-2,4-diones and three 3-)4-bromophénacyl)-5-arylidène-thiazolidine-2,4- diones has been described. These compounds were synthesized by aldolisation-crotonisation reaction from aromatic aldehydes and 3-substituted imidazolidine-2,4-diones or thiazolidine-2,4-diones. In vitro cytotoxic activity was determined for compounds 8, 17, 18, 21 and 22.

Relacao estrutura-atividade em sulfas antibacterianas. / Relationship between structure and activity in antibacterial sulfonamides

A atividade bacteriostatica de derivados sulfalamidicos substituidos em N1, considerando o efeito de dissociacao, foi relacionada com as propriedades fisico-quimicas de suas moleculas, representadas por parametros hidrofobos, eletronicos e estericos, objetivando contribuir para elucidacao do seu mecanismo de acao. A tecnica omega, extensao do metodo aproximado de Huckel, foi utilizada para a determinacao de alguns parametros. Os resultados comprovam a influencia dos efeitos eletronicos dos seus substituintes no mecanismo de acao das sulfas