ABSTRACT
Introdução: Anualmente, são notificados cerca de seis milhões de novos casos de Tuberculose em todo o mundo. No Brasil, a doença é um problema de saúde pública. Objetivo: Analisar os aspectos clínico-epidemiológicos dos pacientes com tuberculose que foram notificados no município de Santa Cruz do Sul-RS. Métodos: Estudo retrospectivo, descritivo e transversal, por meio da revisão de prontuários de pacientes atendidos com tuberculose na cidade de Santa Cruz do Sul-RS, durante os anos de 2009 a 2013. Os dados foram analisados no SPSS 22.0. Resultados: No ano de 2013, a taxa de incidência da tuberculose em Santa Cruz do Sul foi de 77,7 casos novos/100.000 habitantes. A amostra foi composta de 288 casos de tuberculose notificados na cidade. A análise revelou que apenas 88 (32,83%) pacientes atendidos eram do sexo feminino. A média de idade dos pacientes foi de 41,03 anos. Houve 222 (82,83%) novos casos da doença e apenas 19 casos de recidivas. Os atendimentos a presidiários foram expressivos, totalizando 52 pacientes. O sintoma mais prevalente foi a tosse com expectoração em 195 (67,7%) casos. A forma clínica predominante foi tuberculose pulmonar em todos os anos analisados, totalizando 278 (96,52%) casos. A prevalência da coinfecção tuberculose/HIV variou de 8% a 18,7% dentro dos cinco anos. Conclusões: O município está entre os 15 prioritários no estado do Rio Grande do Sul para o controle da tuberculose, mostrando que os altos índices da doença no município devem alertar para a importância de medidas eficazes no combate da doença. (AU)
Introduction: About six million new cases of Tuberculosis are reported annually worldwide. In Brazil, the disease is a public health problem. Objective: To analyze the clinical and epidemiological aspects of patients with tuberculosis reported in the city of Santa Cruz do Sul, RS. Methods: A retrospective, descriptive and cross-sectional study was carried out through the review of medical records of patients treated with tuberculosis in the city of Santa Cruz do Sul -RS during the years 2009 to 2013. Data were analyzed in SPSS 22.0. Results: In 2013, the incidence rate of tuberculosis in Santa Cruz do Sul was of 77.7 new cases / 100,000 inhabitants. The sample consisted of 288 cases of tuberculosis reported in the city. The analysis revealed that only 88 (32.83%) patients attended were female. The mean age of the patients was 41.03 years. There were 222 (82.83%) new cases of the disease and only 19 cases of relapses. Outpatient visits were significant, totaling 52 patients. The most prevalent symptom was cough with sputum in 195 (67.7%) cases. The predominant clinical form was pulmonary tuberculosis in all analyzed years, totaling 278 (96.52%) cases. The prevalence of tuberculosis / HIV co-infection ranged from 8% to 18.7% within five years. Conclusions: The municipality is among the 15 priorities in the state of Rio Grande do Sul for the control of tuberculosis, showing that the high rates of the disease in the municipality should alert to the importance of effective measures to combat the disease. (AU)
Subject(s)
Tuberculosis , Primary Health Care , Risk FactorsABSTRACT
Treatment with tyrosine kinase inhibitors is the standard of care for Philadelphia chromosome positive leukemias. However the eradication of leukemia initiating cells remains a challenge. Circumstantial evidence suggests that the cytokine microenvironment may play a role in BCR-ABL mediated leukemogenesis and in imatinib resistance. Gene expression analyses of BCR-ABL positive ALL long-term cultured cells revealed strong reduction of SOCS mRNA expression after imatinib treatment, thereby demonstrating a strong inhibition of cytokine signaling. In this study we employed SOCS1-a strong inhibitor of cytokine signaling-as a tool to terminate external cytokine signals in BCR-ABL transformed cells in vitro and in vivo. In colony formation assays with primary bone marrow cells, expression of SOCS1 decreased colony numbers under pro-proliferative cytokines, while it conferred growth resistance to anti-proliferative cytokines. Importantly, co-expression of SOCS1 with BCR-ABL led to the development of a MPD phenotype with a prolonged disease latency compared to BCR-ABL alone in a murine bone marrow transplantation model. Interestingly, SOCS1 co-expression protected 20% of mice from MPD development. In summary, we conclude that under pro-proliferative cytokine stimulation at the onset of myeloproliferative diseases SOCS1 acts as a tumor suppressor, while under anti-proliferative conditions it exerts oncogenic function. Therefore SOCS1 can promote opposing functions depending on the cytokine environment.
Subject(s)
Cytokines/metabolism , Fusion Proteins, bcr-abl/metabolism , Myeloproliferative Disorders/metabolism , Suppressor of Cytokine Signaling 1 Protein/metabolism , Animals , Bone Marrow/metabolism , Bone Marrow Transplantation , Cell Line , Female , Fusion Proteins, bcr-abl/genetics , Interleukin-3/metabolism , Mice , Myeloproliferative Disorders/genetics , Phosphorylation , STAT5 Transcription Factor/metabolism , Spleen/metabolism , Suppressor of Cytokine Signaling 1 Protein/geneticsABSTRACT
FLT3 and c-KIT are crucial regulators of hematopoietic stem and progenitor cells. We investigated the role of STS1 and STS2 on FLT3 and c-KIT phosphorylation, activity, and function in normal and stress-induced hematopoiesis. STS1/STS2-deficient mice show a profound expansion of multipotent progenitor and lymphoid primed multipotent progenitor cells with elevated colony-forming capacity. Although long-term hematopoietic stem cells are not increased in numbers, lack of STS1 and STS2 significantly promotes long-term repopulation activity, demonstrating a pivotal role of STS1/STS2 in regulating hematopoietic stem and progenitor cell fitness. Biochemical analysis identified STS1/STS2 as direct phosphatases of FLT3 and c-KIT. Loss of STS1/STS2 induces hyperphosphorylation of FLT3, enhances AKT signaling, and confers a strong proliferative advantage. Therefore, our study reveals that STS1 and STS2 may serve as novel pharmaceutical targets to improve hematopoietic recovery after bone marrow transplantation.
