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Due to its relatively slow clinical progression, B cell chronic lymphocytic leukemia (B-CLL) is classically described as a disease of accumulation rather than proliferation. However, evidence for various forms of clonal evolution suggests that B-CLL clones may be more dynamic than previously assumed. We used a nonradioactive, stable isotopic labeling method to measure B-CLL cell kinetics in vivo. Nineteen patients drank an aliquot of deuterated water (2H2O) daily for 84 days, and 2H incorporation into the deoxyribose moiety of DNA of newly divided B-CLL cells was measured by gas chromatography/mass spectrometry, during and after the labeling period. Birth rates were calculated from the kinetic profiles. Death rates were defined as the difference between calculated birth and growth rates. These analyses demonstrated that the leukemic cells of each patient had definable and often substantial birth rates, varying from 0.1% to greater than 1.0% of the entire clone per day. Those patients with birth rates greater than 0.35% per day were much more likely to exhibit active or to develop progressive disease than those with lower birth rates Thus, B-CLL is not a static disease that results simply from accumulation of long-lived lymphocytes. Rather, it is a dynamic process composed also of cells that proliferate and die, often at appreciable levels. The extent to which this turnover occurs has not been previously appreciated. A correlation between birth rates and disease activity and progression appears to exist, which may help identify patients at risk for worsening disease in advance of clinical deterioration.

Due to its relatively slow clinical progression, B cell chronic lymphocytic leukemia (B-CLL) is classically described as a disease of accumulation rather than proliferation. However, evidence for various forms of clonal evolution suggests that B-CLL clones may be more dynamic than previously assumed. We used a nonradioactive, stable isotopic labeling method to measure B-CLL cell kinetics in vivo. Nineteen patients drank an aliquot of deuterated water (2H2O) daily for 84 days, and 2H incorporation into the deoxyribose moiety of DNA of newly divided B-CLL cells was measured by gas chromatography/mass spectrometry, during and after the labeling period. Birth rates were calculated from the kinetic profiles. Death rates were defined as the difference between calculated birth and growth rates. These analyses demonstrated that the leukemic cells of each patient had definable and often substantial birth rates, varying from 0.1% to greater than 1.0% of the entire clone per day. Those patients with birth rates greater than 0.35% per day were much more likely to exhibit active or to develop progressive disease than those with lower birth rates Thus, B-CLL is not a static disease that results simply from accumulation of long-lived lymphocytes. Rather, it is a dynamic process composed also of cells that proliferate and die, often at appreciable levels. The extent to which this turnover occurs has not been previously appreciated. A correlation between birth rates and disease activity and progression appears to exist, which may help identify patients at risk for worsening disease in advance of clinical deterioration.

Antigenic stimulation of T cells gives rise to short-lived effector cells and long-lived memory cells. We used two stable isotope-labeling techniques to identify kinetically distinct subpopulations of T cells and to determine the effect of advanced infection with HIV-1. Long-term deuterated water (2H2O) incorporation into DNA demonstrated biphasic accrual of total and of memory/effector (m/e)-phenotype but not naive-phenotype T cells, consistent with the presence of short-lived and longer-lived subpopulations within the m/e-phenotype T cell pool. These results were mirrored by biphasic die-away kinetics in m/e- but not naive-phenotype T cells after short-term 2H-glucose labeling. Persistent label retention was observed in a subset of m/e-phenotype T cells (presumably memory T cells), confirming the presence of T cells with very different life spans in humans. In advanced HIV-1 infection, much higher proportions of T cells were short-lived, compared to healthy controls. Effective long-term anti-retroviral therapy restored values to normal. These results provide the first quantitative evidence that long-lived and quiescent T cells do indeed predominate in the T cell pool in humans and determine T cell pool size, as in rodents. The greatest impact of advanced HIV-1 infection is to reduce the generation of long-lived, potential progenitor T cells.

Introdução: O estilo de vida tem se destacado como importante causa para as principais doenças crônicas, como o diabetes mellitus tipo 2, por causar alterações fisiológicas crônicas que tendem a se agravar à medida que o indivíduo envelhece. Comparou-se o nível de atividade física realizada por pessoas com diabetes mellitus tipo 2 na atenção básica e unidade especializada. Materiais e Métodos: Estudo descritivo, de corte transversal, com análise comparativa. Aplicaram-se questionários semiestruturado e o validado Internacional de Atividade Física, submetidos e comparados por análise estatística com os testes do Qui-quadrado de Pearson e t student. Resultados: A idade média dos usuários foi 59 anos, predominância sexo feminino e não praticantes de atividade física. Valores glicêmicos obtidos pelo exame da hemoglobina glicada foram, 8,1% em centro de referência e 9,6% em unidade básica de saúde (p=0,017), diferenciais de controle metabólico e distintas realidades de atendimento. Discussão: O nível de atividade física aliado a mudanças no estilo de vida e adesão terapêutica, é parte fundamental para o controle do diabetes e prevenção de complicações, devendo ser encorajadas pelos profissionais da saúde. Conclusoes: Melhor desempenho no nível de atividade física e melhor controle glicêmico de pessoas acompanhadas em centro especializado. Deve-se considerar ações de educação à saúde na perspectiva do cuidado integral na Rede de Atenção à Saúde, independente do tipo de serviço, como potencializadoras para o automonitoramento e controle do diabetes mellitus. Como citar este artigo: Kolchraiber FC, Rocha JS, César DJ, Monteiro OO, Frederico GA, Gamba MA. Nível de atividade física em pessoas com diabetes mellitus tipo 2. Rev Cuid. 2018; 9(2): 2105-16. http://dx.doi.org/10.15649/cuidarte.v9i2.512

T cell dynamics were studied in human immunodeficiency virus-infected patients who continued using antiretroviral therapy despite detectable plasma viremia (RNA copies > 2500 /mL). CD4+ cell fractional replacement rates, measured by the deuterated glucose technique, were lower in treated patients with detectable viremia than in untreated patients and were similar to those in patients with undetectable viremia. Cell cycle and activation markers exhibited similar trends. For any level of viremia, CD4+ cell fractional replacement rates were lower in patients with drug-resistant virus than in patients with wild-type virus, which suggests that the resistant variant was less virulent. Interruption of treatment in patients with drug-resistant viremia resulted in increased CD4+ cell activation, increased CD4+ cell turnover, and decreased CD4+ cell counts. These data indicate that partial virus suppression reduces CD4+ cell turnover and activation, thereby resulting in sustained CD4+ cell gains, and that measurements of T cell dynamics may provide an in vivo marker of viral virulence.

Antigenic stimulation of T cells gives rise to short-lived effector cells and long-lived memory cells. We used two stable isotope-labeling techniques to identify kinetically distinct subpopulations of T cells and to determine the effect of advanced infection with HIV-1. Long-term deuterated water (2H2O) incorporation into DNA demonstrated biphasic accrual of total and of memory/effector (m/e)-phenotype but not naive-phenotype T cells, consistent with the presence of short-lived and longer-lived subpopulations within the m/e-phenotype T cell pool. These results were mirrored by biphasic die-away kinetics in m/e- but not naive-phenotype T cells after short-term 2H-glucose labeling. Persistent label retention was observed in a subset of m/e-phenotype T cells (presumably memory T cells), confirming the presence of T cells with very different life spans in humans. In advanced HIV-1 infection, much higher proportions of T cells were short-lived, compared to healthy controls. Effective long-term anti-retroviral therapy restored values to normal. These results provide the first quantitative evidence that long-lived and quiescent T cells do indeed predominate in the T cell pool in humans and determine T cell pool size, as in rodents. The greatest impact of advanced HIV-1 infection is to reduce the generation of long-lived, potential progenitor T cells.Antigenic stimulation of T cells gives rise to short-lived effector cells and long-lived memory cells. We used two stable isotope-labeling techniques to identify kinetically distinct subpopulations of T cells and to determine the effect of advanced infection with HIV-1. Long-term deuterated water (2H2O) incorporation into DNA demonstrated biphasic accrual of total and of memory/effector (m/e)-phenotype but not naive-phenotype T cells, consistent with the presence of short-lived and longer-lived subpopulations within the m/e-phenotype T cell pool. These results were mirrored by biphasic die-away kinetics in m/e- but not naive-phenotype T cells after short-term 2H-glucose labeling. Persistent label retention was observed in a subset of m/e-phenotype T cells (presumably memory T cells), confirming the presence of T cells with very different life spans in humans. In advanced HIV-1 infection, much higher proportions of T cells were short-lived, compared to healthy controls. Effective long-term anti-retroviral therapy restored values to normal. These results provide the first quantitative evidence that long-lived and quiescent T cells do indeed predominate in the T cell pool in humans and determine T cell pool size, as in rodents. The greatest impact of advanced HIV-1 infection is to reduce the generation of long-lived, potential progenitor T cells.

Introduction: Lifestyle has emerged as an important cause of major chronic diseases, such as type-2 diabetes mellitus, because it causes chronic physiological changes that tend to worsen as individual age. The study compared the level of physical activity performed by people with type-2 diabetes mellitus in basic care and specialized unit. Materials and Methods: Descriptive, cross-sectional study with comparative analysis. Semistructured questionnaires and the internationally validated Physical Activity questionnaire were applied, submitted and compared through statistical analysis with Pearson’s chi-square and Student’s t tests. Results: The average age of the users was 59 years, with predominance of females and those not engaging in physical activity. Glycemic values obtained by examining glycated hemoglobin were: 8.1% in a reference center and 9.6% in a basic health unit (p = 0.017), differentials of metabolic control and different care realities. Discussion: The level of physical activity, combined with changes in lifestyle and therapeutic adherence, is a fundamental part of diabetes control and prevention of complications and should be encouraged by health professionals. Conclusions: Better performance was noted in the level of physical activity and better glycemic control of individuals monitored at a specialized center. Health education actions should be considered within the perspective of comprehensive care in the Health Care Network, regardless of the type of service, as potential for self-monitoring and control of diabetes mellitus. Introdução: O estilo de vida tem se destacado como importante causa para as principais doenças crônicas, como o diabetes mellitus tipo 2, por causar alterações fisiológicas crônicas que tendem a se agravar à medida que o indivíduo envelhece. Comparou-se o nível de atividade física realizada por pessoas com diabetes mellitus tipo 2 na atenção básica e unidade especializada. Materiais e Métodos: Estudo descritivo, de corte transversal, com análise comparativa. Aplicaram-se questionários semiestruturado e o validado Internacional de Atividade Física, submetidos e comparados por análise estatística com os testes do Qui-quadrado de Pearson e t student. Resultados: A idade média dos usuários foi 59 anos, predominância sexo feminino e não praticantes de atividade física. Valores glicêmicos obtidos pelo exame da hemoglobina glicada foram, 8,1% em centro de referência e 9,6% em unidade básica de saúde (p=0,017), diferenciais de controle metabólico e distintas realidades de atendimento. Discussão: O nível de atividade física aliado a mudanças no estilo de vida e adesão terapêutica, é parte fundamental para o controle do diabetes e prevenção de complicações, devendo ser encorajadas pelos profissionais da saúde. Conclusoes: Melhor desempenho no nível de atividade física e melhor controle glicêmico de pessoas acompanhadas em centro especializado. Deve-se considerar ações de educação à saúde na perspectiva do cuidado integral na Rede de Atenção à Saúde, independente do tipo de serviço, como potencializadoras para o automonitoramento e controle do diabetes mellitus. Introducción: El estilo de vida se ha destacado como una importante causa para las principales enfermedades crónicas, como la diabetes mellitus tipo 2, por causar alteraciones fisiológicas crónicas que tienden a agravarse a medida que el individuo envejece. Se comparó el nivel de actividad física realizada por personas con diabetes mellitus tipo 2 en la atención básica y en unidad especializada. Materiales y Métodos: Estudio descriptivo de corte transversal con análisis comparativo. Se aplicaron cuestionarios semiestructurados y el validado Internacional de Actividad Física, sometidos y comparados por análisis estadístico con las pruebas del Chi-cuadrado de Pearson y t student. Resultados: La edad media de los usuarios fue de 59 años, predominancia del sexo femenino y no practicantes de actividad física. Los valores glucémicos obtenidos por el examen de la hemoglobina glicosilada fue de 8.1% en centro de referencia y 9.6% en unidad básica de salud (p = 0,017), diferenciales de control metabólico y distintas realidades de atención. Discusión: El nivel de actividad física aliado a cambios en el estilo de vida y adhesión terapéutica es parte fundamental para el control de la diabetes y prevención de complicaciones, debiendo ser estimuladas por los profesionales de la salud. Conclusiones: Mejor desempeño en el nivel de actividad física y mejor control glucémico de personas acompañadas en centro especializado. Se debe considerar acciones de educación a la salud en la perspectiva del cuidado integral en la Red de Atención a la Salud, independiente del tipo de servicio, como potencializadoras para el automonitoramiento y control de la diabetes mellitus.

T cell dynamics were studied in human immunodeficiency virus-infected patients who continued using antiretroviral therapy despite detectable plasma viremia (RNA copies %gt;2500 /mL). CD4⁺ cell fractional replacement rates, measured by the deuterated glucose technique, were lower in treated patients with detectable viremia than in untreated patients and were similar to those in patients with undetectable viremia. Cell cycle and activation markers exhibited similar trends. For any level of viremia, CD4⁺ cell fractional replacement rates were lower in patients with drug-resistant virus than in patients with wild-type virus, which suggests that the resistant variant was less virulent. Interruption of treatment in patients with drug-resistant viremia resulted in increased CD4⁺ cell activation, increased CD4⁺ cell turnover, and decreased CD4⁺ cell counts. These data indicate that partial virus suppression reduces CD4⁺ cell turnover and activation, thereby resulting in sustained CD4⁺ cell gains, and that measurements of T cell dynamics may provide an in vivo marker of viral virulence.

Background: The antimicrobial activity of essential oils has been reported in hundreds of studies, however, the great majority of these studies attribute the activity to the most prevalent compounds without analyzing them independently. Therefore, the aim was to investigate the antibacterial activity of 33 free terpenes commonly found in essential oils and evaluate the cellular ultrastructure to verify possible damage to the cellular membrane. Methods: Screening was performed to select substances with possible antimicrobial activity, then the minimal inhibitory concentrations, bactericidal activity and 24-h time-kill curve studies were evaluated by standard protocols. In addition, the ultrastructure of control and death bacteria were evaluated by scanning electron microscopy. Results: Only 16 of the 33 compounds had antimicrobial activity at the initial screening. Eugenol exhibited rapid bactericidal action against Salmonella enterica serovar Typhimurium (2 h). Terpineol showed excellent bactericidal activity against S. aureus strains. Carveol, citronellol and geraniol presented a rapid bactericidal effect against E. coli. Conclusions: The higher antimicrobial activity was related to the presence of hydroxyl groups (phenolic and alcohol compounds), whereas hydrocarbons resulted in less activity. The first group, such as carvacrol, l-carveol, eugenol, trans-geraniol, and thymol, showed higher activity when compared to sulfanilamide. Images obtained by scanning electron microscopy indicate that the mechanism causing the cell death of the evaluated bacteria is based on the loss of cellular membrane integrity of function. The present study brings detailed knowledge about the antimicrobial activity of the individual compounds present in essential oils, that can provide a greater understanding for the future researches.

Glaucoma is a neurodegenerative disease that results in the progressive decline and ultimate death of retinal ganglion cells (RGCs). While multiple risk factors are associated with glaucoma, the mechanisms leading to onset and progression of the disease remain unknown. Molecular analysis in various glaucoma models has revealed involvement of non-neuronal cell populations, including astrocytes, Mueller glia and microglia, at early stages of glaucoma. High-dose irradiation was reported to have a significant long-term protective effect in the DBA/2J (D2) mouse model of glaucoma, although the cellular and molecular basis for this effect remains unclear. In particular, the acute effects of irradiation on specific cell populations, including non-neuronal cells, in the D2 retina and nerve have not been assessed. Here we report that irradiation induces transient reduction in proliferating microglia within the optic nerve head and glial lamina within the first week post-irradiation. This was accompanied by reduced microglial activation, with no effect on astrocyte gliosis in those regions. At later stages we confirm that early high-dose irradiation of the mouse head results in improvement of axonal structural integrity and anterograde transport function, without reduction of intraocular pressure. Thus reduced microglial activation induced by irradiation at early stages is associated with reduced optic nerve and retinal neurodegeneration in the D2 mouse model of glaucoma.