Strength and endurance training in cytokine and body composition of people with hiv/aids / Entrenamiento de fuerza y resistencia en citoquinas y composición corporal de personas con vih/sida / Treinamento de força e resistência em citocinas e composição corporal de pessoas com hiv/aids

ABSTRACT Introduction: HIV/AIDS is considered one of the great cases of public health, but it is seen that patients who use antiretroviral therapy (ART) and practice strength training promote a promotion of their health. Objectives: Assess the impact of strength and resistance training on cytokines and body composition in people living with HIV/AIDS. Methods: Randomized clinical trial, the sample consisted of 12 patients, 7 from the Strength Group (GF) and 5 from Group 2, Muscular Resistance (MGR). We compared the levels of IL-2, IL-4, IL-6, IL-10 and TNF-α cytokines and body composition in the first and last sessions. The patients completed 36 strength and resistance training sessions over 12 weeks. Results: After 36 sessions of GRM resistance training, there was a significant increase from 4,734 pg/mL to 5,050 pg/mL of IL-10 (p=0.002). Regarding the GFR, no significant results were found. For body composition, there were significant differences in GFR due to the increase in lean mass of the arms from 6,441g to 7,014g (p=0.04), legs from 16,379g to 17,281g (p=0.02) and whole body of 45,640g to 47,343g (p=0.01). In G2 there was a significant decrease in the percentage of fat in the arms from 23,160% to 20,750% (p = 0.04). To assess quality of life, the WHOQOL-HIV-Bref questionnaire was used, where significant improvement was found in all domains, except for the level of independence domain. Conclusion: We conclude that muscular resistance training is effective in increasing IL-10 and decreasing the percentage of fat in the arms, whereas strength training increases lean mass in arms, legs, and the whole body. Level of Evidence I; Randomized Clinical Trial.

RESUMEN Introducción: El VIH/SIDA es considerado uno de los grandes casos de salud pública, sin embargo, está comprobado que pacientes que hacen uso de la terapia antirretroviral (TARV) y practican entrenamiento de fuerza provoca una promoción de su salud. Objetivos: Evaluar el impacto del entrenamiento de fuerza en la resistencia a las citoquinas y en la composición corporal de las personas que viven con VIH/SIDA. Métodos: Ensayo clínico aleatorizado, la muestra estuvo compuesta por 12 pacientes, siete del Grupo de Fuerza (TFG) y cinco del Grupo de Resistencia Muscular (GRM). Se compararon los niveles de las citocinas IL-2, IL-4, IL-6, IL-10 y TNF-α y la composición corporal en la primera y la última sesión. Los pacientes completaron 36 sesiones de entrenamiento de fuerza y resistencia durante 12 semanas. Resultados: Tras 36 sesiones de entrenamiento de resistencia GRM, se produjo un aumento significativo de 4.734 pg/mL a 5.050 pg/mL de IL-10 (p=0,002). En cuanto a la TFG, no se encontraron resultados significativos. En cuanto a la composición corporal, hubo diferencias significativas en la TFG debido al aumento de la masa magra en brazos de 6.441g a 7.014g (p=0,04), piernas de 16.379g a 17.281g (p=0,02) y cuerpo entero de 45.640g a 47.343g (p=0,01). En el GRM hubo una disminución significativa del porcentaje de grasa en los brazos de 23.160% a 20.750% (p = 0,04). Para la evaluación de la calidad de vida se utilizó el cuestionario WHOQOL-HIV-Bref, donde se encontró una mejoría significativa en todos los dominios, excepto en el dominio nivel de independencia. Conclusión: Concluimos que el entrenamiento de resistencia muscular es eficaz para aumentar la IL-10 y disminuir el porcentaje de grasa en los brazos, mientras que el entrenamiento de fuerza aumenta la masa magra total. Nivel de Evidencia I; Ensayo clínico aleatorizado.

RESUMO Introdução: O HIV/AIDS é considerado um dos grandes casos de saúde pública, porém verifica-se que pacientes que fazem uso de terapia antirretroviral (TARV) e praticam treinamento de força provocam uma promoção de sua saúde. Objetivos: Avaliar o impacto do treinamento de força sobre a resistência nas citocinas e a composição corporal de pessoas vivendo com HIV/AIDS. Métodos: Ensaio clínico randomizado, a amostra foi composta por 12 pacientes, sendo sete do Grupo Força (TFG) e cinco do Grupo Resistência Muscular (GRM). Comparou-se os níveis das citocinas IL-2, IL-4, IL-6, IL-10 e TNF-α e a composição corporal na primeira e na última sessão. Os pacientes completaram 36 sessões de treinamento de força e resistência ao longo de 12 semanas. Resultados: Após 36 sessões de treinamento resistido GRM, houve um aumento significativo de 4.734 pg/mL para 5.050 pg/mL de IL-10 (p=0,002). Em relação à TFG, não foram encontrados resultados significativos. Para composição corporal, houve diferenças significativas na TFG devido ao aumento da massa magra dos braços de 6.441g para 7.014g (p=0,04), pernas de 16.379g para 17.281g (p=0,02) e corpo inteiro de 45.640g para 47.343g (p=0,01). No GRM houve diminuição significativa do percentual de gordura nos braços de 23.160% para 20.750% (p = 0,04). Para avaliação da qualidade de vida foi utilizado o questionário WHOQOL-HIV-Bref, onde foi encontrada uma melhora significativa em todos os domínios, exceto no domínio nível de independência. Conclusão: Conclui-se que o treinamento de resistência muscular é eficaz em aumentar a IL-10 e diminuir o percentual de gordura nos braços, enquanto o treinamento de força aumenta a massa magra geral. Nível de Evidência I; Ensaio Clínico Randomizado.

Risk factors associated with surgical site infection in patients with musculoskeletal cancer / Fatores de risco associados à infecção de sítio cirúrgico em portadores de câncer musculoesquelético / Factores de riesgo asociados a la infección del sitio quirúrgico en pacientes con cáncer musculoesquelético

Background and objectives: surgical site infections (SSI) continue to be a major concern in orthopedic oncology and pose as great a challenge as cancer recurrence, despite the preventive potential of surgery. SSI can be avoided if evidence-based measures are taken. The objective was to assess the frequency of infections in oncological orthopedic surgeries and associated risk factors and inflammatory markers in a reference hospital in the state of Pernambuco. Methods: the frequency of SSI, the identification of isolated microorganisms, the risk factors and the profile of Th1 and Th2 inflammatory markers (IL-2, IL-4, IL-6, IL-10, TNF and IFN-Ƴ) in patients with musculoskeletal cancer were analyzed. Results: SSI were found in 9.1% of patients undergoing orthopedic surgery. Bivariate analysis revealed that a surgical team comprising more than five members (p=0.041) and the need for intraoperative transfusion (p=0.012) were correlated with a higher risk of SSI. The measurement of ultrasensitive C-reactive protein levels to assess the inflammatory response after SSI showed results that were superior to the reference values for each sample, ranging from >5 to >200mg/dl by the immunoturbidimetric method. Of the IL-2, INFγ and TNF (Th1) and IL-4, IL-6, IL-10 (Th2) levels, only interleukin 6 showed high levels, between 6.68 and 58.76 pg/mL. Conclusion: the study found that surgical team with five or more members and blood transfusion were factors associated with the development of SSI in orthopedic surgery in patients with musculoskeletal cancer. Among the inflammatory markers, interleukin 6 (IL-6) showed the highest correlation with the outcome.(AU)

Justificativa e objetivos: as infecções do sítio cirúrgico (ISC) continuam sendo uma grande preocupação na oncologia ortopédica e representam um desafio tão grande quanto a recorrência do câncer, apesar do potencial preventivo da cirurgia. As ISC podem ser evitadas se forem tomadas medidas baseadas em evidências. O objetivo foi avaliar a frequência de infecções em cirurgias ortopédicas oncológicas e os fatores de risco e marcadores inflamatórios associados em um hospital de referência no estado de Pernambuco. Métodos: foram analisados a frequência de ISC, a identificação de microrganismos isolados, os fatores de risco e o perfil de marcadores inflamatórios Th1 e Th2 (IL-2, IL-4, IL-6, IL-10, TNF e IFN-Ƴ) em pacientes portadores de câncer musculoesquelético. Resultados: as ISC foram encontradas em 9,1% dos pacientes submetidos à cirurgia ortopédica. A análise bivariada revelou que uma equipe cirúrgica composta por mais de cinco membros (p=0,041) e a necessidade de transfusão intraoperatória (p=0,012) foram correlacionadas com maior risco de ISC. A dosagem dos níveis de proteína C reativa ultrassensível para avaliação da resposta inflamatória após ISC apresentou resultados superiores aos valores de referência para cada amostra, variando de >5 a >200mg/dl pelo método imunoturbidimétrico. Dos níveis de IL-2, INFγ e TNF (Th1) e IL-4, IL-6, IL-10 (Th2), apenas a interleucina 6 apresentou níveis elevados, entre 6,68 e 58,76 pg/mL. Conclusão: o estudo constatou que equipe cirúrgica com cinco ou mais membros e transfusão sanguínea foram fatores associados ao desenvolvimento de ISC em cirurgia ortopédica em pacientes com câncer musculoesquelético. Entre os marcadores inflamatórios, interleucina 6 (IL-6) apresentou maior correlação com o desfecho.(AU)

Justificación y objetivos: las infecciones del sitio quirúrgico (ISQ) siguen siendo una preocupación importante en la oncología ortopédica y representan un desafío tan grande como la recurrencia del cáncer, a pesar del potencial preventivo de la cirugía. Las ISQ se pueden prevenir si se toman medidas basadas en la evidencia. El objetivo fue evaluar la frecuencia de infecciones en cirugías ortopédicas oncológicas y los factores de riesgo y marcadores inflamatorios asociados en un hospital de referencia en el estado de Pernambuco. Métodos: se analizaron la frecuencia de ISQ, la identificación de microorganismos aislados, los factores de riesgo y el perfil de marcadores inflamatorios Th1 y Th2 (IL-2, IL-4, IL-6, IL-10, TNF e IFN-Ƴ) en pacientes con cáncer musculoesquelético. Resultados: se encontraron ISQ en el 9,1% de los pacientes sometidos a cirugía ortopédica. El análisis bivariado reveló que un equipo quirúrgico compuesto por más de cinco miembros (p=0,041) y la necesidad de transfusión intraoperatoria (p=0,012) se correlacionaron con un mayor riesgo de ISQ. La medición de los niveles de proteína C reactiva ultrasensible para evaluar la respuesta inflamatoria después de la ISQ presentó resultados superiores a los valores de referencia para cada muestra, variando de >5 a >200 mg/dl por el método inmunoturbidimétrico. De los niveles de IL-2, INFγ y TNF (Th1) e IL-4, IL-6, IL-10 (Th2), solo la interleucina 6 mostró niveles elevados, entre 6,68 y 58,76 pg/mL. Conclusión: el estudio encontró que el equipo quirúrgico con cinco o más miembros y la transfusión el estudio encontró que un equipo quirúrgico con cinco o más miembros y transfusión de sangre fueron factores asociados con el desarrollo de ISQ en cirugía ortopédica en pacientes con cáncer musculoesquelético. Entre los marcadores inflamatorios, la interleucina 6 (IL-6) mostró la mayor correlación con el resultado.(AU)

Benznidazole treatment decreases IL-6 levels in Trypanosoma cruzi-infected human adipocytes differentiated from adipose tissue-derived stem cells

BACKGROUND Trypanosoma cruzi, which causes Chagas disease (CD), is a versatile haemoparasite that uses several strategies to evade the host's immune response, including adipose tissue (AT), used as a reservoir of infection. As it is an effective barrier to parasite evasion, the effectiveness of the drug recommended for treating CD, Benznidazole (BZ), may be questionable. OBJECTIVE To this end, we evaluated the parasite load and immunomodulation caused by BZ treatment in the culture of adipocytes differentiated from human adipose tissue-derived stem cells (ADSC) infected with T. cruzi. METHODS The ADSC were subjected to adipogenic differentiation. We then carried out four cultures in which we infected the differentiated AT with trypomastigote forms of the Y strain of T. cruzi and treated them with BZ. After the incubation, the infected AT was subjected to quantitative polymerase chain reaction (qPCR) to quantify the parasite load and transmission electron microscopy (TEM) to verify the infection. The supernatant was collected to measure cytokines, chemokines, and adipokines. FINDINGS We found elevated secretion of IL-6, CXCL-10/IP-10, CCL2/MCP-1, CCL5/RANTES, and leptin in infected fat cells. However, treatment with BZ promoted a decrease in IL-6. MAIN CONCLUSION Therefore, we believe that BZ has a beneficial role as it reduces inflammation in infected fat cells.

Acute effects of different intensities resistance training on inflammatory markers of women with severe obesity / Efeitos agudos de treinamento de força com diferentes intensidades sobre marcadores inflamatórios de mulheres com obesidade severa

ABSTRACT This study objective to compare the acute effects between one resistance training bout with high versus moderate intensities on inflammatory markers in women with severe obesity. Experimental crossover study, performed with adult women with severe obesity (BMI ≥ 40.0 kg/m²; age ≥ 18 years old). Each participant performed a high and moderate intensity resistance training (HIRT and MIRT, respectively) with an interval of 7 days between bouts. Four exercises were performed in the both protocols, with total training volume equalized. MIRT consisted of 3 sets of 8 repetitions each, with an intensity of 75% of 1RM, while HIRT consisted of 2 sets of 6 repetitions, followed by a 20-second rest, with a new performance of 2 to 3 repetitions, with one more rest of 20s and finishing with 2 to 3 more repetitions, at an intensity of 85% of 1RM. Blood samples were collected before, 15 minutes after and 24 hours after both training protocols. The inflammatory markers analyzed were IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ. Nine participants have completed the intervention (n=9; 35.2 ± 10.93 years old; BMI = 48.3 ± 5.06 kg/m²). The Mann-Whitney U test showed that there was no significant difference between the HIRT and MIRT in the concentration of markers. Friedman's test did not report significant differences between intragroup measures for the HIRT as well as MIRT. This research suggests that a single session of high or moderate intensity resistance training does not change the inflammatory status of women with severe obesity.

RESUMO Este estudo objetivou comparar os efeitos agudos entre uma sessão de treinamento de força de alta versus moderada intensidade sobre marcadores inflamatórios em mulheres com obesidade severa. Estudo experimental do tipo cross-over, realizado com mulheres adultas com obesidade severa (IMC ≥ 40,0 kg/m²; idade ≥ 18 anos). Cada participante realizou uma sessão de treinamento de força de alta e de moderada intensidade (HIRT e MIRT, respectivamente) com intervalo de 7 dias entre as sessões. Quatro exercícios foram realizados em ambos os protocolos, com volume total de treino equalizado. O MIRT consistiu em 3 séries de 8 repetições cada, com intensidade de 75% de 1RM, enquanto o HIRT consistiu em 2 séries de 6 repetições, seguidas de um descanso de 20 segundos, com nova execução de 2 a 3 repetições, com mais um descanso de 20s e finalização com mais 2 a 3 repetições, com intensidade de 85% de 1RM. Amostras de sangue foram coletadas antes, 15 minutos após e 24 horas após ambos os protocolos de treino. Os marcadores inflamatórios analisados foram IL-2, IL-4, IL-6, IL-10, TNF-α e IFN-γ. Nove participantes completaram a intervenção (n=9; 35,2 ± 10,93 anos; IMC = 48,3 ± 5,06 kg/m²). O teste U de Mann-Whitney mostrou que não houve diferença significativa entre HIRT e MIRT na concentração dos marcadores. O teste de Friedman não mostrou diferenças significativas entre as medidas intragrupo para HIRT e MIRT. Esta pesquisa sugere que uma única sessão de treinamento de força de alta ou moderada intensidade não altera o estado inflamatório de mulheres com obesidade severa.

Carga respiratória em obesos e jovens asmáticos: um estudo da cinética diafragmática / Respiratory burden in obese and young asthmatics: a study of diaphragmatic kinetics

RESUMO Objetivo O objetivo deste estudo foi avaliar a cinética diafragmática, a função respiratória e a dosagem sérica de leptina e citocinas inflamatórias (IL-6 e TNF-α) em três grupos clínicos: obeso, asmático e saudável. Métodos Estudo clínico-exploratório realizado com 73 jovens (12-24 anos, sendo 42,5% do sexo masculino) alocados em três grupos: obesidade (GO, n = 33), índice de massa corporal (IMC z-score) ≥ + 2 e asmáticos leves controlados (GA, n = 26), classificados pela GINA, e grupo controle saudável (GC, n = 14). Os participantes foram submetidos à ultrassonografia diafragmática, espirometria, pressão respiratória máxima, níveis séricos de leptina e níveis de IL-6 e TNF-α em hemocultura total. Resultados A espessura do diafragma foi maior no GO em comparação ao GA e GC (2,0 ± 0,4 vs 1,7 ± 0,5 e 1,6 ± 0,2, respectivamente, com p < 0,05). A ventilação voluntária máxima (VVM) foi significativamente menor no GO e GA em relação ao GC (82,8 ± 21,4 e 72,5 ± 21,2 vs 102,8 ± 27,3, respectivamente, com p < 0,05). O GO tem a maior taxa de leptina entre todos os grupos (com os outros dois grupos, p < 0,05). Os três grupos tinham níveis semelhantes de TNF-α e IL-6. Conclusão A hipertrofia muscular encontrada no diafragma de indivíduos obesos pode ser justificada pelo aumento do trabalho respiratório imposto pela condição crônica da doença. Esse aumento de espessura não ocorreu em asmáticos leves controlados. Os marcadores IL-6 e TNF-α não detectaram evidências de inflamação muscular, embora fosse esperado que a leptina estivesse alterada em indivíduos obesos. Pacientes obesos e asmáticos apresentaram menor resistência pulmonar do que os saudáveis.

ABSTRACT Objective The aim of this study was to assess the diaphragm kinetics, respiratory function, and serum dosage of leptin and inflammatory cytokines (IL-6 and TNF-α) in three clinical groups: obese, asthmatic, and healthy. Methods This is a clinical exploratory study performed on 73 youths (12-24 years of age, 42.5% male) allocated into three groups: obesity (OG, n=33), body mass index (BMIz-score) ≥ +2, asthmatic (AG, n=26) controlled mild asthmatics, classified by GINA, and Healthy Control Group (CG, n=14). The participants were subjected to diaphragmatic ultrasound, spirometry, maximal respiratory pressure, serum leptin levels, and IL-6 and TNF-α whole blood cell culture levels. Results Diaphragm thickness was higher in OG in comparison to AG and CG (2.0±0.4 vs 1.7±0.5 and 1.6±0.2, both with p<0.05). Maximal voluntary ventilation (MVV) was significantly lower in OG and AG in relation to the CG (82.8±21.4 and 72.5±21.2 vs 102.8±27.3, both with p<0.05). OG has the highest leptin rate among the groups (with the other two groups had p<0.05). All groups had similar TNF-α and IL-6 levels. Conclusion The muscular hypertrophy found in the diaphragm of the obese individuals can be justified by the increase in respiratory work imposed by the chronic condition of the disease. Such increase in thickness did not occur in controlled mild asthmatics. The IL-6 and TNF-α markers detected no evidence of muscle inflammation, even though leptin was expected to be altered in obese individuals. Both obese and asthmatic patients had lower pulmonary resistance than the healthy ones.

Inflammatory Biomarkers and Carotid Thickness in HIV Infected Patients under Antiretroviral Therapy, Undetectable HIV-1 Viral Load, and Low Cardiovascular Risk / Biomarcadores Inflamatórios e Espessura Carotídea em Pacientes Infectados pelo HIV em Terapia Antirretroviral, com Carga Viral de HIV-1 Indetectável e Baixo Risco Cardiovascular

Abstract Background: People living with HIV are at increased risk of cardiovascular disease and carotid thickness, due to the inflammation caused by the virus, the antiretroviral therapy, and other risk factors. However, few studies have observed the occurrence of cardiovascular diseases and carotid thickness in HIV-positive population at low cardiovascular risk and with undetectable viral load. Objectives: To evaluate the association between levels of inflammatory markers and carotid thickness in people living with HIV, under antiretroviral therapy and at low cardiovascular risk. Methods: To determine low cardiovascular risk in both groups (HIV infected and non-infected individuals), the Framingham Risk Score was used. Inflammatory markers (IFN-γ, TNF-α, IL-1β, IL-6, sVCAM-1, and sICAM-1) were assessed using flow cytometry. Carotid thickness (mm) was measured using Doppler ultrasound. Level of significance was p < 0.05. Results: In People living with HIV, age and smoking status were associated with carotid thickness alterations. In the non-HIV group, age, higher total cholesterol, and LDL levels were associated with increased carotid thickness. Using the multivariate analysis, a significant association between TNF-α and IL- 1( levels, and a higher chance of atherosclerosis development in HIV group were observed. Conclusions: Both groups have a similar risk for developing cardiovascular disease, therefore our study demonstrates that HIV-positive individuals with undetectable viral load in antiretroviral therapy without protease inhibitors and with low cardiovascular risk do not present differences in carotid thickness in relation to uninfected individuals.

Resumo Fundamento: As pessoas que vivem com HIV têm um risco aumentado de doença cardiovascular e espessamento da carótida, devido à inflamação causada pelo vírus, à terapia antirretroviral e a outros fatores de risco. No entanto, poucos estudos observaram a ocorrência de doenças cardiovasculares e espessamento carotídeo na população soropositiva com baixo risco cardiovascular e carga viral indetectável. Objetivos: Avaliar a associação entre níveis de marcadores inflamatórios e espessura da carótida em pessoas vivendo com HIV, sob terapia antirretroviral e com baixo risco cardiovascular. Métodos: Para determinar o baixo risco cardiovascular em ambos os grupos (indivíduos infectados e não-infectados pelo HIV), foi utilizado o Escore de Risco de Framingham. Os marcadores inflamatórios (IFN-γ, TNF-α, IL-1β, IL-6, sVCAM-1 e sICAM-1) foram avaliados por citometria de fluxo. A espessura da carótida (mm) foi mensurada por meio de ultrassom com Doppler. O nível de significância foi de p < 0,05. Resultados: Em pessoas vivendo com HIV, a idade e o tabagismo foram associados a alterações da espessura da carótida. No grupo não-HIV, idade e níveis mais altos de colesterol total e LDL foram associados ao aumento da espessura da carótida. Utilizando a análise multivariada, observou-se associação significativa entre os níveis de TNF-α e IL-1β e maior chance de desenvolvimento de aterosclerose no grupo com HIV. Conclusão: Ambos os grupos têm risco semelhante de desenvolver doença cardiovascular, portanto, nosso estudo demonstra que indivíduos HIV-positivos com carga viral indetectável em terapia antirretroviral sem inibidores de protease e com baixo risco cardiovascular não apresentam diferenças na espessura da carótida em relação aos indivíduos não-infectados.

Evaluation of the immunomodulatory effect against splenocytes of Balb/c mice of biflorin obtained from Capraria biflora by a new isolation method

Abstract Biflorin (6,9-dimethyl-3-(4-methylpent-3-en-1-yl) benzo[de]chromene-7,8-dione) is a promising substance that has been increasingly studied in the past decades due to its diverse pharmacological properties (i.e. antitumor, antioxidant, antiinflamatory, antimicrobial activity etc.). Aiming the comprehension of its antitumoral activity we investigated the cell proliferation and cytotoxicity habilities of biflorin against mice splenocytes Balb/c. Biflorin was able to stimulate mice splenocytes Balb/c in 48 h of incubation at a concentration of 20.2 µM. Its immunostimulation promoted the production of cytokines such as: TNF-α, IFN-γ, IL-2, IL-6 and IL-17, inducing the immune profile toward a Th1 response. Moreover, an original method which led to an excellent yield with less processing time compared to the methods described in the literature was developed to obtain biflorin, from sawdust of Capraria biflora L., Scrophulariaceae. This method shows a great potential of increasing the production of this pharmacological active compound.

Gestation and breastfeeding in schistosomotic mice differentially alters the expression of histone deacetylases (HDACs) in adult offspring

BACKGROUND Breastfeeding or gestation in schistosomotic mothers can cause long-term alterations in the immune response of offspring. OBJECTIVES Evaluate the expression of histone deacetylases (HDACs) (all classes), the production of cytokines by T and B lymphocytes and macrophages, and the frequency of CD4+CD25+FoxP3+-cells in adult offspring born and/or suckled by schistosomotic mothers. METHODS We harvested splenocytes from offspring born to (BIM), suckled by (SIM), or born to/suckled by (BSIM) schistosomotic mothers and animals from noninfected mothers (Control) at seven-weeks old and cultured them with/without Concanavalin A. HDAC expression was evaluated by real-time quantitative polymerase chain reaction (qPCR), and cytokines and membrane markers were evaluated by fluorescence-activated cell sorting (FACS). FINDINGS Compared to Control, BIM mice showed increased expression of HDAC9 and frequency of CD4+IL-10+-cells. The SIM group had increased expression of HDAC1, HDAC2, HDAC6, HDAC7, HDAC10, Sirt2, Sirt5, Sirt6, and Sirt7. The BSIM group only had increased HDAC10 expression. The SIM and BSIM groups exhibited decreased frequencies of CD4+IL-4+-cells and CD4+CD25+FoxP3+-cells, along with a higher frequency of CD14+IL-10+-cells and an increase in CD45R/B220+IL-10+-cells. The BSIM group also showed a high frequency of CD4+IL10+-cells. MAIN CONCLUSIONS Breastfeeding induced the expression of HDACs from various classes involved in reducing inflammatory responses. However, gestation enhanced the expression of a single HDAC and breastfeeding or gestation appears to favour multiple IL-10-dependent pathways, but not cells with a regulatory phenotype.

Maternal schistosomiasis: IL-2, IL-10 and regulatory T lymphocytes to unrelated antigen in adult offspring mice

Abstract INTRODUCTION: We evaluated IL-10, IL-2 and regulatory T cells (Treg), in response to ovalbumin (OA), in offspring from schistosomotic mouse mothers. METHODS: We used animals born (BIM) or suckled (SIM) from infected mothers; and mice born/suckled from infected (BSIM) or non-infected mothers (CONTROL). After OA+adjuvant immunization, spleen cells were cultured, with or without OA, and doubly marked for cytometry. RESULTS: BIM showed fewer CD4+/IL-2+ and more B220+/IL-10+ cells, whereas the SIM group showed increased Treg frequency. BSIM had fewer B220+/IL-10+ and Treg cells. CONCLUSIONS: Separately, gestation or nursing induced immunosuppressive cells in infected mothers, but improved anti-OA immunity when combined.

Impacto da infecção por HTLV-1 nas manifestações clínicas e no tratamento de pacientes com estrongiloidíase / Impact of HTLV-1 infection on clinical presentations and treatment of strongyloidiasis patients

A estrongiloidíase é uma enfermidade que acomete cerca de 100 milhões de pessoas em todo mundo. Essa parasitose apresenta alta prevalência e tem maior gravidade clínica entre indivíduos imunossuprimidos, principalmente aqueles portadores do vírus linfotrópico de células T humana tipo 1 (HTLV). Este fato torna a coinfecção por esse vírus em pacientes parasitados por Strongyloides stercoralis um grave problema de saúde pública. O presente estudo teve por objetivo revisar os estudos sobre coinfecção por HTLV/S. stercoralis. Foi realizada busca eletrônica completa de dados disponíveis sobre a coinfecção entre o vírus e S. stercoralis. As publicações foram capturadas a partir das bases de dados PubMed e SciELO, sendo utilizados os seguintes descritores "vírus linfotrópico de células T humanas tipo 1", "HTLV-1", "S. stercoralis" e "estrongiloidiase". A infecção por HTLV em pacientes parasitados representa fator de risco para o desenvolvimento de estrongiloidíase grave e, nesses indivíduos, o tratamento recomendado deve ser realizado e monitorado para garantir o sucesso terapêutico.(AU)

Strongyloidiasis is a disease that affects approximately 100 million people worldwide. This parasitosis is highly prevalent and more clinically severe among immunosuppressed individuals, particularly those with Human T-lymphotropic virus 1 (HTLV-1). This fact makes the co-infection with this virus in patients parasitized by Strongyloides stercoralis a serious public health problem. The present study aimed at reviewing the studies of co-infection with HTLV/S. stercoralis. A complete electronic search for available data about the co-infection of the virusand S. stercoralis was performed. The publications were obtained from the databases PubMed and SciELO, with the following descriptors being used: "Human T-lymphotropic Virus type 1, "HTLV-1", S. stercoralis, and "strongyloidiasis". The infection with HTLV in infected patients is a risk factor for the development of severe strongyloidiasis, and for these individuals the recommended treatment should be performed and monitored to ensure therapeutic success.(AU)

Single nucleotide polymorphisms of cytokine-related genes and association with clinical outcome in a Chagas disease case-control study from Brazil

BACKGROUND The severity of chronic chagasic cardiomyopathy (CCC), the most frequent clinical outcome of Chagas disease (CD), has been associated with cytokine-enriched heart tissue inflammation, and high serum levels of transforming growth factor (TGFβ), interferon-gamma (IFNγ), and tumour necrosis factor (TNF). Conversely, increased interleukin (IL)-10 serum concentrations have been associated with asymptomatic CD. Cytokines and cytokine-related gene polymorphisms may control cytokine expression and have been proposed to contribute to CCC outcomes. OBJECTIVES We evaluated the association of 13 cytokine-related genes (TGFB: rs8179181, rs8105161, rs1800469; IL10: rs1800890, rs1800871, rs1800896; IFNG: rs2430561; TNF: rs1800629; BAT1: rs3853601; LTA: rs909253, rs2239704; TNFR1: rs767455; TNFR2: rs1061624) with risk and progression of CCC. FINDINGS Four hundred and six seropositive patients from CD endemic areas in the state of Pernambuco, north-eastern Brazil, were classified as non-cardiopathic (A, 110) or cardiopathic (mild, B1, 163; severe, C, 133). We found no evidence of TGFB, IL10, TNF, or TNFR1/2 gene polymorphisms associated with CCC risk or progression. Only BAT1 rs3853601 −22G carriers (B1 vs. C: OR = 0.5; p-value = 0.03) and IFNG rs2430561 +874AT (A vs. C: OR = 0.7; p-value = 0.03; A vs. B1+C: OR = 0.8; p-value = 0.02) showed a significant association with protection from cardiopathy in a logistic regression analysis with adjustment for gender and ethnicity; however, the association disappeared after performing adjustment for multiple testing. A systematic review of TNF rs1800629 −308G>A publications included five studies for meta-analysis (534 CCC and 472 asymptomatic patients) and showed no consensus in pooled odds ratio (OR) estimates for A allele or A carriers (OR = 1.4 and 1.5; p-values = 0.14 and 0.15, respectively). In CD patients, TNF serum levels were increased, but not affected by the TNF rs1800629 −308A allele. MAIN CONCLUSIONS Our data suggest no significant contribution of the analysed gene variants of cytokine-related molecules to development/severity of Chagas' heart disease, reinforcing the idea that parasite/host interplay is critical to CD outcomes.

Gestation and breastfeeding in schistosomotic mothers differently modulate the immune response of adult offspring to postnatal Schistosoma mansoni infection

Schistosoma mansoni antigens in the early life alter homologous and heterologous immunity during postnatal infections. We evaluate the immunity to parasite antigens and ovalbumin (OA) in adult mice born/suckled by schistosomotic mothers. Newborns were divided into: born (BIM), suckled (SIM) or born/suckled (BSIM) in schistosomotic mothers, and animals from noninfected mothers (control). When adults, the mice were infected and compared the hepatic granuloma size and cellularity. Some animals were OA + adjuvant immunised. We evaluated hypersensitivity reactions (HR), antibodies levels (IgG1/IgG2a) anti-soluble egg antigen and anti-soluble worm antigen preparation, and anti-OA, cytokine production, and CD4+FoxP3+T-cells by splenocytes. Compared to control group, BIM mice showed a greater quantity of granulomas and collagen deposition, whereas SIM and BSIM presented smaller granulomas. BSIM group exhibited the lowest levels of anti-parasite antibodies. For anti-OA immunity, immediate HR was suppressed in all groups, with greater intensity in SIM mice accompanied of the remarkable level of basal CD4+FoxP3+T-cells. BIM and SIM groups produced less interleukin (IL)-4 and interferon (IFN)-g. In BSIM, there was higher production of IL-10 and IFN-g, but lower levels of IL-4 and CD4+FoxP3+T-cells. Thus, pregnancy in schistosomotic mothers intensified hepatic fibrosis, whereas breastfeeding diminished granulomas in descendants. Separately, pregnancy and breastfeeding could suppress heterologous immunity; however, when combined, the responses could be partially restored in infected descendants.

Spatiotemporal analysis of reported cases of acute Chagas disease in the State of Pernambuco, Brazil, from 2002 to 2013

INTRODUCTION: Control strategies to eliminate the transmission of Chagas disease by insect vectors have significantly decreased the number of reported acute cases in Brazil. However, data regarding the incidence and distribution of acute Chagas disease cases in the State of Pernambuco are unavailable in the literature. METHODS: A geographical information system was used to delineate the spatiotemporal distribution profile of the cases from 2002 to 2013 in 185 municipalities of Pernambuco based on the municipality where notification occurred. The results were presented in digital maps generated by the TerraView software (INPE). RESULTS: A total of 302 cases of acute disease were recorded in 37.8% of the municipalities, for a total of 0.13 cases per 1,000,000 inhabitants per year. Out of the 302 cases, 99.3% were reported between 2002 and 2006. The most affected municipalities were Carnaubeira da Penha, Mirandiba and Terra Nova. The risk maps showed a significant decrease in the number of notifications and a concentration of cases in the Midwest region. CONCLUSIONS: This study highlights a significant decrease in new cases of acute Chagas disease in Pernambuco starting in 2006 when Brazil received an international certification for the interruption of vectorial transmission by Triatoma infestans. However, control strategies should still be encouraged because other triatomine species can also transmit the parasite; moreover, other transmission modes must not be neglected. .

Clinical and economic aspects of the use of rituximab in non-Hodgkin's lymphoma

Non-Hodgkin's lymphoma (NHL) consists of a group of neoplasias involving mainly B cells and represents 90% of all lymphomas. The current available therapy is based on chemotherapy associated with the monoclonal antibody rituximab (Mab Thera(r)), which targets the CD20 protein, present in over 80% of NHL mature B cells. Recent clinical reports show a preference for combining the benefits of immunotherapy and adjuvant chemotherapy, thus generating safe and effective alternative treatments. The current review aimed at evaluating various aspects related to the use of rituximab for NHL, highlighting the possible inhibitory mechanisms of cell proliferation, the achieved clinical results, and the expected clinical and economic outcomes of treatments. The results from clinical tests indicate the need for a better understanding of the critical mechanisms of action of this antibody, which may maximize its therapeutic efficacy. This therapy not only represents a viable option to treat most types of NHLs, especially when associated with conventional chemotherapy, but also offers cost-utility and cost-effectiveness advantages.

O Linfoma não-Hodgkin (LNH) consiste em um grupo de neoplasias envolvendo, principalmente, as células B e representa 90% de todos os linfomas. A terapia atual disponível é baseada em quimioterapia associada ao anticorpo monoclonal rituximabe (Mab Thera(r)), que tem como alvo a proteína CD20, presente em mais de 80% das células B maduras do LNH. Recentes relatórios clínicos mostram preferência para combinar os benefícios da quimioterapia adjuvante e imunoterapia, gerando alternativas de tratamentos seguro e eficaz. O trabalho de revisão teve por objetivo avaliar vários aspectos relacionados à aplicação do rituximabe no LNH, destacando os possíveis mecanismos inibitórios da proliferação celular, os resultados clínicos obtidos e as implicações clínicas e econômicas esperadas para o tratamento. Os resultados de testes clínicos indicam a necessidade de uma melhor compreensão dos mecanismos críticos de ação deste anticorpo, que poderão maximizar a sua eficácia terapêutica. Essa terapia não representa apenas uma opção viável para o tratamento da maioria dos tipos de LNH, principalmente quando associado à quimioterapia convencional, mas, também, oferece vantagens em termos de custo-utilidade e custo-efetividade.

Evaluation of CD4+CD25+ T lymphocyte response time kinetics in patients with chronic Chagas disease after in vitro stimulation with recombinant Trypanosoma cruzi antigens

Introduction CD4+CD25+ T lymphocytes have been implicated in the regulation of host inflammatory response against Trypanosoma cruzi, and may be involved in the clinical course of the disease. Methods Peripheral blood mononuclear cells from patients with chronic Chagas disease were cultured in the presence of T. cruzi recombinant antigens and assayed for lymphocytes at distinct time points. Results It was possible to differentiate clinical forms of chronic Chagas disease at days 3 and 5 according to presence of CD4+CD25+ T cells in cell cultures. Conclusions Longer periods of cell culture proved to be potentially valuable for prospective evaluations of CD4+CD25+ T lymphocytes in patients with chronic Chagas disease. .

Investigação de infecção tuberculosa latente em pacientes com psoríase candidatos ao uso de drogas imunobiológicas / Investigation of latent tuberculosis infection in patients with psoriasis who are candidate for receiving immunobiological drugs

O uso dos inibidores do fator de necrose tumoral no tratamento de pacientes com psoríase vem sendo relacionado a uma maior incidência de tuberculose, particularmente, nas suas formas extrapulmonar e disseminada. Apesar de sua indiscutível eficácia, essas drogas elevam o risco da reativação de infecção tuberculosa latente (ITBL), tornando obrigatório o diagnóstico da referida condição antes da sua administração. A investigação da infecção tuberculosa latente pelo teste cutâneo da tuberculina é falha, dada sua baixa especificidade, além de apresentar resultados duvidosos em pacientes com psoríase. Ensaios baseados na detecção da produção de interferon-gama in vitro por células monoclonais periféricas, estimuladas por antígenos específicos (Esat-6 e CFP-10), parecem oferecer maior acurácia quando comparados ao teste de Mantoux na identificação de infecção tuberculosa latente. Essa ferramenta diagnóstica tem oferecido maior especificidade, já que não apresenta correlação com medidas indiretas de exposição ao M. tuberculosis, como a vacinação por BCG, e com infecções por outras micobactérias.

The use of tumor necrosis factor inhibitors for the treatment of patients with psoriasis has been related to a higher incidence of tuberculosis, specially the disseminated and extrapulmonary forms. Despite their efficacy, these drugs increase the risk of reactivating latent tuberculosis infection, thus requiring diagnosis of the condition before their administration. Investigation of latent tuberculosis infection with tuberculin skin test is ineffective due to its low specificity and the dubious results that it generates in patients with psoriasis. Assays based on the detection of synthesis of gamma interferon in vitro by peripheral monoclonal cells, stimulated by specific antigens (ESAT-6 and CFP-10), seem to offer better accuracy when compared to the Mantoux test in identifying latent tuberculosis infection. This diagnosis tool has demonstrated higher specificity, since it has no correlation with indirect forms of exposure to M. tuberculosis such as BCG vaccination or with infections by other mycobacteria.

Chagas disease in the State of Pernambuco, Brazil: analysis of admissions and mortality time series / Doença de Chagas no Estado de Pernambuco, Brasil: análise de séries históricas das internações e da mortalidade

INTRODUCTION: A time series study of admissions, deaths and acute cases was conducted in order to evaluate the context of Chagas disease in Pernambuco. METHODS: Data reported to the Information Technology Department of the Brazilian National Health Service between 1980 and 2008 was collected for regions and Federal Units of Brazil; and microregions and municipalities of Pernambuco. Rates (per 100,000 inhabitants) of hospitalization, mortality and acute cases were calculated using a national hospital database (SIH), a national mortality database (SIM) and the national Information System for Notifiable Diseases (SINAN), respectively. RESULTS: The national average for Chagas disease admissions was 0.99 from 1995 to 2008. Pernambuco obtained a mean of 0.39 in the same period, with the highest rates being concentrated in the interior of the state. The state obtained a mean mortality rate of 1.56 between 1980 and 2007, which was lower than the national average (3.66). The mortality rate has tended to decline nationally, while it has remained relatively unchanged in Pernambuco. Interpolating national rates of admissions and deaths, mortality rates were higher than hospitalization rates between 1995 and 2007. The same occurred in Pernambuco, except for 2003. Between 2001 and 2006, rates for acute cases were 0.56 and 0.21 for Brazil and Pernambuco, respectively. CONCLUSIONS: Although a decrease in Chagas mortality has occurred in Brazil, the disease remains a serious public health problem, especially in the Northeast region. It is thus essential that medical care, prevention and control regarding Chagas disease be maintained and improved.

INTRODUÇÃO: Foi realizado estudo de séries históricas de internações, óbitos e casos agudos por doenças de Chagas objetivando avaliar o contexto desta enfermidade em Pernambuco. MÉTODOS: Foram coletados dados notificados de 1980 a 2008 ao Departamento de Informática do Sistema Único de Saúde (DATASUS/MS) para regiões e unidades federativas do Brasil, microrregiões e municípios pernambucanos. As taxas (por 100.000 habitantes) de internações, mortalidade e casos agudos foram obtidas por consulta ao Sistema de Informações Hospitalares (SIH), Sistema de Informação sobre Mortalidade (SIM) e Sistema de Informações de Agravos de Notificação (SINAN), respectivamente. RESULTADOS: A média de internações nacional por doença de Chagas ficou em 0,99 no período de 1995 a 2008. Pernambuco, neste intervalo, apresentou média de 0,39, com as maiores taxas concentradas no interior do estado. Este estado obteve média de óbitos 1,56 entre 1980 e 2007, valor inferior a brasileira (3,66). O país demonstrou declínio de óbitos na análise de tendência, com Pernambuco encontrando-se em estado estacionário para esta taxa. Interpolando os dados referentes a internações e óbitos, evidenciou-se mortalidade em valores superiores as taxas de internações nacionais, entre 1995 e 2007. O mesmo fato ocorreu em Pernambuco, exceto em 2003. Entre 2001 e 2006, a taxa de casos agudos foi de 0,56 e 0,21 respectivamente para Brasil e para Pernambuco. CONCLUSÕES: Mesmo o Brasil demonstrando redução na mortalidade, a doença permanece como grave problema de saúde pública, principalmente no nordeste. Desta forma, é fundamental a manutenção e melhoria das ações de atenção médica, controle e prevenção já existentes.

A comparative analysis of the suitability of different peripheral blood samples for reverse transcriptase polymerase chain reaction / Análise comparativa da adequação de diferentes amostras de sangue periférico em ensaios de reação em cadeia da polimerase via transcriptase reversa

Venipuncture is one of the easiest clinical procedures to obtain viable blood samples to evaluate gene expression using mRNA analysis. However, the use of this sample type in reverse transcriptase polymerase chain reaction tests (RT-PCR) without prior treatment is controversial. We therefore propose to compare the suitability of different peripheral blood samples (whole blood without treatment, whole blood with hemolysis, peripheral blood mononuclear cells and frozen whole blood) for RT-PCR analysis. The results showed that, despite the blood sample being peripheral, it is possible to extract a fair amount of RNA and perform target gene amplification. Thus, peripheral blood without prior treatment could be used to investigate the gene expression using Real Time PCR.

A punção venosa representa um dos procedimentos clínicos mais simples na obtenção de amostras de sangue periférico e avaliação da expressão gênica através da análise do RNA mensageiro. Contudo, a utilização desta amostra, sem um tratamento prévio, em ensaios de Transcrição Reversa (RT-PCR) é controverso. Desta forma, propomos comparar a adequação de diferentes amostras de sangue periférico (sangue total sem tratamento, sangue total após hemólise, células mononucleares do sangue periférico e sangue total congelado) em ensaios de Transcrição Reversa Os resultados mostraram que independente da amostra de sangue periférico é possível extrair RNA em quantidade adequada e realizar a amplificação do gene alvo. Desta forma, o sangue periférico sem tratamento prévio pode ser utilizado em abordagens que envolvam a avaliação da expressão gênica por reação em cadeia da polimerase (PCR) em tempo real.

Diagnosis of Chagas disease: what has been achieved? What remains to be done with regard to diagnosis and follow up studies?

In the acute phase and in the chronic forms of Chagas disease, the etiological diagnosis may be performed by detection of the parasite using direct or indirect parasitological methods and by the presence of antibodies in the serum by way of serological tests. Several techniques are easily available, ranging from the simplest wet smear preparation to immuno-enzymatic assays with recombinant antigens that will meet most diagnostic needs. Other tests under evaluation include a molecular test using polymerase chain reaction, which has shown promising results and may be used as a confirmatory test both in the acute and chronic phases of the disease. Better rapid tests are needed for diagnosis, some of which are already under evaluation. Additionally, there is a need for tools that can identify patients cured shortly after specific treatment. Other needs include a marker for prognosis and early diagnosis of congenital transmission.

Prevalência de infecção chagásica em doadores de sangue no estado de Pernambuco, Brasil / The prevalence of chagasic infection among blood donors in the State of Pernambuco, Brazil

A doença de Chagas é uma infecção sistêmica de evolução crônica cujo agente etiológico é o parasita Trypanosoma cruzi. O último relato encontrado sobre a soroprevalência da doença em doadores de sangue realizado na capital pernambucana, Recife, data de 1970, onde foi encontrada uma prevalência de 4,4 por cento em doadores de um hospital local. Devido à falta de informações divulgadas sobre a infecção por T. cruzi e sendo Pernambuco uma região endêmica para esta enfermidade, o presente estudo se propôs a analisar o perfil dos doadores de sangue do Hemocentro de Pernambuco (Hemope), que apresentaram reatividade para doença de Chagas, no período de 2002 a 2007. O perfil dos doadores inaptos foi avaliado de acordo com gênero, idade e procedência segundo as mesorregiões de Pernambuco. Foi encontrada uma prevalência de 0,17 por cento para doença de Chagas e 6,89 por cento das bolsas descartadas deveram-se a essa reatividade. Em relação ao gênero dos doadores, foi significativamente maior a contribuição dos homens (p<0,0001). A faixa etária de 18-30 anos apresentou menor quantidade de sorologias reativas (20,21 por cento). Foi verificado também que, na Região Metropolitana do Recife, a quantidade de reações inconclusivas foi estatisticamente maior que a quantidade de sorologias reagentes (p=0,0440). Desta forma, estudos epidemiológicos fornecem dados importantes no sentido de se avaliar diretamente o risco de transmissão de uma doença por transfusão sanguínea e permitem que também em regiões endêmicas se avalie a eficácia das medidas para o controle vetorial.

Chagas disease is a systemic infection with a chronic onset transmitted by Trypanosoma cruzi. The last study conducted in Recife, capital of Pernambuco state, was carried out during 1970. At that time a prevalence of 4.4 percent was found among blood donors of a local hospital. Due to the lack of epidemiology data on T. cruzi infection and as Pernambuco is an endemic region, the present study describes the profile of blood donors who presented reactivity for Chagas disease during the period of 2002 to 2007 in the state's blood bank (Hemope). The profile of unsuitable donors was evaluated according to gender, age and according to the meso-regions of Pernambuco. A prevalence of 0.17 percent was found for Chagas disease, whereas 6.89 percent of the rejected blood bags were due to this reactivity. As far as gender is concerned, the reactivity of men was higher than that of women (p<0.0001). Additionally, the age group between 18-30 years was less infected (20.21 percent). On analyzing the reactivity in each one of the meso-regions of the state, it was found that, in the Metropolitan Region of Recife, the number of inconclusive reaction cases was statistically higher than the number of reactive serology cases (p=0.0440). Thus, epidemiological studies provide important data to indirectly evaluate the risk of blood-borne diseases and allow indirect evaluation of the effectiveness of vectorial control measures in endemic regions.