In silico prediction of ADMET parameters and in vitro evaluation of antioxidant and cytotoxic activities promoted by indole-thiosemicarbazone compounds.

Cancer is a complex and multifactorial disease characterized by uncontrolled cell growth and is one of the main causes of death in the world. This work aimed to evaluate a small series of 10 different indole-thiosemicarbazone compounds as potential antitumor agents. This is a pioneering study. For this, the antioxidant and cytotoxic capacity against normal and tumor cells was evaluated. The results showed that the compounds were able to promote moderate to low antioxidant activity for the ABTS radical scavenging assay. ADMET in silico assays showed that the compounds exhibited good oral bioavailability. As for toxicity, they were able to promote low cytotoxicity against normal cells, in addition to not being hemolytic. The compounds showed promising in vitro antitumor activity against the T47D, MCF-7, Jurkat and DU-145 strains, not being able to inhibit the growth of the Hepg2 strain. Through this in vitro study, it can be concluded that the compounds are potential candidates for antitumor agents.

Interaction study with DNA/HSA, anti-topoisomerase IIα, cytotoxicity and in vitro antiproliferative evaluations and molecular docking of indole-thiosemicarbazone compounds.

In this work we will discuss the antiproliferative evaluation and the possible mechanisms of action of indole-thiosemicarbazone compounds LTs with anti-inflammatory activity, previously described in the literature. In this perspective, some analyzes were carried out, such as the study of binding to human serum albumin (HSA) and to biological targets: DNA and human topoisomerase IIα (topo). Antiproliferative study was performed with DU-145, Jukart, MCF-7 and T-47D tumor lines and J774A.1, besides HepG2 macrophages and hemolytic activity. In the HSA interaction tests, the highest binding constant was 3.70 × 106 M-1, referring to LT89 and in the fluorescence, most compounds, except for LT76 and LT87, promoted fluorescent suppression with the largest Stern-Volmer constant for the LT88 3.55 × 104. In the antiproliferative assay with DU-145 and Jurkat strains, compounds LT76 (0.98 ± 0.10/1.23 ± 0.32 µM), LT77 (0.94 ± 0.05/1.18 ± 0.08 µM) and LT87 (0.94 ± 0.12/0.84 ± 0.09 µM) stood out, due to their IC50 values mentioned above. With the MCF-7 and T-47D cell lines, the lowest IC50 was presented by LT81 with values of 0.74 ± 0.12 µM and 0.68 ± 0.10 µM, respectively, followed by the compounds LT76 and LT87. As well as the positive control amsacrine, the compounds LT76, LT81 and LT87 were able to inhibit the enzymatic action of human Topoisomerase IIα.

The Impact of Cardiovascular Risk Factors and Renal Disease on Outcomes in Patients Hospitalized with COVID-19: An Observational Study from Two Public Hospitals in Brazil

Abstract Background Cardiovascular risk factors are prognostic factors in coronavirus disease 2019 (COVID-19) and have been scarcely studied in Brazil. Objective The aim of this study was to assess the impact of cardiovascular risk factors on the outcomes of patients admitted for COVID-19. Methods From July 2020 to February 2021, 200 patients from two public hospitals were enrolled. Patients were included if they had typical symptoms or signs of COVID-19, a positive real-time polymerase chain reaction test (RT-PCR) for COVID-19, and an age above 18 years. This is a prospective, observational, and longitudinal study. Data were collected within 24 h of admission. The primary endpoint was a combination of hospital lethality, mechanical ventilation, hemodialysis, or length of hospital stay >28 days. Continuous variables were compared with the Student's t-test for independent samples or the Mann-Whitney test. For comparisons of proportions, the χ 2 test was applied. ROC curves and survival curves were constructed. Multivariate logistic regression was performed to identify independent predictors of events. The level of significance was 0.05. Results There were 98 (49%) events during the hospital course, and 72 (36%) died in the hospital. Patients with a primary endpoint were older and more likely to have a history of hypertension, diabetes, chronic obstructive pulmonary disease (COPD), and chronic kidney disease (CKD). Vital signs at admission associated with events were diastolic blood pressure, respiratory rate, and oxygen saturation in ambient air (O 2 Sat). Serum creatinine >1.37 mg/dL at admission had a sensitivity of 51.6 and a specificity of 82% to predict the primary endpoint, with an area under the curve (AUC) of 0.68. In multivariate analysis, age, diabetes, CKD, and COPD were independent predictors of the primary endpoint. Age and CKD were independent predictors of in-hospital lethality. Conclusion Cardiovascular risk factors, such as diabetes and CKD, were related to a worse prognosis in patients hospitalized with COVID-19 in this sample from two public hospitals in the state of Rio de Janeiro.

Thiazolidine derivatives: In vitro toxicity assessment against promastigote and amastigote forms of Leishmania infantum and ultrastructural study.

Neglected diseases, such as Leishmaniasis, constitute a group of communicable diseases that occur mainly in tropical countries. Considered a public health problem with limited treatment. Therefore, there is a need for new therapies. In this sense, our proposal was to evaluate in vitro two series of thiazolidine compounds (7a-7e and 8a-8e) against Leishmania infantum. We performed in vitro evaluations through macrophage cytotoxicity assays (J774) and nitric oxide production, activity against promastigotes and amastigotes, as well as ultrastructural analyzes in promastigotes. In the evaluation of cytotoxicity, the thiazolidine compounds presented CC50 values between 8.52 and 126.83 µM. Regarding the evaluation against the promastigote forms, the IC50 values ranged between 0.42 and 142.43 µM. Compound 7a was the most promising, as it had the lowest IC50. The parasites treated with compound 7a showed several changes, such as cell body shrinkage, shortening and loss of the flagellum, intense mitochondrial edema and cytoplasmic vacuolization, leading the parasite to cell inviability. In assays against the amastigote forms, the compound showed a low IC50 (0.65 µM). These results indicate that compound 7a was efficient for both evolutionary forms of the parasite. In silico studies suggest that the compound has good oral bioavailability. These results show that compound 7a is a potential drug candidate for the treatment of Leishmaniasis.

Brazilian Group of Gastrointestinal Tumours' consensus guidelines for the management of oesophageal cancer.

Oesophageal cancer is among the ten most common types of cancer worldwide. More than 80% of the cases and deaths related to the disease occur in developing countries. Local socio-economic, epidemiologic and healthcare particularities led us to create a Brazilian guideline for the management of oesophageal and oesophagogastric junction (OGJ) carcinomas. The Brazilian Group of Gastrointestinal Tumours invited 50 physicians with different backgrounds, including radiology, pathology, endoscopy, nuclear medicine, genetics, oncological surgery, radiotherapy and clinical oncology, to collaborate. This document was prepared based on an extensive review of topics related to heredity, diagnosis, staging, pathology, endoscopy, surgery, radiation, systemic therapy (including checkpoint inhibitors) and follow-up, which was followed by presentation, discussion and voting by the panel members. It provides updated evidence-based recommendations to guide clinical management of oesophageal and OGJ carcinomas in several scenarios and clinical settings.

Brazilian Group of Gastrointestinal Tumours' consensus guidelines for the management of gastric cancer.

Gastric cancer is among the ten most common types of cancer worldwide. Most cases and deaths related to the disease occur in developing countries. Local socio-economic, epidemiologic and healthcare particularities led us to create a Brazilian guideline for the management of gastric carcinomas. The Brazilian Group of Gastrointestinal Tumors (GTG) invited 50 physicians with different backgrounds, including radiology, pathology, endoscopy, nuclear medicine, genetics, oncological surgery, radiotherapy and clinical oncology, to collaborate. This document was prepared based on an extensive review of topics related to heredity, diagnosis, staging, pathology, endoscopy, surgery, radiation, systemic therapy and follow-up, which was followed by presentation, discussion, and voting by the panel members. It provides updated evidence-based recommendations to guide clinical management of gastric carcinomas in several scenarios and clinical settings.

Migração e atenção primária à saúde no estado de Roraima / Migration and primary health care in the state of Roraima / Migración y atención primaria en salud en el estado de Roraima

A migração não é um fenômeno recente e muito menos restrito a uma parte do mundo. Este artigo tem por objetivo chamar atenção para o aumento significativo de demanda pelo direito à saúde no estado de Roraima e como as políticas públicas são de suma importância para ajudar na superação de uma crise humanitária. O estudo foi desenvolvido dentro de uma abordagem da pesquisa qualitativa do tipo teórica, a partir da realização de uma revisão bibliográfica referente à migração e ao direito à saúde desta população e análise de públicos e publicizados por meio do sítio eletrônico do Ministério da Saúde foram obtidos diretamente por meio de busca ativa e solicitados por meio da Lei de Acesso a Informação. Os dados da Atenção Primária apresentam uma evolução ao longo dos últimos anos. Pode-se inferir, a partir dos dados presentados pela ACNUR, bem como pelo aumento significativo de atendimentos, que o fluxo migratório teve um impacto importante nesse primeiro nível de atenção do sistema estadual de saúde. Em que pese a complexidade desse tipo de política pública, cada vez mais os dados apontam para a necessidade de um olhar atento para os fluxos migratórios internos e internacionais, na perspectiva de ações intersetoriais com o intuito de assegurar os direitos humanos, a dignidade da vida, o direito à saúde, à educação, ao trabalho e a liberdade de expressão. (AU)

Migration is not a recent phenomenon and much less restricted to one part of the world. This article is about the significant increase in demand for the right to health in the state of Roraima and how public policies are of paramount importance in helping to overcome a humanitarian crisis. The study was developed within a theoretical qualitative research approach, based on a bibliographic review regarding migration and the right to health of this population and analysis of public and published through the Ministry of Health website, were obtained directly through active search and requested through the Access to Information Act. Primary care data have evolved over the last few years. It can be inferred from the data presented by UNHCR, as well as the significant increase in attendance, that the migratory flow had an important impact on this first level of care of the state health system. Despite the complexity of this type of public policy, data increasingly point to the need for a close look at internal and international migratory flows, from the perspective of intersectoral actions to ensure human rights, the dignity of life. , the right to health, education, work and freedom of expression. (AU)

La migración no es un fenómeno reciente y mucho menos restringido a una parte del mundo. Este artículo tiene como objetivo llamar la atención sobre el aumento significativo de la demanda del derecho a la salud en el estado de Roraima y cómo las políticas públicas son de suma importancia para ayudar a superar una crisis humanitaria. El estudio se desarrolló dentro de un enfoque teórico de investigación cualitativa, basado en una revisión bibliográfica sobre la migración y el derecho a la salud de esta población y el análisis del público y publicado a través del sitio web del Ministerio de Salud, se obtuvieron directamente a través de la búsqueda activa y se solicitaron a través de la Ley de Acceso a la Información. Los datos de atención primaria han evolucionado en los últimos años. Se puede inferir de los datos presentados por ACNUR, así como del aumento significativo en la asistencia, que el flujo migratorio tuvo un impacto importante en este primer nivel de atención del sistema de salud estatal. A pesar de la complejidad de este tipo de política pública, los datos apuntan cada vez más a la necesidad de observar de cerca los flujos migratorios internos e internacionales, desde la perspectiva de acciones intersectoriales para garantizar los derechos humanos, la dignidad de la vida, el derecho a la salud, la educación, el trabajo y la libertad de expresión.

Novel 4-quinoline-thiosemicarbazone derivatives: Synthesis, antiproliferative activity, in vitro and in silico biomacromolecule interaction studies and topoisomerase inhibition.

Twelve 2-(quinolin-4-ylmethylene) hydrazinecarbothioamide derivatives were synthetized and their biological properties were investigated, among which, the ability to interact with DNA and BSA through UV-Vis absorption, fluorescence, Circular Dichroism, molecular docking and relative viscosity, antiproliferative activity against MCF-7 and T-47D mammary tumor cells and RAW-264.7 macrophages and inhibitory capacity of the enzyme topoisomerase IIα. In the binding study with DNA and BSA, all the compounds displayed affinity for interaction with both biomolecules, especially JF-92 (p-ethyl-substituted), with binding constant of 1.62 × 106 and 1.43 × 105, respectively, and DNA binding mode by intercalation. The IC50 values were obtained between 0.81 and 1.48 µM and topoisomerase inhibition results in 10 µM. Thus, we conclude that the reduction of the acridine to quinoline ring did not disrupt the antitumor action and that substitution patterns are important for biomolecule interaction affinity as they demonstrate the potential of these compounds for anticancer therapy.

Static or dynamic stretching program does not change the acute responses of neuromuscular and functional performance in healthy subjects: a single-blind randomized controlled trial / Programa de alongamento estático ou dinâmico não altera as respostas agudas do desempenho neuromuscular e funcional de sujeitos saudáveis: ensaio controlado randomizado e cego / Un programa de estiramientos estáticos o dinámicos no modifica las respuestas agudas del rendimiento neuromuscular y funcional en individuos sanos: ensayo ciego controlado de distribución aleatoria

Abstract The purpose of this study was to compare the effects of a single hamstring static or dynamic stretching session and a 10-session stretching program on the range of motion, neuromuscular performance and functional performance of healthy subjects. Forty-five, healthy, active men were divided into three groups: control; static stretching and dynamic stretching. There were no significant differences in ratings between the experimental and control groups for any of the variables (p > 0.05). It can be concluded that neither a single session of hamstring static or dynamic stretching nor a 10-session stretching program affected range of motion, neuromuscular or functional performance.

Resumo A proposta deste estudo foi comparar os efeitos de uma única sessão de alongamento estático ou dinâmico dos isquiotibias e dez sessões do programa de alongamento na amplitude de movimento e desempenho neuromuscular e funcional de indivíduos saudáveis. Quarenta e cinco homens ativos e saudáveis, foram distribuídos em três grupos: controle, alongamento estático e alongamento dinâmico. Não houve diferença significativa entre os grupos experimentais e controle para todas as variáveis (p >0,05). Pode-se concluir que nem uma única sessão de alongamento estático e dinâmico dos isquiotibiais, nem 10 sessões do programa de alongamento afetaram a amplitude de movimento e o desempenho neuromuscular e funcional.

Resumen El propósito de este estudio fue comparar los efectos de una sola sesión de estiramientos estático o dinámico en los isquiotibiales, y diez sesiones del programa de estiramiento en el rango de movimiento y rendimiento neuromuscular y funcional de individuos sanos. Cuarenta y cinco hombres activos y sanos fueron divididos en tres grupos: control, estiramiento estático y estiramiento dinámico. No hubo ninguna diferencia considerable entre los grupos experimentales y de control respecto a todas las variables (p >0,05). Se puede concluir que ni una sola sesión de estiramiento estático o dinámico de los isquiotibiales ni 10 sesiones del programa de estiramiento afectaron al rango de movimiento ni al rendimiento neuromuscular y funcional.

Synthesis, in vitro and in vivo biological evaluation, COX-1/2 inhibition and molecular docking study of indole-N-acylhydrazone derivatives.

The objective of this work was to obtain and evaluate anti-inflammatory in vitro, in vivo and in silico potential of novel indole-N-acylhydrazone derivatives. In total, 10 new compounds (3a-j) were synthesized in satisfactory yields, through a condensation reaction in a single synthesis step. In the lymphoproliferation assay, using mice splenocytes, 3a and 3b showed inhibition of lymphocyte proliferation of 62.7% (±3.5) and 50.7% (±2), respectively, while dexamethasone presented an inhibition of 74.6% (±2.4). Moreover, compound 3b induced higher Th2 cytokines production in mice splenocytes cultures. The results for COX inhibition assays showed that compound 3b is a selective COX-2 inhibitor, but with less potency when compared to celecoxib, and compound 3a not presented selectivity towards COX-2. The molecular docking results suggest compounds 3a and 3b interact with the active site of COX-2 in similar conformations, but not with the active site of COX-1, and this may be the main reason to the COX-2 selectivity of compound 3b. In vivo carrageenan-induced paw edema assays were adopted for the confirmation of the anti-inflammatory activity. Compound 3b showed better results in suppressing edema at all tested concentrations and was able to induce an edema inhibition of 100% after 5 h of carrageenan injection at the 30 mg kg-1 dosage, corroborating with the COX inhibition and lymphoproliferation results. I addition to our experimental results, in silico analysis suggest that compounds 3a and 3b present a well-balanced profile between pharmacodynamics and pharmacokinetics. Thus, our preliminary results revealed the potentiality of a new COX-2 selective derivative in the modulation of the inflammatory process.

Brazilian Consensus Recommendation on the Use of Polymethylmethacrylate Filler in Facial and Corporal Aesthetics.

BACKGROUND: Considering that aesthetic benefits can be obtained with the use of permanent filling materials, this work focuses on the development of a consensus regarding the facial and corporal use of polymethylmethacrylate (PMMA) filler in Brazil. METHODS: A questionnaire regarding PMMA treatment, which included items on the main indication, application site, volume of product applied, criteria for selection of the material, complications, contraindications, and individual professional experience, was distributed to the Expert Group members. In addition, the responses were summarized, constituting the starting point for the debate regarding the use of PMMA-based fillers on The First Brazilian PMMA Symposium to create a guideline to be followed in PMMA facial and corporal treatments. RESULTS: This survey involved 87,371 cases. PMMA treatment is recommended for restorative and aesthetic purposes in facial and corporal cases, particularly for facial balance. PMMA 30% filler is recommended in specific facial sites (nose, mentum, mandible angle, zygomatic arc, and malar). PMMA filler is contraindicated in other sites (lips) regardless of concentration. With regard to facial treatment, the juxtaperiostal is the application plane most recommended. For PMMA corporal application, intramuscular is the application plane most indicated, while intradermal and justadermal planes are contraindicated. The submuscular plane application is relative to PMMA filler concentration. The experts also inquired regarding the amount of PMMA recommended in each corporal site (50 mL in the calf, 100-150 mL in the gluteal region). CONCLUSION: These recommendations provide a guideline for physicians, supporting them to perform safe and efficacious treatment with PMMA fillers. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to Table of Contents or the online Instructions to Authors www.springer.com/00266 .

GUIDELINE FOR THE MANAGEMENT OF BILE DUCT CANCERS BY THE BRAZILIAN GASTROINTESTINAL TUMOR GROUP.

The Brazilian Gastrointestinal Tumor Group developed guidelines for the surgical and clinical management of patients with billiary cancers. The multidisciplinary panel was composed of experts in the field of radiology, medical oncology, surgical oncology, radiotherapy, endoscopy and pathology. The panel utilized the most recent literature to develop a series of evidence-based recommendations on different treatment and diagnostic strategies for cholangiocarcinomas and gallbladder cancers.

Guideline for the management of bile duct cancers by the brazilian gastrointestinal tumor group

ABSTRACT The Brazilian Gastrointestinal Tumor Group developed guidelines for the surgical and clinical management of patients with billiary cancers. The multidisciplinary panel was composed of experts in the field of radiology, medical oncology, surgical oncology, radiotherapy, endoscopy and pathology. The panel utilized the most recent literature to develop a series of evidence-based recommendations on different treatment and diagnostic strategies for cholangiocarcinomas and gallbladder cancers.

RESUMO O Grupo Brasileiro de Tumores Gastrointestinais desenvolveu diretrizes de tratamento cirúrgico e clínico de pacientes com tumores de vias biliares. O painel multidisciplinar foi composto de especialistas nas áreas radiologia, oncologia, cirurgia, radioterapia, endoscopia e anatomia patológica. O painel utilizou literatura atual para desenvolver recomendações baseadas em evidência científica para as diferentes estratégias terapêuticas e diagnósticas dos colangiocarcinomas e tumores de vesícula biliar.

Prevalência e fatores associados ao risco de quedas em idosos adscritos a uma Unidade Básica de Saúde do município de Natal, RN, Brasil / Prevalence and factors associated with the risk of falls among the elderly registered in a primary healthcare unit of the city of Natal in the state of Rio Grande do Norte, Brazil

Resumo O objetivo deste artigo foi analisar a prevalência e os fatores associados a quedas em idosos adscritos a uma Unidade Básica de Saúde (UBS), no município de Natal/RN. Estudo transversal realizado com 280 idosos cujos dados foram coletados nas dependências da UBS. A associação entre os desfechos “queda” e “queda recorrente” e as variáveis independentes foi verificada mediante análise bivariada e regressão de Poisson, com cálculo das respectivas razões de prevalências. Prevaleceram os idosos do gênero feminino (68,2%), com média de idade de 71,6 anos (± 6,7), alfabetizados (54,6%), não aposentados (73,5%) e sedentários (87,1%). Registraram queda 53,6% dos idosos, porém 27,8% caíram duas ou mais vezes. O modelo preditivo de queda incluiu o gênero feminino (RP = 1,81), presença de doenças osteoarticulares (RP = 1,71) e comprometimento do equilíbrio (RP = 0,88), enquanto a mobilidade funcional (RP = 0,94), medo de cair (RP = 1,21) e déficit de equilíbrio (RP = 0,80) compuseram o modelo final de quedas recorrentes. Encontrou-se maior prevalência de episódio único de queda e os fatores associados incluíram variáveis sociodemográficas, de saúde e performance física. Por outro lado, associaram-se a ocorrência de duas ou mais quedas apenas as variáveis de performance física.

Abstract The scope of the study was to analyze the prevalence and factors associated with falls among the elderly registered in a Primary Healthcare Unit (PHU) in Natal, State of Rio Grande do Norte. It involved a cross-sectional study conducted with 280 elderly individuals with data collected at the primary healthcare unit. The association between falls, recurrent falls and independent variables was assessed using bivariate analysis and Poisson regression with calculation of their respective prevalence ratios. It involved predominantly elderly females (68.2%) with mean age of 71.6 years (± 6.7), literate (54.6%), non-retired (73.5%) and sedentary (87.1%). 53.6% of the elderly recorded falls and 27.8% fell twice or more. The predictive model of falls included the female gender (PR= 1.81), osteoarticular diseases (PR = 1.71) and balance impairment (PR = 0.88), while functional mobility (PR = 0.94), fear of falling (PR = 1.21) and balance deficit disorders (PR = 0.80) constituted the definitive model of recurrent falls. A higher prevalence of single fall episodes was found and the associated factors included sociodemographic, health and physical performance variables. On the other hand, the occurrence of two or more falls were only associated with physical performance variables.

Effectiveness and safety evaluation in the dyslipidemia treatment with statins

Statins are used to reduce morbidity and mortality in patients with a high risk of cardiovascular disease. However, the use of statins does not ensure effectiveness and pharmacotherapeutic safety. In this context, the present study aimed to evaluate the effectiveness and safety of the therapy with statins in patients with dyslipidemia and high cardiovascular risk. To evaluate these parameters, this study selected 113 dyslipidemic patients with regular statins use of at least seven months. It was an observational cross-sectional study, based on data analysis collected from biochemical tests of patients with dyslipidemia in the public health system in the state of Pernambuco, Brazil. Isolated hypercholesterolemia was the most prevalent dyslipidemia type and the most used statin was atorvastatin (84%), followed by simvastatin (16%). The study observed no effectiveness in 58.4% of the patients; 28% had no safety in the treatment, and 48.3% were using doses above the standard dosage. Comparing effectiveness and safety between the same drugs, at standard dosage with higher dosages, there was not any statistical difference in biochemical test results. Therapeutic goals for LDL-C ≤ 70 mg/dL were found in 28% of cases. However, the use of doses above the standard dosage intended to reach very low LDL-C levels should be reevaluated, since there was no statistical difference in reducing the lipid profile, suggesting that the same results can be obtained with a lower standardized dose. This study provides data relevant to the discussion of statins use and to the necessity of strengthening pharmacotherapeutic monitoring in dyslipidemia treatment.

Análise da atuação do comitê nacional de educação popular em saúde no período de 2009 a 2013

A contribuição do Comitê Nacional de Educação Popular em Saúde, no período2009-2013, para o avanço da Educação Popular em Saúde é o objeto deste estudo. Para analisar em que medida o Comitê contribuiu para a Educação Popular em Saúde nesse período, foi realizada uma revisão bibliográfica para a definição dos conceitos de Educação Popular e Educação Popular em Saúde.Em seguida caracterizou-se o CNEPS com base nas portarias do Ministério da Saúde. Após a análise documental e a sistematização das pautas e dos encaminhamentos foi realizada uma avaliação normativa, verificando-se se os objetivos instituídos formam alcançados ou não.

The contribution of the National Popular Education in Health Committee in theperiod 2009-2013, for the advancement of Popular Education in Health is theobject of this study. To analyze the extent to which the Committee contributedto the Popular Education in Health from 2009 to 2013, was carried out aliterature review to define the concepts of Popular Education and PopularEducation in Health. Then characterized the CNEPS based on ordinances ofthe Ministry of Health. After the document analysis and the systematization ofguidelines and referrals a normative evaluation was performed, verifying if theestablished objectives form achieved or not.

A case of conventional treatment failure in visceral leishmaniasis: leukocyte distribution and cytokine expression in splenic compartments.

BACKGROUND: In this paper we study the distribution of leukocyte populations and of cytokine-producing cells in the spleen of a patient with visceral leishmaniasis resistant to clinical treatment. It is the first attempt to compare the distribution of leukocyte populations and cytokine-producing cells in the splenic compartments of a patient with visceral leishmaniasis with those observed in patients without the disease. CASE PRESENTATION: A 25-year-old male, farmer, was hospitalized on several occasions with diagnosis of visceral leishmaniasis and received all recommended treatments for the disease with only transient improvement followed by relapse. He was eventually subjected to splenectomy in order to control the effects of hypersplenism and to potentially overcome infection. After surgery and combined chemotherapy, the disease evolved to cure. In comparison with the spleens of the other two patients without visceral leishmaniasis, an increase was observed in the CD4/CD8 ratio and in the number of IL-10- and FoxP3-producing cells, while the number of IL-17-producing cells was lower in the spleen of the patient with visceral leishmaniasis. CONCLUSION: This report confirms previous data on changes in the CD4/CD8 ratio in the spleens of patients with visceral leishmaniasis. Additionally the data presented herein suggests that splenic FoxP3- and IL-17-producing cells are involved in the chronicity of visceral leishmaniasis.

Distinctive renal cell tumor simulating atrophic kidney with 2 types of microcalcifications. Report of 3 cases.

We report 3 cases of primary renal cell tumor simulating atrophic kidney with distinct gross, morphologic, immunohistochemical, and molecular genetic features. The tumors were retrieved out of more than 17 000 renal tumors from the Plzen Tumor Registry. Tissues for light microscopy had been fixed, embedded, and stained with hematoxylin and eosin using routine procedures. The tumors were further analyzed using immunohistochemistry, array comparative genomic hybridization, and human androgen receptor. Analyses of VHL gene and loss of heterozygosity (LOH) 3p were also performed. The patients were 2 women and 1 man, with ages ranging from 29 to 35 years (mean, 31.3 years). Grossly, the neoplasms were encapsulated and round with largest diameter of 3.5 cm (mean, 3.2 cm). Follow-up available for all patients ranged from 2 to 14 years (mean, 8 years). No aggressive behavior was noted. Histologically, akin to atrophic (postpyelonephritic) kidney parenchyma, the tumors were composed of follicles of varying sizes that were filled by eosinophilic secretion. Rare areas contained collapsed follicles. Each follicle was endowed with a small capillary. The stroma was loose, inconspicuous, and focally fibrotic. Two types of calcifications were noted: typical psammoma bodies and amorphous dark-blue stained calcified deposits. Immunohistochemically, tumors were strongly positive for cytokeratins (OSCAR), CD10, and vimentin, with weak immunopositivity for CAM5.2 and AE1-AE3. WT1 and cathepsin K were weakly to moderately focally to diffusely positive. Tumors were negative for cytokeratin 20, carbonic anhydrase IX, parvalbumin, HMB45, TTF1, TFE3, chromogranin A, thyroglobulin, PAX8, and ALK. Only 1 case was suitable for molecular genetic analyses. No mutations were found in the VHL gene; no methylation of VHL promoter was noted. No numerical aberrations were found by array comparative genomic hybridization analysis. LOH for chromosome 3p was not detected. Analysis of clonality (human androgen receptor) revealed the monoclonal nature of the tumor. We describe an unknown tumor of the kidney that (1) resembles renal atrophic kidney or nodular goiter of thyroidal gland; (2) contains a leiomyomatous capsule and 2 types of calcifications; (3) lacks mitoses, atypias, necroses, and hemorrhages and nearly lack Ki-67 positivity; and (4) so far showed benign biological behavior.

Immediate effects of TENS and cryotherapy in the reflex excitability and voluntary activity in hemiparetic subjects: a randomized crossover trial / Efeitos imediatos da TENS e crioterapia na excitabilidade reflexa e atividade voluntária de sujeitos hemiparéticos: um estudo controlado aleatorizado cruzado

BACKGROUND: The disorder of reflex and motor function in patients affected by stroke causes negative impact on the performance of movement patterns and affects the functional activities. OBJECTIVES: To investigate the immediate effects of transcutaneous electrical nerve stimulation (TENS) and cryotherapy interventions on the spinal reflex excitability and in the voluntary electromyography (EMG) activity in people with chronic stroke. METHOD: Randomized crossover trial. The maximum H-reflex (Hmax), the H-reflex latency and the maximum motor response (Mmax) of the soleus muscle and also the EMG of the tibialis muscle where evaluated before and after the application of TENS, cryotherapy and control conditions. RESULTS: The Hmax/Mmax ratio was statistically significant higher (p=0.0245) and the H-reflex latency was statistically significant lower (p=0.0375) in the soleus muscle of the affected limb. The EMG amplitude of the tibialis anterior was reduced in the compromised limb (p<0.0001). After the use of the TENS, a reduction in the Hmax/Mmax ratio (p=0.0006) was observed leading to lower reflex excitability. However, after the cryotherapy intervention an increase of the Hmax/Mmax ratio was observed, which was accompanied by an increase in the H-reflex latency (p=0.0001). The EMG amplitude has not changed by any of the interventions. CONCLUSIONS: Our findings suggest that TENS may be a choice for immediate reduction of reflex excitability, whereas cryotherapy intervention may increase reflex excitability in hemiparetic subjects. However, none of the changes mediated by either intervention were able to modify the electrical activity in the antagonist muscle of the spastic muscle.

CONTEXTUALIZAÇÃO: O distúrbio da função motora e reflexa em pacientes acometidos por acidente vascular encefálico (AVE) causa impactos negativos na realização de padrões motores, comprometendo as atividades funcionais. OBJETIVOS: Investigar os efeitos imediatos da estimulação elétrica nervosa transcutânea (TENS) e da crioterapia na excitabilidade reflexa e na atividade voluntária de sujeitos vítimas de AVE. MÉTODO: Estudo Crossover. O reflexo H máximo (Hmáx), a latência do reflexo H e a resposta motora máxima (Mmáx) do músculo solear e a eletromiografia (EMG) do músculo tibial anterior foram avaliados antes e após a aplicação de TENS, crioterapia e em condições de controle. RESULTADOS: A razão Hmáx/Mmáx estava significativamente aumentada (p=0,0245) e a latência do reflexo H significativamente diminuída (p=0,0375) no músculo solear do membro afetado. A amplitude do sinal EMG do músculo estava significativamente reduzida no membro comprometido (p<0,0001). Depois da TENS, houve uma diminuição da razão Hmáx/Mmáx (p=0,0006). Porém, após a aplicação do gelo, houve um aumento da razão Hmáx/Mmáx, acompanhado por um aumento da latência do reflexo H (p=0,0001). A amplitude do sinal EMG não foi alterada por nenhuma das intervenções. CONCLUSÕES: Nossos achados indicam que a TENS pode ser uma escolha para redução imediata da excitabilidade reflexa, enquanto a crioterapia pode aumentar a excitabilidade reflexa de sujeitos hemiparéticos. No entanto, nenhuma das alterações mediadas por qualquer um dos tratamentos foi capaz de alterar a atividade elétrica do músculo antagonista ao espástico.