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We analyzed a quantitative multiscale model that describes the epigenetic dynamics during the growth and evolution of an avascular tumor. A gene regulatory network (GRN) formed by a set of ten genes that are believed to play an important role in breast cancer development was kinetically coupled to the microenvironmental agents: glucose, estrogens, and oxygen. The dynamics of spontaneous mutations was described by a Yule-Furry master equation whose solution represents the probability that a given cell in the tissue undergoes a certain number of mutations at a given time. We assumed that the mutation rate is modified by a spatial gradient of nutrients. The tumor mass was simulated by means of cellular automata supplemented with a set of reaction diffusion equations that described the transport of microenvironmental agents. By analyzing the epigenetic state space described by the GRN dynamics, we found three attractors that were identified with cellular epigenetic states: normal, precancer and cancer. For two-dimensional (2D) and three-dimensional (3D) tumors we calculated the spatial distribution of the following quantities: (i) number of mutations, (ii) mutation of each gene and, (iii) phenotypes. Using estrogen as the principal microenvironmental agent that regulates cell proliferation process, we obtained tumor shapes for different values of estrogen consumption and supply rates. It was found that he majority of mutations occurred in cells that were located close to the 2D tumor perimeter or close to the 3D tumor surface. Also, it was found that the occurrence of different phenotypes in the tumor are controlled by estrogen concentration levels since they can change the individual cell threshold and gene expression levels. All results were consistently observed for 2D and 3D tumors.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Proliferação de Células/genética , Difusão , Separação Celular , EstrogêniosRESUMO
This study investigated the impact of Moringa oleifera Lam. meal (MOM) on meat nutritional properties and bone quality of slow-growing layer-type male chickens raised in semi-intensive conditions. A total of 198, 72-d-old Dominant Blue D 107 male chickens, with an average weight of 1093 ± 15.2 g, were randomly assigned to three dietary treatments supplemented with 0, 3, and 6% of MOM that corresponded to T1, T2, and T3, respectively. Each treatment, consisting of six replicated floor pens of 11 birds, had access to the outdoors for 49 days. The results showed that breast muscle ash percentage was significantly greater (P ≤ 0.05) in T2 in comparison to the T1 group. Meat dry matter, protein, and fat content were not influenced by the treatments (P > 0.05). Regardless of the treatments, oleic acid (C18:1N9C) was numerically more abundant in the breast than in the leg muscle. Alternatively, femoral and tibial lengths were shorter (P ≤ 0.05) in birds fed 3% MOM than the two other groups. Moreover, birds fed with MOM had greater tibial diameter (P ≤ 0.05) than those that were fed without MOM. In addition, bone ash content and phosphorous amount were significantly higher (P ≤ 0.05) in birds fed 6% MOM compared to those fed without MOM. The data of this study indicate that up to 6% of MOM may be added to the diet of slow-growing layer-type male chickens raised with outdoor access under tropical conditions to improve bone quality traits.
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In sheep, infection with Haemonchus contortus may increase the need for energy, and this demand may vary according to the infection level. In this study, the energy intake, digestibility, and energy retention of lambs artificially infected with different levels of H. contortus were estimated. A total of 24 hair sheep lambs reared parasite-free were experimentally infected with H. contortus at one of three infection levels: non-infected (n = 6); infected with 300 infective larvae (L3) of H. contortus/kg body weight (BW) (n = 9); and infected with 500 H. contortus L3/kg BW (n = 9). The lambs were fed for an individual weight gain of 100 g/day, and intake of organic matter (OMI) and gross energy (GEI), digestible (DEI) and metabolizable energy (MEI) were measured weekly. The digestibility of organic matter (OMD) and GE (GED) and the metabolizable energy (ME) balance adjusted to zero nitrogen balance (MEadj) were measured for each lamb during the prepatent and patent periods of infection. From day 21 post-infection (PI), the individual eggs per gram (EPG) of feces and the total number of eggs in feces (TEF) were estimated weekly. After humane slaughter on day 42 PI, the worm burden (WB) was determined. Correlation and regression analyses were performed to estimate the relationships between the parasitological variables (L3, EPG, TEF and WB) and the response variables (OMI, GEI, DEI, MEI, OMD, GED, MEadj). During the prepatent period, there were no significant relationships of L3 with the response variables (OMI, GEI, DEI, MEI, OMD, GED, ME, MEadj). Similarly, during the patent period, no relationship was evident between infection (EPG, TEF or WB) and OMI, GEI, DEI, GED, OMD, ME or MEadj. Thus, the gradient of H. contortus infection examined in the present study did not influence energy balance in hair sheep lambs, and infection did not impose any detectable energy cost. Further studies are needed to fully assess the impact of H. contortus infection on energy metabolism in hair sheep.
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Hemoncose , Haemonchus , Doenças dos Ovinos , Animais , Metabolismo Energético , Fezes , Hemoncose/veterinária , Óvulo , Contagem de Ovos de Parasitas/veterinária , OvinosRESUMO
HIV-1 CRF02_AG is responsible for at least 8% of the HIV-1 infections worldwide and is distributed mainly in West Africa. CRF02_AG has recently been reported in countries where it is not native, including Brazil. In a previous study including 10 CRF02_AG Brazilian samples, we found at least four independent introductions and two autochthonous transmission networks of this clade in Brazil. As more CRF02_AG samples have been identified in Brazil, we performed a new phylogeographic analysis using a larger dataset than before. A total of 20 Brazilian (18 from Rio de Janeiro and two from São Paulo) and 1,485 African HIV-1 CRF02_AG pol sequences were analyzed using maximum likelihood (ML). The ML tree showed that the Brazilian sequences were distributed in five different lineages. The Bayesian phylogeographic analysis of the Brazilian and their most closely related African sequences (n = 212) placed the origin of all Brazilian lineages in West Africa, probably Ghana, Senegal, and Nigeria. Two monophyletic clades were identified, comprising only sequences from Rio de Janeiro, and their date of origin was estimated at around 1985 (95% highest posterior density: 1979-1992). These results support the existence of at least five independent introductions of the CRF02_AG lineage from West Africa into Brazil and further indicate that at least two of these lineages have been locally disseminated in the Rio de Janeiro state over the past 30 years.
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Genótipo , Infecções por HIV/transmissão , Infecções por HIV/virologia , HIV-1/classificação , HIV-1/genética , Adulto , África/epidemiologia , Brasil/epidemiologia , Análise por Conglomerados , Biologia Computacional , Feminino , Infecções por HIV/epidemiologia , HIV-1/isolamento & purificação , Humanos , Masculino , Epidemiologia Molecular , Filogeografia , GravidezRESUMO
We carried out Monte Carlo simulations in the N,Π,T ensemble of a Langmuir monolayer coarse-grained molecular model. Considering that the hydrophilic groups can be ionized by modulating acid-base interactions, here we study the phase behavior of a model that incorporates the short-range steric and long-range ionic interactions. The simulations were carried out in the reduced temperature range 0.1≤T*<4.0, where there is a competition of these interactions. Different order parameters were calculated and analyzed for several values of the reduced surface pressure in the interval, 1≤Π*≤40. For most of the surface pressures two directions of molecular tilt were found: (i) towards the nearest neighbor (NN) at low temperatures, T*<0.7, and most of the values of Π* and (ii) towards next-nearest neighbors (NNN) in the temperature interval 0.7≤T*<1.1 for Π*<25. We also found the coexistence of the NN and NNN at intermediate temperatures and Π*>25. A low-temperature reentrant disorder-order-disorder transition in the positions of the molecular heads and in the collective tilt of the tails was found for all the surface pressure values. It was also found that the molecular tails arranged forming "rotating patterns" in the temperature interval, 0.5
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The remarkable viral diversity remains a big challenge to the development of HIV vaccines and optimal therapy worldwide. In the latest years, as a consequence of the large expansion of highly active antiretroviral therapy (HAART) availability worldwide, an increase in transmitted drug resistance mutations (TDRM) has been observed, varying according the region. This study assessed HIV-1 diversity and TDRM profile over time among newly HIV-1 diagnosed individuals from Rio de Janeiro, Brazil. Blood samples were collected from individuals seeking HIV diagnosis in four voluntary counseling and testing (VCTs) sites located in the Rio de Janeiro Metropolitan Area, in 2005-2007. Recent (RS) and long-term (LTS) HIV-1 seroconverters were distinguished using BED-CEIA. Pol viral sequences were obtained for 102 LTS identified in 2005 and 144 RS from 2005-2007. HIV-1 subtype and pol recombinant genomes were determined using Rega HIV-1 Subtyping Tool and by phylogenetic inferences and bootscanning analyses. Surveillance of HIV-1 TDRM to protease and reverse transcriptase inhibitors were performed according to the Calibrated Population Resistance (CPR) Tool 6.0. Overall, subtype B remains the most prevalent in Rio de Janeiro in both LTS and RS HIV-1 infected individuals. An increased proportion of recombinant samples was detected over time, especially in RS heterosexual men, due to the emergence of CRF02_AG and URF samples bearing a subtype K fragment. The prevalence of HIV-1 samples carrying TDRM was high and similar between LTS and RS (15.7% vs 14.6%) or age (<25yo 17.9% vs >25yo 16.6%) along the study period. The high resistance levels detected in both populations are of concern, especially considering the dynamics of HIV-1 diversity over time. Our results suggest that the incorporation of resistance testing prior to HAART initiation should be highly considered, as well as permanent surveillance, aiming to carefully monitoring HIV-1 diversity, with focus on CRF/URF emergence and putative transmission.
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Farmacorresistência Viral/genética , Infecções por HIV/diagnóstico , Infecções por HIV/genética , HIV-1/genética , Mutação/genética , Adolescente , Adulto , Brasil , Aconselhamento , Feminino , Genótipo , Protease de HIV/genética , Transcriptase Reversa do HIV/genética , Humanos , Masculino , Pessoa de Meia-Idade , Filogenia , Prevalência , Adulto JovemRESUMO
BACKGROUND: BED-EIA HIV-1 Incidence Test (BED-CEIA) has been described as a tool to discriminate recent (RS) from long-term (LTS) seroconversion of HIV-1 infection, contributing to a better understanding of the dynamics of the HIV/AIDS epidemic over time. This study determined the prevalence, estimated incidence and HIV-1 subtype infection among individuals seeking testing in Voluntary Counseling and Testing centers (VCTs) from Rio de Janeiro, Brazil. METHODS: Demographics and behavioral data were obtained from 434 individuals, diagnosed as HIV-positive among 9,008 volunteers screened from November 2004 to October 2005 in three VCTs located in the Rio de Janeiro Metropolitan area, Brazil. BED-CEIA protocol was performed to identify RS. DNA samples from RS and a subset of LTS (under a proportion of 1:2) were selected for gp120 C2-V3 and pol (protease and reverse transcriptase) regions genomic sequencing. RESULTS: Overall HIV-1 prevalence was 4.8%. Sixty-one of 434 seropositive individuals were classified as RS, corresponding to an incidence rate of 1.68%/year (95%CI 1.26% -2.10%). Estimated incidence between Men Who Have Sex with Men (MSM) was 11 times higher than among heterosexual men and 55% of the new cases were identified in volunteers aged 25-40 years. A similar distribution of different HIV-1 subtypes was found among RS and LTS. CONCLUSIONS: Our data suggest that prevention for MSM remains a challenge and efforts focusing on prevention targeting this population should be prioritized. No significant changes in HIV-1 subtypes were observed among the RS and LTS subgroups. One case of HIV-1 AUK (pol)/A (env) recombinant genome was detected for the first time in Brazil.
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Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , HIV-1/classificação , HIV-1/genética , Adulto , Brasil/epidemiologia , DNA Viral/química , DNA Viral/genética , Feminino , Genótipo , Infecções por HIV/virologia , HIV-1/isolamento & purificação , Experimentação Humana , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prevalência , Análise de Sequência de DNA , População Urbana , Adulto Jovem , Produtos do Gene pol do Vírus da Imunodeficiência Humana/genéticaRESUMO
An extremely rare subset of patients infected with HIV-1 designated as "non-progressing elite controllers" appears to be able to maintain stable CD4(+) T-cell counts and a median plasma viremia below the detection limit of current ultrasensitive assays (<50-80 copies/ml of plasma) for >10 years in the absence of antiretroviral therapy. Lymphocyte subsets (CD4(+), CD8(+)), immune activation markers (HLA-DR(+), CD38(+), Beta-2-microglobulin), and HIV-specific antibody responses were longitudinally examined in four non-progressing elite controllers over more than 5 years. Two control groups of seronegative healthy individuals and untreated patients infected with HIV-1 presenting detectable viremia were also included. None of the non-progressing elite controllers displayed the high T-cell activation levels generally seen in the seropositive individuals, keeping them within the normal range. Three non-progressing elite controllers showed no significant immune system abnormalities when compared to seronegative individuals, displaying a low proportion of HIV-1-specific binding antibodies and low avidity index, similar to those observed for individuals infected recently with HIV-1. One non-progressing elite controller exhibited CD8(+) T-cell counts and beta2-M levels above normal ranges and developed a low but "mature" (high-avidity) HIV-1-specific antibody response. Thus, the non-progressing elite controllers are able to maintain normal T-cell activation levels, which may contribute to prevent, or greatly reduce, the damage of the immune system typically induced by the HIV-1 over time. They are, however, immunologically heterogeneous and very low levels of antigen exposure seem to occur in these patients, sufficient for sustaining a low, but detectable, HIV-1-specific immunity.
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Anticorpos Anti-HIV/sangue , Infecções por HIV/imunologia , Sobreviventes de Longo Prazo ao HIV , HIV-1/imunologia , Adulto , Afinidade de Anticorpos , Formação de Anticorpos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Feminino , Humanos , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Microglobulina beta-2/sangueRESUMO
Introducción: La encefalitis límbica paraneoplásica es un síndrome poco frecuente que produce síntomas neuropsiquiátricos y, en algunos casos, demencia rápidamente progresiva. Objetivo: Discutir el curso clínico de una paciente con encefalitis límbica paraneoplásica asociado con timoma. Método: Reporte de caso de una mujer de 41 años de edad. Resultados: La mujer presentó pérdida de peso, tos y diarrea crónica, de ocho meses de evolución, por un síndrome de Good; además, cambios comportamentales con pérdida progresiva de la memoria por encefalitis límbica paraneoplásica. A pesar del tratamiento quirúrgico, esteroides y gamaglobulina, la paciente sufrió deterioro clínico progresivo y falleció. Conclusiones: La encefalitis límbica paraneoplásica puede causar alteraciones neuropsiquiátricas y demencia rápidamente progresiva. Es importante para los psiquiatras de enlace conocer las características clínicas de la encefalitis límbica paraneoplásica, lo cual permitirá lograr un diagnóstico precoz y tratamiento oportuno...
Introduction: Paraneoplastic limbic encephalitis is a rare syndrome that causes neuropsychiatric symptoms and in some cases rapidly progressive dementia. Objective: To discuss the clinical course of a patient with paraneoplastic limbic encephalitis associated with thymoma. Method: Case report. Results: We report a 41 year-old female who had weight loss, chronic cough and diarrhea for eight months associated with Good´s syndrome and behavioral changes and progressive loss of memory from paraneoplastic limbic encephalitis. Despite surgical treatment, steroids and gammaglobulin, the patient presented progressive clinical deterioration and died. Conclusions: Paraneoplastic limbic encephalitis may cause neuropsychiatric disturbances and rapidly progressive dementia. It is important for liaison psychiatrists to know the clinical features of paraneoplastic limbic encephalitis thus ensuring early diagnosis and appropriate treatment...
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Encefalite Límbica , Timoma , Sintomas AfetivosRESUMO
OBJETIVO: determinar en futbolistas si el entrenamiento de fuerza en un porcentaje alto (85por ciento) de una repetición máxima (1-RM), buscando el aumento en lafuerza máxima (FM), es más eficaz para mejorar la potencia muscular inmediata que un entrenamiento similar pero al 75por ciento de 1-RM. METODOLOGÍA: sesenta futbolistas de las divisiones inferiores del DIM divididos aleatoriamente en 2 grupos de 30 jugadores cada uno y se diseñaron los siguientes trabajos de fuerza: el grupo experimental realizó un entrenamiento bilateral e individual de fuerza para los extensores y flexores de la rodilla, consistente en 3 series de 5 repeticiones al 85por ciento de 1-RM, con 5 minutos de descanso entre una y otra serie, 2 veces por semana durante 12 semanas. El grupo control hizo un entrenamiento de fuerza para los mismos músculos, consistente en 3 series de 8 repeticiones al 75por ciento de 1-RM, con 5 minutos de descanso entre una y otra serie, 2 veces por semana durante 12 semanas. Al comienzo del estudio y a las 6 y 12 semanas se hicieron mediciones de fuerza máxima (1-RM) de los extensores y flexores de las rodillas y de la potencia muscular inmediata - velocidad en 20 metros, Squat Jump (SJ) y Countermovement Jump (CMJ). RESULTADOS: aunque los 60 jugadores completaron el entrenamiento de fuerza, sólo se analizaron los datos de 29 del grupo experimental y 27 del grupo control; de los 4 restantes, 2 salieron del equipo y 2 sufrieron lesiones no relacionadas con el entrenamiento. No hubo diferencias significativas entre los dos grupos, en ninguna de las variables ni en ninguna de las 3 mediciones. En la mayoría de las variables - fuerza de los extensores de la rodilla derecha, fuerza de los extensores de la rodilla izquierda, fuerza de los flexores de la rodilla derecha, fuerza de los flexores de la rodilla izquierda, Squat Jump y Countermovement Jump - hubo incrementos estadísticamente significativos (p < 0.05) en cada grupo tanto a las 6 semanas como entrelas 6...
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Desenvolvimento Muscular , Futebol/educação , Futebol/fisiologiaRESUMO
OBJETIVOS: Avaliar a sobrevida dos pacientes portadores de carcinoma epidermóide do canal anal submetidos a cirurgia de resgate, por recidiva ou falha do tratamento radioquimioterápico inicial. MÉTODO: Análise retrospectiva dos pacientes portadores de carcinoma epídermóide do canal anal submetidos a cirurgia de resgate, de outubro de 1986 a setembro de 2000. RESULTADOS: Foram matriculados 93 pacientes portadores de carcinoma epidermóide do canal anal no período, e 21 (22,5 por cento) foram submetidos a resgate cirúrgico. Em 19 pacientes (91 por cento) foi realizada amputação abdominoperineal do reto (operação de Miles), em um paciente exenteração pélvica total e em um paciente excisão local. Não houve mortalidade operatória. A sobrevida média do grupo após resgate cirúrgico foi de 24 meses. CONCLUSÕES: Após recidiva e/ou falha da radioquimioterapia, a cirurgia de resgate é importante no controle locorregional do carcinoma epidermóide do canal anal.
BACKGROUND: Carcinoma of the anal canal is a rare neoplasia, the treatment of wich is based on chemoradiation Surgery is recommended alter treatment failure and recurrence. METHOD: A retrospective review from October 1986 to September 2000 of all patients who underwent salvage surgery alter chemoradiotherapy failure. Patients were reviewed as to time until recurrence and overall survival. RESULTS: Ninety-three patients with epidermoid carcinoma of the anal canal were reviewed. Twenty-one patients (22,5 percent) with residual or recurrent disease underwent salvage surgery. 19 patients (91 percent) underwent abdomino-perineal resection, 1 patient underwent pelvic exenteration and local resection was performed in 1 patient. There was no operative mortality. The overall survival was 24 months. CONCLUSIONS: Salvage surgical resection for anal canal carcinoma can be expected te yieid a number of survivors from residual/recurrent disease.
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Introducción. Canavalia ensiformis es una leguminosa que destaca por su contenido de nutrimentos. Sin embargo, posee numerosos compuestos tóxicos que pueden limitar su utilización. Se ha reportado efecto de estos compuestos in vitro sobre fauna ruminal, pero se desconoce su efecto tóxico in vivo. Objetivo. El objetivo del presente trabajo fue analizar los cambios en la población de protozoarios ruminales como respuesta al consumo de canavalia. Materiales y Métodos. Se emplearon cuatro bovinos con un peso de 264.5 Kg en un diseño doble conmutativo con arreglo factorial 2x2. Los animales fueron alimentados con pasto Taiwán ad libitum y canavalia o sorgo como suplemento (c. 27 por ciento de la dieta en base seca). Se colectó líquido ruminal después de tres semanas de adaptación a la dieta y se contaron las poblaciones de protozoarios ruminales. Los datos normalizados utilizando su log10 y fueron analizados mediante un modelo lineal general. Las medias fueron comparadas mediante la prueba de mínima diferencia significativa. Resultados. Se observó un incremento (p<0.05) en los conteos de protozoarios flagelados en las dietas que contenían canavalia (106.345 vs 105.247), pero los holotricos y entodinomorfos disminuyeron (103.717 vs 104.364 y 104.407 vs 104.933 respectivamente p<0.05). Las cuentas totales de protozoarios fueron mayores en dietas con canavalia si el total incluía flagelados (106.369 vs 105.575) y menores si los excluía (104.505 vs 105.093) (p<0.05).Discusión. Los cambios en las diferentes poblaciones de protozoarios son una respuesta de adaptación al consumo de canavalia. Los diferentes grupos de protozoarios ruminales parecen tener diferente respuesta y/o capacidad de adaptación a los tóxicos de la canavalia.
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Animais , Bovinos , Produção Agrícola , Infecções Protozoárias em Animais , Ruminantes , Fenômenos Fisiológicos da Nutrição Animal , Substâncias TóxicasRESUMO
Introducción. Para estudiar la toxicidad y el efecto metabólico de la canavanina en animales o plantas se depende de la disponibilidad de métodos sensibles, específicos y rápidos de análisis. Materiales y métodos. Se desarrolló un método para medir la concentración de L-canavanina por cromatografía líquida en fase reversa utilizando DABS-C1 como agente de derivación y se compararon los resultados con aquellos obtenidos por colorimetría por el método de Rosenthal. Cinco muestras de canavalia fueron utilizadas para validar la técnica. Resultados y discusión. La derivación con DABS-C1 permitió la determinación de éste aminoácido sin interferencia con otros aminoácidos. No se encontraron diferencias entre las concentraciones de L-canavanina en granos de Canavalia ensiformis cuando se midió por estos 2 métodos. El análisis colorimétrico puede ser empleado como una herramienta confiable de primera elección. Debido al alto costo que involucra el análisis por HPLC deberá ser empleado cuando exista evidencia de interferencia en el método colorimétrico de compuesto y/o metabolitos presentes en la muestra
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Canavanina , Colorimetria , Cromatografia Líquida de Alta Pressão/instrumentação , Cromatografia Líquida de Alta Pressão/métodos , EspectrofotometriaRESUMO
La presente revisión tuvo como objetivo recopilar y presentar información actualizada sobre la técnica de los derivados de purina en rumiantes domésticos. La técnica de los derivados de purina representa una alternativa simple y no invasiva para el estudio del aporte de N microbial a nivel intestino delgado en animales rumiantes. Existe información y modelos cuantitativos de respuesta para bovinos y ovinos que permiten el uso de esta técnica, y numerosos métodos analíticos publicados para el análisis de los derivados de purina. El método de los derivados de purina tiene la ventaja de no requerir animales quirúrgicamente preparados, pero tiene la desventaja de requerir colecta total de orina. El uso de submuestras de orina colectada a lo largo del día(s) junto con el índice `derivados de purina:creatinina' puede ser una alternativa a la colección total de orina, pero se necesita más información sobre este punto. La medición de los derivados purínicos en leche no parece ser una alternativa viable a la colección total de orina. Deben de validarse algunos de los parámetros en uso para el cálculo del flujo de nitrógeno microbial al intestino como son; la recuperación de purinas microbiales absorbidas como derivados purínicos en orina y la digestibilidad de la purina en intestino delgado en animales bajo condiciones de alimentación normal. No obstante, comparada con otras téncicas convencionales, la medición de los derivados de purina en orina representa una herramienta simple para profundizar en el estudio y entendimiento de la dinámica ruminal