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Considering the importance of alternative methodologies to animal experimentation, we propose an organoid-based biological model for in vitro blood vessel generation, achieved through co-culturing endothelial and vascular smooth muscle cells (VSMCs). Initially, the organoids underwent comprehensive characterization, revealing VSMCs (α-SMA + cells) at the periphery and endothelial cells (CD31+ cells) at the core. Additionally, ephrin B2 and ephrin B4, genes implicated in arterial and venous formation respectively, were used to validate the obtained organoid. Moreover, the data indicates exclusive HIF-1α expression in VSMCs, identified through various methodologies. Subsequently, we tested the hypothesis that the generated blood vessels have the capacity to modulate the osteogenic phenotype, demonstrating the ability of HIF-1α to promote osteogenic signals, primarily by influencing Runx2 expression. Overall, this study underscores that the methodology employed to create blood vessel organoids establishes an experimental framework capable of producing a 3D culture model of both venous and arterial endothelial tissues. This model effectively guides morphogenesis from mesenchymal stem cells through paracrine signaling, ultimately leading to an osteogenic acquisition phenotype, with the dynamic involvement of HIF-1α.
Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia , Músculo Liso Vascular , Miócitos de Músculo Liso , Organoides , Osteogênese , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Osteogênese/genética , Organoides/metabolismo , Organoides/citologia , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/citologia , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/citologia , Células Cultivadas , Vasos Sanguíneos/metabolismo , Vasos Sanguíneos/citologia , Vasos Sanguíneos/crescimento & desenvolvimento , Técnicas de Cocultura/métodos , Diferenciação Celular , Células Endoteliais/metabolismo , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologiaRESUMO
Objetivo: Analizar la percepción y la satisfacción con la educación en modalidad virtual de los estudiantes de la carrera de Licenciatura en Enfermería de una institución de educación superior de carácter público de la Ciudad Autónoma de Buenos Aires, Argentina, durante el segundo semestre de 2021. Metodología: Estudio analítico, transversal y cuantitativo. La muestra estuvo compuesta por 121 estudiantes, seleccionados mediante muestreo no probabilístico, quienes respondieron un instrumento conformado por 24 preguntas . Resultados: Los encuestados fueron mayormente de sexo femenino (84.30 %), con media de edad de 29.2 años (DE: 8), de tercer año (55.37 %) y con hijos (44.63 %). Respecto a la percepción sobre la modalidad virtual se halló que las clases fueron consideradas como motivantes para el aprendizaje (66.94 %), los alumnos pudieron mantener la atención entre un 75-99 % del tiempo durante la clase (38.84 %), una baja cantidad pudo realizar todas las consultas al docente (16.52 %) y la mayoría sintió nerviosismo ante la evaluación remota al mismo nivel que su contraparte presencial (52.89 %). La satisfacción global con la modalidad fue puntuada con una media de 6.9 sobre 10 y el 75.20 % los encuestados desea continuar con clases virtuales . Conclusiones: La satisfacción fue caracterizada como media. Las variables que se relacionaron con una mayor satisfacción con la educación remota son la tenencia de hijos, la mayor edad, la creencia de que se hubiese aprendido más con clases presenciales, el tiempo que perciben que pueden mantener la atención en clases virtuales, la baja sensación de nerviosismo ante la evaluación virtual y la ausencia de dificultades para la conexión a las clases sincrónicas.
Objetivo: Analisar a percepção e a satisfação com a educação na modalidade virtual dos alunos da Licenciatura em Enfermagem de uma instituição pública de ensino superior da Cidade Autônoma de Buenos Aires, Argentina durante o segundo semestre de 2021. Metodologia: Estudo analítico, transversal e quantitativo. A amostra foi composta por 121 alunos, selecionados por amostragem não probabilística, que responderam a um instrumento composto por 24 questões. Resultados: Os participantes eram maioritariamente do sexo feminino (84,30 %), com idade média de 29,2 anos (DP: 8), cursando o terceiro ano (55,37 %) e com filhos (44,63 %). Quanto à percepção sobre a modalidade virtual, constatou-se que as aulas foram consideradas em sua maioria com motivadoras para a aprendizagem (66,94 %), os alunos conseguiram manter a atenção entre 75- 99 % do tempo durante a aula (38,84 %), um baixo número conseguiu fazer todas as consultas ao professor (16,52 %) e a maioria se sentiu nervosa com a avaliação à distância no mesmo nível da presencial (52,89 %). A satisfação global com a modalidade foi pontuada com média de 6,9 sobre 10 e 75,20 % dos entrevistados desejam continuar com as aulas virtuais. Conclusões: A satisfação caracterizou-se como média. As variáveis que se relacionaram com a maior satisfação com o ensino a distância são ter filhos, a idade, a crença de que aprenderiam mais com as aulas presenciais, o tempo que percebem que conseguem manter a atenção nas aulas virtuais, a baixa sensação de nervosismo perante a avaliação virtual e a ausência de dificuldades para a conexão nas aulas síncronas.
Objective: To analyze the perception and satisfaction with education in virtual modality of Nursing Bachelor's degree students from a public higher education institution in the Autonomous City of Buenos Aires, Argentina during the second semester of 2021. Methods: Analytical, cross-sectional, and quantitative study. The sample consisted of 121 students, selected by non-probabilistic sampling, who answered an instrument made up of 24 questions. Results: The respondents were mostly female (84.30 %), with a mean age of 29.2 years (SD: 8), in their third year (55.37 %) and with children (44.63 %). Regarding the perception of the virtual modality, it was found that the classes were mostly considered as a motivating factor for learning (66.94 %), students were able to maintain their attention between 75-99 % of the time during the class (38.84 %), a low number were able to make all consultations with the teacher (16.52 %) and most of them felt nervousness before the remote evaluation at the same level as their face-to-face counterpart (52.89 %). Overall satisfaction with the modality was rated with an average of 6.9 out of 10 and 75.20 % of respondents would like to continue with virtual classes. Conclusions: Satisfaction was characterized as average. The variables that were associated with greater satisfaction with distance education are having children, older age, the belief that they would have learned more with face-to-face classes, the time they perceive they can maintain their attention in virtual classes, the low feeling of nervousness before the virtual evaluation, and the absence of difficulties in connecting to synchronous classes.
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Resumen El aumento de la población de adultos mayores y su mayor demanda de atención en salud en Paraguay, requiere de una evaluación multidimensional que identifique sus condiciones de riesgo o deterioro. El objetivo de esta investigación, fue evaluar el estado de salud y nutrición de una muestra de adultos mayores que acudieron a la consulta ambulatoria del Hospital Geriátrico de la Previsional, en la Asunción, Paraguay. La investigación tuvo un diseño observacional, descriptivo y de corte transverso, de 108 adultos mayores a quienes se les realizó la Valoración Geriátrica Integral (VGI) y se evaluaron parámetros nutricionales. La edad promedio fue de 71 años con predominio del sexo femenino. De acuerdo al IMC, el 64% presentó sobrepeso u obesidad. De acuerdo a la VGI, 18% presentó riesgo nutricional, 43% dependencia leve para las actividades de la vida diaria y 12% para las actividades instrumentales. El 18% mostró déficit cognitivo, el 6% depresión y el 30% riesgo social. La población se caracterizó por presentar altas frecuencias de exceso de peso e hipertensión, con una baja frecuencia de riesgo de desnutrición, las mayores limitaciones se dieron en las actividades básicas de la vida diaria y en el riesgo social. El ser mujer y el exceso de peso se asociaron significativamente con las limitaciones básicas funcionales. Este trabajo constituyó uno de los primeros en el país sobre adultos mayores ambulatorios, permitiendo configurar una línea de base de las áreas comprometidas o en riesgo de declinación y desarrollar estrategias y acciones preventivas para promover un envejecimiento saludable.
Abstract The increase in the population of older adults and their more significant demand for health care in Paraguay requires a multidimensional evaluation to identify risks or deteriorating conditions. The objective of this research was to evaluate the health and nutrition status of a sample of older adults who attended the Geriatric Hospital of the Social Security for outpatient consultation. The research had a cross-sectional descriptive observational design, which included 108 older adults who underwent the Comprehensive Geriatric Assessment (CGA) and whose nutritional parameters were evaluated. Their average age was 71 years, with a predominance of females. According to their BMI, 64% were overweight or obese. As for the CGA, 18% presented a nutritional risk, 43% had mild dependence on activities of daily living and 12% on instrumental activities, 18% had a cognitive deficit, 6% had depression, and 30% had social risk. The population was characterized by a high prevalence of overweight and hypertension and a low frequency of risk of malnutrition. The most significant limitations were in the basic activities of daily life and social risk. Being female and being overweight were significantly associated with basic functional limitations. This work was one of the first in the country on ambulatory older adults, allowing the establishment of a baseline for areas where health is compromised or at risk of decline and the development of preventive strategies and actions to promote healthy aging.
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To investigate the putative stem cell/tumor stem cell (SC/TSC) niche contribution to hyperplasic/adenomatous pituitary lesions, we analyzed variation in the pituitary stem cell population during the development of experimental pituitary tumors. Pituitary tumors were induced in female F344 rats with estradiol benzoate for 5, 10, 20 and 30 days. Cells positive for GFRa2, Sox2, Sox9, Nestin, CD133 and CD44 were identified in the marginal zone and in the adenoparenchyma in both control and 30D groups, with predominant adenoparenchyma localization of GRFa2 and SOX9 found in tumoral pituitaries. GFRa2, Nestin, CD133 and CD44 were upregulated at the initial stages of tumor growth, whereas Sox9 significantly decreased at 5D, with Sox2 remaining invariable during the hyperplasic/adenomatous development. In addition, isolated pituispheres from normal and tumoral pituitary glands enriched in SC/TSC were characterized. Pituispheres from the 30D glands were positive for the above-mentioned markers and showed a significant increase in the proliferation. In conclusion, our data revealed pituitary SC pool fluctuations during hyperplastic/adenomatous development, with differential localization of the SC/TSC niche in this process. These findings may help to provide a better understanding of these cell populations, which is crucial for achieving advancements in the field of pituitary tumor biology.
Assuntos
Adenoma/patologia , Neoplasias Hipofisárias/patologia , Nicho de Células-Tronco/fisiologia , Animais , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Feminino , Células-Tronco Neoplásicas/patologia , Células-Tronco Neoplásicas/fisiologia , Hipófise/patologia , Hipófise/fisiologia , Ratos , Ratos Endogâmicos F344 , Microambiente Tumoral/fisiologiaRESUMO
Octreotide (OCT) is used to inhibit hormone secretion and growth in somatotroph tumors, although a significant percentage of patients are resistant. It has also been tested in nonfunctioning (NF) tumors but with poor results, with these outcomes having been associated with SSTR2 levels and impaired signaling. We investigated whether OCT inhibitory effects can be improved by TGF-ß1 in functioning and nonfunctioning somatotroph tumor cells. OCT effects on hormone secretion and proliferation were analyzed in the presence of TGF-ß1 in WT and SSTR2-overexpressing secreting GH3 and silent somatotroph tumor cells. The mechanism underlying these effects was assessed by studying SSTR and TGFßR signaling pathways mediators. In addition, we analyzed the effects of OCT/TGF-ß1 treatment on tumor growth and cell proliferation in vivo. The inhibitory effects of OCT on GH- and PRL-secretion and proliferation were improved in the presence of TGF-ß1, as well as by SSTR2 overexpression. The OCT/TGF-ß1 treatment induced downregulation of pERK1/2 and pAkt, upregulation of pSmad3, and inhibition of cyclin D1. In vivo experiments showed that OCT in the presence of TGF-ß1 blocked tumor volume growth, decreased cell proliferation, and increased tumor necrosis. These results indicate that SSTR2 levels and the stimulation of TGF-ß1/TGFßR/Smad2/3 pathway are important for strengthening the antiproliferative and antisecretory effects of OCT.
Assuntos
Antineoplásicos Hormonais/farmacologia , Proliferação de Células/efeitos dos fármacos , Octreotida/farmacologia , Neoplasias Hipofisárias/tratamento farmacológico , Proteína Smad2/metabolismo , Proteína Smad3/metabolismo , Somatotrofos/efeitos dos fármacos , Fator de Crescimento Transformador beta1/farmacologia , Animais , Linhagem Celular , Feminino , Humanos , Camundongos Nus , Fosforilação , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/metabolismo , Neoplasias Hipofisárias/patologia , Ratos , Receptores de Somatostatina/genética , Receptores de Somatostatina/metabolismo , Transdução de Sinais , Somatotrofos/metabolismo , Somatotrofos/patologia , Carga Tumoral/efeitos dos fármacosRESUMO
BACKGROUND: PTP4A3 is a subclass of a protein tyrosine phosphatase super family and is expressed in a range of epithelial neoplasms. We evaluated PTP4A3 expression and its association with clinicopathological parameters in different types of functioning pituitary adenomas. METHODS: A total of 34 functioning pituitary adenomas samples were evaluated in this observational study. PTP4A3 expression was examined by immunohistochemical staining, and, possible correlations between PTP4A3 and some clinicopathological variables were investigated. RESULTS: PTP4A3 was expressed in 19 out of 34 tumours (55%), at the cytoplasmic level of tumorous cells. Moreover, there was significant association (p=0.042) between PTP4A3 expression and tumorous size. CONCLUSIONS: PTP4A3 was expressed in more than half of the tumours analysed, with there being a significant association with the tumorous size of functioning adenomas. This allows to speculate that PTP4A3 may regulate tumour growth, although further investigations are necessary to determine if this phosphatase can serve as a biomarker or used as a therapeutic target in pituitary macroadenomas.
Assuntos
Adenoma/diagnóstico , Regulação Neoplásica da Expressão Gênica , Proteínas de Neoplasias/metabolismo , Neoplasias Hipofisárias/diagnóstico por imagem , Proteínas Tirosina Fosfatases/metabolismo , Adenoma/metabolismo , Adenoma/patologia , Adulto , Citoplasma/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Hipófise/metabolismo , Neoplasias Hipofisárias/metabolismo , Neoplasias Hipofisárias/patologia , Proteínas Tirosina Fosfatases/genética , Estudos Retrospectivos , Adulto JovemRESUMO
Glioblastoma multiforme is the most aggressive type of glioma, with limited treatment and poor prognosis. Despite some advances over the last decade, validation of novel and selective antiglioma agents remains a challenge in clinical pharmacology. Prior studies have shown that leguminous lectins may exert various biological effects, including antitumor properties. Accordingly, this study aimed to evaluate the mechanisms underlying the antiglioma activity of ConBr, a lectin extracted from the Canavalia brasiliensis seeds. ConBr at lower concentrations inhibited C6 glioma cell migration while higher levels promoted cell death dependent upon carbohydrate recognition domain (CRD) structure. ConBr increased p38MAPK and JNK and decreased ERK1/2 and Akt phosphorylation. Moreover, ConBr inhibited mTORC1 phosphorylation associated with accumulation of autophagic markers, such as acidic vacuoles and LC3 cleavage. Inhibition of early steps of autophagy with 3-methyl-adenine (3-MA) partially protected whereas the later autophagy inhibitor Chloroquine (CQ) had no protective effect upon ConBr cytotoxicity. ConBr also augmented caspase-3 activation without affecting mitochondrial function. Noteworthy, the caspase-8 inhibitor IETF-fmk attenuated ConBr induced autophagy and C6 glioma cell death. Finally, ConBr did not show cytotoxicity against primary astrocytes, suggesting a selective antiglioma activity. In summary, our results indicate that ConBr requires functional CRD lectin domain to exert antiglioma activity, and its cytotoxicity is associated with MAPKs and Akt pathways modulation and autophagy- and caspase-8- dependent cell death.
Assuntos
Antineoplásicos/farmacologia , Caspase 8/metabolismo , Ativação Enzimática/efeitos dos fármacos , Glioma/tratamento farmacológico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Lectinas de Plantas/farmacologia , Animais , Apoptose/efeitos dos fármacos , Astrócitos/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Caspase 3/metabolismo , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Glioma/metabolismo , Glioma/patologia , Humanos , Camundongos , Mitocôndrias/efeitos dos fármacos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Simulação de Acoplamento Molecular , Polissacarídeos/metabolismo , Domínios Proteicos/fisiologia , Estrutura Quaternária de Proteína/fisiologia , Estrutura Terciária de Proteína/fisiologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , RatosRESUMO
Androgens play a central role in homeostatic and pathological processes of the prostate gland. At the cellular level, testosterone activates both the genomic signaling pathway, through the intracellular androgen receptor (AR), and membrane-initiated androgen signaling (MIAS), by plasma membrane receptors. We have previously shown that the activation of MIAS induces uncontrolled proliferation and fails to stimulate the beneficial immunomodulatory effects of testosterone in prostatic cells, becoming necessary to investigate if genomic signaling mediates homeostatic effects of testosterone. However, the lack of specific modulators for genomic androgen signaling has delayed the understanding of this mechanism. In this article, we demonstrate that monosialoganglioside (GM1) micelles are capable of delivering testosterone into the cytoplasm to specifically activate genomic signaling. Stimulation with testosterone-loaded GM1 micelles led to the activation of androgen response element (ARE)-regulated genes in vitro as well as to the recovery of normal prostate size and histology after castration in mice. In addition, these micelles avoided MIAS, as demonstrated by the absence of rapid signaling pathway activation and the inability to induce uncontrolled cell proliferation. In conclusion, our results validate a novel tool for the specific activation of genomic androgen signaling and demonstrate the importance of selective pathway activation in androgen-mediated proliferation.
Assuntos
Neoplasias da Próstata , Receptores Androgênicos , Androgênios , Animais , Gangliosídeo G(M1) , Genômica , Humanos , Masculino , Camundongos , Micelas , Receptores Androgênicos/genética , Transdução de Sinais , TestosteronaRESUMO
Humans are exposed to numerous endocrine disruptors on a daily basis, which may interfere with endogenous estrogens, with Di-(2-ethylhexyl) phthalate (DEHP) being one of the most employed. The anterior pituitary gland is a target of 17ß-estradiol (E2) through the specific estrogen receptors (ERs) α and ß, whose expression levels fluctuate in the gland under different contexts, and the ERα/ß index is responsible for the final E2 effect. The aim of the present study was to evaluate in vivo and in vitro the DEHP effects on ERα and ß expression in the pituitary cell population, and also its impact on lactotroph and somatotroph cell growth. Our results revealed that perinatal exposure to DEHP altered the ERα and ß expression pattern in pituitary glands from prepubertal and adult female rats and increased the percentage of lactotroph cells in adulthood. In the in vitro system, DEHP down-regulated ERα and ß expression, and as a result increased the ERα/ß ratio and decreased the percentages of lactotrophs and somatotrophs expressing ERα and ß. In addition, DEHP increased the S + G2M phases, Ki67 index and cyclin D1 in vitro, leading to a rise in the lactotroph and somatotroph cell populations. These results showed that DEHP modified the pituitary ERα and ß expression in lactotrophs and somatotrophs from female rats and had an impact on the pituitary cell growth. These changes in ER expression may be a mechanism underlying DEHP exposure in the pituitary gland, leading to cell growth deregulation.
Assuntos
Dietilexilftalato/toxicidade , Ácidos Ftálicos/toxicidade , Receptores de Estrogênio/metabolismo , Animais , Proliferação de Células/efeitos dos fármacos , Dietilexilftalato/metabolismo , Disruptores Endócrinos/metabolismo , Estradiol/metabolismo , Receptor alfa de Estrogênio/metabolismo , Estrogênios/farmacologia , Feminino , Lactotrofos/efeitos dos fármacos , Lactotrofos/metabolismo , Hipófise/efeitos dos fármacos , RatosRESUMO
The molecular mechanisms underlying the capability of pituitary tumours to avoid unregulated cell proliferation are still not well understood. However, the NF-κB transcription factor, which is able to modulate not only cellular senescence but also tumour progression, has emerged as a targeted candidate. This work was focused on the NF-κB role in cellular senescence during the progression of experimental pituitary tumours. Also, the contribution of the signalling pathways in senescence-associated NF-κB activation and the senescence-associated secretory phenotype (SASP) and pro-survival-NF-κB target genes transcription were analysed. A robust NF-κB activation was seen at E20-E40 of tumour development accompanied by a marked SA-ß-Gal co-reactivity in the tumour pituitary parenchyma. The induction of TNFα and IL1-ß as specific SASP-related NF-κB target genes as well as Bcl-2 and Bcl-xl pro-survival genes was shown to be accompanied by increases in the p-p38 MAPK protein levels, starting at the E20 stage and strengthening from 40 to 60 days of tumour growth. It is noteworthy that p-JNK displayed a similar pattern of activation during pituitary tumour development, while p-AKT and p-ERK1/2 were downregulated. By employing a pharmacological strategy to abrogate NF-κB activity, we demonstrated a marked reduction in SA-ß-Gal activity and a slight decrease in Ki67 immunopositive cells after NF-κB blockade. These results suggest a central role for NF-κB in the regulation of the cellular senescence programme, leading to the strikingly benign intrinsic nature of pituitary adenomas.
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Senescência Celular/genética , NF-kappa B/fisiologia , Neoplasias Hipofisárias/genética , Transdução de Sinais/genética , Animais , Modelos Animais de Doenças , Regulação da Expressão Gênica , Genes bcl-2/fisiologia , Hipoxantina Fosforribosiltransferase/metabolismo , Interleucina-1beta/metabolismo , Masculino , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/metabolismo , Proteína bcl-X/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
La urolitiasis es una enfermedad multifactorial. En los últimos años se ha observado un incremento a nivel mundial de la incidencia de la litiasis urinaria tanto en adultos como en niños. Los cambios en los hábitos alimentarios y un aumento en la prevalencia de exceso de peso podrían asociarse a este fenómeno. El objetivo del trabajo fue describir la frecuencia de alteraciones urinarias presentes en niños con urolitiasis según estado nutricional. En este trabajo observacional transversal se incluyeron 104 niños litiásicos de ambos sexos divididos en dos grupos según estado nutricional: 68 niños con peso adecuado y 36 niños con sobrepeso u obesidad considerando criterios de la OMS. Se determinaron en orina de 24 horas calcio, fósforo, sodio, ácido úrico, citrato y magnesio. Del total de pacientes participantes 54 (51.9%) fueron niñas y 50 (48,1%) fueron niños. El 65,4% de los niños presentó peso normal y el 34,6% de los niños sobrepeso u obesidad con edades medias de 10±4 años y 8±4 años respectivamente. El 80% de los niños presentó al menos una alteración urinaria, siendo las más frecuentes en ambos grupos la hipocitraturia e hiperuricosuria. Es llamativa la elevada frecuencia de alteraciones en las concentraciones de promotores e inhibidores de cristalización, en ambos grupos, indicando un riesgo aumentado de recidivas(AU)
Urolithiasis is a multifactorial disease. Recently the incidence of urolithiasis in adults and children is increasing worldwide. Changes in eating habits and an increase in the prevalence of overweight could be associated with this phenomenon. The objective was to describe the frequency of urinary alterations according to nutritional status in children with urolithiasis. This cross-sectional observational study included 104 lithiasic boys and girls divided into two groups: 68 children with normal weight and 36 children with overweight or obesity considering WHO criteria. Calcium, phosphorus, sodium, uric acid, citrate and magnesium levels were determined in 24-hour urine. The frequency of boys and girls was 51.9% and 48.1% respectively. Sixty five percent of the children presented normal weight and 34.6% of the children were overweight or obese with mean ages of 10±4 years and 8±4 years respectively. Eighty percent of the children had at least one urinary disorder, the most frequent being hypocitraturia and hyperuricosuria in both groups. The high frequency of alterations in the concentrations of urinary promoters and inhibitors of crystallization in both groups was remarkable, indicating an increased risk of recurrence(AU)
Assuntos
Humanos , Masculino , Feminino , Criança , Sobrepeso , Urolitíase , Pediatria , Estado NutricionalRESUMO
La tuberculosis bovina es una enfermedad infectocontagiosa producida por Mycobacterium bovis, que, junto con otras micobacterias, compone el complejo Mycobacterium tuberculosis. Su prevención radica en detectar la infección en el ganado bovino y pasteurizar la leche. El hombre, clásicamente, ha adquirido la enfermedad por contacto con el ganado, en el contexto de una zoonosis laboral, o por consumo de productos lácteos no pasteurizados. Se describe el caso de un paciente de 10 años, sin actividades relacionadas con animales, que presenta una forma de tuberculosis pulmonar por M. bovis, indistinguible clínica y radiológicamente de la tuberculosis humana. Se destaca la importancia de la detección de la enfermedad, del control sanitario de los alimentos y del primer nivel de atención en lo que respecta al reconocimiento de la enfermedad y a su prevención en la población.
Bovine tuberculosis is a contagious infectious disease produced by Mycobacterium bovis, which together with other mycobacteria makes up the Mycobacterium tuberculosis complex. Its prevention lies in detection of the infection in cattle and milk pasteurization. Man has traditionally acquired the disease through contact with livestock, in the context of an occupational zoonosis, or through consumption of unpasteurized dairy products. We describe the case of a 10-year-old male patient, without activities related to animals, that presents a form of pulmonary tuberculosis due to M. bovis, clinically and radiologically indistinguishable from human tuberculosis. The importance of the disease detection, the food sanitary control, and the first level of attention, with respect to the recognition of the disease and its prevention in the population, is highlighted.
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Humanos , Masculino , Criança , Tuberculose Bovina , Zoonoses , Pasteurização , Alimentos , Mycobacterium bovisRESUMO
The molecular mechanisms underlying the ERα nuclear/cytoplasmic pool that modulates pituitary cell proliferation have been widely described, but it is still not clear how ERα is targeted to the plasma membrane. The aim of this study was to analyse ERα palmitoylation and the plasma membrane ERα (mERα) pool, and their participation in E2-triggered membrane-initiated signalling in normal and pituitary tumour cell growth. Cell cultures were prepared from anterior pituitaries of female Wistar rats and tumour GH3 cells, and treated with 10 nM of oestradiol (E2). The basal expression of ERα was higher in tumour GH3 than in normal pituitary cells. Full-length palmitoylated ERα was observed in normal and pituitary tumour cells, demonstrating that E2 stimulation increased both, ERα in plasma membrane and ERα and caveolin-1 interaction after short-term treatment. In addition, the Dhhc7 and Dhhc21 palmitoylases were negatively regulated after sustained stimulation of E2 for 3 h. Although the uptake of BrdU into the nucleus in normal pituitary cells was not modified by E2, a significant increase in the GH3 tumoural cell, as well as ERK1/2 activation, with this effect being mimicked by PPT, a selective antagonist of ERα. These proliferative effects were blocked by ICI 182780 and the global inhibitor of palmitoylation. These findings indicate that ERα palmitoylation modulated the mERα pool and consequently the ERK1/2 pathway, thereby contributing to pituitary tumour cell proliferation. These results suggest that the plasma membrane ERα pool might be related to the proliferative behaviour of prolactinoma and may be a marker of pituitary tumour growth.
Assuntos
Membrana Celular/metabolismo , Proliferação de Células , Receptor alfa de Estrogênio/metabolismo , Neoplasias Hipofisárias/metabolismo , Animais , Antineoplásicos Hormonais/farmacologia , Linhagem Celular Tumoral , Membrana Celular/efeitos dos fármacos , Células Cultivadas , Estradiol/farmacologia , Receptor alfa de Estrogênio/genética , Estrogênios/farmacologia , Feminino , Fulvestranto/farmacologia , Expressão Gênica/efeitos dos fármacos , Lipoilação/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/genética , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/patologia , Ratos WistarRESUMO
Introducción: Se ha descrito la heterogeneidad del impacto de la anemia según el área geográfica; en el sector rural se ve agravado afectando a la población más vulnerable. Objetivo: evaluar el efecto del suplemento nutricional en niños anémicos menores de cinco años indígenas y no indígenas, en comunidades rurales del Departamento de Caazapá. Materiales y métodos: Estudio observacional transversal. Fueron estudiados una cohorte de 109 niños menores de cinco años indígenas y no indígenas cuyos padres brindaron su consentimiento informado, a quienes se les suministró sulfato ferroso según edad y peso. Resultados: Se encontró un aumento significativo de las medianas de hemoglobina, después de la intervención, de 5,0 g/L en el grupo anémico de indígenas y en los no indígenas de 6,0 g/L; el 31% de los niños indígenas y el 84% de los no indígenas dejaron de ser anémicos, post intervención. Conclusión: Ambas poblaciones de niños anémicos indígenas y no indígenas presentaron un aumento significativo de los niveles medios de hemoglobina post tratamiento con suplemento con hierro y una mayoría presentó una mejoría a un estado no anémico o del grado de la anemia.
Introduction: The heterogeneity of the impact of anemia has been described according to geographic area; in rural areas the impact is greater, affecting the most vulnerable populations. Objective: to evaluate the effect of nutritional supplementation in anemic children, both indigenous and non-indigenous, under five years of age, in rural communities in the Department of Caazapá. Materials and methods: This was a cross-sectional, observational study. We studied a cohort of 109 indigenous and non-indigenous children under five years of age whose parents gave their informed consent and were given ferrous sulfate based on age and weight. Results: There was a significant increase in hemoglobin medians, after the intervention, of 5.0 g / L in the anemic group of indigenous children and of 6.0 g / L in the non-indigenous children; 31% of indigenous children and 84% of non-indigenous children ceased to be anemic after the intervention. Conclusion: Both the indigenous and non-indigenous populations of anemic children showed a significant increase in their average levels of hemoglobin after iron supplementation and a majority improved to a milder degree of anemia or to a resolution of their anemia.
RESUMO
Plant lectins have been studied owing to their structural properties and biological effects that include agglutinating activity, antidepressant-like effect and antitumor property. The results from this work showed the effects of the lectin extracted from the Dioclea violacea plant (DVL) on the C6 rat glioma cell line. DVL treatment was able to induce caspase-3 activation, apoptotic cell death and cellular membrane damage. Furthermore, DVL decreased mitochondrial membrane potential and increased the number of acidic vesicles and cleavage of LC3, indicating activation of autophagic processes. DVL also significantly inhibited cell migration. Compared to ConA, a well-studied lectin extracted from Canavalia ensiformes seeds, some effects of DVL were more potent, including decreasing C6 glioma cell viability and migration ability. Taken together, the results suggest that DVL can induce glioma cell death, autophagy and inhibition of cell migration, displaying potential anti-glioma activity.
Assuntos
Autofagia/efeitos dos fármacos , Dioclea/química , Expressão Gênica/efeitos dos fármacos , Neuroglia/efeitos dos fármacos , Lectinas de Plantas/farmacologia , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Autofagia/genética , Canavalia/química , Caspase 3/genética , Caspase 3/metabolismo , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/genética , Linhagem Celular Tumoral , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Membrana Celular/ultraestrutura , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Concanavalina A/isolamento & purificação , Concanavalina A/farmacologia , L-Lactato Desidrogenase/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Neuroglia/metabolismo , Neuroglia/patologia , Lectinas de Plantas/isolamento & purificação , RatosRESUMO
In pituitary adenomas, early recurrences and resistance to conventional pharmacotherapies are common, but the mechanisms involved are still not understood. The high expression of epidermal growth factor receptor 2 (HER2)/extracellular signal-regulated kinase (ERK1/2) signal observed in human pituitary adenomas, together with the low levels of the antimitogenic transforming growth factor beta receptor 2 (TBR2), encouraged us to evaluate the effect of the specific HER2 inhibition with trastuzumab on experimental pituitary tumor cell growth and its effect on the antiproliferative response to TGFB1. Trastuzumab decreased the pituitary tumor growth as well as the expression of ERK1/2 and the cell cycle regulators CCND1 and CDK4. The HER2/ERK1/2 pathway is an attractive therapeutic target, but its intricate relations with other signaling modulators still need to be unraveled. Thus, we investigated possible cross-talk with TGFB signaling, which has not yet been studied in pituitary tumors. In tumoral GH3 cells, co-incubation with trastuzumab and TGFB1 significantly decreased cell proliferation, an effect accompanied by a reduction in ERK1/2 phosphorylation, an increase of SMAD2/3 activation. In addition, through immunoprecipitation assays, a diminution of SMAD2/3-ERK1/2 and an increase SMAD2/3-TGFBR1 interactions were observed when cells were co-incubated with trastuzumab and TGFB1. These findings indicate that blocking HER2 by trastuzumab inhibited pituitary tumor growth and modulated HER2/ERK1/2 signaling and consequently the anti-mitogenic TGFB1/TBRs/SMADs cascade. The imbalance between HER2 and TGFBRs expression observed in human adenomas and the response to trastuzumab on experimental tumor growth may make the HER2/ERK1/2 pathway an attractive target for future pituitary adenoma therapy.
Assuntos
Adenoma/metabolismo , Proliferação de Células/efeitos dos fármacos , Neoplasias Hipofisárias/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Trastuzumab/farmacologia , Adenoma/patologia , Adulto , Ciclo Celular/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fosforilação , Neoplasias Hipofisárias/patologia , Adulto JovemRESUMO
El mundo, actualmente se enfrenta a una doble carga de malnutrición que incluye la desnutrición y la alimentación excesiva. A ello se suman las parasitosis intestinales que es una enfermedad frecuente con importante morbimortalidad en la población infantil, ligadas a la pobreza y malas condiciones higiénico-sanitarias. El objetivo de este trabajo fue describir el estado nutricional-hematológico y parasitológico de niños escolares de cuatro comunidades rurales de Paraguay. Estudio observacional descriptivo de corte transverso en el que participaron 102 niños de ambos sexos de 5 a 12 años de edad. Se realizó medición de peso y talla, utilizando balanza calibrada, y un altímetro fijado a la pared. Toma de muestra sanguínea por punción venosa para determinación de parámetros hematológicos, procesados en contador hematológico por impedancia. Muestras de heces de una sola toma fueron recogidas en frascos apropiados con formol al 10%, utilizándose 4 métodos: directo, flotación de Willis, Graham y de concentración. En relación al estado nutricional-hematológico se encontró que el 3,9% de los niños estaba con desnutrición moderada y el 9,8% presentó riesgo de desnutrición; anemia se observó en el 38,2% de los niños. En relación a la parasitosis, el estudio diagnóstico se realizó a 94 niños y se encontró que el 72,2% estaba parasitado, siendo Blastocystis hominis el más frecuente. Tanto la frecuencia de anemia como de parasitosis es alta en esta población, sin embargo no se pudo establecer una relación entre ellas(AU)
Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Criança , Transtornos da Nutrição Infantil/sangue , Estado Nutricional , Anemia/sangue , Enteropatias Parasitárias/parasitologia , Estudos TransversaisRESUMO
The cellular transformation of normal functional cells to neoplastic ones implies alterations in the cellular metabolism and mitochondrial function in order to provide the bioenergetics and growth requirements for tumour growth progression. Currently, the mitochondrial physiology and dynamic shift during pituitary tumour development are not well understood. Pituitary tumours present endocrine neoplastic benign growth which, in previous reports, we had shown that in addition to increased proliferation, these tumours were also characterized by cellular senescence signs with no indication of apoptosis. Here, we show clear evidence of oxidative stress in pituitary cells, accompanied by bigger and round mitochondria during tumour development, associated with augmented biogenesis and an increased fusion process. An activation of the Nrf2 stress response pathway together with the attenuation of the oxidative damage signs occurring during tumour development were also observed which will probably provide survival advantages to the pituitary cells. These neoplasms also presented a progressive increase in lactate production, suggesting a metabolic shift towards glycolysis metabolism. These findings might imply an oxidative stress state that could impact on the pathogenesis of pituitary tumours. These data may also reflect that pituitary cells can modulate their metabolism to adapt to different energy requirements and signalling events in a pathophysiological situation to obtain protection from damage and enhance their survival chances. Thus, we suggest that mitochondria function, oxidative stress or damage might play a critical role in pituitary tumour progression.
Assuntos
Transformação Celular Neoplásica/metabolismo , Mitocôndrias/metabolismo , Estresse Oxidativo/fisiologia , Neoplasias Hipofisárias/metabolismo , Adaptação Fisiológica/fisiologia , Animais , Antioxidantes/metabolismo , Metabolismo Energético/fisiologia , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismoRESUMO
In this study, we focused on ERß regulation in the adenohypophysis under different estrogenic milieu, by analyzing whether ER modulates the phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression and its subcellular localization on anterior pituitary glands from Wistar rats and GH3 lactosomatotroph cells that over-expressed ERß. ERß was regulated in a cyclic manner, and underwent dynamic changes throughout the estrous cycle, with decreased ERß+ cells in estrus and under E2 treatment, but increased in ovariectomized rats. In addition, the ERα/ß ratio increased in estrus and under E2 stimulation, but decreased in ovariectomized rats. Double immunofluorescence revealed that lactotroph and somatotroph ERß+ were significantly decreased in estrus. Also, variations in the PTEN expression was observed, which was diminished with high E2 conditions but augmented with low E2 milieu. The subcellular localization of this phosphatase was cell cycle-dependent, with remarkable changes in the immunostaining pattern: nuclear in arrested pituitary cells but cytoplasmic in stimulated cells, and responding differently to ER agonists, with only DPN being able to increase PTEN expression and retaining it in the nucleus. Finally, ERß over-expression increased PTEN with a noticeable subcellular redistribution, and with a significant nuclear signal increase in correlation with an increase of cells in G0/G1 phase. These results showed that E2 is able to inhibit ERß expression and suggests that the tumoral suppressor PTEN might be one of the signaling proteins by which E2, through ERß, acts to modulate pituitary cell proliferation, thereby adapting endocrine populations in relation with hormonal necessities.