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Fundamento: la aterosclerosis es una enfermedad de origen multifactorial que se agrava a consecuencia de un medio ambiente adverso y de estilos de vida no saludables. Las evidencias confirman su inicio desde las etapas más tempranas de la vida. Objetivo: describir la presencia de lesiones ateroscleróticas tempranas en las aortas de fetos y neonatos fallecidos hijos de madres hipertensas. Método: se realizó un estudio descriptivo de tipo transversal que incluyó a los fetos mayores de 22 semanas y neonatos fallecidos hijos de madres hipertensas, a quienes se les realizó autopsia en el departamento de anatomía patológica, del Hospital Universitario Ginecobstétrico Eusebio Hernández Pérez, en el período comprendido entre enero del 2021 hasta diciembre 2022, con un total de 18. Se recogieron los siguientes datos en las historias clínicas: sexo del fallecido, edad gestacional en el momento del parto, peso postparto, edad materna y antecedentes de hipertensión arterial (crónica o gestacional). Se analizaron las 18 aortas (torácicas y abdominales) de los fallecidos seleccionados. Resultados: del total de fallecidos estudiados el 70,6 % presentó lesiones ateroscleróticas tempranas, caracterizadas por engrosamiento de la íntima a modo de cojinete, presencia de linfocitos en la íntima o en la pared arterial cercana a ella y/o macrófagos. En algunos casos se observó una de estas variantes histológicas y en otros la combinación de dos o tres. Conclusiones: las lesiones ateroscleróticas tempranas están presentes en las aortas de la mayoría de los fetos y neonatos estudiados, con predominio en las que presentaban hipertensión gestacional.
Foundation: atherosclerosis is a disease of multifactorial origin that is aggravated as a result of an adverse environment and unhealthy lifestyles. Evidence confirms its onset from the earliest stages of life. Objective: to describe the presence of early atherosclerotic lesions in the aortas of deceased fetuses and neonates born to hypertensive mothers. Method: a descriptive cross-sectional study was carried out that included fetuses older than 22 weeks and deceased neonates born to hypertensive mothers, who underwent autopsy in the pathological anatomy department of the Eusebio Hernández Pérez Gynecobstetric University Hospital, in the period between January 2021 and December 2022, with a total of 18. The following data were collected in the medical records: sex of the deceased, gestational age at the time of delivery, postpartum weight, maternal age, and history of arterial hypertension (chronic or gestational). The 18 aortas (thoracic and abdominal) of the selected deceased were analyzed. Results: of the total number of deceased studied, 70.6 % presented early atherosclerotic lesions, characterized by thickening of the intima as a cushion, presence of lymphocytes in the intima or in the arterial wall close to it and/or macrophages. In some cases, one of these histological variants was observed and in others a combination of two or three. Conclusions: early atherosclerotic lesions are present in the aortas of the majority of the fetuses and neonates studied, with a predominance in those with gestational hypertension.
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RESUMEN Introducción. El consumo de alimentos industrializados que contienen organismos genéticamente modificados (OGM) se ha incrementado notablemente. Desde su inicio ha generado crecientes controversias debido a que se considera de riesgo para la salud. En Perú se carece de información científica sobre los OGM en alimentos industrializados. Objetivo. Detectar y cuantificar molecularmente los indicadores de transgenicidad P35S y TNOS, y la soya transgénica Roundup Ready en alimentos industrializados de soya; y verificar su mención en la etiqueta. Métodos. Analizamos 30 muestras, para extraer el ADN utilizamos los kits Dneasy Mericon Food y Dneasy Power Soil. Para la detección y cuantificación de las secuencias transgénicas usamos la técnica PCR en tiempo real con los kits Mericon. Resultados. Detectamos transgenicidad en el 100% de las muestras y soya Roundup Ready en el 66,7%. El número de copias/mL o g de muestra osciló entre 1,21E+0 y 8,88E+7. En el etiquetado del 93,3% de las muestras no hubo referencia a componentes transgénicos. Conclusión. Los hallazgos evidencian la urgente necesidad de que la legislación vigente se actualice de acuerdo con los conocimientos científicos y el desarrollo socioeconómico del país, protegiendo la salud y el derecho a la información de la población.
ABSTRACT Introduction. The consumption of industrialized foods that contain genetically modified organisms (GMOs) has increased significantly. Since its inception, it has generated growing controversies because it is considered a health risk. In Peru there is a lack of scientific information on GMOs in industrialized foods. Objetive. Molecularly detect and quantify transgenicity indicators P35S and TNOS, and of Roundup Ready transgenic soybeans in industrialized soy foods and verify their mention on the label. Methods. 30 samples were analyzed; To extract the DNA, the Dneasy Mericon Food and Dneasy Power Soil Kits were used, and for the detection and quantification of the transgenic sequences, the real-time PCR technique with the Mericon kits. In addition, the labeling was reviewed. Results. Transgenicity was detected in 100% of the samples and Soy RR in 66,67%; The number of copies/mL or g of sample ranged between 1,21E+0 and 8,88E+7 and in the labeling of 93,3% of the samples there was no reference to transgenic components. Conclusion. The findings show the urgent need for current legislation to be updated in accordance with the scientific knowledge and the socioeconomic development of the country, protecting health and the right to population information.
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Introducción. El consumo de alimentos transgénicos constituye un riesgo potencial para la salud. Sin embargo, en el Perú se carece de información actualizada y confiable sobre la presencia de transgénicos en los alimentos y sobre los datos pertinentes en su etiquetado; de igual manera sobre los alimentos que consumen los animales de abasto, cuyos productos van a ser ingeridos por el humano. Objetivo. Determinar la transgenicidad, mediante la detección del promotor 35S, en productos alimenticios industrializados de maíz para consumo humano y animal, que se comercializan en Lima y verificar sí en el etiquetado se menciona si contiene o no secuencias transgénicas. Métodos. Se analizaron 30 muestras de alimentos para consumo humano y 10 para consumo de animales de abasto; y se revisó el etiquetado. Para la extracción del ADN se utilizó el kit Dneasy Mericon Food, para la detección del P35S el método Real Time-PCR empleando el kit Mericon Screen 35S y para determinar la concentración de copias el kit Mericon Quant Mon 810. Resultados. Se detectó el P35S en el 66,66% de las muestras para consumo humano, y en el 90,00% de las muestras para consumo animal. En el etiquetado del 100% de las muestras para consumo humano y animal no se menciona si contiene o no componentes transgénicos. Conclusiones. La detección de contenido transgénico en la mayoría de los alimentos industrializados de maíz para humanos y animales evidencian la necesidad de su mención en el etiquetado y de la implementación de una política exigente en bioseguridad alimentaria.
Introduction. Consumption of transgenic foods constitutes a potential health risk. However, in Peru there is a lack of updated and reliable information on the presence of transgenics in food and on the relevant data on their labeling; in the same way about the food consumed by animals for supply, whose products are going to be ingested by humans. Objetive. To determine the transgenicity, through the detection of the 35S promoter, in industrialized corn food products for human and animal consumption, which are marketed in Lima and to verify if the labeling mentions whether or not it contains transgenic sequences. Methods. 30 food samples for human consumption and 10 for consumption by animals for production were analyzed; and the labeling was revised. The Dneasy Mericon Food kit was used for DNA extraction, the Real Time-PCR method for P35S detection using the Mericon Screen 35S kit, and the Mericon Quant Mon 810 kit to determine the copy concentration. Results. P35S was detected in 66,66% of the samples for human consumption, and in 90.00% of the samples for animal consumption. The labeling of 100% of the samples for human and animal consumption does not mention whether or not it contains transgenic components. Conclusions. The detection of transgenic content in the majority of industrialized corn foods for humans and animals demonstrates the need to mention them on the label and the implementation of a demanding policy on food biosafety.
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Virus-like particles (VLPs) from Parvovirus B19 (B19V) can be obtained by the self-assembly of the structural proteins VP1 and VP2. It is possible to produce B19V VLPs either from VP2 or a mixture of VP1 and VP2, through its heterologous expression in eukaryotic cells. The difference between VP1 and VP2 protein is a tract of 227 residues located at the N-terminal region of VP1, known as the VP1 unique region (VP1u). This region is critical for B19V infection, including tropism, cell internalization, and lysosomal scape through its phospholipase 2A activity. Herein, we report the in vitro self-assembly of VP1 to form VLPs. These species have phospholipase activity, suggesting that the phospholipase domain is correctly folded. Furthermore, VP1 and VP2 were co-assembled to produce hybrid VLPs which were able to bind and internalize in the non-permissive HepG2 cells, another evidence of the functionality of the in vitro refolded VP1u.
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Parvovirus B19 Humano , Proteínas do Capsídeo/metabolismo , Parvovirus B19 Humano/genética , FosfolipasesRESUMO
Brasilicardinâ A (1) consists of an unusual anti/syn/anti-perhydrophenanthrene skeleton with a carbohydrate side chain and an amino acid moiety. It exhibits potent immunosuppressive activity, yet its mode of action differs from standard drugs that are currently in use. Further pre-clinical evaluation of this promising, biologically active natural product is hampered by restricted access to the ready material, as its synthesis requires both a low-yielding fermentation process using a pathogenic organism and an elaborate, multi-step total synthesis. Our semi-synthetic approach included a) the heterologous expression of the brasilicardinâ A gene cluster in different non-pathogenic bacterial strains producing brasilicardinâ A aglycone (5) in excellent yield and b) the chemical transformation of the aglycone 5 into the trifluoroacetic acid salt of brasilicardinâ A (1 a) via a short and straightforward five-steps synthetic route. Additionally, we report the first preclinical data for brasilicardinâ A.
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Aminoglicosídeos/metabolismo , Engenharia Genética , Imunossupressores/síntese química , Alquil e Aril Transferases/genética , Aminoglicosídeos/síntese química , Aminoglicosídeos/química , Aminoglicosídeos/farmacologia , Animais , Produtos Biológicos/síntese química , Produtos Biológicos/química , Produtos Biológicos/metabolismo , Produtos Biológicos/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Humanos , Imunossupressores/química , Imunossupressores/metabolismo , Imunossupressores/farmacologia , Camundongos , Plasmídeos/genética , Plasmídeos/metabolismo , Streptomyces/genética , Streptomyces/metabolismo , Terpenos/químicaRESUMO
Brasilicardin A (BraA) is a promising immunosuppressive compound produced naturally by the pathogenic bacterium Nocardia terpenica IFM 0406. Heterologous host expression of brasilicardin gene cluster showed to be efficient to bypass the safety issues, low production levels and lack of genetic tools related with the use of native producer. Further improvement of production yields requires better understanding of gene expression regulation within the BraA biosynthetic gene cluster (Bra-BGC); however, the only so far known regulator of this gene cluster is Bra12. In this study, we discovered the protein LysRNt, a novel member of the LysR-type transcriptional regulator family, as a regulator of the Bra-BGC. Using in vitro approaches, we identified the gene promoters which are controlled by LysRNt within the Bra-BGC. Corresponding genes encode enzymes involved in BraA biosynthesis as well as the key Bra-BGC regulator Bra12. Importantly, we provide in vivo evidence that LysRNt negatively affects production of brasilicardin congeners in the heterologous host Amycolatopsis japonicum. Finally, we demonstrate that some of the pathway related metabolites, and their chemical analogs, can interact with LysRNt which in turn affects its DNA-binding activity.
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BACKGROUND: The current study evaluated the metalloproteinases MMP-2 and MMP-9 expression in epithelial cells and the surrounding stroma in ovarian tumors and the association of MMPs with the histological subtypes, the clinical stage and the presence of steroid hormone receptors. Tumor samples were obtained from 88 patients undergoing surgical cytoreduction of primary ovarian tumors in Instituto Nacional de Cancerología, from México City. The formalin fixed and paraffin embedded samples were processed in order to demonstrate the presence of androgen receptor,estrogen receptor alpha, progesterone receptor, MMP-2,MMP-9 and collagen IV by immunohistochemistry and/or immunofluorescence. RESULTS: MMP-2 and MMP-9 were differentially expressed in the epithelium and the stroma of ovarian tumors associated to histological subtype, clinical stage and sexual steroid hormone receptor expression. Based on Cox proportional hazard regression model we demonstrated that MMP-2 located in the epithelium and the stroma are independent prognostic biomarkers for overall survival in epithelial ovarian tumors. Kaplan Meir analysis of the combination of AR (+) with MMP-2 (+) in epithelium and AR (+) with MMP-2 (-) in stroma displayed a significant reduction of survival. CONCLUSIONS: The presence of MMP-2 in the stroma of the tumor was a protective factor while the presence of MMP-2 in the epithelium indicated an adverse prognosis. The presence of AR associated with MMP-2 in the tumor cells was a risk factor for overall survival in epithelial ovarian cancer.
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Carcinoma Epitelial do Ovário/patologia , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Neoplasias Ovarianas/patologia , Receptores Androgênicos/metabolismo , Adulto , Carcinoma Epitelial do Ovário/metabolismo , Epitélio/metabolismo , Epitélio/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/metabolismo , Prognóstico , Estudos Retrospectivos , Células Estromais/metabolismo , Células Estromais/patologia , Análise de SobrevidaRESUMO
Epithelial ovarian cancer (EOC) is a heterogeneous disease that can be categorized into four major histological subtypes. Its etiology remains poorly understood due mainly to this heterogeneity. Follicle-stimulating hormone (FSH) has been implicated as a risk factor in EOC and has been suggested that may influence the development of specific subtypes. In addition, FSH regulates different aspects of ovarian cancer tumorigenesis. FSH downstream target genes in EOC have not been fully identified. Progranulin (PGRN) overexpression is associated with cell proliferation, invasion, chemoresistance, and shortened overall survival in ovarian cancer. Recently, we demonstrated that PGRN expression is regulated through the PI3K signaling pathway in clear cell ovarian carcinoma (CCOC) cells. In contrast, we also demonstrated that PGRN synthesis in serous ovarian cancer (SOC) cells is regulated via PKC but not by the PI3K signaling pathway. Several studies have demonstrated that FSH induces PKC and PI3K activation. Thus, this study was to investigate the effect of FSH on PGRN production in the CCOC cell line TOV-21G as compared to the SOC cell lines SKOV3 and OVCAR3. Cultured TOV-21G, SKOV3, and OVCAR3 cells were incubated with different concentrations of FSH for 48 h. PGRN mRNA and protein expression were assessed by RT-PCR and Western blotting, while PGRN secretion was measured by ELISA. PGRN mRNA and protein expression, as well as PGRN secretion, significantly increased after FSH stimulation in TOV-21G but not in SKOV3 and OVCAR3 cells. These data indicate that FSH induces PGRN expression and secretion only in CCOC cells. Establishing specific features for CCOC could reveal potential diagnostic and therapeutic targets.
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Carcinoma Epitelial do Ovário/metabolismo , Hormônio Foliculoestimulante/farmacologia , Neoplasias Ovarianas/metabolismo , Progranulinas/biossíntese , Apoptose/efeitos dos fármacos , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/genética , Carcinoma Epitelial do Ovário/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Progranulinas/genética , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Proteínas Recombinantes/farmacologiaRESUMO
BACKGROUND: Ovarian cancer is the most lethal of all gynecologic malignancies. The relationship between sexual steroids receptors and ovarian cancer progression has been largely evaluated. The presence of progesterone receptors has been associated with an increase of a disease-free period and overall survival in patients with ovarian carcinoma. In the present study, primary cultures of ovarian carcinoma obtained from 35 patients diagnosed with epithelial ovarian cancer were evaluated for cell survival after treatment with 10- 8 M of 17ß-estradiol, progesterone, testosterone and dihydrotestosterone. RESULTS: The results were analyzed considering histological subtypes: low grade serous, high grade serous, endometrioid and mucinous carcinoma; clear cell carcinoma was not included due to failure in obtaining successful cultures of this subtype. A significant reduction of cell survival was observed after progesterone treatment in endometrioid ovarian carcinoma. Changes were not observed in low grade serous, high grade serous and mucinous carcinoma. The effect of progesterone was related to the presence of progesterone receptor (PR), a 43% reduction in the cell number was observed in PR (+) endometrioid ovarian carcinoma. CONCLUSIONS: This study supports the importance of progesterone and the presence of progesterone receptor in the reduction of ovarian cancer progression in the endometrioid ovarian carcinoma.
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Antineoplásicos Hormonais/farmacologia , Carcinoma Endometrioide/patologia , Sobrevivência Celular/efeitos dos fármacos , Neoplasias Ovarianas/patologia , Progesterona/farmacologia , Adulto , Carcinoma Endometrioide/metabolismo , Carcinoma Epitelial do Ovário/metabolismo , Carcinoma Epitelial do Ovário/patologia , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/metabolismo , Estudos Prospectivos , Receptores de Progesterona/metabolismo , Receptores de Esteroides/metabolismo , Células Tumorais Cultivadas/efeitos dos fármacosRESUMO
The significance of the presence of androgen receptor (AR), estrogen receptor alpha (ER) and progesterone receptor (PR) in ovarian cancer patient survival has been a matter of numerous studies. This study was aimed to describe the expression profile of the three sexual steroid receptors in high-grade serous, endometrioid, mucinous and low-grade serous ovarian carcinoma and its association to the proliferation index in patients with primary ovarian carcinoma diagnosis, before any treatment. Eighty-one samples were obtained from the National Institute of Cancerology in Mexico City and were evaluated for the presence of AR, ER, PR and Ki67 by immunohistochemistry. The four subtypes of ovarian carcinoma displays a specific profile of the eight possible combinations of the steroid receptors with significant differences within the profile and the histological subtypes. High-grade serous carcinoma was characterized by a high frequency of both, triple-negative and AR+ ER- PR+ profiles. Endometrioid carcinoma presented a higher frequency of triple-positive profile. The presence of only AR+ profile was not observed in the endometrioid tumors. The relationship of the receptor profile with the proliferation index in the tumor epithelium shows that the expression of only ER is associated to a reduced proliferation index in endometrioid carcinoma. Steroid hormone receptor expression and co-expression could help characterize ovarian carcinoma.
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BACKGROUND: Previous studies show that androgens are involved in hypertrophy and excitability of cardiomyocytes and that their effects are mediated through their receptor. The aim of this study was to evaluate the presence of androgen receptor (AR) in mouse heart during prenatal and early postnatal stages. RESULTS: The expression of AR and related genes, alpha myosin heavy chain -Myh6-, beta myosin heavy chain -Myh7- and atrial natriuretic factor -Nppa- was simultaneously evaluated by semiquantitative RT-PCR. AR was also detected by immunohistochemistry. Androgen receptor mRNA was detected in hearts from 10.5 days post coitum to 16 postnatal days. A higher expression of AR mRNA in atria compared to ventricles was observed in neonatal mouse. A positive correlation between mRNA levels of AR and Nppa was observed in mouse heart at early postnatal development. Androgen receptor expression is similar in males and females during cardiac development. Finally, androgen receptor protein was observed by immunohistochemistry in myocardial cells of atria and ventricles from 12.5 days onwards and restricted after 16.5 days post-coitum to nuclei of cardiomyocytes. CONCLUSION: Present results provide evidence that androgen receptor is expressed from prenatal stages in mouse heart, supporting the proposition that androgens could be involved in mammalian heart development.
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Coração/embriologia , Miócitos Cardíacos/metabolismo , Receptores Androgênicos/metabolismo , Animais , Fator Natriurético Atrial , Feminino , Camundongos , Cadeias Pesadas de Miosina/metabolismo , Peptídeo Natriurético Tipo C/metabolismo , Precursores de Proteínas/metabolismo , RNA Mensageiro/metabolismoRESUMO
The bacterium Nocardia terpenica IFM 0406 is known as the producer of the immunosuppressant brasilicardin A. Here, we report the completely sequenced genome of strain IFM 0406, which facilitates the heterologous expression of the brasilicardin biosynthetic gene cluster but also unveils the intriguing biosynthetic capacity of the strain to produce secondary metabolites.
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BACKGROUND: Serum levels of CA125 measured before any treatment have been evaluated in epithelial ovarian cancer (EOC) as a predictor of patient survival; however, results in survival index are controversial, as CA125 levels are influenced by several variables. Taking this into consideration, the present study evaluated the association of pretreatment levels of CA125 serum with the clinical stage, histology and differentiation grade of the tumor and the survival rate in a group of patients from an oncology referral center in Mexico, all of them diagnosed with ovarian carcinoma. This retrospective study consisted of 1009 patients with EOC, diagnosed between 2006 and 2013 at the National Cancerology Institute (Instituto Nacional de Cancerología-INCan), considering only those with CA125 measurements before any chemotherapy or surgical cytoreduction. Patients with three years of medical follow-up having pretreatment CA125 value and simultaneous diagnoses of histological subtype, clinical stage and differentiation grade of the tumor (n = 656) were studied in order to determine their survival rate. RESULTS: The abnormal level (>35 U/mL) of CA125 was observed in 99 % of serous carcinoma cases rated I to IV in the FIGO stages. Abnormal CA125 proportions were 89 % in endometrioid subtype and 69 % in mucinous tumors, with the highest absolute value of CA125 observed in serous carcinoma surpassing any other histological subtype. Clinical stages III and IV displayed increased CA125 values compared to stages I and II. Undifferentiated carcinomas show the highest level of this indicator compared with those of low and moderate differentiated grade. Survival evaluation by Kaplan-Meier analysis including only high grade serous carcinoma at FIGO stage III (n = 57) demonstrated 57.1 % chances of survival in patients with CA125 pretreatment levels higher than 500 U/mL. Survival was 26.7 % in patients with CA125 lower than 500 U/mL and the hazard ratio for CA125 ≤ 500 U/mL was 2.28, 95 % CI 1.08-4.84, P = 0.032. CONCLUSIONS: Clinical stage associated with pretreatment absolute values of CA125 should be considered as prognostic factor in EOC patients. Values of CA125 higher than 500 U/mL in high grade serous carcinoma with FIGO stage III resulted in an enhanced survival rate of the patients.
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Biomarcadores Tumorais , Antígeno Ca-125/sangue , Cistadenocarcinoma Seroso/sangue , Cistadenocarcinoma Seroso/mortalidade , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cistadenocarcinoma Seroso/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Adulto JovemRESUMO
This study explores the assessments made by the inhabitants of eight Latin American countries regarding the current state of the environment, at a local, national and global scale, and how it is perceived looking ahead to the future. It also examines the assignment of responsibility in the future management of the environment. A total of 944 people took part in the study from the eight participating countries, men and women over the age of 18 with different levels of education. The study uses the Environmental Futures Scale to which two relevant items have been added to assess the environment in the region, as well as the Assignment of Environmental Responsibility Scale. The results show differences between the countries, although in general they are pessimistic regarding the current and future state of the environment at the local, national and global level, with the exception of Brazil. In general, and with the exception of Brazil, in the countries surveyed, people assign a high level of responsibility to external social agents at the different levels, increasing their judgement of external responsibility at the national and global levels of analysis. The implications of these findings for environmental policy and education in the countries of this region are also discussed.
El presente estudio explora las evaluaciones realizadas por los habitantes de ocho países de América Latina en relación con su percepción sobre el estado actual del medio ambiente a escala local, nacional y mundial, así como las expectativas hacia el futuro del ambiente y la asignación de responsabilidades en cuanto a la gestión del futuro ambiental. Participaron un total de 944 personas de ocho países, hombres y mujeres de más 18 años con diferentes niveles de educación. Se aplicó la Escala de Futuros Ambientales a la que se le añadieron dos ítems pertinentes para evaluar el medio ambiente en la región y los ítems correspondientes a la Escala de Responsabilidad Ambiental. Los resultados muestran diferencias entre los países, aunque en general son pesimistas sobre el estado actual y futuro del medio ambiente a nivel local, nacional y mundial, con la excepción de Brasil. Igualmente en general, y con la excepción de Brasil, en los diferentes países encuestados las personas asignan un alto nivel de responsabilidad a los agentes sociales externos en los diferentes niveles, siendo más grande la responsabilidad asignada en los ámbitos nacional y mundial. También se discuten las implicaciones de estos hallazgos para la política del medio ambiente y las implicaciones para la educación en los países de esta región.
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Educação em Saúde Ambiental , Princípio do Poluidor-PagadorRESUMO
BACKGROUND: Rifampicin (RMP) is the most effective first-line antituberculosis drug. One of the most critical aspects of using it in fixed-drug combination formulations is to ensure it reaches therapeutic levels in blood. The determination of the area under the concentration-time curve (AUC) and appropriate dose adjustment of this drug may contribute to optimization of therapy. Even when the maximal concentration (Cmax) of RMP also predicts its sterilizing effect, the time to reach it (Tmax) takes 40 minutes to 6 hours. The aim of this study was to develop a limited sampling strategy (LSS) for therapeutic drug monitoring assistance for RMP. METHODS: Full concentration-time curves were obtained from 58 patients with tuberculosis (TB) after the oral administration of RMP in fixed-drug combination formulation. A validated high-performance liquid chromatographic method was used. Pharmacokinetic parameters were estimated with a noncompartmental model. Generalized linear models were obtained by forward steps, and bootstrapping was performed to develop LSS to predict AUC curve from time 0 to the last measured at 24 hours postdose (AUC0-24). The predictive performance of the proposed models was assessed using RMP profiles from 25 other TB patients by comparing predicted and observed AUC0-24. RESULTS: The mean AUC0-24 in the current study was 91.46 ± 36.7 mg·h·L, and the most convenient sampling time points to predict it were 2, 4 and 12 hours postdose (slope [m] = 0.955 ± 0.06; r = 0.92). The mean prediction error was -0.355%, and the root mean square error was 5.6% in the validation group. Alternate LSSs are proposed with 2 of these sampling time points, which also provide good predictions when the 3 most convenient are not feasible. CONCLUSIONS: The AUC0-24 for RMP in TB patients can be predicted with acceptable precision through a 2- or 3-point sampling strategy, despite wide interindividual variability. These LSSs could be applied in clinical practice to optimize anti-TB therapy based on therapeutic drug monitoring.
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Antibióticos Antituberculose/sangue , Área Sob a Curva , Rifampina/sangue , Adulto , Coleta de Amostras Sanguíneas/métodos , Coleta de Amostras Sanguíneas/normas , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida de Alta Pressão/normas , Feminino , Previsões , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto JovemRESUMO
BACKGROUND: The importance of surface epithelium and epithelial inclusion cysts in the ovary arises from studies demonstrating that these structures are susceptible to epithelial ovarian cancer development. The expression of estrogen receptor alpha (ER alpha), androgen receptor (AR), in epithelial cells of the ovary from premenopausal and postmenopausal women is interesting because sexual steroid hormones are involved in cell growth and differentiation. METHODS: The presence of ER alpha, AR, and the orphan G protein-coupled receptor 30 (GPR30) was demonstrated by immunofluorescence in ovaries obtained from 79 pre and postmenopausal patients, undergoing histero-salpingo-oophorectomy for proliferative gynecological diseases. The proportion of patients that displayed positive reaction for estrogen and androgen receptors in epithelial cells of the ovary was evaluated according to menopausal status and associated pathology. RESULTS: The proportion of patients that displayed a positive receptor expression in the epithelial cells of the ovarian surface and cortical inclusion cysts shows that ER alpha is present in 20 of 79 patients (0.25), AR in 33 of 79 (0.42) and GPR30 in 38 of 55 (0.69). There are no differences in ER alpha, AR, and GPR30 expression between pre and postmenopausal patients and considering the associated pathology, proportions for ER alpha and GPR30 are similar. The patients with cervical cancer show a higher proportion of AR expression in epithelial cells of the ovary, which is statistically significant (P < 0.01) compared with patients with other proliferative diseases. CONCLUSIONS: The presence of ER alpha, AR, and GPR30 in the surface epithelial ovarian cells and its derivatives are observed with a proportion that is specific for each receptor. The proportion of expression for these receptors in the epithelial cells of the ovary does not change after menopause. The proportion of ovaries with AR positive epithelial cells in patients with cervical squamous carcinoma is higher compared with other gynecological pathologies.
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El objetivo del estudio fue aislar y caracterizar E. coli O157:H7 a partir de carne molida fresca de bovino obtenida en diferentes mercados de abastos. Se analizaron 195 muestras; para el aislamiento y enumeración de E. coli se utilizó la técnica del Numero Más probable mediante tubos múltiples; para el aislamiento y caracterización de E. coli O157:H7 el enriquecimiento selectivo y el análisis bioquímico, las colonias características se confirmaron mediante pruebas serológicas. Para determinar la presencia de shigatoxina (stx1, stx2) e intimina (eae A) se empleó la técnica de PCR multiplex en tiempo real y para enterohemolisina la prueba de hemólisis. El 87.18% de la muestras fue positivo para E. coli y el 77.95% presentó un recuento igual o superior a 50 NMP/g. Se obtuvieron 3 (1.54%) cepas de E. coli O157:H7, una stx1 +/ stx2 +/ eaeA - y enterohemolisina -, una stx 1 +/ stx2 -/ eaeA + y enterohemolisina - y la otra stx1 -/ stx2 -/ eaeA - y enterohemolisina +. También se obtuvieron 4 cepas (2.05%) de E. coli O157 no H7, ninguna presentó factores de virulencia. El estudio reveló el riesgo potencial de que E. coli O157:H7 afecte a la población de Lima
The aim of the study was to isolate and characterize E. coli O157: H7 from fresh ground beef obtained in different food markets. 195 samples were analyzed, for isolation and enumeration of E. coli was used most probable number technique using multiple tubes, for the isolation and characterization of E. coli O157: H7 selective enrichment and biochemical analysis, characteristic colonies were confirmed serologically. To determine the presence of shigatoxin (stx1, stx2) and intimin (eaeA) was done with multiplex real time PCR and for enterohemolysin the hemolysis test. The 87.18% of the samples were positive for E. coli and 77.95% had a count greater than or equal to 50 NMP/g. Were obtained 3 (1.54%) strains of E. coli O157: H7, one stx1 +/ stx2 +/eaeA - and enterohemolysin -, one stx1 +/stx2 -/eaeA + and enterohemolysin - and the other stx1 -/stx2 -/eaeA - and enterohemolysin +. Also obtained 4 (2.05%) strains of E. coli O157 non H7, no virulence factors presented. The study found that the risk potential E. coli O157: H7 affecting the population of Lima
RESUMO
The expression pattern of transforming growth factor beta (TGFß) isoforms in chicken embryo gonads was studied at 6-10 days of incubation. TGFß2 mRNA was expressed predominantly in the cortex of the left ovary from day 8 of incubation onwards. TGFß3 mRNA was not detected at any of the stages studied. Similarly, immunofluorescence for the TGFß protein revealed that at day 9 it was located throughout the cortex of the left ovary and in the medulla of both the left and right ovaries. The presence of phosphorylated Smad2 in the nuclei of these regions suggests that TGFß signaling is most likely active at this developmental stage. Culturing the left ovary in a TGFß1-supplemented medium induced a shift of cortical structures toward the medulla, suggesting a role for TGFß in the morphogenesis of the female gonad in chickens.
Assuntos
Ovário/embriologia , Ovário/metabolismo , RNA Mensageiro/metabolismo , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo , Animais , Núcleo Celular/metabolismo , Embrião de Galinha , Feminino , Imunofluorescência , Morfogênese , Técnicas de Cultura de Órgãos , Fosforilação , Isoformas de Proteínas/biossíntese , Isoformas de Proteínas/genética , RNA Mensageiro/genética , Transdução de Sinais , Proteína Smad2/metabolismoRESUMO
Maternal low-protein diets (LP) impair pancreatic ß-cell development, resulting in later-life failure and susceptibility to type 2 diabetes (T2D). We hypothesized that intrauterine and/or postnatal developmental programming seen in this situation involve altered ß-cell structure and relative time course of expression of genes critical to ß-cell differentiation and growth. Pregnant Wistar rats were fed either control (C) 20% or restricted (R) 6% protein diets during pregnancy (1st letter) and/or lactation (2nd letter) in four groups: CC, RR, RC, and CR. At postnatal days 7 and 21, we measured male offspring ß-cell fraction, mass, proliferation, aggregate number, and size as well as mRNA level for 13 key genes regulating ß-cell development and function in isolated islets. Compared with CC, pre- and postnatal LP (RR) decreased ß-cell fraction, mass, proliferation, aggregate size, and number and increased Hnf1a, Hnf4a, Pdx1, Isl1, Rfx6, and Slc2a2 mRNA levels. LP only in pregnancy (RC) also decreased ß-cell fraction, mass, proliferation, aggregate size, and number and increased Hnf1a, Hnf4a, Pdx1, Rfx6, and Ins mRNA levels. Postnatal LP offspring (CR) showed decreased ß-cell mass but increased ß-cell fraction, aggregate number, and Hnf1a, Hnf4a, Rfx6, and Slc2a2 mRNA levels. We conclude that LP in pregnancy sets the trajectory of postnatal ß-cell growth and differentiation, whereas LP in lactation has smaller effects. We propose that LP promotes differentiation through upregulation of transcription factors that stimulate differentiation at the expense of proliferation. This results in a decreased ß-cell reserve, which can contribute to later-life predisposition to T2D.
Assuntos
Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Dieta com Restrição de Proteínas , Células Secretoras de Insulina/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Separação Celular , Dieta , Ingestão de Alimentos/efeitos dos fármacos , Feminino , Imunofluorescência , Regulação da Expressão Gênica/efeitos dos fármacos , Imuno-Histoquímica , Insulina/sangue , Masculino , Tamanho do Órgão/efeitos dos fármacos , Pâncreas/citologia , Pâncreas/efeitos dos fármacos , Pâncreas/crescimento & desenvolvimento , Gravidez , Ratos , Ratos Wistar , Fatores de Transcrição/biossíntese , Fatores de Transcrição/genéticaRESUMO
Cadherins are adhesion molecules that play a crucial role in tissue morphogenesis. Studies on N-cadherin and E-cadherin in the ovary of fetal hamster suggest that these adhesion molecules are involved in primordial follicle formation. In chicken embryo, present results demonstrate that N-cadherin is located on the surface epithelium and in the cortical cords of the ovary. Moreover, N-cadherin is identified in germ cells on day 14 of chicken embryo development. Quantification of mRNA of N-cadherin and E-cadherin demonstrates that treatments with follicle-stimulating hormone (FSH) or human chorionic gonadotropin (hCG), increase N-cadherin expression. Whereas, E-cadherin expression is decreased by gonadotropin treatments. The negative correlation between both cadherins expression is demonstrated after 18 h of hormonal treatment. Regulation of cadherin expression by gonadotropins and the presence of N-cadherin in the ovarian cortex suggest that these adhesion molecules are involved in ovarian morphogenesis in the chicken embryo.