RESUMO
CONTEXT: Currently, Chagas disease represents an important public health problem affecting more than 8 million people worldwide. The vector of this disease is the Trypanosoma cruzi (Tc) parasite. Our research specifically focuses on the structure and aggregation states of the enzyme aldo-keto reductase of Tc (TcAKR) reported in this parasite. TcAKR belongs to the aldo-keto reductase (AKR) superfamily, enzymes that catalyze redox reactions involved in crucial biological processes. While most AKRs are found in monomeric forms, some have been reported to form dimeric and tetrameric structures. This is the case for some TcAKR. To better understand how TcAKR multimers form and remain stable, we conducted a comprehensive computational analysis using molecular dynamics (MD) simulations. Our approach to elucidating the aggregation states of TcAKR involved two strategies. Initially, we explored the dynamic behaviour of pre-assembled TcAKR dimers. Subsequently, we examined the self-aggregation of eight monomers. This investigation led to the identification of crucial residues that contribute to the stabilization of protein-protein interactions. It was also found that TcAKRs can form stable supramolecular assemblies, with each monomer typically surrounded by three first neighbours. These findings align with experimental reports of tetrameric or more complex supramolecular structures. Our computational studies could guide further experimental investigations aiming at drug development and assist in designing strategies to modulate aggregation. METHOD: Atomistic molecular dynamics simulations were carried out. The TcAKR 3D model structure was obtained by homology modelling using the Swiss Model for the TcAKR sequence (GenBank accession no. EU558869). Further, we checked the model with Alphafold2 and found a high degree of similarity between models. Several tools were used to build the dimers including CLUSPRO, GRAMM-Docking, Hdock, and Py-dock. Protein superstructures were built using the PACKMOL package. CHARMM-GUI was used to set up the simulation systems. GROMACS version 2020.5 was used to perform the simulations with the CHARMM36 force field for the protein and ions and the TIP3P model for water. Further analyses were performed using VMD, GROMACS, AMBER tools, MDLovoFit, bio3d, and in-house programs.
Assuntos
Aldo-Ceto Redutases , Simulação de Dinâmica Molecular , Trypanosoma cruzi , Trypanosoma cruzi/enzimologia , Aldo-Ceto Redutases/química , Aldo-Ceto Redutases/metabolismo , Multimerização Proteica , Proteínas de Protozoários/química , Proteínas de Protozoários/metabolismoRESUMO
Background: HER-2 positive (+) breast cancer (BC) accounts for 20-25% of BC, it is more aggressive, and it has a lower survival rate. Since the approval of trastuzumab in 1998, other HER-2-targeted therapies such as pertuzumab and trastuzumab emtansine (TDM1) have been introduced, improving patient survival. However, cardiotoxicity is an adverse effect of these treatments. Objective: To estimate the incidence of cardiotoxicity with trastuzumab, trastuzumab/pertuzumab, and TDM1 in women with HER-2 + BC treated over a 6-year period at the Hospital de Clínicas and the Hospital Departamental de Soriano. Material and methods: Observational, descriptive, and retrospective study which included patients with HER-2 + BC treated with trastuzumab, trastuzumab/pertuzumab, or TDM1. Results: 81 patients were included, with a cardiotoxicity incidence of 23.4%. Cardiotoxicity was determined by a > 10% decrease in left ventricular ejection fraction (LVEF) (57.9%) and a LVEF < 50% evident during treatment (42.1%). Only 1 patient presented symptomatic heart failure. 63.1% of those who discontinued treatment due to cardiotoxicity managed to resume it. No relationship was evident between cardiovascular history or the administration regimen and the development of cardiotoxicity. Conclusion: The study showed a cardiotoxicity incidence similar to the international one. Most did not present cardiac toxicity, and if they did, it was asymptomatic and reversible.
Introducción: el cáncer de mama (CM) HER-2 positivo (+) representa el 20-25% de los CM, es más agresivo y tiene menor sobrevida. Desde la aprobación del trastuzumab en 1998, se han introducido otras terapias dirigidas al HER-2 como pertuzumab y trastuzumab emtansina (TDM1), con lo cual ha mejorado la supervivencia de las pacientes. Sin embargo, la cardiotoxicidad representa un efecto adverso de estos tratamientos. Objetivo: estimar la incidencia de cardiotoxicidad con trastuzumab, trastuzumab/pertuzumab y TDM1 en mujeres con CM HER-2 +, tratadas en un periodo de 6 años en el Hospital de Clínicas y el Hospital Departamental de Soriano. Material y métodos: estudio observacional, descriptivo y retrospectivo que incluyó pacientes con CM HER-2 +, tratadas con trastuzumab, trastuzumab/pertuzumab o TDM1. Resultados: se incluyeron 81 pacientes. La incidencia de cardiotoxicidad fue del 23.4%. La cardiotoxicidad se determinó por una disminución > 10% de la fracción de ejección del venticulo izquierdo (FEVI) (57.9%) y por una FEVI < 50%, evidenciada durante el tratamiento (42.1%). Únicamente una paciente presentó insuficiencia cardiaca sintomática. El 63.1% de quienes suspendieron el tratamiento por cardiotoxicidad logró reanudarlo. No se evidenció una relación entre los antecedentes cardiovasculares ni con el esquema de administración y el desarrollo de cardiotoxicidad. Conclusión: el estudio mostró una incidencia de cardiotoxicidad similar a la internacional. La mayoría no tuvo toxicidad cardiaca y si la hubo fue asintomática y reversible.
Assuntos
Ado-Trastuzumab Emtansina , Anticorpos Monoclonais Humanizados , Neoplasias da Mama , Cardiotoxicidade , Receptor ErbB-2 , Trastuzumab , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Estudos Retrospectivos , Cardiotoxicidade/etiologia , Pessoa de Meia-Idade , Receptor ErbB-2/metabolismo , Receptor ErbB-2/antagonistas & inibidores , Trastuzumab/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Idoso , Adulto , Ado-Trastuzumab Emtansina/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Incidência , Maitansina/análogos & derivados , Maitansina/efeitos adversosRESUMO
Genome editing in pigs for xenotransplantation has seen significant advances in recent years. This study compared three methodologies to generate gene-edited embryos, including co-injection of sperm together with the CRISPR-Cas9 system into oocytes, named ICSI-MGE (mediated gene editing); microinjection of CRISPR-Cas9 components into oocytes followed by in vitro fertilization (IVF), and microinjection of in vivo fertilized zygotes with the CRISPR-Cas9 system. Our goal was to knock-out (KO) porcine genes involved in the biosynthesis of xenoantigens responsible for the hyperacute rejection of interspecific xenografts, namely GGTA1, CMAH, and ß4GalNT2. Additionally, we attempted to KO the growth hormone receptor (GHR) gene with the aim of limiting the growth of porcine organs to a size that is physiologically suitable for human transplantation. Embryo development, pregnancy, and gene editing rates were evaluated. We found an efficient mutation of the GGTA1 gene following ICSI-MGE, comparable to the results obtained through the microinjection of oocytes followed by IVF. ICSI-MGE also showed higher rates of biallelic mutations compared to the other techniques. Five healthy piglets were born from in vivo-derived embryos, all of them exhibiting biallelic mutations in the GGTA1 gene, with three displaying mutations in the GHR gene. No mutations were observed in the CMAH and ß4GalNT2 genes. In conclusion, in vitro methodologies showed high rates of gene-edited embryos. Specifically, ICSI-MGE proved to be an efficient technique for obtaining homozygous biallelic mutated embryos. Lastly, only live births were obtained from in vivo-derived embryos showing efficient multiple gene editing for GGTA1 and GHR.
Assuntos
Sistemas CRISPR-Cas , Edição de Genes , Animais , Suínos/genética , Humanos , Masculino , Animais Geneticamente Modificados , Edição de Genes/veterinária , Transplante Heterólogo/veterinária , Injeções de Esperma Intracitoplásmicas/veterinária , Sêmen , Fertilização in vitro/veterináriaRESUMO
Introducción: La hipertensión endocraneana idiopática (HEI) o pseudotumor cerebri es una enfermedad de origen y fisiopatología desconocida que puede generar graves consecuencias. El abordaje terapéutico clásico inicial es la dieta hipocalórica y la acetazolamida. La fenestración de la vaina del nervio óptico y la colocación de un sistema de derivación de LCR constituyen procedimientos quirúrgicos clásicos aceptados para esta entidad en los casos sin respuesta al manejo farmacológico. En 1995 se describió la asociación de la HEI y la estenosis de senos transversos y en 2002 se publicó el primer caso de angioplastía de seno transverso como tratamiento exitoso de la HEI en un paciente. En los últimos 20 años se han reportado múltiples casos y series de casos con excelentes resultados pasando a formar parte de las herramientas válidas para el tratamiento de esta entidad. Objetivo: Describir la técnica de angioplastía e implantación de stent en el seno transverso como tratamiento de la hipertensión endocraneana idiopática. Material y métodos: Descripción de la técnica quirúrgica y los dispositivos utilizados para la angioplastía del seno transverso en un paciente con HEI asociado a estenosis del mismo. Conclusiones: Se describe la técnica de angioplastía e implantación de un stent en el seno transverso en una paciente con diagnóstico de HEI asociado a estenosis de seno trasverso con buena evolución(AU)
Background: Idiopathic intracranial hypertension (IIH) is a disease of unknown etiology and physiopathology that can generate serious consequences. The initial classical treatment is weight loss and acetazolamide. Optic nerve fenestration surgery and CSF diversion are accepted as surgical procedures for the treatment of this entity. In 1995, the association of IIH and dural sinus stenosis by venography was described and in 2002 the first case of stent implantation in transverse sinus as a successful treatment of IIH in a patient was published. In the last 20 years have been published multiple case reports and case series with excellent results, becoming part of the valid tools for the treatment of this disease. Objective: To describe surgical technique of stenting the transverse sinus in a patient with IIH diagnosis. Material and methods: Description of diagnosis steps and stenting technique of transverse sinus in a patient with IIH associated to transverse sinus stenosis. Conclusions: We describe stenting technique of transverse sinus in a patient with IIH diagnosis(AU)
Assuntos
Hipertensão , Stents , Angioplastia , Constrição Patológica , Trombose do Seio LateralRESUMO
Introduction: Tuberculosis (TB) is now the 2nd leading infectious killer after COVID-19 and the 13th leading cause of death worldwide. Moreover, TB is a lethal combination for HIV-patients. Th1 responses and particularly IFN-γ are crucial for immune protection against Mycobacterium tuberculosis infection. Many gene variants for IFNG that confer susceptibility to TB have been described in multiple ethnic populations. Likewise, some epigenetic modifications have been evaluated, being CpG methylation the major epigenetic mark that makes chromatin inaccessible to transcription factors, thus avoiding the initiation of IFNG transcription. Methods: We evaluated both genetic and epigenetic changes involved in IFN-γ production and TB susceptibility in Argentine population. Amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) was performed for the IFN-γ +874 A/T polymorphism (rs2430561) genotyping in 199 healthy donors (HD) and 173 tuberculosis (TB) patients. IFN-γ levels from M. tuberculosis-stimulated PBMCs were measured by ELISA. The methylation status at the -53 CpG site of the IFNG promoter in individuals with latent infection (LTBI), TB and HD was determine by pyrosequencing. Results: Using a case-control study, we found that A allele and, consequently, AA genotype were overrepresented in patients with active disease. Moreover, HD carrying T allele (AT or TT genotype) evidenced an augmented IFN-γ secretion compared to TB patients. Codominance was the genetic model that best fits our results according to the Akaike information criterion (AIC). In addition, increased methylation levels at the -53 CpG site in the IFN-γ promoter were observed in whole blood of patients with active TB compared to LTBI individuals. Discussion: IFN-γ is regulated by genetic variants and epigenetic modifications during TB. Besides, AA genotype of the rs2430561 single nucleotide polymorphism could be considered as a potential TB susceptibility genetic biomarker in Argentina and the methylation of the -53 CpG site could result in a useful predictor of TB reactivation.
Assuntos
COVID-19 , Interferon gama , Mycobacterium tuberculosis , Tuberculose , Humanos , Estudos de Casos e Controles , Predisposição Genética para Doença , Genótipo , Interferon gama/genética , Polimorfismo de Nucleotídeo Único , Tuberculose/genéticaRESUMO
Microplastics (MPs) from the coastal areas of a highly anthropised estuary were sampled to assess their distribution in coastal sediments and their role as potential vectors of pollution. The average MP density was 1693 ± 2315 MPs/kg, which mainly accumulated in the high tide and storm berm areas of the beach. The Microplastic Pollution Index (MPPI), Microplastic Impact Coefficient (CMPI), Hierarchical Cluster Analysis and Principal Component Analysis revealed spatial variation in MPs pollution. High-density polyethylene plastic pellets were abundant at two beaches (192 ± 218 MPs/kg sediment). Furthermore, the presence of sorbed chemicals on pellets was assessed through GC-MS, showing 0.95 ± 0.09 ng/g of ∑7OCPs, 4.03 ± 0.89 ng/g of ∑7PCBs, 108.76 ± 12.88 ng/g of ∑16 PAHs and 122.79 ± 11.13 g/g of ∑29 PAHs. The sorption capacity of plastics, combined with their abundance, poses an environmental concern and also highlights their suitability as indicators of chemical exposure.
Assuntos
Plásticos , Poluentes Químicos da Água , Plásticos/análise , Microplásticos/análise , Estuários , Argentina , Brasil , Monitoramento Ambiental , Poluição Ambiental/análise , Poluentes Químicos da Água/análise , Sedimentos Geológicos/análiseRESUMO
Cytochrome P450cam (CYP101A1) catalyzes the hydroxylation of d-camphor by molecular oxygen. The enzyme-catalyzed hydroxylation exhibits a high degree of regioselectivity and stereoselectivity, with a single major product, d-5-exo-hydroxycamphor, suggesting that the substrate is oriented to facilitate this specificity. In previous work, we used an elastic network model and perturbation response scanning to show that normal deformation modes of the enzyme structure are highly responsive not only to the presence of a substrate but also to the substrate orientation. This work examines the effects of mutations near the active site on substrate localization and orientation. The investigated mutations were designed to promote a change in substrate orientation and/or location that might give rise to different hydroxylation products, while maintaining the same carbon and oxygen atom balances as in the wild type (WT) enzyme. Computational experiments and parallel in vitro site-directed mutations of CYP101A1 were used to examine reaction products and enzyme activity. 1H-15N TROSY-HSQC correlation maps were used to compare the computational results with detectable perturbations in the enzyme structure and dynamics. We found that all of the mutant enzymes retained the same regio- and stereospecificity of hydroxylation as the WT enzyme, with varying degrees of efficiency, which suggests that large portions of the enzyme have been subjected to evolutionary pressure to arrive at the appropriate sequence-structure combination for efficient 5-exo hydroxylation of camphor.
Assuntos
Cânfora 5-Mono-Oxigenase , Cânfora , Cânfora/química , Cânfora 5-Mono-Oxigenase/química , Domínio Catalítico , Sistema Enzimático do Citocromo P-450/metabolismo , Hidroxilação , Mutação , Oxigênio , Especificidade por SubstratoRESUMO
A partir del trabajo de Lacan, se analizan distintos aspectos de la escritura durante el proceso de psicoanálisis. En la segunda parte del artículo se precisa el trabajo que Lacan despliega durante su seminario sobre La identificación (1961-1962), y más tarde en De un discurso que no sería (del) semblante (1971), con las escrituras china y japonesa.
Assuntos
Psicanálise/instrumentação , Psicanálise/tendências , Redação , IdiomaRESUMO
Iron molecule is of great importance in the synthesis of hemoglobin which is essential for oxygen transport. Iron levels are quantified by accurately high sensitivity tests, such as serum ferritin (SF). However, common studies to quantify SF are long and strenuous (~ 5 h), for example enzyme-linked immunosorbent assay (ELISA). In this paper, blood serum samples were analyzed by Raman spectroscopy (RS), and a computational analysis of spectra is proposed to detect differences in SF as an alternative procedure. Serum samples were obtained from 22 patients, 9 who were clinically diagnosed with anemia and 13 controls. Patients with anemia had low levels of SF (< 30 ng/ml), and a control group had levels between 30 and 500 ng/ml. The spectra obtained were conditioned with a baseline correction and smoothing, then evaluated by principal component analysis (PCA), and a predictive model was estimated by lineal discrimination analysis (LDA). The results showed a clear differentiation of the study groups by PCA, also 99.69% sensitivity and 100% specificity by LDA. This study suggest that Raman spectroscopy is a fast (~ 5 min) and a powerful tool capable to qualitative differentiate ferritin concentrations.
Assuntos
Ferritinas/sangue , Análise de Componente Principal , Análise Espectral Raman , Análise Discriminante , Humanos , Ferro , Curva ROCRESUMO
Production of IFN-γ contributes to host defense against Mycobacterium tuberculosis (Mtb) infection. We previously demonstrated that Signaling lymphocytic activation molecule-associated protein (SAP) expression on cells from tuberculosis (TB) patients was inversely correlated with IFN-γ production. Here we first investigated the role of NK, T- and B-cell antigen (NTB-A)/SAP pathway in the regulation of Th1 response against Mtb. Upon antigen stimulation, NTB-A phosphorylation rapidly increases and afterwards modulates IFN-γ and IL-17 secretion. To sustain a healthy immune system, controlled expansion and contraction of lymphocytes, both during and after an adaptive immune response, is essential. Besides, restimulation-induced cell death (RICD) results in an essential homeostatic mechanism for precluding excess T-cell accumulation and associated immunopathology during the course of certain infections. Accordingly, we found that the NTB-A/SAP pathway was required for RICD during active tuberculosis. In low responder (LR) TB patients, impaired RICD was associated with diminished FASL levels, IL-2 production and CD25high expression after cell-restimulation. Interestingly, we next observed that SAP mediated the recruitment of the Src-related kinase FYNT, only in T cells from LR TB patients that were resistant to RICD. Together, we showed that the NTB-A/SAP pathway regulates T-cell activation and RICD during human TB. Moreover, the NTB-A/SAP/FYNT axis promotes polarization to an unfavorable Th2-phenotype.
Assuntos
Mycobacterium tuberculosis/imunologia , Família de Moléculas de Sinalização da Ativação Linfocitária/metabolismo , Células Th2/imunologia , Tuberculose/imunologia , Adulto , Morte Celular , Diferenciação Celular , Células Cultivadas , Feminino , Homeostase , Humanos , Imunidade , Terapia de Imunossupressão , Interferon gama/metabolismo , Interleucina-17/metabolismo , Ativação Linfocitária , Masculino , Proteínas de Neoplasias/metabolismo , Proteínas Tirosina Quinases/metabolismo , Transdução de SinaisRESUMO
The poor prognosis, few available treatment options, and multidrug resistance present in hepatocellular carcinoma are major problems, and new early biomarkers are needed to reduce the liver cancer death rate. ATP-binding cassette sub-family C member 3 (Abcc3) is overexpressed in different cancers and is associated with multidrug resistance and a carcinogenic stem cell phenotype. We present evidence for the first time that ABCC3 is a potential sanguine biomarker and anticancer target in hepatocellular carcinoma. Abcc3 mRNA expression was elevated in liver nodules and tumors in rat hepatocarcinogenesis model. Accordingly, the ABCC3 protein was preferentially overexpressed within the nodules and tumors during hepatocellular carcinoma progression and was secreted into the bloodstream of rat hepatocarcinogenesis model. The ABCC3 protein was expressed in human hepatoma cells and, importantly, was also present in HepG2- and Huh7-conditioned media. Furthermore, ABCC3 was overexpressed in human hepatocellular carcinoma. This report is the first to describe liver overexpression of Abcc3 during the cancer initiation, promotion, and progression periods in rat hepatocarcinogenesis model and in human hepatocellular carcinoma.
Assuntos
Biomarcadores Tumorais/análise , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Animais , Western Blotting , Progressão da Doença , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imuno-Histoquímica , Masculino , Ratos , Ratos Endogâmicos F344 , Reação em Cadeia da Polimerase em Tempo Real , TranscriptomaRESUMO
BACKGROUND AND AIMS: Secreted frizzled-related protein 5 (SFRP5) was recently described as a new adipokine protective for hepatic steatosis and other obesity-related complications in the mouse model. To date, SFRP5 expression in non-alcoholic fatty liver disease (NAFLD) has not been fully assessed in humans. We measured circulating SFRP5 levels and its expression in liver and adipose tissue, and evaluated its association with NAFLD in morbidly obese women. MATERIAL AND METHODS: Fifty-four morbidly obese women undergoing bariatric surgery were included in the study. Liver biopsies were used for histology and hepatic triglyceride content quantification. Circulating SFRP5 levels were measured through enzyme-linked immunoabsorbent assay, and SFRP5 expression was performed in hepatic and adipose tissue (subcutaneous and visceral). RESULTS: Although circulating SFRP5 levels showed a tendency to decrease with NAFLD progression, no significant differences were observed among non-alcoholic steatosis, steatohepatitis, and control subjects. Hepatic SFRP5 expression showed a negative correlation with hepatic triglyceride content (r = -0.349, P = 0.016 for mRNA and r = -0.291, P = 0.040 for SRFP5 protein) and ALT serum levels (r = -0.437, P = 0.001 for SRFP5 protein). In addition, hepatic SFRP5 protein levels were significantly lower in NASH than in control subjects (P = 0.006). CONCLUSION: This is the first study reporting an association of hepatic SFRP5 expression with NAFLD in humans.
Assuntos
Proteínas do Olho/análise , Fígado/química , Proteínas de Membrana/análise , Hepatopatia Gordurosa não Alcoólica/etiologia , Obesidade Mórbida/complicações , Proteínas Adaptadoras de Transdução de Sinal , Adulto , Cirurgia Bariátrica , Biópsia , Estudos Transversais , Regulação para Baixo , Ensaio de Imunoadsorção Enzimática , Proteínas do Olho/sangue , Proteínas do Olho/genética , Feminino , Humanos , Imuno-Histoquímica , Gordura Intra-Abdominal/química , Proteínas de Membrana/sangue , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Obesidade Mórbida/diagnóstico , Obesidade Mórbida/cirurgia , Reação em Cadeia da Polimerase , RNA Mensageiro/genética , Índice de Gravidade de Doença , Gordura Subcutânea/química , Triglicerídeos/análise , Adulto JovemRESUMO
Horizontal gene transfer (HGT) is a central process in prokaryotic evolution. Once a gene is introduced into a genome by HGT, its contribution to the fitness of the recipient cell depends in part on its expression level. Here we show that in Synechococcus elongatus PCC 7942, xenologs derived from non-cyanobacterial sources exhibited lower expression levels than native genes in the genome. In accord with our observation, xenolog codon adaptation indexes also displayed relatively low expression values. These results are in agreement with previous reports that suggested the relative neutrality of most xenologs. However, we also demonstrated that some of the xenologs detected participated in cellular functions, including iron starvation acclimation and nitrate reduction, which corroborate the role of HGT in bacterial adaptation. For example, the expression levels of some of the xenologs detected are known to increase under iron-limiting conditions. We interpreted the overall pattern as an indication that there is a selection pressure against high expression levels of xenologs. However, when a xenolog protein product confers a selective advantage, natural selection can further modulate its expression level to meet the requirements of the recipient cell. In addition, we show that ORFans did not exhibit significantly lower expression levels than native genes in the genome, which suggested an origin other than xenology.
Assuntos
Proteínas de Bactérias/genética , Regulação Bacteriana da Expressão Gênica , Transferência Genética Horizontal , Genoma Bacteriano , Synechococcus/genética , Adaptação Fisiológica/genética , Algoritmos , Proteínas de Bactérias/metabolismo , Mapeamento Cromossômico , Códon , Aptidão Genética , Ferro/metabolismo , Anotação de Sequência Molecular , Nitratos/metabolismo , Fases de Leitura Aberta , Oxirredução , Synechococcus/metabolismoRESUMO
El objetivo fue determinar los factores de riesgo que predisponen a hipertensión arterial en enfermeras en el servicio de emergencia del Hospital Nacional Edgardo Rebagliati Martins Lima-Perú 2013. Material y Método: El estudio fue de nivel aplicativo, tipo cuantitativo, método descriptivo de corte transversal. La población estuvo conformado por 55 enfermeros. La técnica fue la encuesta y el instrumento un formulario tipo cuestionario, aplicado previo consentimiento informado. Resultados: Del 100 por ciento (55), 58 por ciento (32) está ausente y 42 por ciento (23) presente. Respecto a los factores de riesgo por dimensiones en el psicosocial 78 por ciento (43) está ausente y 22 por ciento (12) presente; y en la dimensión factores mórbidos 56 por ciento (31) está ausente y 44 por ciento (24) presente. Conclusiones: Los factores de riesgo que predisponen a hipertensión en enfermeras en el servicio de emergencia, el mayor porcentaje expresan que está ausente el carácter hostil, y nervioso flemático, la hipertensión, diabetes, antecedentes de obesidad, no consumen cigarros, ni alcohol, sin embargo un porcentaje considerable manifiesta que está presente la apatía, lo sentimental, colérico y placido, antecedentes patológicos de la madre por hipertensión, glucosa normal, consumo de 2 a 3 cucharaditas de sal, grasas, gaseosas, realizar deporte solo cuando se acuerda, clima laboral de regular a malo, descansan solo 6 horas al día, experimentan sentimientos de ira, desmotivación y cansancio...
The objective was to determine the risk factors that predispose to high blood pressure in nurses in emergency of National Hospital Edgardo Rebagliati Martins Lima-Peru 2013 service. Material and method: The study was of application level, quantitative, descriptive cross-sectional method. The population was comprised of 55 nurses technique was the survey and the instrument a form type questionnaire, applied prior informed consent. Results: 100 per cent (55), 58 per cent (32) is absent and 42 per cent (23) present. Regarding risk factors for dimensions in psychosocial 78 per cent (43) is absent and 22 per cent (12) present; and in the dimension factors morbid 56 per cent (31) is absent and 44 per cent (24) present. Conclusions: The risk factors that they predispose to hypertension in nurses in emergency service, the highest percentage expressed that the hostile character, is absent and nervous phlegmatic, hypertension, diabetes, previous history of obesity, do not consume cigarettes or alcohol, however a manifest considerable percentage that is this apathy, the emotional, angry and placid, pathological antecedents of the mother for hypertension normal glucose, 2 to 3 teaspoons of salt consumption, fat, gaseous, realize single sport when agreed, work of regulating bad, climate rest only 6 hours a day, they experience feelings of anger, discouragement and fatigue...
Assuntos
Humanos , Masculino , Adulto , Feminino , Pessoa de Meia-Idade , Condições de Trabalho , Fatores de Risco , Hipertensão/etiologia , Estudos de Avaliação como Assunto , Estudos TransversaisRESUMO
Carcinogenesis is driven by the accumulation of mutations and abnormal DNA methylation patterns, particularly the hypermethylation of tumorsuppressor genes. Changes in genomic DNA methylation patterns are established by the DNA methyltransferases (DNMTs) family: DNMT1, DNMT3a and DNMT3b. The DNMTs are known to be overexpressed in tumors. However, when the DNMTs expression profile is altered in earlier stages of carcinogenesis remains to be elucidated. The resistant hepatocyte model (RHM) allows the analysis of the hepatocellular carcinoma (HCC) from the formation of altered cell foci to the appearance of tumors in rats. To investigate the DNMTs expression in this model, we first observed that timp3, rassf1a and p16 genes became methylated during cancer development by methylationspecific PCR (MSP) and the bisulphate sequencing PCR (BSP) of timp3. The differential expression at the RNA and protein level of the three DNMTs was also assessed. dnmt1 expression was higher in tumors than in normal and early cancer stages. However, no evident overexpression of the enzyme was identified by immunohistochemistry. By contrast, DNMT3a and DNMT3b were consistently subexpressed in tumors. In the present study, we report a carcinogenesis model that does not feature the overexpression of DNMT1 but exhibits a transient expression of DNMT3a and DNMT3b.
Assuntos
DNA (Citosina-5-)-Metiltransferases/genética , DNA (Citosina-5-)-Metiltransferases/metabolismo , Neoplasias Hepáticas Experimentais/patologia , 2-Acetilaminofluoreno , Animais , Inibidor p16 de Quinase Dependente de Ciclina/genética , Metilação de DNA , DNA Metiltransferase 3A , Dietilnitrosamina , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas Experimentais/induzido quimicamente , Neoplasias Hepáticas Experimentais/enzimologia , Masculino , Ratos , Inibidor Tecidual de Metaloproteinase-3/genética , Proteínas Supressoras de Tumor/genética , DNA Metiltransferase 3BRESUMO
INTRODUCCION: El prospecto que acompaña a los medicamentos de venta libre contiene información importante, que no siempre es comprendida correctamente. OBJETIVOS: Explorar en qué medida se comprende la información incluida en los prospectos de especialidades medicinales de venta libre con paracetamol como principio activo. METODOS: Se realizó un estudio cualitativo, con entrevistas semiestructuradas a 20 adultos a cargo de niños usuarios del medicamento. Se llevó a cabo con un equipo multidisciplinario: dos médicas, una psicóloga, una socióloga y una ling³ista. Se utilizó el prospecto de un medicamento con paracetamol destinado a niños mayores de cuatro años. Se analizó cada respuesta como variable dicotómica (sí/no), de acuerdo con la comprensión de la información. Se identificaron las características discursivas de los prospectos y, a partir de ellas, se evaluaron los datos de las entrevistas. RESULTADOS: Ninguno de los entrevistados comprendió la posología, mientras que un 30% tuvo dificultades para entender las contraindicaciones. CONCLUSIONES: Es necesario seguir realizando estudios de comprensibilidad para identificar las dificultades que tienen los usuarios de medicamentos de venta libre para entender los prospecto (AU)
INTRODUCTION: Over-the-counter medicine leaflets include important information, which is not alway sunderstood by users. OBJECTIVES: To explore the level of understanding of information stated in over-the-countermedicine leaflets, containing paracetamol as active ingredient. METHODS: A qualitative study was conducted, with semi-structured interviews to 20 adults in charge of children using the medicine. The multidisciplinary team was composed by two physicians, one psychologist, one sociologist and one linguist. It used a leaflet of a medicine containing paracetamol for children older than four years. The study analyzed every response as a yes/no variable according to information comprehension. The leaflet speech features were identified, so as to evaluate the data collected by the interviews. RESULTS: None of the interviewed people understood the dosage, while 30% of them had difficulties regarding contraindications. CONCLUSIONS: It is necessary to perform further comprehensibility studies to identify the difficulties faced by over-the-counter medicine users while reading the leaflets (AU)
Assuntos
Humanos , Bulas de Medicamentos , Medicamentos sem Prescrição/administração & dosagem , Compreensão , Pesquisa Qualitativa , Inquéritos e Questionários , Posologia Homeopática , Entrevistas como Assunto , Rotulagem de MedicamentosRESUMO
INTRODUCCIÓN: El prospecto que acompaña a los medicamentos de venta libre contiene información importante, que no siempre es comprendida correctamente. OBJETIVOS: Explorar en qué medida se comprende la información incluida en los prospectos de especialidades medicinales de venta libre con paracetamol como principio activo. MÉTODOS: Se realizó un estudio cualitativo, con entrevistas semiestructuradas a 20 adultos a cargo de niños usuarios del medicamento. Se llevó a cabo con un equipo multidisciplinario: dos médicas, una psicóloga, una socióloga y una lingüista. Se utilizó el prospecto de un medicamento con paracetamol destinado a niños mayores de cuatro años. Se analizó cada respuesta como variable dicotómica (sí/no), de acuerdo con la comprensión de la información. Se identificaron las características discursivas de los prospectos y, a partir de ellas, se evaluaron los datos de las entrevistas. RESULTADOS: Ninguno de los entrevistados comprendió la posología, mientras que un 30% tuvo dificultades para entender las contraindicaciones. CONCLUSIONES: Es necesario seguir realizando estudios de comprensibilidad para identificar las dificultades que tienen los usuarios de medicamentos de venta libre para entender los prospecto
INTRODUCTION: Over-the-counter medicine leaflets include important information, which is not alway sunderstood by users. OBJECTIVES: To explore the level of understanding of information stated in over-the-countermedicine leaflets, containing paracetamol as active ingredient. METHODS: A qualitative study was conducted, with semi-structured interviews to 20 adults in charge of children using the medicine. The multidisciplinary team was composed by two physicians, one psychologist, one sociologist and one linguist. It used a leaflet of a medicine containing paracetamol for children older than four years. The study analyzed every response as a yes/no variable according to information comprehension. The leaflet speech features were identified, so as to evaluate the data collected by the interviews. RESULTS: None of the interviewed people understood the dosage, while 30% of them had difficulties regarding contraindications. CONCLUSIONS: It is necessary to perform further comprehensibility studies to identify the difficulties faced by over-the-counter medicine users while reading the leaflets
Assuntos
Humanos , Compreensão , Rotulagem de Medicamentos , Entrevistas como Assunto , Bulas de Medicamentos , Medicamentos sem Prescrição/administração & dosagem , Posologia Homeopática , Pesquisa Qualitativa , Inquéritos e QuestionáriosRESUMO
Se presentan los resultados de un estudio para evaluar la respuesta de la glucemia después a la administración de una dosis de insulina por vía sublingual en un grupo de pacientes dabéticos tipo 2. Se seleccionaron 10 sujetos del Hospital General Regional No. 72 y 50 sujetos del Hospital de Solidaridad de Jimiltepec Oaxaca. Todos los sujetos suspendieron el tratamiento antidiabético 24 horas previas. Se administró una dosis de insulina regular dentro de cápsulas de gelatina a razón de 16 unidades en promedio. Se tomaron muestras sanguíneas a los 0 y 15, 30, 45, 60, 90 y 120 minutos. La glucemia se determinó por técnica de glucosa-oxidasa. En el grupo de Insulina se observa disminución de la glucemia inicial a los 120 minutos; no hubo modificación de los niveles de glucemia con placebo. La insulina administrada en cápsulas por vía sublingual disminuye los niveles de glucemia en sujetos con diabetes mellitus tipo 2
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Administração Sublingual , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/urina , Insulina/administração & dosagem , Placebos/administração & dosagemRESUMO
Variaciones en los niveles de marcadores tumorales pueden atribuirse a cambios de reactivos o ténica. En este estudio comparamos dos métodos de cuantificación, ensayo inmunoenzimático de micropartículas (IMx, Abbott) e inmunofluorescencia indirecta en placas (Stratus DaDe), para antígeno prostático específico, antígeno carcinoembrionario y alfafetoproteína. Método: Se analizaron sueros de 100 pacientes con solicitud para antígeno carcinoembrionario, 97 para alfafetoproteína y 98 para antígeno prostático específico. Se revisaron expedientes para corroborar diagnósticos; se obtuvo sensibilidad y especificidad y se realizan curvas de correlación lineal. Resultados: La sensibilidad para los tres marcadores fue superior a 97 por ciento; la especificidad para alfafetoproteína fue del 100 por ciento, para antígeno carcinoembrionario de 95 por ciento y para antígeno prostático específico de 84 por ciento. Los valores predictivos positivos y negativos estuvieron arriba del 92 por ciento. Los coeficientes de correlación fueron 0.97 para antígeno carcinoembrionario, 0.86 para alfafetoproteína y 0.66 para antígeno prostático específico. Existieron casos discrepantes; uno para alfafetoproteína, dos para antígeno carcinoembrionario y seis para antígeno prostático específico. Conclusiones: Basados en los coeficientes de correlación, los métodos son sustituibles para antígeno carcinoembrionario, pero no para antígeno prostático específico y alfafetoproteína. Con estos resultados se prueba que no es conveniente cambiar metodología cuando se sigue a pacientes oncológicos, ya que las variaciones pueden deberse a cambios en el método de medición y no al proceso maligno