RESUMEN
Insulin-like growth factor 1 (IGF1) is primarily synthesized in and secreted from the liver; however, estrogen (E2), through E2 receptor α (ERα), increases uterine Igf1 mRNA levels. Previous ChIP-seq analyses of the murine uterus have revealed a potential enhancer region distal from the Igf1 transcription start site (TSS) with multiple E2-dependent ERα-binding regions. Here, we show E2-dependent super enhancer-associated characteristics and suggest contact between the distal enhancer and the Igf1 TSS. We hypothesized that this distal super-enhancer region controls E2-responsive induction of uterine Igf1 transcripts. We deleted 430 bp, encompassing one of the ERα-binding sites, thereby disrupting interactions of the enhancer with gene-regulatory factors. As a result, E2-mediated induction of mouse uterine Igf1 mRNA is completely eliminated, whereas hepatic Igf1 expression remains unaffected. This highlights the central role of a distal enhancer in the assembly of the factors necessary for E2-dependent interaction with the Igf1 TSS and induction of uterus-specific Igf1 transcription. Of note, loss of the enhancer did not affect fertility or uterine growth responses. Deletion of uterine Igf1 in a PgrCre;Igf1f/f model decreased female fertility but did not impact the E2-induced uterine growth response. Moreover, E2-dependent activation of uterine IGF1 signaling was not impaired by disrupting the distal enhancer or by deleting the coding transcript. This indicated a role for systemic IGF1, suggested that other growth mediators drive uterine response to E2, and suggested that uterine-derived IGF1 is essential for reproductive success. Our findings elucidate the role of a super enhancer in Igf1 regulation and uterine growth.
Asunto(s)
Elementos de Facilitación Genéticos , Receptor alfa de Estrógeno/metabolismo , Estrógenos/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Factor I del Crecimiento Similar a la Insulina/fisiología , Transcripción Genética/efectos de los fármacos , Útero/metabolismo , Animales , Femenino , Ratones , Ratones Noqueados , Útero/efectos de los fármacosRESUMEN
Pausing of RNA polymerase II (Pol II) during early transcription, mediated by the negative elongation factor (NELF) complex, allows cells to coordinate and appropriately respond to signals by modulating the rate of transcriptional pause release. Promoter proximal enrichment of Pol II occurs at uterine genes relevant to reproductive biology; thus, we hypothesized that pausing might impact endometrial response by coordinating hormonal signals involved in establishing and maintaining pregnancy. We deleted the NELF-B subunit in the mouse uterus using PgrCre (NELF-B UtcKO). Resulting females were infertile. Uterine response to the initial decidual stimulus of NELF-B UtcKO was similar to that of control mice; however, subsequent full decidual response was not observed. Cultured NELF-B UtcKO stromal cells exhibited perturbances in extracellular matrix components and also expressed elevated levels of the decidual prolactin Prl8a2, as well as altered levels of transcripts encoding enzymes involved in prostaglandin synthesis and metabolism. Because endometrial stromal cell decidualization is also critical to human reproductive health and fertility, we used small interfering to suppress NELF-B or NELF-E subunits in cultured human endometrial stromal cells, which inhibited decidualization, as reflected by the impaired induction of decidual markers PRL and IGFBP1. Overall, our study indicates NELF-mediated pausing is essential to coordinate endometrial responses and that disruption impairs uterine decidual development during pregnancy.-Hewitt, S. C., Li, R., Adams, N., Winuthayanon, W., Hamilton, K. J., Donoghue, L. J., Lierz, S. L., Garcia, M., Lydon, J. P., DeMayo, F. J., Adelman, K., Korach, K. S. Negative elongation factor is essential for endometrial function.
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Células Madre Embrionarias/fisiología , Endometrio/fisiología , Infertilidad Femenina/fisiopatología , Células del Estroma/fisiología , Factores de Transcripción/fisiología , Animales , Decidua/citología , Decidua/fisiología , Células Madre Embrionarias/citología , Endometrio/citología , Femenino , Voluntarios Sanos , Humanos , Ratones , Ratones Noqueados , Embarazo , Células del Estroma/citología , Útero/citología , Útero/fisiologíaRESUMEN
Semen liquefaction changes semen from a gel-like to watery consistency and is required for sperm to gain mobility and swim to the fertilization site in the Fallopian tubes. Kallikrein-related peptidases 3 (KLK3) and other kallikrein-related peptidases from male prostate glands are responsible for semen liquefaction by cleaving gel-forming proteins (semenogelin and collagen). In a physiological context, the liquefaction process occurs within the female reproductive tract. How seminal proteins interact with the female reproductive environment is still largely unexplored. We previously reported that conditional genetic ablation of Esr1 (estrogen receptor α) in the epithelial cells of the female reproductive tract (Wnt7aCre/+;Esr1f/f) causes female infertility, partly due to a drastic reduction in the number of motile sperm entering the oviduct. In this study, we found that post-ejaculated semen from fertile wild-type males was solidified and the sperm were entrapped in Wnt7aCre/+;Esr1f/f uteri, compared to the watery semen (liquefied) found in Esr1f/f controls. In addition, semenogelin and collagen were not degraded in Wnt7aCre/+;Esr1f/f uteri. Amongst multiple gene families aberrantly expressed in the absence of epithelial ESR1, we have identified that a lack of Klks in the uterus is a potential cause for the liquefaction defect. Pharmacological inhibition of KLKs in the uterus replicated the phenotype observed in Wnt7aCre/+;Esr1f/f uteri, suggesting that loss of uterine and seminal KLK function causes this liquefaction defect. In human cervical cell culture, expression of several KLKs and their inhibitors (SPINKs) was regulated by estrogen in an ESR1-dependent manner. Our study demonstrates that estrogen/ESR1 signaling in the female reproductive tract plays an indispensable role in normal semen liquefaction, providing fundamental evidence that exposure of post-ejaculated semen to the suboptimal microenvironment in the female reproductive tract leads to faulty liquefaction and subsequently causes a fertility defect.
Asunto(s)
Receptor alfa de Estrógeno/genética , Infertilidad Femenina/genética , Calicreínas/genética , Motilidad Espermática/genética , Proteínas Wnt/genética , Animales , Estrógenos/genética , Estrógenos/metabolismo , Trompas Uterinas/metabolismo , Trompas Uterinas/patología , Femenino , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Humanos , Infertilidad Femenina/patología , Calicreínas/antagonistas & inhibidores , Masculino , Ratones , Inhibidores de Proteasas/administración & dosificación , Semen/efectos de los fármacos , Semen/metabolismo , Motilidad Espermática/efectos de los fármacos , Espermatozoides/efectos de los fármacos , Espermatozoides/metabolismo , Espermatozoides/patología , Útero/metabolismo , Útero/patologíaRESUMEN
The plant microbiome is a key determinant of plant health and productivity, and changes in the plant microbiome can alter the tolerance to biotic and abiotic stresses and the quality of end produce. Little is known about the microbial diversity and its effect on carbohydrate metabolism in ripe fruits. In this study, we aimed to understand the diversity and function of microorganisms in relation to carbohydrate metabolism of ripe watermelon fruits. We used 16S metagenomics and RNAseq metatranscriptomics for analysis of red (PI459074, Congo, and SDRose) and yellow fruit-flesh cultivars (PI227202, PI435990, and JBush) of geographically and metabolically diverse watermelon cultivars. Metagenomics data showed that Proteobacteria were abundant in SDRose and PI227202, whereas Cyanobacteria were most abundant in Congo and PI4559074. In the case of metatranscriptome data, Proteobacteria was the most abundant in all cultivars. High expression of genes linked to infectious diseases and the expression of peptidoglycan hydrolases associated to pathogenicity of eukaryotic hosts was observed in SDRose, which could have resulted in low microbial diversity in this cultivar. The presence of GH28, associated with polygalacturonase activity in JBush and SDRose could be related to cell wall modifications including de-esterification and depolymerization, and consequent loss of galacturonic acid and neutral sugars. Moreover, based on the KEGG annotation of the expressed genes, nine α-galactosidase genes involved in key processes of galactosyl oligosaccharide metabolism, such as raffinose family were identified and galactose metabolism pathway was reconstructed. Results of this study underline the links between the host and fruit-associated microbiome in carbohydrate metabolism of the ripe fruits. The cultivar difference in watermelon reflects the quantum and diversity of the microbiome, which would benefit watermelon and other plant breeders aiming at the holobiont concept to incorporate associated microbiomes in breeding programs.
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RESUMEN El linfoma difuso de células B es el tipo más común de linfoma no Hodgkin en adultos y se caracteriza por su agresividad y amplia localización. La primera señal de su presencia es una masa de nódulos linfáticos que crece rápidamente. Se presenta el caso de una paciente de 64 años de edad, con antecedentes patológicos de hipertensión arterial, exfumadora, que fue ingresada porque desde hacía 3 meses presentaba aumento de volumen de la región lateral izquierda del cuello. Los estudios clínicos, de imágenes, de citología por aspiración, medulograma y biopsia medular y biopsia de ganglio permitieron realizar el diagnóstico y estadiamiento para comenzar tratamiento con ciclofosfamida, doxorrubicina, vincristina y prednisona más el anticuerpo monoclonal rituximab según protocolo para estos tumores. A dos meses de tratamiento se había logrado la reducción de las masas ganglionares. Se presenta el caso porque es de interés para especialistas y personal en formación.
ABSTRACT Diffuse B-cell lymphoma is the most common type of non-Hodgkin lymphoma in adults characterized by its aggressiveness and wide location. The first sign of its presence is a rapidly growing mass of lymph nodes. The case of a 64-year-old patient is presented, with a pathological history of arterial hypertension, ex-smoker, who was admitted because for 3 months she had increased volume of the left lateral region of the neck. Clinical studies, imaging, aspiration cytology, medullogram and spinal biopsy and lymph node biopsy allowed diagnosis and staging to begin treatment with cyclophosphamide, doxorubicin, vincristine and prednisone plus the monoclonal antibody rituximab according to the protocol for these tumors. Two months after treatment, the reduction of ganglionic masses had been achieved. The case is presented because it is of interest to specialists and training personnel.
RESUMEN
El tratamiento de las enfermedades crónicas no transmisibles constituye en la actualidad uno de los mayores retos que enfrentan los sistemas de salud a nivel mundial. Esto se debe a que dichas enfermedades afectan a todos los grupos de edad y a todas las regiones y países, con independencia de su grado de desarrollo. Cuba no está exenta de ello. Sin embargo, la Organización Mundial de la Salud señala que se realiza un manejo inadecuado de estos padecimientos, por diferentes razones, en la mayoría de los sistemas de salud. El objetivo del presente artículo, es lograr la concientización de la problemática actual y futura de las enfermedades crónicas, donde la prevención y promoción de salud sigue siendo el arma fundamental para combatir el reto. Se debe tener en cuenta la importancia de estos conocimientos para el personal profesional en formación, la necesidad de establecer estrategias presentes y futuras para garantizar la salud de nuestra población, fundamentalmente desde la atención primaria y las organizaciones vinculados a ellas. La población, que resulta la más afectada, debe tomar mayor conciencia de lo que representa, en general, padecer una enfermedad crónica.
The treatment to non-transmissible chronic diseases is currently on of the greatest challenges faced by the health systems worldwide. This is due to the fact that these diseases affect all age groups, all regions and countries regardless their level of development. Cuba is not the exception. The World Health Organization, however, points out that there is an inadequate management of these ailments, for different reasons, in most of the health systems. The objective of this article is the awareness of the current and future problem of chronic diseases where health promotion and prevention still is the main weapon to fight the challenge. The importance of these elements should be taken into consideration from the personnel in training, the need to set present and future strategies to guarantee the health of our population, mainly from the primary health care attention and organizations linked to them. The most affected population should be aware of what suffering from a chronic disease represents in general.
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Existe incongruencia en las definiciones e interpretación del abuso hacia los adultos mayores. Una definición apropiada y unificada es la que expone la Organización Mundial de la Salud, según la cual el abuso hacia el adulto mayor es cualquier acto aislado o repetitivo, o la falta de acción apropiada, ocurrida en cualquier relación de la que se espera confianza y seguridad, que causa daño o malestar a la persona mayor. El maltrato y el no mejor trato de este grupo de personas, es un problema a resolver a escala mundial. En este artículo se abordan los aspectos relacionados con el tema, algunos tipos de maltrato y causas identificadas en estudios realizados, así como la necesidad de estrategias y medidas para combatirlo, no solo en el sector salud, sino en la sociedad en general. Cuba no permanece al margen de esta problemática; la población cubana envejece y es preocupante el reto que representan las enfermedades crónicas no transmisibles en ese sentido, sobre todo el cáncer, la demencia, la discapacidad y la postración por diferentes causas, dolencias más frecuentes en las personas ancianas.
There is inconsistency in the definition and understanding of abuse to the elder. An appropriate and unified definition is presented by the World Health Organization. It states that elder abuse is any isolated or repeated act, or the absence of appropriate action, that occurs in any relation from which confidence and safety is expected and produces damage or general discomfort. Mistreatment and the not best treatment to these people is a problem to be solved worldwide. In this article issues related to the topic are approached, some types of mistreatment, causes identified in studies carried out so as strategies and actions to fight them. These aspects are presented not only for the health system but for the society as well. Cuba is not exempted of this situation; the Cuban population ages and chronic non communicable diseases are a challenge to be concerned, mainly cancer, dementia, disability and prostration due to different causes which are the most frequent illnesses in elder people.
Asunto(s)
Humanos , Anciano , Anciano de 80 o más Años , Abuso de Ancianos/psicologíaRESUMEN
En la lucha por la excelencia en todos los servicios de salud el empleo sistemático y generalizado del método clínico, es sin duda, un factor clave. Existen deficiencias encontradas en la didáctica de impartición de los contenidos del programa de estudio del 3er. año de la carrera de Medicina por parte de los docentes. El objetivo del presente trabajo es insistir en las didácticas particulares de impartición, que garantizan la formación y sientan las bases para el posterior desarrollo de los métodos de trabajo de la profesión médica, encaminadas a que el estudiante logre las habilidades que se requieren en la correcta aplicación del método clínico y esto se lo enseña la Semiología y la Clínica Propedéutica. Cada tarea docente posee definido el objetivo a alcanzar por el alumno, la habilidad a adquirir. Debe haber un dominio del programa de la asignatura por los profesores: conocer bien los objetivos, los contenidos y las orientaciones metodológicas y didácticas para su impartición...
In striving for excellence in all health services, the systematic and generalized use of the clinical method is beyond any doubt a key factor. There are deficiencies in teaching the contents of the 3rd year medical curricula. The objective of the present paper was to put emphasis on the particular didactics that guarantee the formation and lay the bases for the further development of the working methods of the medical profession; they are also aimed at making the student attain the required abilities to correctly follow the clinical method and this is specifically taught in Semiology and Clinical Propaedeutics. Each educational task has the defined goal that the student should meet and the ability that he should acquire. The professors must master the curricula of their subject, which includes knowing well the objectives, the contents and the methodological and didactic guidelines to teach it...
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Humanos , Educación Médica/métodos , Educación Médica/organización & administraciónRESUMEN
genéticos. Los individuos con Diabetes e Infarto del Miocardio tienen mayor riesgo de mortalidad. Material y métodos: Se realizó una investigación descriptiva, retrospectiva con egresados vivos de Terapia Intensiva, con diagnóstico de Infarto Agudo del Miocardio en 2002-2004, para caracterizar a los infartados, diabéticos o no, según el comportamiento de factores de riesgo. Se revisaron las historias clínicas. Resultados: Se encontró que entre los no diabéticos predomina el sexo masculino con 65,3 % y entre los diabéticos predominó el sexo femenino tanto en la Diabetes tipo1 (60.0%) como en la tipo 2 (79,4%). El grupo de edad más afectado fue el de los mayores de 60 años, 55,13% corresponde a los Diabéticos tipo 2. 79,4% de los fumadores eran no diabéticos frente a 90% de Diabéticos tipo 1 infartados y 78,3 de fumadores infartados Diabéticos tipo 2. 80% de diabéticos tenían cifras elevadas de tensión arterial (130 / 85). Se encontró que 84,6% de Diabéticos tipo 2 reunían 3 ó más factores de riesgo. La estadía en los Diabéticos tipo 2 en 74,1% de los pacientes fue más de 11 días (11 _ 19 días) 24,1% y (20 días o más) 50%, y menos de 10 días en los no diabéticos con 35,8%. Conclusiones: Predominó el sexo femenino y el grupo de 60 y más años. La hipertensión arterial y el hábito de fumar, factores de riesgo predominantes en los infartados.
Introduction: Atherosclerosis is a complex multifactorial disease of multiple processes and factors that could be either enviromental or genetics. Diabetic patients with myocardial infarction have a bigger risk of mor tality. Material and methods: It was carried out a retrospective and descriptive study in 229 patients who came out from intensive therapy with myocardial infarction diagnosis during the period 2002-2004. Records were analyzed to characterize people who suffered from heart attacks either diabetic or not according to the behaviour of the risk factors. Their clinical records were also checked. Results: Masculine sex prevailed in the non diabetic group of patients with 65,3%, however, femenine sex prevailed among diabetic patients in both types:1 and 2 with 60% and 79,4% respectively. The group of patients over 60 years old was the most affected, corresponding 55,13% to diabetic type 2. From this sample of patients with myocardial infarction diagnosis a 79,4% of the smokers group were not diabetics but there was a 90% of diabetics type 1 and a 78,3% of smokers who were diabetic type 2. There was 80% of diabetic patients with high blood pressure(130/85) and 84,6% of diabetics type 2 had three or more risk factors for infarction. Permanency in the hospital of diabetic type 2 patients was over 11 days in the 74,1% of the cases.( from 11 to 19 days 24,1% and 20 days or more 50%). Non diabetics stayed at the hospital less than 10 days in a 35,8% of the cases. Conclusions: Female sex and age group over 60 years prevailed among the most affected. Hypertension and smoking habit were the most predominant risk factors in patients with myocardial infarction.
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Introducción: Los meningiomas son tumores benignos que se originan en células aracnoideas y como consecuencia pueden crecer en cualquier lugar donde exista duramadre. Suelen aparecer generalmente entre los 35 y 55 años de edad y son más frecuentes en mujeres. Objetivo: Presentar un caso clínico cuyo diagnóstico pudo realizarse antes teniendo en cuenta la forma de presentación. Caso clínico: Mujer de 38 años de edad con antecedentes de estar diagnosticada de migraña de más de 1 año de evolución y que ingresa en el Servicio de Medicina Interna del Hospital General Docente Enrique Cabrera, de La Habana, con síntomas en los últimos 3 meses de intensificación de la cefalea y modificación de sus características, con hipertensión intracraneal y focalización motora. El examen clínico y la realización de TAC definen el diagnóstico y se corrobora con tratamiento quirúrgico. Posterior al tratamiento evoluciona satisfactoriamente. Conclusiones. Un correcto interrogatorio y examen del paciente, y el uso adecuado y preciso de las imágenes en los diagnósticos reduce la posibilidad de errores en la práctica clínica.
Introduction: Meningiomas are benign tumors which are originated in arachnoid cells so they can grow anywhere it exists dura mater. They generally appear in ages between 35 and 55 years. They are more frequently found in women. Objective: To present a case report that could be diagnosed long before taking into account its form of manifestation. Case report: It's a 38 years old woman already diagnosed for migrain with more than a year of evolution who enters the service of internal medicine at the teaching hospital "Enrique Cabrera" in Havana. She has symptoms in the last three months of a strong migraine and modification of its characteristics with motor focalization and intracranial hypertension.After clinical examination with computed axial tomography included a diagnosis is established and surgical treatment is corroborated. After this treatment the patient evolves satisfactorily. Conclusions: Correct questioning and clinical examination of the patients and use of images when necessary reduces the possibility of errors in clinical practice.
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Se estudió un paciente masculino, de 20 años de edad, que sólo refería como síntoma dolor en hombro izquierdo de 1 año de evolución. De forma fortuita se le realiza rayos X de tórax y se observa ensanchamiento mediastinal. Se diagnosticó, por citología, un seminoma extragonadal de localización mediastinal
A male patient aged 20 was studied presenting a painful symptom in his left shoulder of a year of course. In a causal way he undergoes thorax Ray-X observing mediastinum widening. According to cytology an extra-gonadal seminoma of mediastinum location was diagnosed
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Neoplasias del Mediastino/diagnóstico , Seminoma/diagnósticoRESUMEN
Se revisaron los certificados de defunción de 3 387 pacientes diabéticos fallecidos como causa básica de muerte en Ciudad de La Habana durante los años 1991, 1993, 1994, 1995 y 1997. Los certificados obran en poder de la Dirección Nacional de Estadísticas del Ministerio de Salud Pública, de ellos 2 189 correspondían al sexo femenino (64,6 por ciento) y 1 198, al masculino (35,4 por ciento). El 64 por ciento de los fallecidos tenía más de 70 años y el 16 por ciento, menos de 60. Se hallaron como causas directas de muerte más frecuentes, el infarto del miocardio con 905 fallecidos (tasa 45,25), la bronconeumonía con 575 (tasa 28,75), el trastorno metabólico con 327 (tasa 16,35) y la insuficiencia renal con 229 (tasa 11,45). Según el sitio del fallecimiento, durante 3 años, el 75 por ciento murió en el hospital y el 20,6 por ciento, en el domicilio. En cuanto a los fallecidos por trastorno metabólico agudo (total 235) no han ocurrido cambios positivos respecto a 1991