Modificación ultraestructural de las membranas derivadas del retículo endoplasmático y morfogénesis del virus de la hepatitis C en muestras de hígado humano / Ultrastructural remodelling of e ndoplasmic reticulum-derived membranes and hepatitis C virus morphogenesis in human liver samples

Introducción: la infección por el virus de la hepatitis C es una de las causas principales de la enfermedad del hígado a nivel mundial. La utilización de la cepa del virus de la hepatitis C, JFH1 en cultivo de células de hepatoma ha permitido el avance de la comprensión del ciclo de vida viral. No obstante, se conoce poco sobre la morfogénesis del virus de la hepatitis C. Las dificultades para detectar el ensamblaje viral en este modelo de cultivo celular, así como los bajos niveles y complejidad de las partículas del virus de la hepatitis C en pacientes y chimpancés infectados limitan el estudio de la morfogénesis viral.Objetivo: estudiar las características ultraestructurales y los eventos de ensamblaje viral en hepatocitos de pacientes infectados con el virus de la hepatitis C.Métodos: se utilizaron muestras de biopsias de hígado de pacientes infectados, anticuerpos específicos para el virus de la hepatitis C y técnicas de microscopía e inmunomicroscopía electrónica.Resultados: la infección por el virus de la hepatitis C se relacionó con una modificación de las membranas derivadas del retículo endoplasmático y con diferentes microambientes citoplasmáticos en los hepatocitos de individuos infectados. La dilatación del retículo endoplasmático y la formación de diferentes vesículas de membrana son características que se asocian con los complejos de replicación viral. Resulta interesante destacar la detección del ensamblaje de partículas semejantes a la cápsida y al virus de la hepatitis C cerca de complejos de membrana con alta densidad electrónica y estructuras tubulares. Las proteínas estructurales del virus de la hepatitis C se detectaron en el retículo endoplasmático .Conclusiones: estos eventos sugieren que el proceso temprano de ensamblaje de las nucleocápsidas y del virión ocurre en las membranas del retículoendoplasmático que se asocian con estos microambientes citoplasmáticos en los hepatocitos humanos(AU)

Introduction: hepatitis C virus infection is considered as a leading cause of liver disease worldwide. Despite recent advances in understanding the hepatitis C virus life cycle using the highly replicative JFH1 strain in human hepatoma cells, little is known about hepatitis C virus morphogenesis. Low levels of hepatitis C virus assembly in this cell culture model as well as low levels and complexity of hepatitis C virus particles in infected humans and chimpanzees have hampered the study of hepatitis C virus morphogenesis in vivo.Objetivo: to study the ultrastructural features and viral assembly events in hepatocytes from HCV hepatitis C virus-infected patients.Methods: liver needle biopsies samples of patients with hepatitis C virus infection, specific antibodies against hepatitis C virus and transmission electron microscopy and immunoelectron microscopy analyses were used in this study.Results: ultrastructural studies in liver biopsies from hepatitis C virus-infected patients revealed that hepatitis C virus infection was related with remodelling of endoplasmic reticulum-derived membranes and with a variety of cytoplasmic microenvironments in hepatocytes. Dilated endoplasmic reticulum and formation of various membrane vesicles are features that have been associated with the viral replication complex. Interestingly, hepatitis C virus-like particles and core-like particles budding and assembly were observed near convoluted electron-dense membranes and tubular structures. Particularly, hepatitis C virus structural proteins localize to the endoplasmic reticulum.Conclusions: these events indicate that hepatitis C virus nucleocapsids and early virion assembly take place atendoplasmic reticulum membranes that are associated with these cytoplasmic microenvironments in human hepatocytes(AU)

Osteopontin expression and localization of Ca++ deposits in early stages of osteoarthritis in a rat model.

Calcium deposits have been related to articular cartilage (AC) degeneration and have been observed in late stages of osteoarthritis (OA). However, the role of those deposits, whether they induce the OA pathogenesis or they appear as a consequence of such process, is still unknown. In this work, we present the kinetics of expression and tissue localisation of osteopontin (OPN), a mineralisation biomarker, and calcium deposits in samples from (normal, sham) and osteoarthritic cartilage (in a rat model). Immunohistochemical and Western blot assays for OPN, as well as Alizarin red staining for calcium deposits were performed; superficial, middle, and deep zones of AC were analysed. An increased expression of OPN and calcium deposits was found in the osteoarthritic cartilage compared with that of control groups, particularly in the superficial zone of AC in early stages of OA. In addition, the expression and localisation of OPN and calcium deposits during the OA pathogenesis suggest that the pathological AC mineralisation starts in the superficial zone during OA pathogenesis.

Kinetics of the ultrastructural changes in apoptotic chondrocytes from an osteoarthrosis rat model: a window of comparison to the cellular mechanism of apoptosis in human chondrocytes.

It is conceivable that apoptosis plays a relevant role in the pathogenesis of osteoarthrosis. We have dissected certain ultrastructural changes in apoptosis when comparing chondrocytes from the rat osteoarthrosis-induced model to those of human osteoarthrosis. Chondrocytes displayed a typical ultrastructural pattern prevailing according to the days following osteoarthrosis induction. These notable modifications included cell shape changes, a distinctive nuclear chromatin condensation, prominent Golgi and rough endoplasmic reticulum (RER), an increased cytosol osmiophilic reaction, matrix vesicles blebbing from the plasma membrane, and cell fragmentation, with the consequent formation of apoptotic bodies. In addition, small particles and fibers were seen engulfed inside chondrocytes in vacuoles, which may well be related to phagocytosis. Similar modifications were observed in human osteoarthrosic cartilage, predominantly those linked to late stages in the rat model. Interestingly, we observed a peculiarly arranged structure inside a chondrocyte's mitochondrion. It consisted of aggregated particles (5-8 nm diameter) forming rounded granules (38-50 nm diameter) lined up between double membranes, probably cristae, running parallel to the long axis of the mitochondrion. All these changes could be linked to different stages in chondrocytes' apoptotic cell death in osteoarthrosic rat cartilage, similar to what happen in humans. The study of the cellular mechanism of apoptosis facilitates the understanding of the process and might shed additional light on the potential role of apoptotic chondrocyte in osteoarthrosis pathogenesis.

El impacto de la revolución cientificotécnica en la medicina y sus implicaciones para la educación médica superior / The impact of the scientific and technological revolution on medicine and its implications for higher medical education

Se valoran las posibilidades que tiene Cuba de introducir los logros y adelantos científicos alcanzados en el país y en el extranjero gracias al avance obtenido en la creación de centros educacionales, planes de estudios y métodos de enseñanza encaminados a la formación de profesionales con una fuerte base experimental que coadyuve dedicadamente al desarrollo del pensamiento científico. La asimilación de los beneficios de la revolución cientificotécnica mundial, requier de cuadros capaces de asimilar e introducir las nuevas tecnologías y de cuadros capaces de entenderlas y llevarlas a la práctica social: institutos, hospitales, policlínicos y a la comunidad(AU)