Vivimos más, pero vemos menos: We live more, but we see less

There is no doubt that we live longer, that is, the world population is aging; partly thanks to advances in science and technology, and its application to medicine for the prevention, cure, and recovery of different nosological entities previously considered lethal. The world life expectancy in 1990 was 65.45 years; for the dawn of the new millennium, it increased to 67.68, for 2010 to 70.68 and for 2017 to 72.25 years of life at birth. In general terms, the world population of people over 50 almost doubled from 878 million in 1990 to 1,640 million in 2015. As is already known, the fact that the population is living longer brings with it the increase of so-called degenerative diseases, among which is age-related macular degeneration (AMD). We live longer, but we see less.No hay duda que vivimos más, es decir, la población mundial está envejeciendo; en parte gracias a los avances en ciencia y tecnología, y su aplicación a la medicina para la prevención, curación y recuperación de las diferentes entidades nosológicas antes consideradas letales. La esperanza de vida mundial en 1990 era 65.45 años; para los albores del nuevo milenio incrementó a 67.68, para 2010 a 70.68 y para 2017 a 72.25 años de vida al nacer. En términos generales, la población mundial de personas mayores de 50 años casi se dobló de 878 millones en 1990 a 1640 millones en 2015. Como es ya conocido, el hecho que la población esté viviendo más, trae consigo el incremento de enfermedades llamadas degenerativas, entre las cuales se encuentra la degeneración macular relacionada a la edad (DMRE). Vivimos más, pero vemos menos

Evaluación del riesgo volcánico en el sur del Perú, situación de la vigilancia actual y requerimientos de monitoreo en el futuro. Informe técnico

En el presente trabajo se efectúa una estimación semicuantitativa, orientada a la evaluación objetiva del riesgo volcánico que representa la actividad volcánica a nivel nacional. Este sistema es una adaptación del modelo utilizado por el Servicio Geológico de los Estados Unidos (USGS) denominado “National Volcano Early Warning System” (NVEWS) desarrollado por Ewert et al. (2005). En todas las etapas de análisis (factores de peligro, y de factores de exposición) para la determinación del nivel de riesgo volcánico, así como la compilación de la instrumentación actualmente instalada sobre los volcanes del sur del Perú, se ha trabajado conjunta y coordinadamente entre especialistas del Observatorio Vulcanológico del Sur (OVS), Observatorio Vulcanológico de INGEMMET (OVI) y del Observatorio Geofísico de la Universidad Nacional de San Agustín (UNSA). Con este trabajo se busca clasificar a los 16 volcanes activos y potencialmente activos de nuestro país, en grupos de nivel de Riesgo Volcánico Relativo. Por otro lado, en este trabajo se establece también el grado o nivel óptimo de monitoreo y vigilancia actual para cada uno de los volcanes según su respectivo nivel de riesgo, de modo que posteriormente se hace una comparación entre el nivel óptimo y el nivel de vigilancia actualmente alcanzado. Se determina así cuánto falta aún por avanzar en la implementación de instrumental especializado para alcanzar una adecuada vigilancia de la actividad volcánica en el Perú

Diagnóstico y tratamiento de la retinopatía diabética y edema macular diabético: guía de práctica clínica del Seguro Social de Salud del Perú (EsSalud)

Introducción. El presente artículo resume la guía de práctica clínica (GPC) para el diagnóstico y tratamiento de la retinopatía diabética y el edema macular diabético en el Seguro Social de Salud del Perú (EsSalud). Objetivo. Proveer recomendaciones clínicas basadas en evidencia para el diagnóstico y tratamiento de la retinopatía diabética y el edema macular diabético en EsSalud. Métodos. Se conformó un grupo elaborador de la guía (GEG) que incluyó médicos especialistas y metodólogos. El GEG formuló 4 preguntas clínicas a ser respondidas por la presente GPC. Para cada una de estas preguntas se realizó búsquedas de revisiones sistemáticas y de estudios primarios (cuando se consideró pertinente) en PubMed durante el 2018. Se seleccionó la evidencia para responder cada una de las preguntas clínicas planteadas. La certeza de la evidencia fue evaluada usando la metodología Grading of Recommendations Assessment, Development, and Evaluation (GRADE). En reuniones de trabajo periódicas, el GEG usó la metodología GRADE para revisar la evidencia y formular las recomendaciones, los puntos de buena práctica clínica y el flujograma de manejo. Resultados. La presente GPC abordó 4 preguntas clínicas sobre el tamizaje, diagnóstico, tratamiento de elección y tratamiento adyuvante. En base a estas preguntas se formularon 6 recomendaciones (4 fuertes y 2 condicionales), 19 puntos de buena práctica clínica y 1 flujograma de manejo. Conclusión. El presente artículo resume la metodología y las conclusiones basadas en evidencias de la GPC para el diagnóstico y tratamiento de la retinopatía diabética y el edema macular diabético en EsSalud

Brimonidine Can Prevent In Vitro Hydroquinone Damage on Retinal Pigment Epithelium Cells and Retinal Müller Cells.

PurposeBrimonidine is a selective alpha-2 adrenergic agonist used to reduce intraocular pressure and it has been shown to have some neuroprotective effects. Hydroquinone (HQ) is a toxicant present in cigarette smoke, and other sources. In this study, we investigated the cyto-protective effects in vitro of Brimonidine on human retinal pigment epithelium cells (ARPE-19) and human retinal Müller cells (MIO-M1) that had been treated with HQ.MethodsCells were pretreated for 6 h with different doses of Brimonidine tartrate 0.1% (1/2×, 1×, 5×, 10×), followed by a 24-h exposure to 100 μM of HQ, while the Brimonidine was still present. Assays were used to measure cell viability, mitochondrial membrane potential (ΔΨm), reactive oxygen species (ROS) production, and lactate dehydrogenase (LDH) release.ResultsBrimonidine increased the cell viability at all concentrations studied in both cell lines studied. ΔΨm also improved at all Brimonidine doses in ARPE-19 cells and in the 5× and 10× dosages MIO-M1 cells. The ROS levels decreased at 1×, 5×, and 10× doses of Brimonidine in ARPE-19 but only at 10× on MIO-M1 cells. The 10×-Brimonidine ARPE-19 cells had decreased LDH release, but no LDH changes were observed on MIO-M1 cells.ConclusionHQ-induced toxicity is mediated through mitochondrial damaging, oxidative stress-related and necrosis-related pathways; Brimonidine significantly prevented the mitochondrial damaging and oxidative stress-related effects but had little effect on blocking the necrosis component of HQ-toxicity. Brimonidine protective effects differ between the different retinal cell types and high concentrations of Brimonidine (10×) have minimal damaging effects on human retinal cells

Increased expression of ApoE and protection from amyloid-beta toxicity in transmitochondrial cybrids with haplogroup K mtDNA.

Mitochondrial (mt) DNA haplogroups, defined by specific single nucleotide polymorphism (SNP) patterns, represent populations of diverse geographic origins and have been associated with increased risk or protection of many diseases. The H haplogroup is the most common European haplogroup while the K haplogroup is highly associated with the Ashkenazi Jewish population. Transmitochondrial cybrids (cell lines with identical nuclei, but mtDNA from either H (n=8) or K (n=8) subjects) were analyzed by the Seahorse flux analyzer, quantitative polymerase chain reaction (Q-PCR) and immunohistochemistry (IHC). Cybrids were treated with amyloid-β peptides and cell viabilities were measured. Other cybrids were demethylated with 5-aza-2'-deoxycytidine (5-aza-dC) and expression levels for APOE and NFkB2 were measured. Results show K cybrids have (a) significantly lower mtDNA copy numbers, (b) higher expression levels for MT-DNA encoded genes critical for oxidative phosphorylation, (c) lower Spare Respiratory Capacity, (d) increased expression of inhibitors of the complement pathway and important inflammasome-related genes; and (e) significantly higher levels of APOE transcription that were independent of methylation status. After exposure to amyloid-β1-42 peptides (active form), H haplogroup cybrids demonstrated decreased cell viability compared to those treated with amyloid-β42-1 (inactive form) (p<0.0001), while this was not observed in the K cybrids (p=0.2). K cybrids had significantly higher total global methylation levels and differences in expression levels for two acetylation genes and four methylation genes. Demethylation with 5-aza-dC altered expression levels for NFkB2, while APOE transcription patterns were unchanged. Our findings support the hypothesis that mtDNA-nuclear retrograde signaling may mediate expression levels of APOE, a key factor in many age-related diseases. Future studies will focus on identification of the mitochondrial-nuclear retrograde signaling mechanism(s) contributing to these mtDNA-mediated differences

Mitochondrial DNA variants can mediate methylation status of inflammation, angiogenesis and signaling genes

Mitochondrial (mt) DNA can be classified into haplogroups representing different geographic and/or racial origins of populations. The H haplogroup is protective against age-related macular degeneration (AMD), while the J haplogroup is high risk for AMD. In the present study, we performed comparison analyses of human retinal cell cybrids, which possess identical nuclei, but mtDNA from subjects with either the H or J haplogroups, and demonstrate differences in total global methylation, and expression patterns for two genes related to acetylation and five genes related to methylation. Analyses revealed that untreated-H and -J cybrids have different expression levels for nuclear genes (CFH, EFEMP1, VEGFA and NFkB2). However, expression levels for these genes become equivalent after treatment with a methylation inhibitor, 5-aza-2′-deoxycytidine. Moreover, sequencing of the entire mtDNA suggests that differences in epigenetic status found in cybrids are likely due to single nucleotide polymorphisms (SNPs) within the haplogroup profiles rather than rare variants or private SNPs. In conclusion, our findings indicate that mtDNA variants can mediate methylation profiles and transcription for inflammation, angiogenesis and various signaling pathways, which are important in several common diseases

Human retinal transmitochondrial cybrids with J or H mtDNA haplogroups respond differently to ultraviolet radiation: implications for retinal diseases.

BackgroundIt has been recognized that cells do not respond equally to ultraviolet (UV) radiation but it is not clear whether this is due to genetic, biochemical or structural differences of the cells. We have a novel cybrid (cytoplasmic hybrids) model that allows us to analyze the contribution of mitochondrial DNA (mtDNA) to cellular response after exposure to sub-lethal dose of UV. mtDNA can be classified into haplogroups as defined by accumulations of specific single nucleotide polymorphisms (SNPs). Recent studies have shown that J haplogroup is high risk for age-related macular degeneration while the H haplogroup is protective. This study investigates gene expression responses in J cybrids versus H cybrids after exposure to sub-lethal doses of UV-radiation.Methodology/principal findingsCybrids were created by fusing platelets isolated from subjects with either H (n = 3) or J (n = 3) haplogroups with mitochondria-free (Rho0) ARPE-19 cells. The H and J cybrids were cultured for 24 hours, treated with 10 mJ of UV-radiation and cultured for an additional 120 hours. Untreated and treated cybrids were analyzed for growth rates and gene expression profiles. The UV-treated and untreated J cybrids had higher growth rates compared to H cybrids. Before treatment, J cybrids showed lower expression levels for CFH, CD55, IL-33, TGF-A, EFEMP-1, RARA, BCL2L13 and BBC3. At 120 hours after UV-treatment, the J cybrids had decreased CFH, RARA and BBC3 levels but increased CD55, IL-33 and EFEMP-1 compared to UV-treated H cybrids.Conclusion/significanceIn cells with identical nuclei, the cellular response to sub-lethal UV-radiation is mediated in part by the mtDNA haplogroup. This supports the hypothesis that differences in growth rates and expression levels of complement, inflammation and apoptosis genes may result from population-specific, hereditary SNP variations in mtDNA. Therefore, when analyzing UV-induced damage in tissues, the mtDNA haplogroup background may be important to consider