Inclisiran, ARN interferente pequeño: un nuevo enfoque para el tratamiento del colesterol / Inclisiran, small interfering RNA: a new approach to cholesterol treatment

Resumen: La hiperlipidemia es altamente prevalente y contribuye de forma sustancial a la enfermedad cardiovascular aterosclerótica, que es una de las principales causas de morbilidad y mortalidad en Colombia. La reducción del colesterol LDL (c-LDL) produce una disminución del riesgo de enfermedad cardiovascular aterosclerótica y de eventos cardiovasculares adversos. La terapia dirigida a la proproteína convertasa subtilisina/kexina tipo 9 (PCSK9; su sigla en inglés) ha surgido como una herramienta novedosa para el tratamiento de la hiperlipidemia. Inclisiran es un ARN pequeño de doble hebra, que actúa inhibiendo la transcripción de PCSK-9 en los hepatocitos, lo que conduce a una reducción marcada y sostenida del c-LDL. En contraste con otras terapias hipolipemiantes, como estatinas, ezetimibe y anticuerpos monoclonales (MAbs; su sigla en inglés) e inhibidores de PCSK9, inclisiran propone un régimen de dosificación infrecuente de dos o tres veces al año. Su efecto prolongado representa una ventaja frente al incumplimiento del tratamiento, que es una de las principales causas por las que no se alcanzan los objetivos de c-LDL con la terapia estándar. Esta revisión tiene como objetivo presentar y discutir los datos científicos actuales con relación a la eficacia, tolerabilidad y seguridad del inclisiran en el tratamiento de la hipercolesterolemia.

Abstract: Hyperlipidemia is a highly prevalent condition and contributes substantially to atherosclerotic cardiovascular disease (ASCVD), which is one of the main causes of morbidity and mortality in Colombia. The reduction of LDL cholesterol (LDL-C) decreases the risk of ASCVD and adverse cardiovascular events. Targeted therapy for the proprotein convertase subtilisin/kexin type 9 (PCSK-9) has emerged as a novel tool for the treatment of hyperlipidemia. Inclisiran is a small double-stranded small interfering RNA that acts by blocking PCSK-9 transcription in hepatocytes, leading to a marked and sustained reduction in circulating LDL-C levels. In contrast to other lipid-lowering therapies such as statins, ezetimibe and monoclonal antibodies (MAbs) PCSK-9 inhibitors, Inclisiran proposes an infrequent dosing regimen of twice or three times a year. Its prolonged effect represents an advantage over non-compliance of the treatment, which is one of the main reasons why LDL-C goals are not achieved with standard therapy. This review aims to present and discuss current scientific data regarding the efficacy, tolerability and safety of Inclisiran in the treatment of hypercholesterolemia.

Evaluation of perfusion-driven cell seeding of small diameter engineered tissue vascular grafts with a custom-designed seed-and-culture bioreactor.

Tissue engineering commonly entails combining autologous cell sources with biocompatible scaffolds for the replacement of damaged tissues in the body. Scaffolds provide functional support while also providing an ideal environment for the growth of new tissues until host integration is complete. To expedite tissue development, cells need to be distributed evenly within the scaffold. For scaffolds with a small diameter tubular geometry, like those used for vascular tissue engineering, seeding cells evenly along the luminal surface can be especially challenging. Perfusion-based cell seeding methods have been shown to promote increased uniformity in initial cell distribution onto porous scaffolds for a variety of tissue engineering applications. We investigate the seeding efficiency of a custom-designed perfusion-based seed-and-culture bioreactor through comparisons to a static injection counterpart method and a more traditional drip seeding method. Murine vascular smooth muscle cells were seeded onto porous tubular electrospun polycaprolactone scaffolds, 2 mm in diameter and 30 mm in length, using the three methods, and allowed to rest for 24 hours. Once harvested, scaffolds were evaluated longitudinally and circumferentially to assess the presence of viable cells using alamarBlue and live/dead cell assays and their distribution with immunohistochemistry and scanning electron microscopy. On average, bioreactor-mediated perfusion seeding achieved 35% more luminal surface coverage when compared to static methods. Viability assessment demonstrated that the total number of viable cells achieved across methods was comparable with slight advantage to the bioreactor-mediated perfusion-seeding method. The method described is a simple, low-cost method to consistently obtain even distribution of seeded cells onto the luminal surfaces of small diameter tubular scaffolds.

¿Cuál es el impacto de la vajilla en la aceptabilidad de una sopa instantánea reducida en sodio? / Which is the impact of the dishes in the acceptability of a sodium-reduced instant soup?

Introducción: los atributos de la vajilla pueden transferirse a los alimentos y bebidas que se consumen. La transferencia de sensaciones es el fenómeno por el cual ciertos atributos sensoriales percibidos en un producto, a través de uno o más de los sentidos, puede influir en la percepción que el sujeto tiene respecto de otros atributos sensoriales del producto. Objetivos: analizar cómo afecta el color del tazón y el material de la cuchara en diferentes atributos de un producto alimenticio. Materiales y métodos: se utilizó un diseño factorial de 2x2 para analizar el efecto del color del tazón (azul o blanco) y el material de las cucharas (de plástico o acero inoxidable) empleados para el consumo de la sopa de vegetales de primavera deshidratada instantánea reducida en un 40% en sodio. Se realizó una prueba de aceptabilidad para los siguientes atributos: apariencia, olor, sabor, calidad de la preparación y placer producido (medidos en escala de 1 a 10 puntos). Se aplicó un cuestionario para indicar los motivos del uso de las cucharas que se presentaron en las muestras. Resultados: todas las variables analizadas obtuvieron buenos puntajes de aceptabilidad. Para apariencia, olor y sabor no se hallaron diferencias significativas. Para calidad y placer sólo para el efecto principal tazón se hallaron diferencias significativas, obteniendo puntajes más elevados el de color blanco. La cuchara de plástico fue elegida por considerarla más higiénica y la de acero inoxidable por mejor apariencia visual, mejor percepción del material en la boca y ser la más usada cotidianamente. Conclusiones: en este estudio se comprobó la transferencia de sensaciones desde el color del tazón hacia los atributos de calidad de la preparación y placer producido de la sopa instantánea reducida en sodio, siendo el color blanco en comparación al azul el mejor puntuado.

Introduction: the attributes of the dishes can be transferred to food and beverages consumed. Sensation transference is the phenomenon by which certain sensory attributes perceived in a product, through one or more of the senses, can influence the perception of the subject from other sensory attributes of the product. Objectives: to analyze how the color of the bowl and the material of the spoon affect on different attributes of a food product. Materials and methods: 2x2 factorial design was used to analyze the effect of the bowl color (blue or white) and material of the spoons (plastic or stainless steel) used for drinking the dehydrated vegetables reduced 40% sodium instant soup. An acceptability test was performed for the following attributes: appearance, aroma, flavor, quality of the product and pleasure produced (measured on a scale of 1 to 10 points). A questionnaire was applied to indicate the reasons for the use of spoons. Results: all variables analyzed showed good acceptability scores. For appearance, aroma and taste, no significant differences were found. For quality and pleasure produced only for the main bowl effect significant differences were found, obtaining the white ones the highest scores. Plastic spoon is chosen by considering it more hygienic and stainless steel spoon for better visual appearance, better perception of the material in the mouth and the fact that it can be used daily. Conclusions: in this study, the transfer of sensations was tested from the color of the bowl to the quality of the product and pleasure produced of the reduced sodium instant soup, being white color compared with the blue one, the one with the highest score

Lipodistrofia congénita generalizada en un paciente con anomalía de Dandy Walker / Congenital generalized lipodystrophy in pacient with Dandy Walker anomaly

La asociación entre la lipodistrofia congénita generalizada y la anomalía de Dandy Walker no es habitual. Se reporta el caso de una niña de 1 año de edad que ingresa al hospital a los 4 meses por riesgo social, con diagnóstico de anomalía de Dandy Walker. Durante su internación, se evidencia en forma progresiva aspecto acromegaloide, facies triangular, hirsutismo, lipoatrofia, hipertrofia muscular, clitoromegalia, distensión abdominal con hepatomegalia progresiva e hpertrigliceridernia. Se arriba así al diagnóstico clínico de lipodistrofia congénita generalizada. Se revisan los aspectos clínicos y el seguimiento interdisciplinario para la detección oportuna de insulinorresistencia y diabetes, pubertad precoz, miocardiopatía, entre otras. Respecto de la anomalía de Dandy Walker, se realizan controles evolutivos en búsqueda de la aparición de signos de hipertensión endocraneana. Por el carácter autosómico recesivo de la lipodistrofia congénita generalizada, es importante realizar el asesoramiento genético a los padres.

The objective of this study is to describe the unexpected association between the congenital generalized lipodystrophy (CGL) and Dandy Walker anomaly. We report the case of a 1-year-old infant who was hospitalized at her fourth month of life with Dandy Walker anomaly diagnosis and an increased social risk. During her hospitalization, she developed progressively: acromegaloid aspect, triangular fascia, hirsutism, lipoatrophy, muscle hypertrophy, clitoromegaly, abdominal distention, progressive hepatomegaly, and hypertriglyceridemia. This led to the clinical diagnosis of congenital generalized lipodystrophy. Importance shouldbe given to the examination of clinical aspects as well as the interdisciplinary follow-up for proper detection of insulin resistance and diabetes, early puberty, cardiomyopathy, among others. In case of Dandy Walker anomaly, it should be checked the evolution to search intracranial hypertension signs. Due to its autosomal recessive nature, it is important to provide genetic counseling to the parents.

Lipodistrofia congénita generalizada en un paciente con anomalía de Dandy Walker / Congenital generalized lipodystrophy in pacient with Dandy Walker anomaly

La asociación entre la lipodistrofia congénita generalizada y la anomalía de Dandy Walker no es habitual. Se reporta el caso de una niña de 1 año de edad que ingresa al hospital a los 4 meses por riesgo social, con diagnóstico de anomalía de Dandy Walker. Durante su internación, se evidencia en forma progresiva aspecto acromegaloide, facies triangular, hirsutismo, lipoatrofia, hipertrofia muscular, clitoromegalia, distensión abdominal con hepatomegalia progresiva e hpertrigliceridernia. Se arriba así al diagnóstico clínico de lipodistrofia congénita generalizada. Se revisan los aspectos clínicos y el seguimiento interdisciplinario para la detección oportuna de insulinorresistencia y diabetes, pubertad precoz, miocardiopatía, entre otras. Respecto de la anomalía de Dandy Walker, se realizan controles evolutivos en búsqueda de la aparición de signos de hipertensión endocraneana. Por el carácter autosómico recesivo de la lipodistrofia congénita generalizada, es importante realizar el asesoramiento genético a los padres.(AU)

The objective of this study is to describe the unexpected association between the congenital generalized lipodystrophy (CGL) and Dandy Walker anomaly. We report the case of a 1-year-old infant who was hospitalized at her fourth month of life with Dandy Walker anomaly diagnosis and an increased social risk. During her hospitalization, she developed progressively: acromegaloid aspect, triangular fascia, hirsutism, lipoatrophy, muscle hypertrophy, clitoromegaly, abdominal distention, progressive hepatomegaly, and hypertriglyceridemia. This led to the clinical diagnosis of congenital generalized lipodystrophy. Importance shouldbe given to the examination of clinical aspects as well as the interdisciplinary follow-up for proper detection of insulin resistance and diabetes, early puberty, cardiomyopathy, among others. In case of Dandy Walker anomaly, it should be checked the evolution to search intracranial hypertension signs. Due to its autosomal recessive nature, it is important to provide genetic counseling to the parents.(AU)

[Congenital generalized lipodystrophy in a patient with Dandy Walker anomaly]. / Lipodistrofia congénita generalizada en un paciente con anomalía de Dandy Walker.

The objective of this study is to describe the unexpected association between the congenital generalized lipodystrophy (CGL) and Dandy Walker anomaly. We report the case of a 1-year-old infant who was hospitalized at her fourth month of life with Dandy Walker anomaly diagnosis and an increased social risk. During her hospitalization, she developed progressively: acromegaloid aspect, triangular fascia, hirsutism, lipoatrophy, muscle hypertrophy, clitoromegaly, abdominal distention, progressive hepatomegaly, and hypertriglyceridemia. This led to the clinical diagnosis of congenital generalized lipodystrophy. Importance should be given to the examination of clinical aspects as well as the interdisciplinary follow-up for proper detection of insulin resistance and diabetes, early puberty, cardiomyopathy, among others. In case of Dandy Walker anomaly, it should be checked the evolution to search intracranial hypertension signs. Due to its autosomal recessive nature, it is important to provide genetic counseling to the parents.

Lipodistrofia congénita generalizada en un paciente con anomalía de Dandy Walker. / [Congenital generalized lipodystrophy in a patient with Dandy Walker anomaly].

The objective of this study is to describe the unexpected association between the congenital generalized lipodystrophy (CGL) and Dandy Walker anomaly. We report the case of a 1-year-old infant who was hospitalized at her fourth month of life with Dandy Walker anomaly diagnosis and an increased social risk. During her hospitalization, she developed progressively: acromegaloid aspect, triangular fascia, hirsutism, lipoatrophy, muscle hypertrophy, clitoromegaly, abdominal distention, progressive hepatomegaly, and hypertriglyceridemia. This led to the clinical diagnosis of congenital generalized lipodystrophy. Importance should be given to the examination of clinical aspects as well as the interdisciplinary follow-up for proper detection of insulin resistance and diabetes, early puberty, cardiomyopathy, among others. In case of Dandy Walker anomaly, it should be checked the evolution to search intracranial hypertension signs. Due to its autosomal recessive nature, it is important to provide genetic counseling to the parents.