Cardiopulmonary phenotype in systemic sclerosis associated pulmonary hypertension.

INTRODUCTION: Pulmonary hypertension (PH) associated with systemic sclerosis (SSc) increases morbidity and mortality. Cardiopulmonary comorbidities, as per the 2021 PH consensus, play a role in the choice of therapy between monotherapy and combination therapy. METHODS: A cross-sectional study was conducted in patients with SSc based on the 2013 ACR/EULAR criteria or very early disease (VEDOSS 2011). PH was considered if they met the following criteria: pulmonary artery systolic pressure (PASP)>39mmHg or peak tricuspid regurgitation velocity (PTRV)>3.4m/s, PASP between 33 and 39mmHg or PTRV between 2.9 and 3.4m/s plus two additional findings suggestive of PH. PH was classified as type 2 if LVEF<50% or moderate to severe diastolic dysfunction was present; type 3 if extensive interstitial disease on tomography>20% or forced vital capacity (FVC)<75%; type 4 if abnormalities related to embolism were detected on scintigraphy or tomography. If patients did not meet these criteria, they were classified as type 1 PH. Complete data on cardiopulmonary risk factors and other factors were required. The frequency of these factors in the population and differences between groups based on risk factors were estimated. RESULTS: A total of 228 patients were selected. Three had type 2 PH, 24 had type 3, and 40 had type 1 PH, with the majority (75%) having at least one cardiopulmonary risk factor, and 47.5% having more than one. Mild diastolic dysfunction (25%) and hypertension (35%) were the most prevalent. In the type 1 PH group, those with risk factors experienced an increase in the number of years with Raynaud's phenomenon, anticentromere antibodies, and gastrointestinal symptoms (p<0.05). CONCLUSION: In patients with PH, 75% have one, and 45% have two or more risk factors.

Estado de la investigación científica y el acceso a los recursos genéticos por grupos de investigación colombianos / Status of scientific research and the Access to genetic resources by Colombian research groups

RESUMEN Colombia participa actualmente con el 14% de la biodiversidad del planeta, que se considera uno de los activos más importantes del país. En todo el mundo ocupa el primer lugar en diversidad de especies de aves y el segundo en plantas, de ahí la importancia de controlar el acceso a las especies nativas. Por lo tanto, el objetivo del estudio fue analizar el estado actual de la investigación científica y el acceso a los recursos genéticos por parte de los grupos de investigación colombianos a través de la revisión de sus proyectos de investigación descritos en la base de datos nacional de Minciencias GrupLAC para el período 2013-2018. Los grupos de investigación se clasificaron en seis áreas según el programa nacional de ciencia y tecnología (Biotecnología, Ciencias Básicas, Ciencias del Mar, Salud, Ciencias Agrícolas y Biodiversidad y Hábitat) y los proyectos de investigación se dividieron según en las actividades exceptuadas de solicitar contrato de acceso y las que lo requieren, según las modificaciones a la legislación colombiana entre 2013 y 2017. Los resultados muestran que del total de 2168 proyectos revisados, (que incluyen modalidades exceptuadas de solicitar contrato de acceso como los que lo requieren) 198 (9,1%) emplearon especies nativas en sus investigaciones divididas en las siguientes categorías: sistemática molecular (38,3%), ecología molecular (18,1%), biogeografía (2,7 %), y otros (40, 9%). El Ministerio del medio ambiente reporto un total de 273 solicitudes de contratos de Acceso a Recurso Genéticos para el mismo periodo. Los últimos desarrollos legislativos en Colombia, diferencian y simplifican el procedimiento para realizar investigaciones sobre recursos genéticos, han tenido un impacto positivo, dado que el número de solicitudes de contratos de acceso a recursos genéticos se incrementó en los últimos 5 años.

ABSTRACT Colombia currently participates with 14% of the planet's biodiversity, which is considered one of the most important assets in the country. Around the world it occupies the first place in diversity of bird species and second in plants, hence the importance of controlling access to native species. Therefore, the objective of the study was to analyze the current state of scientific research and access to genetic resources by Colombian research groups through the review of their research projects described in the national database of Minciencias GrupLAC for the 2013-2018 period. The research groups were classified into six areas according to the national science and technology program (Biotechnology, Basic Sciences, Marine Sciences, Health, Agricultural Sciences and Biodiversity and Habitat); and the research projects were divided according to the activities excepted from requesting an access contract and those that require it, according to the modifications to Colombian legislation between 2013 and 2017. The results show that of the total of 2168 projects reviewed, 198 (9, 1%) used native species in their research divided into the following categories: molecular systematics (38.3%), molecular ecology (18.1%), biogeography (2.7%), and others (40, 9%). For its part, the Ministry of the environment reported a total of 273 applications for Genetic Resource Access contracts for the same period. It is clear that the latest legislative developments in Colombia, differentiate and simplify the procedure for conducting research on genetic resources, have had a positive impact, given that the number of requests for contracts for access to genetic resources has increased in the last 5 years.

A clinical practice guideline for the prevention and treatment of peri-implant diseases / Guía de práctica clínica para la prevención y el tratamiento de enfermedades periimplantares

ABSTRACT Introduction: the incidence of peri-implant diseases is high, and their optimal management is still debated. The purpose was to explore the levels of available evidence and to suggest evidence-based recommendations for the treatment of peri-implant mucositis and peri-implantitis. Methods: a clinical practice guideline was developed using the Scottish Intercollegiate Guidelines Network (SIGN) criteria. A search strategy was formulated, and a critical review of the following evidence was performed: 1) prevention of peri-implant diseases, 2) treatment of peri-implant mucositis, and 3) treatment of peri-implantitis. Systematic reviews and randomized controlled clinical trials were the primary study types identified in the literature. Current levels of evidence were established and recommendations were provided. Results: a total of 67 articles were included. Regarding the prevention of peri-implant diseases, there is strong evidence for the involvement of patients in a regular maintenance program according to their risk profile. Regarding the treatment of peri-implant mucositis, infection control measures are recommended; controversy exists over the usefulness of antimicrobial agents, and there is evidence against the use of antibiotics. Selection of the peri-implantitis treatment method depends on the severity of the condition and patient-related factors. Resective and regenerative therapies may be used for treatment. The use of systemic antibiotics favors the response of clinical parameters. There is conditional evidence for the use of other adjunctive therapies. Conclusions: the best way to prevent peri-implantitis is to prevent peri-implant mucositis through adherence to supportive periodontal therapy. Treatment of peri-implant diseases depends on local and systemic conditions that affect the success of other treatment options.

RESUMEN Introducción: la incidencia de las enfermedades periimplantarias es alta, y todavía existe polémica en torno a su óptima administración. El propósito del presente estudio consistió en explorar los niveles de evidencia disponibles y ofrecer recomendaciones basadas en la evidencia para el tratamiento de la mucositis periimplantaria y la periimplantitis. Métodos: se elaboró una guía de práctica clínica utilizando los criterios de la Red de Directrices Intercolegiales Escocesas (Scottish Intercollegiate Guidelines Network, SIGN). Se formuló una estrategia de búsqueda y se realizó una revisión crítica de las siguientes evidencias: 1) prevención de enfermedades periimplantarias, 2) tratamiento de la mucositis periimplantaria y 3) tratamiento de la periimplantitis. Las revisiones sistemáticas y los ensayos clínicos controlados aleatorios fueron los principals tipos de estudio identificados en la literatura. Se establecieron los niveles actuales de evidencias y se ofrecieron recomendaciones. Resultados: se incluyeron 67 artículos. En cuanto a la prevención de enfermedades periimplantarias, hay claras evidencias de la participación de los pacientes en los programas de mantenimiento regular, de acuerdo con su perfil de riesgo. En cuanto al tratamiento de la mucositis periimplantaria, se recomiendan medidas de control de infecciones; existe controversia sobre la utilidad de los agentes antimicrobianos, y hay evidencia en contra del uso de antibióticos. La selección del método de tratamiento de la periimplantitis depende de la gravedad de la afección y de los factores relacionados con el paciente. Para el tratamiento se pueden utilizar terapias resectivas y regenerativas. El uso de antibióticos sistémicos favorece la respuesta de los parámetros clínicos. Hay evidencia condicional en cuanto al uso de otras terapias adyuvantes. Conclusiones: la mejor manera de prevenir la periimplantitis es prevenir la mucositis periimplantar mediante la adherencia a la terapia periodontal de apoyo. El tratamiento de las enfermedades periimplantarias depende de las condiciones locales y sistémicas que afectan el éxito de otras opciones de tratamiento.

Exploración preliminar del potencial de adopción de un paquete biotecnológico para el control de T. solanivora por parte de productores de papa de la región Cundiboyacense de Colombia / Preliminary exploration of the potential for adoption of a biotechnology package for the control of T. solanivora by potato producers in the Cundiboyacense region of Colombia

RESUMEN La papa es afectada por el ataque de Tecia solanivora que causa pérdidas hasta del 80%. Variedades genéticamente modificadas y biocontroladores, pueden ser usados para su manejo. Este estudio pretendió determinó el potencial socioeconómico de pequeños productores de papa de la región Cundiboyacense para la adopción de estas estrategias biotecnológicas, mediante encuestas cara a cara y el uso de metodologías como presupuestos parciales y modelo de regresión logística. Los resultados revelan que el tipo de semilla define la adopción, existiendo un interés por tecnologías que permitan el control de la plaga, por lo cual estarían dispuestos a pagar hasta un 30% más del valor actual por esta. La metodología de presupuestos parciales evidenció un efecto económico positivo en los diferentes escenarios planteados. Se concluyó que los pequeños productores de papa de los municipios analizados cuentan con un alto potencial socioeconómico para la adopción del paquete biotecnológico.

ABSTRACT The potato is affected by the attack of Tecia solanivora that causes losses of up to 80%. Genetically modified varieties and biocontrol agents, can be used for its control. This study aimed to determine the socioeconomic potential of small potato producers in the Cundiboyacense region for the adoption of these biotechnological strategies, through face-to-face surveys and the use of methodologies such as partial budgets and logistic regression model. The results reveal that the type of seed defines adoption, there being an interest in technologies that allow pest control, so they would be willing to pay up to 30% more of the current value for this. The methodology of partial budgets showed a positive economic effect in the different scenarios proposed. It was concluded that small potato producers in the municipalities analyzed have a high socioeconomic potential for the adoption of the biotechnology package.

Transthoracic Echocardiographic Examination in the Rabbit Model.

Large animal models such as the rabbit are valuable for translational preclinical research. Rabbits have a similar cardiac electrophysiology compared to that of humans and that of other large animal models such as dogs and pigs. However, the rabbit model has the additional advantage of lower maintenance costs compared to other large animal models. The longitudinal evaluation of cardiac function using echocardiography, when appropriately implemented, is a useful methodology for preclinical assessment of novel therapies for heart failure with reduced ejection fraction (e.g. cardiac regeneration). The correct use of this non-invasive tool requires the implementation of a standardized examination protocol following international guidelines. Here we describe, step by step, a detailed protocol supervised by veterinary cardiologists for performing echocardiography in the rabbit model, and demonstrate how to correctly obtain the different echocardiographic views and imaging planes, as well as the different imaging modes available in a clinical echocardiography system routinely used in human and veterinary patients.

Percutaneous Contrast Echocardiography-guided Intramyocardial Injection and Cell Delivery in a Large Preclinical Model.

Cell and gene therapy are exciting and promising strategies for the purpose of cardiac regeneration in the setting of heart failure with reduced ejection fraction (HFrEF). Before they can be considered for use, and implemented in humans, extensive preclinical studies are required in large animal models to evaluate the safety, efficacy, and fate of the injectate (e.g., stem cells) once delivered into the myocardium. Small rodent models offer advantages (e.g., cost effectiveness, amenability for genetic manipulation); however, given inherent limitations of these models, the findings in these rarely translate into the clinic. Conversely, large animal models such as rabbits, have advantages (e.g., similar cardiac electrophysiology compared to humans and other large animals), whilst retaining a good cost-effective balance. Here, we demonstrate how to perform a percutaneous contrast echocardiography-guided intramyocardial injection (IMI) technique, which is minimally invasive, safe, well tolerated, and very effective in the targeted delivery of injectates, including cells, into several locations within the myocardium of a rabbit model. For the implementation of this technique, we also have taken advantage of a widely available clinical echocardiography system. After putting in practice the protocol described here, a researcher with basic ultrasound knowledge will become competent in the performance of this versatile and minimally invasive technique for routine use in experiments, aimed at hypothesis testing of the capabilities of cardiac regenerative therapeutics in the rabbit model. Once competency is achieved, the whole procedure can be performed within 25 min after anaesthetizing the rabbit.

Diseño in silico y evaluación funcional de genes semisintéticos que confieran tolerancia a fosfinotricina / In silico design and functional assessment of semisynthetic genes that confer tolerance to phosphinothricin

La tolerancia a herbicidas es una de las características más usadas en los cultivos GM, con resultados positivos para los agricultores y el ambiente. El punto de partida, es el desarrollo de casetes de expresión que expresen la característica de interés, inicialmente construidos mediante técnicas de biología molecular convencionales. Actualmente, con herramientas de bioinformática y biología sintética, es posible diseñar y probar el constructo in silico, para luego contratar su síntesis. Esta aproximación, permite optimizar la expresión mediante la modificación del uso codónico. En este trabajo se diseñaron y evaluaron en Nicotiana benthamiana versiones semisintéticas de genes que confieren tolerancia al herbicida fosfinotricina. Se realizó un análisis de libertad de operación, con el fin de asegurar que los constructos diseñados no violen derechos de propiedad intelectual en Colombia. Se obtuvieron dos casetes de expresión con libertad de operación, que expresan versiones del gen bar.

Herbicide tolerance is one of the features most used in GM crops, which has shown positive results for farmers and the environment. The starting point is the development of expression cassettes that express the characteristic of interest, they are initially constructed by standard molecular biology techniques. Currently, by bioinformatics and synthetic biology tools, it is possible to design and test the construct in silico, and then hire their synthesis. This approach allows optimizing expression by modifying the codon usage. In this work there were designed and evaluated semi-synthetic versions of genes in Nicotiana benthamiana, these genes confer tolerance to the herbicide phosphinothricin. It was made an analysis of freedom to operate in order to ensure that the designed constructs not violate intellectual property in Colombia. There were obtained two expression cassettes with freedom to operate, which express versions of the bar gene.

DISEÑO DE CASETES DE EXPRESIÓN QUE CONFIERAN TOLERANCIA A SEQUÍA Y A GLUFOSINATO EN MAÍZ (Zea mays) / Design of Expression Cassettes that Confer Drought and Glufosinate Tolerance to Maize (Zea mays)

Como primera aproximación en la obtención de una línea transgénica de maíz tolerante a sequía y al herbicida glufosinato de amonio, se seleccionaron genes y elementos reguladores para el diseño in silico de casetes de expresión, a través del análisis de literatura científica y bases de datos de genes y patentes. Las secuencias génicas fueron modificadas con base en el criterio de uso codónico del maíz para optimizar su expresión. Los casetes de expresión diseñados con el software DNA 2.0., fueron sintetizados por una empresa especializada. La presencia del transgen y la expresión a nivel de mARN fue demostrada mediante PCR y RT-PCR en la planta modelo Nicotiana benthamiana transformada vía Agrobacterium tumefaciens. Un ensayo preliminar in vitro en condiciones simuladas de sequía en medio MS con PEG (PM 6000)10 % no demostró incremento notorio en la tolerancia de las plántulas transformantes, posiblemente debido a que el uso codónico del diseño no favorece la expresión génica en la planta modelo.

As a first approach in obtaining a transgenic drought and glufosinate ammonium tolerant maize line, genes and regulatory elements for the in silico design of the expression cassettes were selected through analysis of scientific literature and databases of genes and patents. Gene sequences were modified based on the criterion of maize codon usage to optimize their expression. The constructs designed with DNA 2.0 Software, were synthesized by a specialized company. The presence of the transgene and the expression of mRNA was demonstrated by PCR and RT-PCR in the model plant Nicotiana benthamiana transformed via Agrobacterium tumefaciens. A preliminary experiment in vitro under simulated drought conditions in MS medium with 10 % PEG (PM 6000) showed no noticeable increase in drought tolerance of the transformants, possibly because the codon usage of the design does not promote gene expression in the model plant.

Detección de proteínas transgénicas en harinas de maíz comercializadas en Bogotá, Colombia / Detection of transgenic proteins in maize flour marketed in Bogotá, Colombia

Objetivo Detectar la presencia o ausencia de proteínas transgénicas derivadas de cultivos genéticamente modificados (GM) en harina de maíz comercializadas en Bogotá D.C., Colombia. Métodos Se evaluaron 11 protocolos de extracción de proteína total en 17 harinas pre-cocidas, dos no cocidas y tres controles positivos. Posteriormente, se determinó la presencia de 7 proteínas transgénicas (CP4EPSPS, Cry1Ab, Cry1Ac, Cry1F, Cry2A, Cry34Ab1 y Cry3Bb1) utilizando kits de ELISA comerciales. Resultados Se determinó que el mejor protocolo de extracción de proteína total fue el buffer con Tritón X-100, con el que se obtienen concentraciones de proteína mayores a 0,5 mg/g de harina y no genera interferencia con la técnica de ELISA. Se detectaron cuatro proteínas transgénicas: CP4EPSPS, Cry1F, Cry1Ab y Cry34Ab1 en harinas pre-cocidas y sin pre-cocción, con porcentajes que varían entre el 20 y 100 %. Conclusión Siete de las 19 harinas de maíz evaluadas contienen trazas de proteínas transgénicas (B2,B8,A3,O3,O1,C1 y C2), que confieren resistencia a lepidópteros o coleópteros y tolerancia al herbicida glifosato (CP4EPSPS, Cry1Ab, Cry1F, Cry34Ab1 y Cry3Bb1), todos los eventos detectados están aprobados para el consumo humano en Colombia según el Ministerio de Salud y Protección Social.(AU)

Objective To detect the presence or absence of transgenic proteins derived from GM crops in maize flour marketed in Bogota D.C., Colombia. Methods 11 extraction protocols for total protein were evaluated in 17 precooked flour, two uncooked and three positive controls. Subsequently, the presence of 7 transgenic proteins (CP4-EPSPS, Cry1Ab, Cry1Ac, Cry1F, Cry2A, Cry34Ab1 and Cry3Bb1) using commercial ELISA kits was determined. Results It was determined that the best protocol for total protein extraction was buffer with Triton X-100, which allowed obtaining protein concentrations greater than 0.5 mg per gram of flour and does not generate interference with the ELISA technique. Four transgenic proteins were detected: CP4EPSPS, Cry1F, Cry1Ab and Cry34Ab1 in precooked and uncooked flour with percentages varying between 20 and 100 %. Conclusion Seven of the 19 maize flours contain traces of transgenic protein (B2,B8,A3,O3,O1,C1 and C2) that provide resistance to lepidopterans and coleopterans, and tolerance to glyphosate herbicide, (CP4EPSPS- Cry1Ab, Cry1F, Cry34Ab1 and Cry3Bb1). All detected events are approved for human consumption in Colombia, according to the Ministry of Health and Social Protection.(AU)

Aproximación al estudio de libertad de operación para una línea transgénica de arroz en Colombia / Aproach study of freedom to operate for transgenic line rice in Colombia

El desarrollo de una variedad genéticamente modificada (GM) es un reto científico y legal, tanto por las técnicas de ingeniería genética, como por los derechos de propiedad intelectual (DPI) implicados. Se realizó una aproximación al análisis de libertad de operación para una línea GM derivada de una variedad colombiana de arroz, que exprese una versión optimizada del gen cry1Ac, con el propósito de procurar su liberación comercial en Colombia. Para ello, se efectuó una deconstrucción de la innovación, con la cual se determinaron los elementos potencialmente protegibles por DPI, sobre los cuales se efectuaron búsquedas de patentes y solicitudes de patentes en el contexto nacional e internacional, en bases de datos de acceso público. Se encontraron 59 patentes y solicitudes de patentes en el escenario internacional. En la Superintendencia de Industria y Comercio de Colombia (SIC) se encontraron tres solicitudes de patentes que pueden incidir en la libertad de operación para esta innovación. Se concluye que es alta la posibilidad de desarrollar una línea GM de arroz que exprese el gen cry1Ac sin afectar interés de terceros, siempre y cuanto se cree para comercializarla en el país.

The development of a genetically modified variety (GM) is a scientific and legal challenge, by genetic engineering techniques used and the intellectual property rights (IPR) involved. Approximate analysis of freedom of operation for a GM line derived from a Colombian rice variety, express an optimized version of the cry1Ac gene; in order to pursue their commercial release in Colombia was made. To do this, a deconstruction of innovation, which potentially protectable elements DPI on which patent searches and patent applications were made in the national and international context, databases were determined public access was performed. 59 patents and patent applications were found in the international arena. The Superintendency of Industry and Trade of Colombia (SIC) three applications for patents that may affect the freedom of operation for this innovation were found. It is concluded that the higher the possibility of developing a GM rice line expressing cry1Ac gene without affecting the interest of third parties , as long as it is done in the country to commercialize.

[Detection of transgenic proteins in maize flour marketed in Bogotá, Colombia]. / Detección de proteínas transgénicas en harinas de maíz comercializadas en Bogotá, Colombia.

Objective To detect the presence or absence of transgenic proteins derived from GM crops in maize flour marketed in Bogota D.C., Colombia. Methods 11 extraction protocols for total protein were evaluated in 17 precooked flour, two uncooked and three positive controls. Subsequently, the presence of 7 transgenic proteins (CP4-EPSPS, Cry1Ab, Cry1Ac, Cry1F, Cry2A, Cry34Ab1 and Cry3Bb1) using commercial ELISA kits was determined. Results It was determined that the best protocol for total protein extraction was buffer with Triton X-100, which allowed obtaining protein concentrations greater than 0.5 mg per gram of flour and does not generate interference with the ELISA technique. Four transgenic proteins were detected: CP4EPSPS, Cry1F, Cry1Ab and Cry34Ab1 in precooked and uncooked flour with percentages varying between 20 and 100 %. Conclusion Seven of the 19 maize flours contain traces of transgenic protein (B2,B8,A3,O3,O1,C1 and C2) that provide resistance to lepidopterans and coleopterans, and tolerance to glyphosate herbicide, (CP4EPSPS- Cry1Ab, Cry1F, Cry34Ab1 and Cry3Bb1). All detected events are approved for human consumption in Colombia, according to the Ministry of Health and Social Protection.

Coded wire tagging of juvenile curimbatá, Prochilodus lineatus (Valenciennes, 1837) (Characiformes): mortality, tag retention, and growth

In recent decades, Brazilian hydroelectric reservoirs have been stocked with hundreds of millions of juvenile migratory fish, but almost no research on stocking has been conducted. In order to study stocking it is essential to tag the fish to be stocked. In this investigation we determined handling-induced mortality, tag retention rate, and absolute growth rate of hatchery-reared juvenile curimbatá (Prochilodus lineatus) tagged with coded wire tags (CWT), a tag widely used on stocked fish. We injected CWT into the dorsal musculature just below the first dorsal fin ray. Despite the need for frequent tag injector maintenance, this tagging location proved to be suitable for tagging juvenile curimbatá. We found no short-term mortality of juvenile curimbatá handled for CWT tagging, high retention rate for CWT (≥ 98.2%) even after 174 d of tagging, and no influence on absolute growth rate by CWT. We conclude that CWT is effective at tagging juvenile curimbatá, and we expect that it will also be effective for many other Brazilian fish species used for stocking.

Nas últimas décadas, reservatórios de hidrelétricas do Brasil foram estocados com centenas de milhões de jovens peixes migradores, mas quase nenhuma pesquisa sobre a estocagem foi conduzida. Para estudo da estocagem, etiquetar os peixes a serem estocados é essencial. Neste estudo, nós determinamos a mortalidade devido ao manejo, taxa de retenção da marca e taxa de crescimento absoluto de juvenis de curimbatá de cativeiro (Prochilodus lineatus) marcados com 'coded wire tag' (CWT), etiqueta amplamente utilizada em peixes estocados. Nós injetamos o CWT na musculatura dorsal logo abaixo do primeiro raio da nadadeira dorsal. Apesar de exigir manutenção frequente do injetor de CWT, esse local mostrou ser apropriado para a marcação de jovens de curimbatá. Não houve mortalidade de curto prazo nos juvenis manejados para marcação com CWT, a taxa de retenção do CWT foi elevada (≥ 98,2%), mesmo após 174 dias da marcação. Além disso, o CWT não influenciou na taxa de crescimento absoluto dos peixes etiquetados. O CWT mostrou ser efetivo para marcar juvenis de curimbatá, e acreditamos que ele também o será para muitas outras espécies de peixes brasileiros utilizadas em estocagem.

La ingeniería gnnética de plantas en Colombia: un camino en construcción / Genetic Engineering of Plants in Colombia: A Road Under Construction

Se reportan en Colombia trabajos en el desarrollo de líneas genéticamente modificadas (GM) de arroz, yuca, algodón, papa, caña de azúcar, café, maíz, soya, estevia y crisantemo, por parte de cinco centros de investigación (CIAT, CENICAÑA, CENICAFE, CIB, CORPOICA) y tres universidades (Universidad Nacional de Colombia, Universidad Javeriana, Universidad de Antioquia). Para llegar a la liberación comercial de variedades GM, se requiere de verdaderas políticas públicas en ciencia y tecnología, que den financiación suficiente y oportuna, así como resolver problemas con la maraña de patentes que limitan o impiden el desarrollo de innovaciones biotecnológicas, además de con el paquete regulatorio, que incrementa significativamente los costos de desarrollo.

Here in Colombia have been reported efforts on the development of genetically modified (GM) crops, like: rice, cassava, cotton, potato, sugar cane, coffee, corn, soy, stevia and chrysanthemum, by five research center (CIAT, CENICAÑA, CENICAFE, CIB, CORPOICA) and three universities (Universidad Nacional de Colombia, Universidad Javeriana, Universidad de Antioquia). To get to the commercial release of GM varieties, real public policies on science and technology are needed, giving sufficient and timely funding, as well as to solve problems with the tangle of patents that limit or prevent the development of biotechnological innovations, and it is also required suffice funding to go through the regulatory issues, which significantly increase the cost of those developments.

An Upgrade on the Rabbit Model of Anthracycline-Induced Cardiomyopathy: Shorter Protocol, Reduced Mortality, and Higher Incidence of Overt Dilated Cardiomyopathy.

Current protocols of anthracycline-induced cardiomyopathy in rabbits present with high premature mortality and nephrotoxicity, thus rendering them unsuitable for studies requiring long-term functional evaluation of myocardial function (e.g., stem cell therapy). We compared two previously described protocols to an in-house developed protocol in three groups: Group DOX2 received doxorubicin 2 mg/kg/week (8 weeks); Group DAU3 received daunorubicin 3 mg/kg/week (10 weeks); and Group DAU4 received daunorubicin 4 mg/kg/week (6 weeks). A cohort of rabbits received saline (control). Results of blood tests, cardiac troponin I, echocardiography, and histopathology were analysed. Whilst DOX2 and DAU3 rabbits showed high premature mortality (50% and 33%, resp.), DAU4 rabbits showed 7.6% premature mortality. None of DOX2 rabbits developed overt dilated cardiomyopathy; 66% of DAU3 rabbits developed overt dilated cardiomyopathy and quickly progressed to severe congestive heart failure. Interestingly, 92% of DAU4 rabbits showed overt dilated cardiomyopathy and 67% developed congestive heart failure exhibiting stable disease. DOX2 and DAU3 rabbits showed alterations of renal function, with DAU3 also exhibiting hepatic function compromise. Thus, a shortened protocol of anthracycline-induced cardiomyopathy as in DAU4 group results in high incidence of overt dilated cardiomyopathy, which insidiously progressed to congestive heart failure, associated to reduced systemic compromise and very low premature mortality.

Optimization of an in vitro regeneration system for colombian indica rice varieties / Optimización de un sistema in vitro de regeneración para variedades colombianas de arroz indica

In order to optimize an in vitro regeneration system for colombian rice varieties, the amount of plant regulators used for each step of the process was modified, together with other factors such as seed position and time of exposition to plant regulators. Modification of 2,4-D concentration during callus induction and coculture has a negative effect on regeneration potential. However, it is possible to increase the amount of produced calli by modifying the position in which the seed is placed on the culture medium. Moreover, a longer callus induction time decreased the regeneration percentage. During the regeneration step, for FEDEARROZ 2000 variety, a combination of 1,0 mg/l g/l mg/l of naftalenacetic acid + 4,0 mg/l g/l mg/l of kinetin increases the regeneration percentage, without increasing the amount of abnormal shoots and without decreasing their size. For FEDEARROZ 50 variety, the best combination of plant regulators is 0,5 mg/l g/l mg/l of naftalenacetic acid + 2,0 mg/l g/l mg/l of kinetin.

Para optimizar un sistema de regeneración in vitro de variedades colombianas de arroz, se modificaron las concentraciones de los reguladores utilizados a lo largo de cada etapa del proceso de cultivo, junto con otros factores como la posición de siembra de la semilla y el tiempo de exposición a los reguladores. Se encontró que la modificación de la concentración de 2,4-D para las etapas de inducción de callo y cocultivo repercute de forma negativa en la regeneración. Por otra parte, es posible incrementar el porcentaje de formación de callo cambiando la posición de siembra de la semilla. Adicionalmente, un mayor tiempo de formación de callo provocó una disminución del porcentaje de regeneración. En la etapa de regeneración, para la variedad FEDEARROZ 2000 se encontró que una combinación de 1,0 mg/l g/l mg/l de ácido naftalenacético + 4,0 mg/l g/l mg/l de kinetina aumenta el porcentaje de regeneración, sin incrementar la cantidad de brotes anormales y sin disminuir de forma considerable el tamaño de los brotes. Para la variedad FEDEARROZ 50, la mejor combinación de reguladores durante la regeneración es de 0,5 mg/l g/l mg/l de ácido natfalenacético + 2,0 mg/l g/l mg/l de kinetina.

Estudio de libertad de operación para una línea genéticamente modificada de papa (Solanum tuberosum L. ) / Study of freedom to operate for a genetically modified potato (Solanum tuberosum L. ) line

Durante el desarrollo de los productos biotecnológicos son utilizados materiales y procesos, que pueden estar protegidos por derechos de propiedad intelectual. Para evitar problemas legales en su comercialización, se deben realizar estudios de libertad de operación. Este estudio se realizó sobre una línea genéticamente modificada (GM) de papa (Solanum tuberosum L.) derivada de la variedad Pastusa Suprema, que expresa el gene Cry1Ac de Bacillus thuringiensis, desarrollada por la Corporación de Ciencias Biológicas y la Universidad Nacional de Colombia, Sede Medellín. El punto de partida, fue la deconstrucción del producto, cuyo resultado fue la lista de materiales y procesos usados en el desarrollo del producto. Se buscaron en bases de datos nacionales e internacionales de acceso público, las solicitudes de patentes y patentes relacionadas. En el nivel internacional, se encontraron cuatro solicitudes de patentes y dieciocho patentes relacionadas, la mayoría de las cuales, no han sido solicitadas en Colombia. En el nivel nacional, se encontraron 13 solicitudes de patentes, que han caducado, han sido negadas, abandonadas, desistidas, o están en requerimiento. Se encontró que la variedad tiene registro comercial, pero no título de obtentor. También se examinaron documentos de las instituciones participantes, que contuvieran cláusulas sobre propiedad intelectual, y otros documentos de interés, como los acuerdos de transferencia de materiales (ATM). Se concluye que la libertad de operación puede estar afectada más por problemas detectados en los ATM y en la complejidad de los acuerdos interinstitucionales suscritos, que por los derechos de propiedad intelectual.

During the development of biotechnological products, some materials and processes are used, which can be protected by intellectual property rights (IPR's). In order to avoid legal problems related to their marketing, freedom-to-operate studies need to be done. This study was made on a genetically modified (GM) potato (Solanum tuberous L.) derived from variety "Pastusa Suprema", which expresses the gene cry1Ac from Bacillus thuringiensis, developed by Corporation for Biological Research (Corporación para Investigaciones Biológicas - CIB) and National University of Colombia at Medellín (Universidad Nacional de Colombia, sede Medellín). The starting point was the deconstruction of the product, whose result was the list of materials and processes used in the development of the new product. Patents and related applications were searched in national and international databases. At the international level, four applications and eighteen patents were found, most of which have not been applied for in Colombia. At the national levee, thirteen applications were found, which have expired, have been denied, abandoned, desisted or are currently on request. The plant variety has commercial registration but not breeder's certificate. Documents of the partaker institutions with IP clauses and other documents of interest, such as Material Transfer Agreements (ATM), were examined. It can be concluded that the freedom to operate might be affected for issues related to the ATMs and to the complexity of inter-institutional agreements, rather than for intellectual property rights.

Ibuprofen inhibits migration and proliferation of human coronary artery smooth muscle cells by inducing a differentiated phenotype: role of peroxisome proliferator-activated receptor γ.

OBJECTIVES: The search for agents that are capable of preventing restenosis and reduce the risk of late thrombosis is of utmost importance. In this study we aim to evaluate the in vitro effects of ibuprofen on proliferation and migration of human coronary artery smooth muscle cells and on endothelial cells. METHODS: Cell proliferation was evaluated by trypan blue exclusion. Cell migration was assessed by wound-healing 'scratch' assay and time-lapse video microscopy. Protein expression was assessed by immunoblotting, and morphology by immunocytochemistry. The involvement of the PPARγ pathway was studied with the agonist troglitazone, and the use of selective antagonists such as PGF2α and GW9662. KEY FINDINGS: We demonstrate that ibuprofen inhibits proliferation and migration of HCASMCs and induces a switch in HCASMCs towards a differentiated and contractile phenotype, and that these effects are mediated through the PPARγ pathway. Importantly we also show that the effects of ibuprofen are cell type-specific as it does not affect migration and proliferation of endothelial cells. CONCLUSIONS: Taken together, our results suggest that ibuprofen could be an effective drug for the development of novel drug-eluting stents that could lead to reduced rates of restenosis and potentially other complications of DES implantation.

Multiplex ligation-dependent probe amplification to subtelomeric rearrangements in idiopathic intellectual disability in Colombia.

BACKGROUND: A cause cannot be determined in 30% to 50% of patients with intellectual disability. Determining the etiology of intellectual disability is important and useful for pediatric neurologists, geneticists, pediatricians, and patients' families because it allows assessment of recurrence risk, appropriate genetic counseling, and focus on treatment options and prognosis. This study aims to determine the prevalence, origin, and characterization of subtelomeric rearrangements through the Multiplex Ligation-Dependent Probe Amplification method in pediatric patients with idiopathic intellectual disability. METHODS: A cross-sectional descriptive study was undertaken with patients seen in consultation at the neuropediatrics or genetic service of the Central Military Hospital, the Mercy' Hospital, or the Genetics Institute National University of Colombia. Patients were diagnosed with idiopathic intellectual disability between December 2010 and September 2011 and underwent a complete medical history, physical examination, and assessment to rule out other etiologies of intellectual disability. Then we applied the genetic test of Multiplex Ligation-Dependent Probe Amplification to each patient's sample of peripheral blood to determine subtelomeric rearrangements. RESULTS: We studied a group of 119 patients with idiopathic intellectual disability; Multiplex Ligation-Dependent Probe Amplification showed subtelomeric rearrangements in five. In the group with subtelomeric rearrangements, the most frequent results were de novo rearrangements (80%), deletion type (60%), moderate and severe intellectual disability (80%), minor phenotypic abnormalities (80%), and family history of neurological disorders (80%). No dependence relationship was observed between subtelomeric rearrangements and family history of neurological disorders, family history of intellectual disability, severity of intellectual disability, phenotypic abnormalities, and consanguinity. CONCLUSIONS: This study determined a prevalence of subtelomeric rearrangements of 4.2% in a group of Colombian pediatric patients with idiopathic intellectual disability using the genetic test Multiplex Ligation-Dependent Probe Amplification.

Mutation spectrum in South American Lynch syndrome families.

BACKGROUND: Genetic counselling and testing for Lynch syndrome have recently been introduced in several South American countries, though yet not available in the public health care system. METHODS: We compiled data from publications and hereditary cancer registries to characterize the Lynch syndrome mutation spectrum in South America. In total, data from 267 families that fulfilled the Amsterdam criteria and/or the Bethesda guidelines from Argentina, Brazil, Chile, Colombia and Uruguay were included. RESULTS: Disease-predisposing mutations were identified in 37% of the families and affected MLH1 in 60% and MSH2 in 40%. Half of the mutations have not previously been reported and potential founder effects were identified in Brazil and in Colombia. CONCLUSION: The South American Lynch syndrome mutation spectrum includes multiple new mutations, identifies potential founder effects and is useful for future development of genetic testing in this continent.

Tolerancia al aluminio en especies vegetales: mecanismos y genes / Aluminum tolerance: mechanisms and genes / Tolerância ao alumínio em espécies vegetais: mecanismos e genes

Un problema para la producción agrícola en la Orinoquia colombiana, son los 4,5 millones de hectáreas con altos contenidos de aluminio. Genotipos de diferentes especies presentan niveles de tolerancia a través de diversos mecanismos, las vías de señalización también pueden diferir, por lo que no se cuenta con un modelo único. Algunas de las moléculas comunes que participan en la respuesta de tolerancia se determinaron. Para identificar genes candidatos a utilizar en el desarrollo de cultivares tolerantes al aluminio, se consultó artículos científicos publicados entre 1987 y 2013. Mediante el reporte de uso de técnicas convencionales de hibridación, mutación, selección asistida por marcadores moleculares y transferencia de genes, se obtuvieron datos de materiales tolerantes evidenciándose mecanismos moleculares para tolerancia al aluminio. Se encontraron reportados genes total y parcialmente caracterizados, con uso potencial en ingeniería genética y en selección asistida por marcadores, para la obtención de genotipos tolerantes al aluminio.

Agricultural production in the Colombian Orinoco is affected by the high aluminum content found in 4.5 million hectares. Genotypes of different species have acquired different levels of tolerance and signaling pathways through various mechanisms, making a single model impossible. Some of the molecules commonly involved in the tolerance response have already been identified. To identify candidate genes to produce aluminum-tolerant cultivars, we consulted scientific articles published between 1987 and 2013. We obtained data of aluminum-tolerant materials and molecular mechanisms for tolerance through reports of techniques using hybridization, mutation, molecular marker-assisted selection and gene transfer. We found several reports on wholly or partially characterized genes with potential use in genetic engineering and in marker assisted selection to obtain aluminum tolerant genotypes.

Um problema para a produção agrícola no Orinoco da Colômbia, são os 4,5 milhões de hectares com alto teor de alumínio. Genótipos de diferentes espécies apresentam tolerância através de diferentes mecanismos, as vias de sinalização também podem ser diferentes, de modo que não existe um modelo único. Algumas das moléculas comuns envolvidas na resposta da tolerância foram determinadas. A fim de identificar genes candidatos para uso no desenvolvimento de cultivos tolerantes ao alumínio foram consultados artigos científicos publicados entre 1987 e 2013. Por meio de técnicas convencionais que utilizam a hibridização, mutação, seleção assistida por marcadores moleculares e de transferência de genes, obtiveram-se dados de materiais tolerantes e se evidenciou mecanismos moleculares para tolerância ao alumínio. Encontraram-se reportados vários genes total e parcialmente caracterizados, com uso potencial na engenharia genética e na seleção assistida por marcadores, para a obtenção de genótipos tolerantes ao alumínio.