Examinando por Autor "López Casillas, Marcos"
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- PublicaciónAcceso abiertoCardioprotección por antioxidantes mitocondriales en cardiomiocitos humanos infectados con Trypanosoma cruzi(Bucaramanga : Universidad de Santander, 2017, 2017-10-15) Rodríguez Avila, Yudy A.; López Casillas, MarcosLa cardiomiopatía chagásica es el evento más serio y más frecuente de la enfermedad de chagas. La invasión por T. cruzi genera alteraciones en la función mitocondrial del cardiomiocito que se traducen a pérdida del potencial de membrana mitocondrial, generación de especies reactivas de oxígeno ROS y alteración en el balance antioxidante, contribuyendo a un desequilibrio metabólico y oxidativo en el miocardio chagásico. Nosotros evaluamos los efectos de nitróxidos miméticos de SOD (SG1 y Mito-SG1) y del tratamiento de referencia BZN sobre la capacidad pro-oxidante, la bioenergética celular e infectividad de cardiomiocitos humanos AC16 infectados con T. cruzi. Materiales y Métodos: La citotoxicidad celular fue realizada por el ensayo MTT. La infectividad parasitaria fue determinada por citometría de flujo, utilizando el reactivo CFSE. La bioenergética celular se determinó con el sistema Seahorse XFe-24 Analyzer y la producción de ROS Mitocondrial por MitoSOX™ Red. Resultados: El CC50 para SG1 fue de 4790 μM, para Mito-SG1 de 5,0 μM. BZN y Mito-SG1 tuvieron efectos en la disminución de la tasa de infectividad de los cardiomiocitos humanos. Se obtuvo diferencias significativas en los efectos pro-oxidantes de los cardiomiocitos tratados con BZN. Se observaron cambios importantes estadísticamente en los parámetros de respiración basal, producción de ATP, protón leak y respiración máxima en los cardiomiocitos infectados con T. cruzi. La capacidad de reserva respiratoria disminuyo en los cardiomiocitos infectados y sometidos a los tratamientos con BZN, SG1 y Mito-SG1. Conclusiones: El cardiomiocito humano sufre perturbaciones metabólicas tempranas que involucran cambios en el consumo de oxígeno y perfil bioenergético hacia la utilización de la vía glucolítica. La disminución de la infectividad en los cardiomiocitos tratados con Mito-SG1, es un hallazgo que permite realizar estudios futuros con el fin de determinar posibles efectos antiparásitarios del mitocompuesto.
- PublicaciónRestringidoDouble blind, randomized controlled trial, to evaluate the effectiveness of a controlled nitric oxide releasing patch versus meglumine antimoniate in the treatment of cutaneous leishmaniasis [NCT00317629](2006-05-15) Silva, Sandra Y.; Rueda, Ligia C.; López Casillas, Marcos; Vélez, Iván D.; Rueda Clausen, Christian F.; Smith, Daniel J.; Muñoz, Gerardo; Mosquera, Hernando; Silva Sieger, Federico Arturo; Buitrago, Adriana; Díaz, Holger; Lopez-Jaramillo, PatricioBackground: Cutaneous Leishmaniasis is a worldwide disease, endemic in 88 countries, that has shown an increasing incidence over the last two decades. So far, pentavalent antimony compounds have been considered the treatment of choice, with a percentage of cure of about 85%. However, the high efficacy of these drugs is counteracted by their many disadvantages and adverse events. Previous studies have shown nitric oxide to be a potential alternative treatment when administered topically with no serious adverse events. However, due to the unstable nitric oxide release, the topical donors needed to be applied frequently, making the adherence to the treatment difficult. The electrospinning technique has allowed the production of a multilayer transdermal patch that produces a continuous and stable nitric oxide release. The main objective of this study is to evaluate this novel nitric oxide topical donor for the treatment of cutaneous leishmaniasis. Methods and design: A double-blind, randomized, double-masked, placebo-controlled clinical trial, including 620 patients from endemic areas for Leishmaniasis in Colombia was designed to investigate whether this patch is as effective as meglumine antimoniate for the treatment of cutaneous leishmaniasis but with less adverse events. Subjects with ulcers characteristic of cutaneous leishmaniasis will be medically evaluated and laboratory tests and parasitological confirmation performed. After checking the inclusion/exclusion criteria, the patients will be randomly assigned to one of two groups. During 20 days Group 1 will receive simultaneously meglumine antimoniate and placebo of nitric oxide patches while Group 2 will receive placebo of meglumine antimoniate and active nitric oxide patches. During the treatment visits, the medicationswill be daily administered and the presence of adverse events assessed. During the follow-up, the research group will visit the patients at days 21, 45, 90 and 180. The healing process of the ulcer, the health of the participants, recidivisms and/or reinfection will also be assessed. The evolution of the ulcers will be photographically registered. In case that the effectiveness of the patches is demonstrated, a novel and safe therapeutic alternative for one of the most important public health problems in many countries will be available to patients.
- PublicaciónRestringidoDouble blind, randomized, placebo controlled clinical trial for the treatment of diabetic foot ulcers, using a nitric oxide releasing patch : PATHON(2007-09-26) Silva, Sandra Y.; Rueda, Ligia C.; Márquez, Gustavo; López Casillas, Marcos; Smith, Daniel J.; Calderón, Carlos A.; Castillo, Juan C.; Matute, Jaime; Rueda Clausen, Christian F.; Orduz, Arturo; Silva Sieger, Federico Arturo; Kampeerapappun, Piyaporn; Bhide, Mahesh; Lopez-Jaramillo, PatricioBackground: Diabetes Mellitus constitutes one of the most important public health problems due to its high prevalence and enormous social and economic consequences. Diabetic foot ulcers are one of the chronic complications of diabetes mellitus and constitute the most important cause of non-traumatic amputation of inferior limbs. It is estimated that 15% of the diabetic population will develop an ulcer sometime in their lives. Although novel therapies have been proposed, there is no effective treatment for this pathology. Naturally produced nitric oxide participates in the wound healing process by stimulating the synthesis of collagen, triggering the release of chemotactic cytokines, increasing blood vessels permeability, promoting angiogenic activity, stimulating the release of epidermical growth factors, and by interfering with the bacterial mitochondrial respiratory chain. Topically administered nitric oxide has demonstrated to be effective and safe for the treatment of chronic ulcers secondary to cutaneous leishmaniasis. However, due to their unstable nitric oxide release, the topical donors needed to be applied frequently, diminishing the adherence to the treatment. This difficulty has led to the development of a multilayer polymeric transdermal patch produced by electrospinning technique that guarantees a constant nitric oxide release. The main objective of this study is to evaluate the effectiveness and safety of this novel nitric oxide releasing wound dressing for the treatment of diabetic foot ulcers. Methods and design: A double-blind, placebo-controlled clinical trial, including 100 diabetic patients was designed. At the time of enrollment, a complete medical evaluation and laboratory tests will be performed, and those patients who meet the inclusion criteria randomly assigned to one of two groups. Over the course of 90 days group 1 will receive active patches and group 2 placebo patches. The patients will be seen by the research group at least every two weeks until the healing of the ulcer or the end of the treatment. During each visit the healing process of the ulcer, the patient's health status and the presence of adverse events will be assessed. Should the effectiveness of the patches be demonstrated an alternative treatment would then be available to patients.
- PublicaciónAcceso abiertoThe role of the L-arginine-nitric oxide pathway in preeclampsia(2008-08-01) Lopez-Jaramillo, Patricio; Arenas, William D.; García, Ronald G.; Rincón, Melvin Y.; López Casillas, Marcos: Preeclampsia (PE) is a major cause of maternal and perinatal mortality, especially in developing countries. Its etiology involves multiple factors, but no specific cause has been identified. Evidence suggests that clinical manifestations are caused by endothelial dysfunction. Nitric oxide (NO), which is synthesized from L-arginine in endothelial cells by the endothelial nitric oxide synthase (eNOS), provides a tonic dilator tone and regulates the adhesion of white blood cells and platelet aggregation. Alterations in the L-arginine-NO pathway have been associated with the development of PE. Various studies, reporting decreased, elevated or unchanged levels of nitrite (NO2) and nitrate (NO3), two end products of NO metabolism, have been published. Our group contributed to those contradictory reports describing cases of PE with both elevated and decreased levels of NO2 and NO3. Apparently, diminished levels of NO could be related to deficiencies in the ingestion of dietary calcium associated to low levels of plasma ionic calcium, which is crucial to the eNOS’ activity. Also, low levels of NO could be associated with the presence of eNOS polymorphisms or the presence of increased levels of ADMA, the endogenous inhibitor of NO. High levels of NO associated to low levels of cGMP suggest a decreased bioactivity of NO, which is probably related to an increased degradation of NO caused by a high production of superoxide in states of infection and inflammation. The present article analyses and reviews the reported paradoxical roles of the L-arginine-NO pathway in PE and gives a possible explanation for these results.