Effects of Bothrops asper Snake Venom on Lymphatic Vessels: Insights into a Hidden Aspect of Envenomation

Envenomations by snakes of the family Viperidae (pit vipers) induce severe pathological alterations at the site of venom injection, such as edema, necrosis, hemorrhage, and blistering, which may lead to permanent tissue damage and disability. Edema is a prominent and common manifestation in these envenomations. The effect of viperid snake venoms in lymphatic vessels has not been previously investigated. This study analyzed the effect of the venom of Bothrops asper, the most important venomous snake in Central America, on the collecting lymphatic vessels of the mouse mesentery. The venom induced a rapid reduction in the lumen of these lymphatics, associated with a halting in the flow of lymph. These effects were reproduced by a myotoxic phospholipase A2 homologue isolated from this venom, but not by a hemorrhagic metalloproteinase nor by a coagulant serine proteinase. B. asper venom, and the purified myotoxin, were cytotoxic for smooth muscle cells in culture, thus suggesting that the alterations observed in lymphatics are due to the effect on smooth muscle cells of the lymphatic vessel wall. These results demonstrate a direct effect of B. asper venom on lymphatics, which is likely to contribute to the prominent edema characteristic of these envenomations

Effects of buffer insertion on the average/peak power ratio in CMOS VLSI digital circuits

The buffer insertion has been a mechanism widely used to increase the performances of advanced VLSI digital circuits and systems. The driver or repeater used to this purpose has effect on the timing characteristics on the signal on the wire, as propagation delay, signal integrity, transition time, among others. The power concerns related to buffering have also received much attention, because of the low power requirements of modern integrated systems. In the same way, the buffer insertion has strong impact on the reliability of synchronous systems, since the suited distribution of clock requires reduced or controlled clock-skew, being the buffer and wire sizing, a crucial aspect. In a different way, buffer insertion has been also used to reduce noise generation, especially in heavily loaded nets, since the inclusion of buffers help to desynchronize signal transitions. However, the inclusion of buffers of inverters to improve one or more of these characteristics have often negative effect on another parameters, as it happens in the average and peak of supply current. Mainly, the inclusion of a buffer to reduce noise (peak power), via desynchronizing transitions, could introduce more dynamic consumption, but reducing the short-circuit current because of the increment of signal slope. Thus, the average/peak current optimization can be considered a design trade-off. In this paper, the mechanism to obtain an average/peak power optimization procedure are presented. Selected examples show the feasibility of minimizing switching noise with negligible impact on average power consumption.MEC TEC2004-01509 DOCJunta de Andalucía TIC2006-635 Project

Inflammatory infiltrate in skeletal muscle injected with Bothrops asper venom

The time-course and composition of inflammatory infiltrate in mouse gastrocnemius injected with Bothrops asper venom was studied. The venom induced myonecrosis, and a prominent decrease in muscle levels of creatine kinase (CK) as early as 3 hr after envenomation. Inflammatory infiltrate was scarce by 6 hr. but increased markedly at 24, 48 and 72 hr. Samples of infiltrate obtained at 6 and 24 hr contained polymorphonuclear leucocytes as the predominant cell type, whereas at 48 hr and 72 hr the relative number of macrophages increased. Inflammatory cells were located within necrotic muscle cells, as well as in the interstitial space, but there were some necrotic areas devoid of inflammatory cells even one week after envenomation. When correlating the presence of inflammatory cells with degradation of myofibrillar proteins, it was observed that at 6 hr there was little muscle protein degradation. By 48 hr a decrease in "non collagen" proteins was observed, together with a reduction in some myofibrillar components, as judged by electrophoresis. Proteolytic enzymes of inflammatory cells may play an important role in myofibrillar protein degradation after myonecrosis induced by B. asper venom.UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP

Role of nitric oxide in the local and systemic pathophysiological effects induced by Bothrops asper snake venom in mice

Objective To assess the role of nitric oxide in the most relevant local and systemic manifestations in mice injected with the venom of the snake Bothrops asper. Mice were pretreated with nitric oxide synthase inhibitors, and the modifications of the pathological effects induced by the venom were tested. Results Inhibition of NO synthesis did not affect acute local myonecrosis and hemorrhage in muscle tissue upon intramuscular injection of venom. Local footpad edema was reduced in mice pretreated with the NO synthase inhibitor L-NAME, and a reduction in the extent of inflammatory infiltrate in muscle tissue was observed after envenomation in mice pretreated with L-NAME and aminoguanidine. The most pronounced effect of NOS inhibition by L-NAME was an increment in the lethal activity of the venom, when injected by the intraperitoneal route. Conclusion Nitric oxide does not seem to play a significant role in the local acute pathological alterations (hemorrhage and myonecrosis) induced by B. asper venom in mice, although it contributes to edema and inflammatory infiltrate. Nitric oxide exerts a protective role in the systemic pathophysiological manifestations leading to lethality.Universidad de Costa Rica/[2075-06-01]/UCR/Costa RicaUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP

Micropropagation of Cissus tiliacea, plant native of the South of the state of Mexico

Se micropropagó Cissus tiliacea, recurso fitogenético con potencial agronómico y farmacológico, en los medios de cultivo Murashige-Skoog (MS) y Lloyd y McCown (WPM). En ambos medios se generaron resultados similares para número de brotes, nudos, hojas y raíces adventicias, sólo existió diferencia significativa (p ≤ 0,05) en la formación de callo. Para la multiplicación in vitro se utilizó WPM adicionado con 0; 0,5; 1,0; 1,5 ó 2,0 mg L-1 de benciladenina (BA) y se emplearon tres tipos de segmentos nodales (basal, medio y apical). Las concentraciones de 0 y 0,5 mg L-1 de BA resultaron en un mayor tamaño y desarrollo del explante, además permitieron la formación de 1,2 a 1,6 raíces por explante. Las concentraciones de 1,5 y 2,0 mg L-1 de BA indujeron la formación de callo. No existió diferencia significativa en las variables evaluadas por efecto del tipo de segmento nodal establecido in vitro. En el enraizamiento, en el medio MS, se evaluaron tres tipos de auxinas: ácido naftalen-1-acético (ANA), ácido indol-3-butírico (AIB) y ácido indol- 3-acético (AIA) a 0,5 mg L-1; el mayor número de raíces secundarias y diámetro de la raíz principal fue inducido por ANA, sin embargo AIB indujo una mayor elongación de la raíz principal. Los resultados del presente trabajo sugieren que el cultivo in vitro de C. tiliacea es una alternativa para su conservación y multiplicación.Murashige-Skoog (MS) or Lloyd and McCown (WPM) medium were used for micropropagation of Cissus tiliacea, an herb plant with potential in agriculture and pharmacology; in both medium similar results for shoot regeneration, number of leaves, leaves nodes, and adventitious roots were observed; only formation of callus was influenced (p ≤ 0.05) by the medium. For in vitro multiplication, benzyl adenine (BA) was added to WPM at 0, 0.5, 1.0, 1.5 or 2.0 mg L-1 and we used three types of explants that is basal, medium an upper. BA at 0 and 0.5 mg L-1 resulted in higher size and well developed plantlets; moreover, those concentrations allowed 1.2 or 1.6 roots per vitro plant. Those explants cultured in 1.5 or 2.0 BA resulted in callus development. Type of explant did not influence the evaluated explants responses. Rooting was evaluated in MS adding naphthalene acetic acid (NAA), indol butiric acid (IBA) or indol acetic acid (IAA) at 0.5 mg L-1; the higher number of secondary roots and the diameter of the main root was induced by NAA, but IBA resulted in longer main roots. Present results suggested that micropropagation of C. tiliaceae might be and alternative for conservation and multiplication of this wild plant.Fil: Jiménez-Martínez, José Humberto. Universidad Autónoma del Estado de México. Facultad de Ciencias AgrícolasFil: Franco-Mora, Omar. Universidad Autónoma del Estado de México. Facultad de Ciencias AgrícolasFil: Gutiérrez-Martínez, María de Guadalupe. Universidad Autónoma del Estado de México. Facultad de Ciencias AgrícolasFil: González-Huerta, Andrés. Universidad Autónoma del Estado de México. Facultad de Ciencias AgrícolasFil: Castañeda-Vildózola, Álvaro. Universidad Autónoma del Estado de México. Facultad de Ciencias Agrícola

Production of monovalent anti-Bothrops asper antivenom: development oí immune response in horses and neutralizing ability

En el Instituto Clodomiro Picado se produjo un suero monovalente contra el veneno de la serpiente Bothrops asper (terciopelo). Durante las primeras etapas del proceso los caballos inmunizados mostraron un título similar en lo que respecta a la neutralización del veneno; sin embargo, uno de ellos mostró un título muy superior en la última fase de la inmunización. El suero monovalente fue más efectivo que el suero polivalente comercial para neutralizar el veneno de B. asper. Por otra parte, el suero monovalente fue menos efectivo que el polivalente para neutralizar las actividades letal y hemorrágica de los venenos de Lachesis muta (cascabel muda) y Crotalus durissus (cascabel). Más aún, el monovalente no neutralizó la actividad desfibrinante de estos dos venenos. Se propone que el suero monovalente anti-B. asper es altamente efectivo en la neutralización del veneno homólogo, en tanto que su empleo en el tratamiento de envenenamientos por L. muta y C. durissus se justifica sólo cuando el suero polivalente no esté disponible.A monovalent antivenom was produced by immunizing two horses with venom of the pit viper Bothrops asper (Ophidia: VipeIidae). Although development of the immune response against four toxic and enzymatic activities of the venom was similar in both horses during the the two thirds of the immunization schedule, antibody response in one of the horses reached much higher levels in the last part of the immunization. Immunoelectrophoretic analysis indicates that there were precipitating antibodies in the sera of these horses during all the stages of immunization. However, immunoprecipitation did not correlate with the ability of sera to neutralize toxic activities of B. asper venom. Monovalent antivenom was more effective than the commercially available polyvalent antivenom in the neutralization of Bothrops asper venom. On the other hand, despite the fact that it neutralizes lethal and hemorrhagic activities of the venoms of Lachesia muta and Crotalus durissus durissus, it was less effective than polyvalent antivenom in these neutralizations. Moreover, it does not neutralize defibrinating activity induced by these two venoms, whereas it neutralizes this effect in the case of B. asper venom. It is proposed that monovalent antivenom may be highly effective in the case of envenomations induced by Bothrops asper venom; its use in treating accidents by L. muta and C. durissus would be indicated only if polyvalent antivenom is not available. Results also demonstrate that it is important to monitor antibody response individually in horses being immunized for antivenom production, due to the conspicuous variability in the response of different animals

Propuestas para la formación y desarrollo de investigadores universitarios mexicanos

Ante la necesidad que emerge en la sociedad del conocimiento de buscar estrategias que permitan formar investigadores críticos, y que impacten favorablemente en la solución de problemas en beneficio de la sociedad, para ello se realizó este estudio cualitativo en 3 universidades públicas mexicanas con el objetivo de avanzar y profundizar cuáles son los principales condicionantes organizacionales en la formación y desarrollo de investigadores educativos en los posgrados mexicanos. Se realizaron 27 entrevistas temáticas y se trabajó con la teoría fundamentada como método analítico. Se exploraron posibles estrategias de cambio derivadas de la reconstrucción de algunas propuestas planteadas por los entrevistados, específicamente las relacionadas a las estructuras jerárquicas, las formas de organización académica, la internacionalización y los procesos de enseñanza aprendizaje. La información empírica evidencia que las posibilidades de cambio organizacional implican trastocar las estructuras administrativas y académicas de estas universidades, además muestran la necesidad de sustituir algunas prácticas vigentes en la formación de investigadores por otras modalidades que tengan como base el desarrollo de habilidades para la reflexión, la argumentación y la creatividad, principalmente. Palabras clave: formación y desarrollo de investigadores; universidades públicas mexicanas; cambio organizacional; cambio en procesos de formación

Desarrollo de metodologías de apoyo basadas en el uso de plataformas virtuales de enseñanza para asignaturas de planes de estudio en extinción

En este trabajo se presenta una experiencia sobre la aplicación de diversas metodologías de apoyo cuyo objetivo principal es ofrecer a los alumnos de la Escuela Técnica Superior de Ingenieros Navales (ETSIN) de la Universidad Politécnica de Madrid (UPM) pertenecientes a un Plan de Estudios en extinción (Plan 2002) y del que ya han dejado e recibir clases presenciales en los primeros cursos, las herramientas adecuadas por medio de la plataforma virtual Moodle, para que puedan prepararse con garantías de éxito los exámenes finales de estas asignaturas, evitando cambiar obligatoriamente de plan de estudios. Se pretende dar a conocer a los profesores de las asignaturas sin docencia, la posibilidad de diseñar una metodología con tres niveles distintos de aprendizaje, solicitar el alta en el espacio virtual de enseñanza de aquellas asignaturas que no figuren en la plataforma virtual y poner a disposición del alumno el material necesario para lograr superar la asignatura. Los objetivos principales para el alumno son posibilitar el aprendizaje autónomo mediante recursos docentes y actividades alojados en la plataforma virtual, de forma que pueda estudiar la asignatura según el nivel de seguimiento que exija la misma

Differential effects of Anti-TNFα and Anti-α4β7 drugs on circulating dendritic cells migratory capacity in inflammatory bowel disease

Inflammatory bowel disease (IBD) is an idiopathic and chronic disorder that includes ulcerative colitis (UC) and Crohn’s disease (CD). Both diseases show an uncontrolled intestinal immune response that generates tissue inflammation. Dendritic cells (DCs) are antigen-presenting cells that play a key role in tolerance maintenance in the gastrointestinal mucosa. Although it has been reported that DC recruitment by the intestinal mucosa is more prominent in IBD patients, the specific mechanisms governing this migration are currently unknown. In this study, the expression of several homing markers and the migratory profile of circulating DC subsets towards intestinal chemo-attractants were evaluated and the effect of biological drugs with different mechanisms of action, such as anti-TNFα or anti-integrin α4β7 (vedolizumab), on this mechanism in healthy controls (HCs) and IBD patients was also assessed. Our results revealed that type 2 conventional DCs (cDC2) express differential homing marker profiles in UC and CD patients compared to HCs. Indeed, integrin β7 was differentially modulated by vedolizumab in CD and UC. Additionally, although CCL2 displayed a chemo-attractant effect over cDC2, while biological therapies did not modulate the expression of the homing markers, we paradoxically found that anti-TNF-treated cDC2 increased their migratory capacity towards CCL2 in HCs and IBD. Our results therefore suggest a key role for cDC2 migration towards the intestinal mucosa in IBD, something that could be explored in order to develop novel diagnostic biomarkers or to unravel new immunomodulatory targets in IBD.This study has been funded through the Instituto de Salud Carlos III (Sara Borrell fellowships, CD17/00014; CD21/00014), Asociación Española de Gastroenterología (Beca del Grupo Joven), Programa Estratégico Instituto de Biología y Genética Molecular (IBGM Junta de Castilla y León. Ref. CCVC8485), Plan Nacional (PID2019-104218RB-I00) from the Spanish Government, Janssen and MSD

Layer-dependence of macroscopic and atomic magnetic correlations in Co/Pd multilayers

The development of multilayered materials with engineered magnetic properties compels a deep knowledge of physical properties at the atomic scale. The magnetic anisotropy is a key property in these materials. This work accounts for the magnetic anisotropy energy and its correlation with atomic properties of Co/Pd multilayers with the number of Co/Pd repetitions. Magnetometry measurements confirm stronger perpendicular magnetic anisotropy energies as the number of repetitions increases up to 40. However, the intrinsic anisotropy, related to the Co-Pd orbital hybridization and spin-orbit coupling, saturates at 15 repetitions. This finding is supported by x-ray magnetic circular dichroism analysis that reveals a direct correlation of the atomic Co and Pd orbital magnetic moments and the effective anisotropy of the system. The proximity effect that accounts for the Pd induced magnetization, along with the increasing Co moment, provides a suitable mechanism for the observed anisotropy energy layer dependence