Piezo buffers mechanical stress via modulation of intracellular Ca2+ handling in the Drosophila heart.

Throughout its lifetime the heart is buffeted continuously by dynamic mechanical forces resulting from contraction of the heart muscle itself and fluctuations in haemodynamic load and pressure. These forces are in flux on a beat-by-beat basis, resulting from changes in posture, physical activity or emotional state, and over longer timescales due to altered physiology (e.g. pregnancy) or as a consequence of ageing or disease (e.g. hypertension). It has been known for over a century of the heart's ability to sense differences in haemodynamic load and adjust contractile force accordingly (Frank, Z. biology, 1895, 32, 370-447; Anrep, J. Physiol., 1912, 45 (5), 307-317; Patterson and Starling, J. Physiol., 1914, 48 (5), 357-79; Starling, The law of the heart (Linacre Lecture, given at Cambridge, 1915), 1918). These adaptive behaviours are important for cardiovascular homeostasis, but the mechanism(s) underpinning them are incompletely understood. Here we present evidence that the mechanically-activated ion channel, Piezo, is an important component of the Drosophila heart's ability to adapt to mechanical force. We find Piezo is a sarcoplasmic reticulum (SR)-resident channel and is part of a mechanism that regulates Ca2+ handling in cardiomyocytes in response to mechanical stress. Our data support a simple model in which Drosophila Piezo transduces mechanical force such as stretch into a Ca2+ signal, originating from the SR, that modulates cardiomyocyte contraction. We show that Piezo mutant hearts fail to buffer mechanical stress, have altered Ca2+ handling, become prone to arrhythmias and undergo pathological remodelling.

Profesionalismo en tiempos de crisis: análisis de las principales controversias éticas durante la pandemia del COVID-19 / Professionalism in times of crisis: the analysis of the main ethical controversies during the COVID-19 pandemic

El cuidado del equipo interprofesional de salud es un factor indispensable para que el sistema sanitario funcione de manera estable y resi-liente, especialmente cuando la presión se vuelve extrema. La pandemia, además de poner a prueba los sistemas de salud y sus actores, ha dejado algunas dudas respecto a los alcances del profesionalismo, frente a las demandas y expectativas que la sociedad tiene. Para efectos de la presente revisión, el concepto de profesionalismo en tiempos de crisis incluye controversias y dilemas que surgen en la relación con la sociedad, ética profesional y responsabilidad sobre el autocuidado. El compromiso y la resiliencia para garantizar el cuidado del paciente son evidentes en el actuar de los profesionales de la salud; sin embargo, en ocasiones esto ha ido en detrimento de su propia integridad física y moral. La agenda de salud en México está en deuda con médicos, residentes y profesionales de enfermería, una vía para saldarla es a través del fortalecimiento de las instituciones, la definición de políticas y normativas institucionales que promuevan el autocuidado y, entre otras medidas, el establecimiento de sistemas que no obliguen a aquéllos a convertirse en héroes enfrentados a los riesgos de una crisis.

The care of the interprofessional health team is an indispensable factor for the health system to function in a stable and resilient manner, especially when the pressure becomes extreme. In addition to putting health systems and their actors to the test, the pandemic has left some doubts about the scope of professionalism in the face of society's demands and expectations. For this review, the concept of professionalism in times of crisis includes controversies and dilemmas that arise in the relationship with the community, professional ethics, and responsibility for self-care. Commitment and resilience to ensure patient care are evident in the actions of health professio-nals; however, at times, this has been to the detriment of their own physical and moral integrity. The health system in Mexico is indebted to physicians, residents, and nursing professionals, and a way to settle it is through the strengthening of institutions, the definition of institutional policies and regulations that promote self-care, and, among other measures, the establishment of systems that do not force them to become heroes facing the risks of a crisis.

The Effect of Specifications Grading on Students' Learning and Attitudes in an Undergraduate-Level Cell Biology Course.

Specifications (specs) grading is a grading system in which mastery of specific educational outcomes is the basis for the final grade a student earns in the course. Implementation of the types of assessments used for specs grading has shown to be beneficial for student learning and motivation compared to traditional grading systems. We designed a specs grading strategy in an undergraduate Cell Biology course, creating 20 individual learning outcomes (LOs). The grade earned in lecture depended on the number of LOs the student mastered. If students were unable to master the content on their initial attempt, they could earn retakes for each LO assessment by completing an assignment associated with the information covered in that LO. A student's final class grade was dependent on the number of LOs mastered combined with the grade earned on their final exam. Here, we present how specifications grading was implemented in Cell Biology, differences in overall grade distribution between grading systems, improved performance on content-related assessment questions in sections using specifications grading, and more-positive attitudes for sections using specifications grading than for traditionally graded sections.

Impacto socioeconómico de la variabilidad climática en pesca y turismo: antecedentes y propuesta metodológica

Introducción: La variabilidad climática tiene efectos importantes sobre las diferentes actividades económicas que se desarrollan en zonas costeras y que emplean servicios ecosistémicos para su funcionamiento. Actualmente, no existen metodologías integrales que permitan realizar un proceso de valoración teniendo en cuenta todas las variables y las interacciones entre ellas. Objetivo: Proponer una aproximación metodológica que incluya de manera integral las diferentes etapas en el proceso de valoración económica de servicios ecosistémicos en zonas costeras, ante la variabilidad climática. Métodos: Se realizó una revisión bibliográfica, consulta a expertos y se empleó un ejemplo de aplicación usando la actividad turística de buceo con tiburones martillos en la Isla del Coco. Resultados: La aproximación metodológica propuesta inicia con la caracterización socioeconómica y ambiental de la actividad que emplea el recurso natural como insumo, posteriormente se realiza una identificación y caracterización de las variables ambientales que afectan el recurso natural y los efectos que la variación de este recurso tiene sobre la actividad económica. Conclusiones: Las variables que conforman el sistema climático, que tienen relación con los recursos naturales y las actividades económicas, al ser influenciadas por fenómenos externos, producen efectos que deben ser analizados por medio de aproximaciones metodológicas integrales, dentro de las cuales uno de los pasos es la metodología de valoración, que permitan generar recomendaciones de política que contribuyan a minimizar esos efectos.

Introduction: Climate variability has important effects on the different economic activities that take place in marine areas. Currently, there are no comprehensive methodologies to carry out an assessment process that consider all the variables and interactions between them. Objective: To propose a methodological approach that comprehensively includes the different stages in the process of economic valuation of ecosystem services in coastal areas, in the face of climate variability. Methods: A bibliographic review, expert consultations and an application of a methodological example using the impact over shark diving activities at Isla del Coco were conducted. Results: The proposed methodological approach begins with the socio-economic and environmental characterization of the activity that uses a natural resource as input, followed by the identification and characterization of the environmental variables that affect the natural resource and of the effects that the variation of this resource has on the economic activity. Conclusions: The variables that make up the climate system, which relate to natural resources and economic activities, being influenced by external phenomena, produce effects that must be analyzed by comprehensive methodological approximations, within which one of the steps is the valuation methodology, that will allow generating policy recommendations that help to minimize these effects.

Síndrome de Burnout en profesores y su relación con el aprendizaje de los estudiantes de básica primaria de una institución educativa oficial de Sincelejo (Colombia), 2016 / Burnout syndrome in teachers and its relation with the learning of primary students of an official educational institution of Sincelejo (Colombia), 2016

Resumen Objetivo: Determinar la relación existente entre el síndrome de Burnout de los docentes de básica primaria y el aprendizaje de los estudiantes de una institución educativa del sector oficial durante 2016. Materiales y métodos: Estudio cuantitativo, descriptivo, correlacional, con muestra de 758 estudiantes y 25 docentes. Análisis de variables del estudio partiendo de la identificación de los niveles de aprendizaje en los estudiantes mediante un simulacro de Prueba Saber, y las manifestaciones de Burnout en los docentes a través del Cuestionario de Burnout del Profesorado Revisado (CBP -R). Resultados: Los docentes presentan entre uno a tres síntomas asociados al síndrome de Burnout en sus niveles moderado o alto (12 % un síntoma, 32 % dos síntomas y 56 % tres síntomas; sin embargo, de este 56 % solo el 8 % presenta los 3 síntomas asociados al Burnout); los grados primero y segundo obtuvieron más altos niveles de aprendizaje; en cuanto a la relación entre síndrome de Burnout y aprendizaje, todas las puntuaciones son estadísticamente significativas en la variable Agotamiento Emocional (AE) y la variable Despersonalización (DE). Conclusiones: Las manifestaciones del síndrome de Burnout en los docentes señalan puntuaciones en su mayoría moderadas en los 3 síntomas: Agotamiento Emocional, Despersonalización y Realización Personal. En la variable Agotamiento Emocional, los estudiantes que tienen docentes con puntuaciones bajas o moderadas obtienen mejores puntuaciones que aquellos con un docente con alto agotamiento. Para la variable Despersonalización, las calificaciones de los estudiantes puntúan mejor cuando los docentes presentan bajo o moderado en esta variable.

Abstract Objective: To determine the relationship between burnout syndrome or elementary school teachers and the learning of students of the educational institution of the official sector during the year 2016. Materials and methods: A quantitative, descriptive, correlational study with a sample of 758 students and 25 teachers. The study variables were analyzed, starting from the identification of the levels of learning in the students through a simulation of Saber Test and the manifestations of Burnout in the teachers through the Questionnaire of Burnout of the Revised teaching staff (CBP-R). Results: Teachers present between one, two or three symptoms associated with Burnout syndrome in their moderate or high levels (12 % one symptom, 32 % two symptoms and 56% three symptoms, however of this 56 % only 8 % presents The 3 symptoms associated with Burnout). The first and second grades obtained higher levels of learning; In relation to the relationship between Burnout syndrome and learning; All scores are statistically significant in the Emotional Exhaustion (AE) variable, and the variable Depersonalization (DE). Conclusions: The manifestations of Burnout syndrome in teachers indicate mostly moderate scores in the 3 symptoms Emotional Exhaustion, Depersonalization and Personal Realization. In the Emotional Exhaustion variable, students who have teachers with low or moderate scores, obtain better scores than those with a teacher with high exhaustion. For the variable Depersonalization the students' scores score better, when the teachers present low or moderate in this variable.

Glucocorticoid receptor alters isovolumetric contraction and restrains cardiac fibrosis.

Corticosteroids directly affect the heart and vasculature and are implicated in the pathogenesis of heart failure. Attention is focussed upon the role of the mineralocorticoid receptor (MR) in mediating pro-fibrotic and other adverse effects of corticosteroids upon the heart. In contrast, the role of the glucocorticoid receptor (GR) in the heart and vasculature is less well understood. We addressed this in mice with cardiomyocyte and vascular smooth muscle deletion of GR (SMGRKO mice). Survival of SMGRKO mice to weaning was reduced compared with that of littermate controls. Doppler measurements of blood flow across the mitral valve showed an elongated isovolumetric contraction time in surviving adult SMGRKO mice, indicating impairment of the initial left ventricular contractile phase. Although heart weight was elevated in both genders, only male SMGRKO mice showed evidence of pathological cardiomyocyte hypertrophy, associated with increased myosin heavy chain-ß expression. Left ventricular fibrosis, evident in both genders, was associated with elevated levels of mRNA encoding MR as well as proteins involved in cardiac remodelling and fibrosis. However, MR antagonism with spironolactone from birth only modestly attenuated the increase in pro-fibrotic gene expression in SMGRKO mice, suggesting that elevated MR signalling is not the primary driver of cardiac fibrosis in SMGRKO mice, and cardiac fibrosis can be dissociated from MR activation. Thus, GR contributes to systolic function and restrains normal cardiac growth, the latter through gender-specific mechanisms. Our findings suggest the GR:MR balance is critical in corticosteroid signalling in specific cardiac cell types.

Mineralocorticoid Excess or Glucocorticoid Insufficiency: Renal and Metabolic Phenotypes in a Rat Hsd11b2 Knockout Model.

Obesity and hypertension are 2 major health issues of the 21st century. The syndrome of apparent mineralocorticoid excess is caused by deficiency of 11ß-hydroxysteroid dehydrogenase type 2 (Hsd11b2), which normally inactivates glucocorticoids, rendering the mineralocorticoid receptor aldosterone-specific. The metabolic consequences of Hsd11b2 knockout in the rat are investigated in parallel with electrolyte homeostasis. Hsd11b2 was knocked out, by pronuclear microinjection of targeted zinc-finger nuclease mRNAs, and 1 line was characterized for its response to renal and metabolic challenges. Plasma 11-dehydrocorticosterone was below detection thresholds, and Hsd11b2 protein was undetected by Western blot, indicating complete ablation. Homozygotes were 13% smaller than wild-type littermates, and were polydipsic and polyuric. Their kidneys, adrenals, and hearts were significantly enlarged, but mesenteric fat pads and liver were significantly smaller. On a 0.3% Na diet, mean arterial blood pressure was ≈65 mm Hg higher than controls but only 25 mm Hg higher on a 0.03% Na(+) diet. Urinary Na/K ratio of homozygotes was similar to controls on 0.3% Na(+) diet but urinary albumin and calcium were elevated. Corticosterone and aldosterone levels showed normal circadian variation on both a 0.3% and 0.03% Na(+) diet, but plasma renin was suppressed in homozygotes on both diets. Plasma glucose responses to an oral glucose challenge were reduced despite low circulating insulin, indicating much greater sensitivity to insulin in homozygotes. The rat model reveals mechanisms linking electrolyte homeostasis and metabolic control through the restriction of Hsd11b1 substrate availability.

Expression of Basal-like Biomarkers in Triple Negative Invasive Breast Carcinoma in Puerto Rico.

OBJECTIVE: Routine Progesterone and Estrogen hormone receptor proteins and human epidermal growth factor receptor 2 (HER-2) analysis on invasive breast carcinomas provide therapeutic and prognostic values, revealing significant subgroups: luminal A, luminal B, HER-2 and the "triple negative" tumors. The aim of this study was to determine the expression of basal cytokeratins and Epidermal Growth Factor Receptor in "triple negative" invasive breast carcinomas in Puerto Rico women. METHODS: All invasive breast carcinoma cases received from 2008 to 2010 were included. Assessment of tumoral expression of Estrogen Receptor, Progesterone Receptor and HER-2 was performed. The cases were divided into groups based on their molecular categories and analyzed according to the age. "Triple negative" tumors were further analyzed according to their expression of Epidermal Growth Factor Receptor and cytokeratins 5/6 and 14. RESULTS: From 717 cases reviewed, 487 cases of invasive breast carcinoma were included. The molecular categories were 66%, 10%, 9% and 15% for the luminal A, luminal B, Her-2 and "triple negative" groups, respectively. No significant difference (p= 0.64) was observed between the molecular categories and the age of the patients. Assessment of basal cytokeratins and Epidermal Growth Factor Receptor expression was performed on 41 "triple negative" tumors; 71% expressed at least one basal cytokeratin or Epidermal Growth Factor Receptor and 29% were negative to all markers. CONCLUSION: Prevalence and relation between the molecular categories and the expression of basal cytokeratins in "triple negative" tumors in our population is comparable to other published data.

Human myocardial pericytes: multipotent mesodermal precursors exhibiting cardiac specificity.

Perivascular mesenchymal precursor cells (i.e., pericytes) reside in skeletal muscle where they contribute to myofiber regeneration; however, the existence of similar microvessel-associated regenerative precursor cells in cardiac muscle has not yet been documented. We tested whether microvascular pericytes within human myocardium exhibit phenotypes and multipotency similar to their anatomically and developmentally distinct counterparts. Fetal and adult human heart pericytes (hHPs) express canonical pericyte markers in situ, including CD146, NG2, platelet-derived growth factor receptor (PDGFR) ß, PDGFRα, alpha-smooth muscle actin, and smooth muscle myosin heavy chain, but not CD117, CD133, and desmin, nor endothelial cell (EC) markers. hHPs were prospectively purified to homogeneity from ventricular myocardium by flow cytometry, based on a combination of positive- (CD146) and negative-selection (CD34, CD45, CD56, and CD117) cell lineage markers. Purified hHPs expanded in vitro were phenotypically similar to human skeletal muscle-derived pericytes (hSkMPs). hHPs express mesenchymal stem/stromal cell markers in situ and exhibited osteo-, chondro-, and adipogenic potentials but, importantly, no ability for skeletal myogenesis, diverging from pericytes of all other origins. hHPs supported network formation with/without ECs in Matrigel cultures; hHPs further stimulated angiogenic responses under hypoxia, markedly different from hSkMPs. The cardiomyogenic potential of hHPs was examined following 5-azacytidine treatment and neonatal cardiomyocyte coculture in vitro, and intramyocardial transplantation in vivo. Results indicated cardiomyocytic differentiation in a small fraction of hHPs. In conclusion, human myocardial pericytes share certain phenotypic and developmental similarities with their skeletal muscle homologs, yet exhibit different antigenic, myogenic, and angiogenic properties. This is the first example of an anatomical restriction in the developmental potential of pericytes as native mesenchymal stem cells.

Actividades socioeconómicas en el Parque Nacional Isla del Coco, Costa Rica y posibles efectos de la variabilidad climática / Socio-economic activities at Isla del Coco National Park, Costa Rica and possible effects of climate variability

Socioeconomic activities and their gross income in Isla del Coco National Park have been poorly evaluated and systematized, as well as the effects on them climate variability may have. A methodology that combines cluster analysis with a dynamic value chain was developed to identify the most important socioeconomic activities and quantify the gross income derived by the existence of Isla del Coco National Park. The possible effects of climate variability on these activities were also analyzed. A detailed literature review, consultation and interviews with researchers, entrepreneurs and tourists were conducted in order to apply the methodology. The main clusters of activities around this park are leisure and spiritual experiences, research and education, economic activities and park management. An approximation of the gross income from the activities carried out around the National Park in 2010 was calculated. The gross income generated at the national level was $5.7 million dollars and at the international level was $2.5 million dollars. The overall gross income was approximately $8.3 million dollars. But, if the natural resources being visited by tourists degrade due to the effects of climate variability these benefits could decrease by 30%.

Las actividades socioeconómicas y sus ingresos en el Parque Nacional Isla del Coco han sido poco evaluados y sistematizados, al igual que los efectos que sobre ellos pueda tener la variabilidad climática. empleó una metodología que combina análisis de conglomerados con una dinámica de valor agregado en una cadena productiva, para identificar las actividades socioeconómicas más importantes y cuantificar los ingresos que obtienen por la existencia del PNIC, además se analizó los posibles efectos de la variabilidad climática sobre estas actividades. Para lo anterior, se realizó una revisión bibliográfica detallada, consulta con empresarios, investigadores y turistas. Se obtuvo que los principales conglomerados de actividades alrededor del PNIC son la recreación y la vivencia espiritual, la investigación, las actividades económicas y la gestión y manejo del Parque. Se realizó una aproximación de las contribuciones de la existencia del PNIC en estos cuatro conglomerados en el 2010, y se obtuvo que la contribución el ámbito nacional fue de US$5.7 millones de dólares, el internacional de US$2.5 millones de dólares, el global del PNIC ascendió aproximadamente a US$8.3 millones de dólares. También se obtuvo que si los recursos naturales objeto de la visita de los turistas disminuyen debido a efectos de la variabilidad climática esto ingresos podrían disminuir en 30%.

Functional hypervariability and gene diversity of cardioactive neuropeptides.

Crustacean cardioactive peptide (CCAP) and related peptides are multifunctional regulatory neurohormones found in invertebrates. We isolated a CCAP-related peptide (conoCAP-a, for cone snail CardioActive Peptide) and cloned the cDNA of its precursor from venom of Conus villepinii. The precursor of conoCAP-a encodes for two additional CCAP-like peptides: conoCAP-b and conoCAP-c. This multi-peptide precursor organization is analogous to recently predicted molluscan CCAP-like preprohormones, and suggests a mechanism for the generation of biological diversification without gene amplification. While arthropod CCAP is a cardio-accelerator, we found that conoCAP-a decreases the heart frequency in Drosophila larvae, demonstrating that conoCAP-a and CCAP have opposite effects. Intravenous injection of conoCAP-a in rats caused decreased heart frequency and blood pressure in contrast to the injection of CCAP, which did not elicit any cardiac effect. Perfusion of rat ventricular cardiac myocytes with conoCAP-a decreased systolic calcium, indicating that conoCAP-a cardiac negative inotropic effects might be mediated via impairment of intracellular calcium trafficking. The contrasting cardiac effects of conoCAP-a and CCAP indicate that molluscan CCAP-like peptides have functions that differ from those of their arthropod counterparts. Molluscan CCAP-like peptides sequences, while homologous, differ between taxa and have unique sequences within a species. This relates to the functional hypervariability of these peptides as structure activity relationship studies demonstrate that single amino acids variations strongly affect cardiac activity. The discovery of conoCAPs in cone snail venom emphasizes the significance of their gene plasticity to have mutations as an adaptive evolution in terms of structure, cellular site of expression, and physiological functions.

The effects of membrane potential, SR Ca2+ content and RyR responsiveness on systolic Ca2+ alternans in rat ventricular myocytes.

Previous work has shown that small depolarizing pulses produce a beat to beat alternation in the amplitude of the systolic Ca(2+) transient in ventricular myocytes. The aim of the present work was to investigate the role of changes of SR Ca(2+) content and L-type Ca(2+) current in this alternans. As the amplitude of the depolarizing pulse was increased from 10 to 30 mV the magnitude of alternans decreased. Confocal linescan studies showed that this was accompanied by an increase in the number of sites from which Ca(2+) waves propagated. A sudden decrease in the depolarisation amplitude resulted in three classes of behaviour: (1) a gradual decrease in Ca(2+) transient amplitude before alternans developed accompanied by a loss of SR Ca(2+), (2) a gradual increase in Ca(2+) transient amplitude before alternans accompanied by a gain of SR Ca(2+), and (3) immediate development of alternans with no change of SR content. We conclude that alternans develops if the combination of decreased opening of L-type channels and change of SR Ca(2+) content results in spatially fragmented release from the SR as long as there is sufficient Ca(2+) in the SR to sustain wave propagation. Potentiation of the opening of the ryanodine receptor (RyR) by low concentrations of caffeine (100 microm) abolished alternans for a few pulses but the alternans then redeveloped once SR Ca(2+) content fell to the new threshold for wave propagation. Finally we show evidence that inhibiting L-type Ca(2+) current with 200 mum Cd(2+) produces alternans by means of a similar fragmentation of the Ca(2+) release profile and propagation of mini-waves of Ca(2+) release.

The impact of integrating the elimination programme for lymphatic filariasis into primary health care in the Dominican Republic.

Integration of disease-specific programmes into existing health care delivery systems is a challenge for many countries, made more salient as the scope and scale of disease-specific programmes increases. This paper reports on the programmatic outcomes of 2 years of integrating the lymphatic filariasis (LF) elimination programme into primary health care (PHC) in the Dominican Republic during a period of national health care reform and decentralization. Data were collected retrospectively from community volunteers, PHC staff and LF programme staff using a mix of quantitative and qualitative methods. Benefits of integration for LF elimination included increasing the extent of the geographic coverage of mass drug administration (MDA) and a 21% increase in municipalities achieving the MDA target coverage rate of 80%. Benefits which accrued to PHC included improved information systems and strengthened relationships between the health services and the community. This study also identified challenges to implementing integration and the solutions found. These include the importance of focusing on the professional development of disease-specific program staff as their roles change, strengthening specific weakness in the general health system and finding alternative solutions where these are not easily solved, actively engaging senior management at an early stage, continually evaluating the impact of integration and not pushing integration for the sake of integration.

Caracterización parasitológica, patogénica e inmunogénica de cepas salvajes de T. cruzi aisladas en los estados Lara y Yaracuy Venezuela / Parasitologic, pathogenic and inmunogenic's characteristics were determined from wild strains isolated from vectors and reservoirs in the states of Lara and Yaracuy Venezuela

Se determinaron las características parasitológicas, patogénicas e inmunogénicas de cepas salvajes de T. cruzi, aislados en los estados Lara y Yaracuy en Venezuela, comparadas con la cepa patrón YBM. la muestra consistió de cuarenta ratas (40) Sprague Dawley de 03 semanas de edad, divididas en 04 grupos de 10 ratas c/u. Cada rata fue inoculada con 100 tripomastigotes metacíclicos/gr. peso del animal, vía intradérmica. Cada grupo fue tratado con una cepa diferente, cuya identificación y procedencia era desconocida para los investigadores (método doble ciego). La parasitemia fue evaluada cada semana por 8 semanas mediante un Hemocitómetro. La integridad del Sistema Nervioso Autónomo (SNA) y de la funcionalidad cardíaca fue evaluada mediante estudios electrocardiográficos realizados antes y después de administrar Felinefrina 1mg/kg. Se realizaron tres estudios electrocardiográficos: animal sano (pre-inoculación), etapa aguda) 4 semanas post-inoculación) y etapa subaguda (9 semanas post-inoculación). La inmunogenicidad fue medida a los dos meses post inoculación, mediante la titulación de anticuerpos tipo IgG anti-T. cruzi y mediante Hipersensibilidad retardada. Nuestros estudios revelaron que la cepa Cauderales mostró la mayor (p<0.05) parasitemia comparadas con las cepas Nirgua y YBM, las cuales mostraron niveles menores de parasitemia; Guariquito no indujo parasitemia. La cepa de Nirgua fue la que evidenció una mayor inmunogenicidad del tipo humoral (p<0.05) y una mayor alteración del SNA reflejado por un aumento significativo de la respuestas bradicardizante en el período agudo y una respuesta taquicardizante significativa en el período subagudo ante la administración de FE. Cauderales mostró una inmunogenicidad humoral similar a YBM y no presentaron alteraciones en el SNA. Gúariquito no mostró respuesta inmune humoral, sin embargo; presentaron alteraciones en el SNA.

Sarcoplasmic reticulum calcium content fluctuation is the key to cardiac alternans.

The aim of this work was to investigate whether beat-to-beat alternation in the amplitude of the systolic Ca(2+) transient (Ca(2+) alternans) is due to changes of sarcoplasmic reticulum (SR) Ca(2+) content, and if so, whether the alternans arises due to a change in the gain of the feedback controlling SR Ca(2+) content. We found that, in rat ventricular myocytes, stimulating with small (20 mV) depolarizing pulses produced alternans of the amplitude of the Ca(2+) transient. Confocal measurements showed that the larger transients resulted from propagation of Ca(2+) waves. SR Ca(2+) content (measured from caffeine-evoked membrane currents) alternated in phase with the alternans of Ca(2+) transient amplitude. After a large transient, if SR Ca(2+) content was elevated by brief exposure of the cell to a Na(+)-free solution, then the alternans was interrupted and the next transient was also large. This shows that changes of SR Ca(2+) content are sufficient to produce alternans. The dependence of Ca(2+) transient amplitude on SR content was steeper under alternating than under control conditions. During alternation, the Ca(2+) efflux from the cell was also a steeper function of SR Ca(2+) content than under control. We attribute these steeper relationships to the fact that the larger responses in alternans depend on wave propagation and that wave propagation is a steep function of SR Ca(2+) content. In conclusion, alternans of systolic Ca(2+) appears to depend on alternation of SR Ca(2+) content. This, in turn results from the steep dependence on SR Ca(2+) content of Ca(2+) release and therefore Ca(2+) efflux from the cell as a consequence of wave propagation.