Intraventricular Pressure Gradients in Heart Failure

The aim of the present study was to characterize intraventricular pressure gradients (IVPGs) in an animal model of chronic heart failure. New Zealand rabbits were treated with doxorubicin (heart failure group, n=5) or saline (control group, n=5) and instrumented with pressure catheters placed in the apex and outflow-tract of left ventricle (LV) and with sonomicrometer crystals placed in the apex and base of the LV free wall. In heart failure animals, ventricular filling was delayed and slower when compared with control animals. Moreover, the physiological nonuniformity observed between apical and basal segments in normal hearts was abolished in failing hearts. Simultaneously, physiological IVPGs observed during normal ventricular filling were entirely lost in heart failure animals. During ventricular emptying physiological nonuniformity between apical and basal segments observed in control animals was also abolished in heart failure animals. In failing hearts minimal length occurred later and almost at same time both in apical and in basal myocardial segments. Simultaneously, the characteristic IVPG pattern observed in healthy hearts during systole, which promotes ventricular emptying, was not observed in failing hearts. The present study showed that diastolic IVPGs, a marker of normal ventricular filling, and systolic IVPGs, a marker of normal ventricular emptying, are abolished in heart failure

Prime movers : mechanochemistry of mitotic kinesins

Mitotic spindles are self-organizing protein machines that harness teams of multiple force generators to drive chromosome segregation. Kinesins are key members of these force-generating teams. Different kinesins walk directionally along dynamic microtubules, anchor, crosslink, align and sort microtubules into polarized bundles, and influence microtubule dynamics by interacting with microtubule tips. The mechanochemical mechanisms of these kinesins are specialized to enable each type to make a specific contribution to spindle self-organization and chromosome segregation

Therapeutic DNA Vaccine Encoding Peptide P10 against Experimental Paracoccidioidomycosis

Paracoccidioidomycosis (PCM), caused by Paracoccidioides brasiliensis, is the most prevalent invasive fungal disease in South America. Systemic mycoses are the 10th most common cause of death among infectious diseases in Brazil and PCM is responsible for more than 50% of deaths due to fungal infections. PCM is typically treated with sulfonamides, amphotericin B or azoles, although complete eradication of the fungus may not occur and relapsing disease is frequently reported. A 15-mer peptide from the major diagnostic antigen gp43, named P10, can induce a strong T-CD4+ helper-1 immune response in mice. The TEPITOPE algorithm and experimental data have confirmed that most HLA-DR molecules can present P10, which suggests that P10 is a candidate antigen for a PCM vaccine. In the current work, the therapeutic efficacy of plasmid immunization with P10 and/or IL-12 inserts was tested in murine models of PCM. When given prior to or after infection with P. brasiliensis virulent Pb 18 isolate, plasmid-vaccination with P10 and/or IL-12 inserts successfully reduced the fungal burden in lungs of infected mice. In fact, intramuscular administration of a combination of plasmids expressing P10 and IL-12 given weekly for one month, followed by single injections every month for 3 months restored normal lung architecture and eradicated the fungus in mice that were infected one month prior to treatment. The data indicate that immunization with these plasmids is a powerful procedure for prevention and treatment of experimental PCM, with the perspective of being also effective in human patients

Structure and regional representativeness of the herpetofauna from Parque Estadual da Serra de Caldas Novas, Cerrado, Central Brazil

Amphibians and reptiles are diversified in the Cerrado biome but have been threatened by habitat loss and fragmentation, as well as lack of understanding of their distribution. Therefore, collection and organization of information about species in natural environments are essential for conservation, especially in Protected areas (PAs) and their adjacent zones. We present information about the composition and structure of the herpetofauna from Parque Estadual da Serra de Caldas Novas (PESCAN) and its representativeness in comparison to other PAs in the Cerrado. Fieldwork was conducted in 12 sampling sites from February 2009 to February 2010, using active search and pitfall traps. We recorded 41 species of amphibians, with greatest richness in sites with open vegetation and water bodies. Reptiles were represented by 32 species, with the greatest species richness in cerrado open environments. Both amphibian and reptile communities were more similar to those from geographically closer PAs and located in the central region of the Cerrado (State of Goiás and Distrito Federal). The PESCAN holds 24.85% and 17.98% of amphibians and reptiles species occurring in Cerrado PAs, respectivelly. This large representativeness and the high number of endemisms (18 amphibians and 7 reptiles) emphasize the importance of the PESCAN, together with other PAs, for the maintenance of regional biodiversity. In addition, we also encourage researches evaluating amphibian and reptile communities outside PAs, such as legal reserves, and we suggest new approaches to study the biodiversity of protected areas. © 2019, © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group

Global Metabolomic Profiling of Acute Myocarditis Caused by Trypanosoma cruzi Infection

© 2014 Gironès et al. Chagas disease is caused by Trypanosoma cruzi infection, being cardiomyopathy the more frequent manifestation. New chemotherapeutic drugs are needed but there are no good biomarkers for monitoring treatment efficacy. There is growing evidence linking immune response and metabolism in inflammatory processes and specifically in Chagas disease. Thus, some metabolites are able to enhance and/or inhibit the immune response. Metabolite levels found in the host during an ongoing infection could provide valuable information on the pathogenesis and/or identify deregulated metabolic pathway that can be potential candidates for treatment and being potential specific biomarkers of the disease. To gain more insight into those aspects in Chagas disease, we performed an unprecedented metabolomic analysis in heart and plasma of mice infected with T. cruzi. Many metabolic pathways were profoundly affected by T. cruzi infection, such as glucose uptake, sorbitol pathway, fatty acid and phospholipid synthesis that were increased in heart tissue but decreased in plasma. Tricarboxylic acid cycle was decreased in heart tissue and plasma whereas reactive oxygen species production and uric acid formation were also deeply increased in infected hearts suggesting a stressful condition in the heart. While specific metabolites allantoin, kynurenine and p-cresol sulfate, resulting from nucleotide, tryptophan and phenylalanine/tyrosine metabolism, respectively, were increased in heart tissue and also in plasma. These results provide new valuable information on the pathogenesis of acute Chagas disease, unravel several new metabolic pathways susceptible of clinical management and identify metabolites useful as potential specific biomarkers for monitoring treatment and clinical severity in patients.This work was supported by ‘‘Ministerio de Ciencia e Innovación’’ (SAF2010-17833); ‘‘Fondo de Investigaciones Sanitarias’’ (PS09/00538 and PI12/00289); ‘‘Red de Investigación de Centros de Enfermedades Tropicales’’ (RICET RD12/0018/0004); European Union (HEALTH-FE-2008-22303, ChagasEpiNet);‘‘Universidad Autónoma de Madrid’’ and ‘‘Comunidad de Madrid’’ (CC08-UAM/SAL-4440/08); AECID Cooperation with Argentine (A/025417/09 and A/031735/10), Comunidad de Madrid (S-2010/BMD-2332) and ‘‘Fundación Ramón Areces’Peer Reviewe