Inducible Nitric Oxide Synthase in Heart Tissue and Nitric Oxide in Serum of Trypanosoma cruzi-Infected Rhesus Monkeys: Association with Heart Injury

Chagas disease, a neglected tropical disease caused by the protozoan Trypanosoma cruzi, afflicts from 8 to 15 million people in the Latin America. Chronic chagasic cardiomyopathy (CCC) is the most frequent manifestation of Chagas disease. Currently, patient management only mitigates CCC symptoms. The pathogenic factors leading to CCC remain unknown; therefore their comprehension may contribute to develop more efficient therapies. In patients, high nitric oxide (NO) levels have been associated with CCC severity. In T. cruzi-infected mice, NO, mainly produced via inducible nitric oxide synthase (iNOS/NOS2), is proposed to work in parasite control. However, the participation of iNOS/NOS2 and NO in T. cruzi control and heart injury has been questioned. Here, infected rhesus monkeys and iNOS/NOS2-deficient mice were used to explore the participation of iNOS/NOS2-derived NO in heart injury in T. cruzi infection. Chronically infected monkeys presented electrical abnormalities, myocarditis and fibrosis, resembling the spectrum of human CCC. Moreover, cardiomyocyte lesion correlated with iNOS/NOS2+ cells infiltrating the cardiac tissue. Our findings support that parasite-driven iNOS/NOS2+ cells accumulation in the cardiac tissue and NO overproduction contribute to cardiomyopathy severity, mainly disturbing the pathway involved in electrical synchrony in T. cruzi infection

Migratory timing, rate, routes and wintering areas of White-crested Elaenia (Elaenia albiceps chilensis), a key seed disperser for Patagonian forest regeneration.

Migratory animals often play key ecological roles within the communities they visit throughout their annual journeys. As a consequence of the links between biomes mediated by migrants, changes in one biome could affect remote areas in unpredictable ways. Migratory routes and timing of most Neotropical austral migrants, which breed at south temperate latitudes of South America and overwinter closer to or within tropical latitudes of South America, have yet to be described in detail. As a result, our understanding about how these birds provide links between South American biomes is almost non-existent. White-crested Elaenia (Elaenia albiceps chilensis) is a long-distance austral migrant that breeds in the Patagonian Forest biome and overwinters in tropical South America. Because this small flycatcher plays a key role in the regeneration of this ecosystem, our objective was to describe the annual cycle of White-crested elaenias to evaluate the degree of migratory connectivity between breeding and wintering areas and therefore to determine if there are specific biomes of northern South America linked by elaenias to Patagonian forests. Fifteen individuals were successfully tracked throughout a complete migration cycle using miniature light-level geolocators. All individuals resided and moved through the same general regions. During fall (March-April-May), elaenias were located in the Caatinga and the Atlantic Forest biomes, from Rio de Janeiro to the region near Salvador da Bahia, Brazil. During winter (June-July-Aug.), birds were located further inland, within the Cerrado biome. Birds used three different routes during fall migration. Our results indicate that some individuals use a direct route, flying between 500-600 km/day, crossing desert and grasslands, while others took a detour, flying 100-200 km/day through forested areas with refueling opportunities. All birds used the Yunga forest during spring migration, with ten out of 15 individuals showing a clear counterclockwise loop trajectories throughout their annual cycle. None of the elaenias passed through Amazonia, traveled to western South America or crossed the Equator. Eleanias exhibited a high migratory connectivity between breeding area in Patagonian Forests and winter areas, Atlantic Forest and Cerrado. Our results suggest that Patagonian Forests could be strongly impacted by changes in those biomes or in the Yungas

Effect of high-dose intravenous vitamin C on inflammation in cancer patients

<p>Abstract</p> <p>Background</p> <p>An inflammatory component is present in the microenvironment of most neoplastic tissues. Inflammation and elevated C-reactive protein (CRP) are associated with poor prognosis and decreased survival in many types of cancer.</p> <p>Vitamin C has been suggested as having both a preventative and therapeutic role in a number of pathologies when administered at much higher-than-recommended dietary allowance levels.</p> <p>Since in vitro studies demonstrated inhibition of pro-inflammatory pathways by millimolar concentrations of vitamin C, we decided to analyze the effects of high dose IVC therapy in suppression of inflammation in cancer patients.</p> <p>Methods</p> <p>45 patients with prostate cancer, breast cancer, bladder cancer, pancreatic cancer, lung cancer, thyroid cancer, skin cancer and B-cell lymphoma were treated at the Riordan Clinic by high doses of vitamin C (7.5 g -50 g) after standard treatments by conventional methods.</p> <p>CRP and tumor markers were measured in serum or heparin-plasma as a routine analysis. In addition, serum samples were collected before and after the IVCs for the cytokine kit tests.</p> <p>Results</p> <p>According to our data positive response to treatment, which was demonstrated by measurements of C- reactive protein, was found in 75% of patients and progression of the inflammation in 25% of patients. IVC treatments on all aggressive stage cancer patients showed the poor response of treatment.</p> <p>There was correlation between tumor markers (PSA, CEA, CA27.29 and CA15-3) and changes in the levels of C-reactive protein.</p> <p>Our test of the effect of IVC on pro-inflammatory cytokines demonstrated that inflammation cytokines IL-1α, IL-2, IL-8, TNF-α, chemokine eotaxin and CRP were reduced significantly after treatments.</p> <p>Conclusions</p> <p>The high dose intravenous ascorbic acid therapy affects C-reactive protein levels and pro-inflammation cytokines in cancer patients. In our study, we found that modulation of inflammation by IVC correlated with decreases in tumor marker levels.</p> <p>In summary, our data support the hypothesis that high dose intravenous ascorbate treatments may reduce inflammation in cancer patients. Our results suggest that further investigations into the use of IVC to reduce inflammation in diseases where inflammation is relevant are warranted.</p