Chagas disease caused by Trypanosoma cruzi is a neglected disease that affects about 7 million people in Latin America, recently emerging on other continents due to migration. As infection in mice is characterized by depletion of plasma L-arginine, the effect on infection outcome was tested in mice with or without L-arginine supplementation and treatment with 1400W, a specific inhibitor of inducible nitric oxide synthase (iNOS). We found that levels of L-arginine and citrulline were reduced in the heart and plasma of infected mice, whereas levels of asymmetric dimethylarginine, an endogenous iNOS inhibitor, were higher. Moreover, L-arginine supplementation decreased parasitemia and heart parasite burden, improving clinical score and survival. Nitric oxide production in heart tissue and plasma was increased by L-arginine supplementation, while pharmacological inhibition of iNOS yielded an increase in parasitemia and worse clinical score. Interestingly, electrocardiograms improved in mice supplemented with L-arginine, suggesting that it modulates infection and heart function and is thus a potential biomarker of pathology. More importantly, L-arginine may be useful for treating T. cruzi infection, either alone or in combination with other antiparasitic drugs. Author summaryTrypanosoma cruzi is the causative agent of the neglected Chagas disease in humans. During infection in mice, depletion of plasma L-arginine is correlated with mortality. L-arginine is a semi-essential amino acid needed for cell proliferation, and is the substrate of arginase 1 (Arg-1) and inducible nitric oxide synthase (iNOS), which is involved in the immune response against infections. Observed L-arginine depletion is likely caused by increased Arg-1 activity, but the effect on immune response are still unknown. Our PLOS Neglected Tropical Diseases | https://doi

Background Snakebite is a collective health problem that afflicts areas with poor healthcare coverage. Venezuela has an important population of snakes, including the endemic species Crotalus vegrandis and Crotalus pifanorum, whose venom has not been fully characterized, especially of those aspects related to cardiac electrophysiology. Aims In this sense, this work aims to characterize the electrocardiographic and histopathological effect of crude venom of C. vegrandis and C. pifanorum on albino Naval Medical Research Institute (NMRI) mice. Results For this, mice were gathered in C. pifanorum and C. vegrandis experimental groups, including normal controls and envenomed mice injected with commercial antivenom. C. vegrandis venom showed a significant T and S wave flattening and pulmonic (pulmonary) regurgitation (PR) enlargement, in addition to atrial ectopic activity, notched R wave, triggered activity, and T wave inversion. C. pifanorum was the only group that registered triggered activity. Antivenom was able to revert conduction disorders showing a statistical increase in arrhythmogenic compared by χ2 . The multidimensional comparison confirmed the statistical differences between C. vegrandis and C. pifanorum venoms and between antivenom vs non-antivenom groups, detecting variables associated with cardiac conduction, as the most important variables. Conclusion In conclusion, this work demonstrated, as far as we know, for the first time the cardiotoxic effects associated with C. vegrandis and C. pifanorum venom injection, subsequently suggesting the duty of including an electrocardiogram in the consultation of any accident caused by these species.

No abstract