Oral transmission of Trypanosoma cruzi has gained relevance because of its association with high morbidity and lethality rates. This transmission route is responsible for maintaining the infection of the parasite in sylvatic cycles, and human cases have been associated mainly with the consumption of food contaminated with triatomine feces or didelphid secretions. Several ecological changes allow the intrusion of sylvatic reservoirs and triatomines to the domestic environments with subsequent food contamination. Here, high-resolution molecular tools were used to detect and genotype T. cruzi across humans, reservoirs, and insect vectors in 2 acute outbreaks of presumptive oral transmission in eastern Colombia.Keywords. Chagas disease; oral transmission; outbreaks; triatomines; Trypanosoma cruzi; opossums; canines; food.Oral transmission of Trypanosoma cruzi is considered ancient, allowing the circulation and maintenance of the parasite in the sylvatic cycle of transmission. T. cruzi has been classified into 6 discrete typing units (DTUs), TcI-TcVI, and, within TcI, into 2 genotypes (domestic TcI [TcI Dom ] and sylvatic TcI). In humans, this mechanism has been described in >1000 cases corresponding to 138 outbreaks, with a fatality rate of 8%-35% across Latin America [1,2]. In Colombia, between 1992 and 2009, 11 outbreaks were reported, with a lethality rate of 16.0% [3]. In 2014, 2 outbreaks occurred in the Colombian Orinoco region.The aim of this study was to determine the possible sources of oral transmission, by using molecular tools, during the outbreaks that occurred in the municipalities of Restrepo, Meta Department, and Paz de Ariporo, Casanare Department. METHODSA total of 70 patients with suspected T. cruzi oral infection, along with 39 samples from reservoir organisms (opossums and canines) and 23 samples from triatomines (Panstrongylus geniculatus, Rhodnius pictipes, and Rhodnius prolixus) during the 2 outbreaks were included. Patients were confirmed as infected, using direct parasitological tests (thick blood smears), serological tests (trypomastigote excreted-secreted antigen [TESA] [5,6]. Finally, in all qPCR-positive samples, amplification and analysis by Microsat (a program for microsatellite analysis) was performed using 7 microsatellite markers [7]. RESULTS Restrepo OutbreakThis outbreak occurred in a family comprising 4 adults and 1 child, who visited Restrepo, including a farm, which contains forests and savannas, as well as some restaurants located along the road in Cumaral municipality, between February 13 and 16, 2014. The family returned to Bogota (the capital of Colombia) afterward, where the 4 adults were hospitalized for fever and edema. Thick blood smears were positive in 2 of 4 symptomatic patients. Results of conventional serological analyses, TESA blots, and molecular tests were positive for the 4 symptomatic patients. The median parasite load was 6.2 equivalent parasites/mL. The child was asymptomatic and had negative results of all diagnostic tests (Supplementary Table 1).The fi...

To characterize the metabolic actions of D-Pinitol, a dietary inositol, in male Wistar rats, we analyzed its oral pharmacokinetics and its effects on (a) the secretion of hormones regulating metabolism (insulin, glucagon, IGF-1, ghrelin, leptin and adiponectin), (b) insulin signaling in the liver and (c) the expression of glycolytic and neoglucogenesis enzymes. Oral D-Pinitol administration (100 or 500 mg/Kg) resulted in its rapid absorption and distribution to plasma and liver compartments. Its administration reduced insulinemia and HOMA-IR, while maintaining glycaemia thanks to increased glucagon activity. In the liver, D-Pinitol reduced the key glycolytic enzyme pyruvate kinase and decreased the phosphorylation of the enzymes AKT and GSK-3. These observations were associated with an increase in ghrelin concentrations, a known inhibitor of insulin secretion. The profile of D-Pinitol suggests its potential use as a pancreatic protector decreasing insulin secretion through ghrelin upregulation, while sustaining glycaemia through the liver-based mechanisms of glycolysis control.

Deficiency of pregnancy-associated plasma protein-A2 (PAPP-A2), an IGF-1 availability regulator, causes postnatal growth failure and dysregulation of bone size and density. The present study aimed to determine the effects of recombinant murine IGF-1 (rmIGF-1) on bone composition and remodeling in constitutive Pappa2 knock-out (ko/ko) mice. To address this challenge, X-ray diffraction (XRD), attenuated total reflection-fourier transform infra-red (ATR-FTIR) spectroscopy and gene expression analysis of members of the IGF-1 system and bone resorption/formation were performed. Pappa2ko/ko mice (both sexes) had reduced body and bone length. Male Pappa2ko/ko mice had specific alterations in bone composition (mineral-to-matrix ratio, carbonate substitution and mineral crystallinity), but not in bone remodeling. In contrast, decreases in collagen maturity and increases in Igfbp3, osteopontin (resorption) and osteocalcin (formation) characterized the bone of Pappa2ko/ko females. A single rmIGF-1 administration (0.3 mg/kg) induced short-term changes in bone composition in Pappa2ko/ko mice (both sexes). rmIGF-1 treatment in Pappa2ko/ko females also increased collagen maturity, and Igfbp3, Igfbp5, Col1a1 and osteopontin expression. In summary, acute IGF-1 treatment modifies bone composition and local IGF-1 response to bone remodeling in mice with Pappa2 deficiency. These effects depend on sex and provide important insights into potential IGF-1 therapy for growth failure and bone loss and repair.