Identification of in vitro metabolites of an Allium organosulfur compound and environmental toxicity prediction as part of its risk assessment.

Propyl-propane-thiosulfonate (PTSO) is an organosulfur compound found inAllium spp. Due to its antioxidant and antimicrobial activities, PTSO has been proposed for applications in the agri-food sector, such as feed additive. However, its use with commercial purposes depends on its toxicity evaluation. The present work aimed to perform a pilot-study of toxicokinetic profile of PTSO combining in silico and in vitro techniques, important steps in the risk assessment process. In silico ecotoxicity studies were also performed considering the importance of the environmental impact of the compound before its commercial use. First, an analytical method has been developed and validated to determine the original compound and its metabolites by ultra-performance liquid chromatography-tandem mass spectrometry. The phase I and II metabolism of PTSO was predicted using Meta-Pred Web Server. For the phase I metabolism, rat (male and female) and human liver microsomes were incubated with PTSO and NADPH regeneration system. Furthermore, in the phase II, microsomes were incubated with PTSO and glutathione or uridine 5'- diphosphoglucuronic acid. The analysis revealed the presence of propylpropane thiosulfinate (PTS) originated by redox reaction in phase I, and two conjugates from the phase II: S-propylmercaptoglutathione (GSSP) and S-propylmercaptocysteine (CSSP). Additionally, considering the environmental fate of PTSO and its metabolites, the ADME parameters and the potential ecotoxicity were also predicted using in silico softwares. The results of the ecotoxicity in silico study evidenced that the metabolism induced the formation of detoxified metabolites from the parent compound, except for dimercaprol and 3-mercaptopropane1,2-diol. Further in vivo assays are needed to confirm this prediction.

Analytical Platform for the Study of Metabolic Pathway of Propyl Propane Thiosulfonate (PTSO) from Allium spp.

The present work is focused on the development of an analytical platform to elucidate the metabolic pathway of PTSO from onion, an organosulfur compound well-known for its functional and technological properties and its potential application in animal and human nutrition. This analytical platform consisted of the use of gas chromatography-mass spectrometry (GC-MS) and ultra-high performance liquid chromatography quadrupole with time-of-flight MS (UHPLC-Q-TOF-MS) in order to monitor volatile and non-volatile compounds derived from the PTSO. For the extraction of the compounds of interest, two different sample treatments were developed: liquid-liquid extraction (LLE) and salting-out assisted liquid-liquid extraction (SALLE) for GC-MS and UHPLC-Q-TOF-MS analysis, respectively. Once the analytical platform was optimised and validated, an in vivo study was planned to elucidate PTSO metabolisation, revealing the presence of dipropyl disulfide (DPDS) in liver samples with concentrations between 0.11 and 0.61 µg g-1. The DPDS maximum concentration in the liver was observed at 0.5 h after the intake. DPDS was also present in all plasma samples with concentrations between 2.1 and 2.4 µg mL-1. In regard to PTSO, it was only found in plasma at times above 5 h (0.18 µg mL-1). Both PTSO and DPDS were excreted via urine 24 h after ingestion.

Successful unilateral vasectomy reversal in a lion (Panthera leo).

Background: In 2016, the veterinarian team of Buin Zoo in Chile decided to try to increase the lion population. At that time, the zoo had three lions; two females and one male. The 9-year-old male had been vasectomized 5 years ago at the same institution for birth control. Considering the fact that in humans, vasectomy reversal has excellent reproductive outcomes, a team of human urologists, highly experienced in vasectomy reversal was contacted to perform the procedure. Case description: Surgery was performed on June 16, 2016 under general anesthesia, with the vasectomy site accessed through the previous scar localized in the lower groin. After opening the skin, dartos and tunica vaginalis, we were able to identify the previous vasectomy site. After liberating both vas ends and checking for permeability, a microsurgical anastomosis (magnification 25×) was performed. The surgery took 80 minutes with minimal bleeding, and no surgical complications were observed. After 2 weeks, the lion joined the lionesses and reproductive follow-up was started. Seven months after surgery, one lioness became pregnant, and 4 months later gave birth to two female lion cubs, with no incidents at the zoo. Both cubs were healthy and are still living at the zoo. Conclusion: Vasectomy reversal constitutes a valid perspective to reassume fertility in previous vasectomized lions.

Litiasis urinaria y su relación con el consumo de aguas duras en la comuna de Maipú / Urinary lithiasis and its relation to the consumption of hard water in the Maipu Borough

INTRODUCCIÓN: La litiasis urinaria es una patología frecuente, que afecta principalmente a adultos en edad productiva, y que en el último tiempo ha presentado un aumento en la incidencia global. Cerca del 80 % de los cálculos se componen mayoritariamente de calcio. Existe controversia en la literatura sobre el rol que podría tener el consumo de aguas con altos índices de dureza y el riesgo de padecer litiasis. El objetivo de este estudio es identificar una posible asociación entre dureza de agua para consumos e incidencia de litiasis urinaria en la poblacion de Maipú. MATERIALES Y METODOS: Se incluyen en el estudio todos los pacientes atendidos por urólogos en forma ambulatoria electiva en el Hospital El Carmen de Maipú, por diagnóstico de litiasis urinaria, en los años 2015 y 2016, que residen en la comuna. Se georreferenciaron de acuerdo a sus direcciones en los distintos sectores de distribución de agua potable.Se realizó análisis fisicoquímico de muestras de agua extraídas de cada sector para determinar su dureza. Se estudiaron a través del índice de correlación de Pearson las posibles asociaciones entre dureza del agua e incidencia de litiasis. RESULTADOS: La dureza promedio del agua de Maipú es de 484 mg/L de CaCO3, valor que se encuentra por sobre el promedio regional y nacional. La incidencia anual de litiasis en la poblacion estudiada fue de 4,4 casos/10.000 habitantes, valor similar al promedio nacional. El índice de correlación de Pearson entre dureza de agua e incidencia anual fue de -0,51. CONCLUSIONES: No fue posible establecer una relación causal entre dureza de agua e incidencia de litiasis en la población estudiada. Se sugiere avanzar en esta misma línea con estudios futuros de casos y controles.AU

INTRODUCTION: Urinary lithiasis is a frequent pathology, which mainly affects adults in a productive age, and which-in recent times- has increased in terms of global incidence. About 80 % of the stones are composed mainly of calcium.There is controversy in literature addressing the possible relation amongst water consumption with high hardnessindexes and the risk of lithiasis. The objective of this study is to identify a possible association between water hardnessfor consumption and urinary lithiasis incidence in the Maipu population. MATERIALS AND METHODS: All patients assisted by urologists on an elective ambulatory basis, at the El Carmen Hospital in Maipú, diagnosed with urinary lithiasis, in the years 2015 and 2016, and who reside in the Borough have been included in the study. They were georeferenced according to their address in the different drinking water distribution areas. Physiochemical analysis of water samples extracted from each sector was carried out to determine its hardness. The possible associations between hardness of water and incidence of lithiasis were studied through the Pearson correlation index. RESULTS: The average water hardness in Maipu is 484 mg / L of CaCO3, a value that is above the regional and national average. The annual incidence of lithiasis in the studied population was 4.4 cases / 10,000 inhabitants, a value that is similar to the national average. The Pearson correlation index between water hardness and annual incidence was -0.51. CONCLUSIONS: It was not possible to establish a causal relation between water hardness and incidence of lithiasis in the studied population. It is suggested to advance in this same line with future case and control studies.