Background: In dairy mixed production systems, maximizing pasture intake and total mixed ration (TMR) supplementation are management tools used to increase dry matter and energy intake in early lactation. The objective was to evaluate metabolic and endocrine profiles and hepatic gene expression of Holstein cows fed either TMR ad libitum (without grazing) or diets combining TMR (50 % ad libitum DM intake) and pasture with different grazing strategies (6 h in one grazing session or 9 h in two grazing sessions) in early lactation. Pluriparous cows were grouped by calving date, blocked within group by body weight and body condition score (BCS) and randomly assigned to one of three feeding strategies from calving (day 0) to 60 days postpartum: control cows fed TMR ad libitum (G0; confined cows fed 100 % TMR without access to pasture), pasture grazing with 6 h of access in one session supplemented with 50 % TMR (G1), and 9 h of access in two sessions supplemented with 50 % TMR (G2). Results: Net energy (NE), but not metabolizable protein (MP), demands for maintenance and/or milk increased in G2 when compared with G1 and G0 cows, respectively. However, NE and MP balances were lower in G1 and G2 than G0 cows. Cow BCS at +55 days was greater in G0 than G2 cows and probability of cows cycling during the first month was greater in G0 and G1 than G2 cows. During the postpartum period, non-esterified fatty acids were greater in G1 than G2 and G0 and β-hydroxybutyrate was greater in G1 and G2 than G0 cows. Plasma insulin was greater and insulin-like growth factor (IGF)-I tended to be greater in G0 than G2 cows, leptin was greater in G2 and G0 and adiponectin were greater in G2 cows. Hepatic expression of growth hormonereceptor- 1A and IGF1 mRNA decreased while IGF binding proteins 1,2,4,5 and 6 ( IGFBP ) mRNA as well as mRNA expression of insulin, leptin ( LEPRb) and adiponectin-2 receptors increased from pre to postpartum in all cows. However, only hepatic IGFBP6 and LEPRb mRNA were greater in G2 than G0 and G1 cows, respectively. Conclusion: Metabolic-endocrine profiles of cows with different feeding strategies in early lactation reflected not only changes in milk energy output and energy balance but also in walking and grazing activity. Concentrations of insulin and IGF-I were increased in G0 cows whereas plasma adiponectin and both, insulin and leptin sensitivity were improved G2 cows. Increased NE demands in G2 cows when compared to G1 and G0 cows, implied a metabolic stress that impacted negatively on reproductive function.

Infections caused by Fasciola species are widely distributed in cattle and sheep causing significant economic losses, and are emerging as human zoonosis with increasing reports of human cases, especially in children in endemic areas. The current treatment is chemotherapeutic, triclabendazole being the drug of preference since it is active against all parasite stages. Due to the emergence of resistance in several countries, the discovery of new chemical entities with fasciolicidal activity is urgently needed. In our continuous search for new fasciolicide compounds, we identified and characterized six quinoxaline 1,4-di-N-oxide derivatives from our in-house library. We selected them from a screening of novel inhibitors against FhCL1 and FhCL3 proteases, two essential enzymes secreted by juvenile and adult flukes. We report compounds C7, C17, C18, C19, C23, and C24 with an IC₅₀ of less than 10 µM in at least one cathepsin. We studied their binding kinetics in vitro and their enzyme-ligand interactions in silico by molecular docking and molecular dynamic (MD) simulations. These compounds readily kill newly excysted juveniles in vitro and have low cytotoxicity in a Hep-G2 cell line and bovine spermatozoa. Our findings are valuable for the development of new chemotherapeutic approaches against fascioliasis, and other pathologies involving cysteine proteases.

Rhipicephalus microplus, the “common cattle tick”, is the most important ectoparasite in livestock worldwide due to the economic and health losses it produces. This tick is a vector for pathogens of several tick-borne diseases. In Latin American countries, damages reach approximately USD 500 million annually due to tick infections, as well as tick-borne diseases. Currently, resistant populations for every chemical group of acaricides have been reported, posing a serious problem for tick control. This study aims to find new alternatives for controlling resistant ticks with compounds derived from small synthetic organic molecules and natural origins. Using BME26 embryonic cells, we performed phenotypic screening of 44 natural extracts from 10 Mexican plants used in traditional medicine, and 33 compounds selected from our chemical collection. We found 10 extracts and 13 compounds that inhibited cell growth by 50% at 50 µg/mL and 100 µM, respectively; the dose-response profile of two of them was characterized, and these compounds were assayed in vitro against different life stages of Rhipicephalus microplus. We also performed a target-directed screening of the activity of triosephosphate isomerase, using 86 compounds selected from our chemical collection. In this collection, we found the most potent and selective inhibitor of tick triosephosphate isomerase reported until now. Two other compounds had a potent acaricidal effect in vitro using adults and larvae when compared with other acaricides such as ivermectin and Amitraz. Those compounds were also selective to the ticks compared with the cytotoxicity in mammalian cells like macrophages or bovine spermatozoids. They also had a good toxicological profile, resulting in promising acaricidal compounds for tick control in cattle raising.