Current status of resistance to ivermectin in Rhipicephalus sanguineus sensu stricto infesting dogs in three provinces in Argentina.

Intensive use of macrocyclic lactones for parasite control exerts strong selective pressure for arthropods such as ticks to become resistant to them. Rhipicephalus sanguineus sensu stricto is a tick and disease vector of significant public health and veterinary importance worldwide. We assessed the toxicological response to the macrocyclic lactone ivermectin (IVM) in R. sanguineus s.s. infesting dogs in Argentina. Samples of nine tick populations were obtained by inspecting dogs at veterinary clinics, hospitals, or rural areas in the provinces of San Luis, Rio Negro, and Buenos Aires. Pet owners were interviewed to gather data on the history of dog treatment with ectoparasiticides. The larval immersion test was used to assess the toxicological response of R. sanguineus s.s. to IVM. Dose-response mortality regressions, lethal concentrations (LC), and slope were calculated by probit analysis. The lowest LC concentrations were used to designate the reference susceptible population because a laboratory reference strain of R. sanguineus s.s. does not exist in Argentina. Compared with the most susceptible tick population in this study, six populations (66.66%) were classified as resistant to IVM. A clear interpopulation variation in the level of IVM resistance was present (resistance ratios at LC50% ranged from 1.0 to 18.33 and at LC99% ranged from 1.0 to 8.96). In San Luis Province, all tick populations were classified as resistant. The highest level of IVM resistance (resistance ratio at LC50%:18.83 and LC99%:8.96) was found in a population of R. sanguineus s.s. from a rural area in the province of Buenos Aires. It is concluded that populations of R. sanguineus s.s. from dogs in three provinces of Argentina were resistant to IVM. Clear interpopulation variation in the level of IVM resistance was present.

Safety and Pharmacokinetic Assessments of a Novel Ivermectin Nasal Spray Formulation in a Pig Model.

Recently published data indicates that high ivermectin (IVM) concentrations suppress in vitro SARS-CoV-2 replication. Nasal IVM spray administration may contribute to attaining high drug concentrations in nasopharyngeal tissue, a primary site of virus entrance/replication. The safety and pharmacokinetic performances of a novel IVM spray formulation were assessed in a pig model. Piglets received IVM either orally (0.2 mg/kg) or by one or two nasal spray doses. The overall safety, and histopathology of the IVM-spray application site tissues, were assessed. The IVM concentration profiles measured in plasma and respiratory tract tissues after the nasal spray were compared with those achieved after the oral administration. Animals tolerated well the nasal spray formulation. No local/systemic adverse events were observed. After nasal administration, the highest IVM concentrations were measured in nasopharyngeal and lung tissues. The nasal/oral IVM concentration ratios in nasopharyngeal and lung tissues markedly increased by repeating (12 h apart) the spray application. The fast attainment of high and persistent IVM concentrations in nasopharyngeal tissue is the main advantage of the nasal over the oral route. These original results support the undertaking of future clinical trials to evaluate the safety/efficacy of the nasal IVM spray application in the prevention and/or treatment of COVID-19.

Anti-tumoral Effect of a Cell Penetrating and Interfering Peptide Targeting PP2A/SET Interaction.

OBJECTIVE: To test cell penetrating and interfering peptide Mut3DPT-PP2A/SET in interaction between serine threonine phosphatase PP2A and its physiological inhibitor, the oncoprotein SET. MATERIALS AND METHODS: Adult male C3H/S-strain mice, 60 days old, were given a graft of breast adenocarcinoma cells (TN60) into subcutaneous tissue. Mut3DPT-PP2A/SET peptide was used to block PP2A and SET oncoprotein interaction. The graft-bearing animals were divided into a control group (injected with saline buffer), and an intervention group injected intraperitoneally with Mut3DPT-PP2A/SET peptide (5 mg/kg) every day from day 5 to day 37. The variables we used to compare the outcome in both groups were tumor size in mm (length×width) and histological changes. In the statistical analysis we used ANOVA and Student-Keuls multiple comparisons test and Tuckey for the post-test analysis. RESULTS: 48 mice were grafted at day 0 with breast UNLP-C3H/S tumor cells, and after randomization, they were assigned to one of the two study groups. At day 5 all mice were injected either with placebo or with the peptide. The treated group showed significant tumor reduction (p<0.07). Histological changes showed presence of apoptosis and necrosis of tumor in treated group. CONCLUSION: The peptide Mut3DPT-PP2A/SET has demonstrated anti-tumor activity by reduction in vivo of tumor growth becoming a promising future in anticancer therapy.

Quantification of residual enrofloxacin and ciprofloxacin in feathers of broiler chickens by high-performance liquid chromatography-fluorescence after oral administration of the drugs.

Enrofloxacin (ENR) and ciprofloxacin (CIP) are drugs used in poultry feeding. In general, feathers that are incorporated in the food chain as a protein source for animal feed, have residues of these drugs. In order to study the pharmacokinetic of ENR/CIP residues in feathers of broiler chickens, to calculate the waiting times for these drugs, before human consumption, we developed the present research. Feathers of broiler chickens were enriched with ENR/CIP. After adding acetone, the mix was agitated and centrifuged and supernatant evaporated under nitrogen. The dry residue was suspended in a tetrahydrofuran solution and the supernatant was injected into the chromatographic system for analysis. Animals showed high levels of ENR/CIP in their feathers after administration of 10 mg/kg enrofloxacin dissolved in drinking water for 5 days. Both compounds were detected in feathers during 9 days. The analytical method developed in this paper to determine ENR and CIP in feathers of broiler chicken showed good linearity, selectivity, accuracy and precision in the analysis conditions. This technique could have important applications in the studies on residues of ENR/CIP in feathers, since the effect of this component in animal diets has not been considered yet.

Nicotina en leche materna y sus consecuencias en los lactantes / Nicotine in mother’s milk and its consequences in breastfeeding infants

El tabaquismo, principal causa de muerte prevenible, es una pandemia cuya prevalencia en mujeres ha aumentado en las últimas décadas. Este trabajo pretende exponer los principales efectos de la nicotina en el lactante y su influencia en la composición de la leche materna. La lactancia materna exclusiva durante los primeros 6 meses de vida es la alimentación ideal para el desarrollo del neonato, por lo que su pureza debe ser conservada. La nicotina pasa a la leche materna, exponiendo a los lactantes a posibles efectos tóxicos: mayor riesgo de infecciones, cólicos, irritabilidad, síndrome de muerte súbita del lactante y síndrome de abstinencia. El tabaquismo disminuye el volumen de leche producido y altera la composición de ésta, disminuyendo su contenido de yodo, vitaminas y de grasas e incrementando los niveles de compuestos policíclicos aromáticos.El análisis fisiopatológico, clínico y socioeconómico de la problemática es complejo, por lo que es necesario generar alianzas interdisciplinarias para afrontarla...