Generating Cloned Goats by Somatic Cell Nuclear Transfer-Molecular Determinants and Application to Transgenics and Biomedicine.

The domestic goat (Capra aegagrus hircus), a mammalian species with high genetic merit for production of milk and meat, can be a tremendously valuable tool for transgenic research. This research is focused on the production and multiplication of genetically engineered or genome-edited cloned specimens by applying somatic cell nuclear transfer (SCNT), which is a dynamically developing assisted reproductive technology (ART). The efficiency of generating the SCNT-derived embryos, conceptuses, and progeny in goats was found to be determined by a variety of factors controlling the biological, molecular, and epigenetic events. On the one hand, the pivotal objective of our paper was to demonstrate the progress and the state-of-the-art achievements related to the innovative and highly efficient solutions used for the creation of transgenic cloned does and bucks. On the other hand, this review seeks to highlight not only current goals and obstacles but also future challenges to be faced by the approaches applied to propagate genetically modified SCNT-derived goats for the purposes of pharmacology, biomedicine, nutritional biotechnology, the agri-food industry, and modern livestock breeding.

Comparative Study of Wound-Healing Activity of Dihydroquercetin Pseudopolymorphic Modifications.

Wound-healing activity of the crystalline form of dihydroquercetin and its microtubular pseudopolymorphic modification obtained by crystal engineering was compared using the rat model of IIIA degree burn. The rate of wound healing in the group treated with microtubular pseudopolymorphic modification of dihydroquercetin was 4.8±0.1%, which was higher by 11.6% than in the group treated with crystalline form (4.3±0.1%). Bioavailability analysis on MDCK cell culture showed that the apparent permeability coefficient of microtubular pseudopolymorphic modification was higher than that of crystalline form by 31.1% (19.4±0.2×10-4 and 14.8±0.3×10-4 cm/sec, respectively). It was proven that the use of crystal engineering improved the biopharmaceutical parameters of dihydroquercetin and increased its pharmacological efficiency.

Las 100 revistas de mayor impacto sobre farmacología, toxicología y farmacia / The 100 highest impact pharmacology, toxicology and pharmacy journals

Introducción: Los indicadores bibliométricos ayudan a evaluar la repercusión de la evidencia disponible. Objetivo: Comparar el Factor de Impacto, el Eigenfactor Score, SCImago Journal & Country Rank y el Source Normalized Impact per Paper, en revistas de farmacología, toxicología y farmacia de mayor impacto a nivel mundial en sus ediciones 2018. Métodos: Estudio descriptivo, retrospectivo, obtenido del análisis bibliométrico. Se realizó una búsqueda electrónica en el Instituto para la Información Científica en revistas incluidas en el Journal Citation Report (https://scijournal.org/), para la obtención del Factor de Impacto y Puntuación del factor propio, en el portal web oficial de Scimago Journal para acceder al SCImago Journal & Country Rank (https://www.scimagojr.com/) y para la obtención del Source Normalized Impact per Paper en el portal Journal Indicators (https://www.journalindicators.com/indicators), edición 2018. Los datos se cuantificaron mediante el paquete estadístico STATA v.14.0. Se analizó las características de las revistas para cada indicador, la correlación entre las variables se estimó mediante la prueba de Spearman. Resultados: Se analizaron 100 revistas, todas indizadas en las bases de datos seleccionadas. Los coeficientes de correlación de Spearman obtenidos entre los indicadores estudiados fueron: Factor de Impacto y Puntuación del factor propio = 0,246; Factor de Impacto y Scimago Journal & Country Rank = 0,758; Factor de impacto y Source Normalized Impact per Paper = 0,680; Puntuación del factor propio y Scimago Journal & Country Rank = 0,367, Puntuación del factor propio y Source Normalized Impact per Paper = 0,264 y SCImago Journal & Country Rank y Source Normalized Impact per Paper = 0,541; además fueron estadísticamente significativas (p < 0,05). Conclusiones: Se encontró una correlación moderada a alta y significativa entre el factor de impacto, Puntuación del factor propio, SCImago Journal & Country Rank y el Source Normalized Impact per Paper(AU)

Introduction: Bibliometric indicators are useful to evaluate the impact of the evidence available. Objective: Compare the Impact Factor, the Eigenfactor Score, the SCImago Journal & Country Rank and the Source Normalized Impact per Paper of the highest worldwide impact pharmacology, toxicology and pharmacy journals in their 2018 editions. Methods: A retrospective descriptive study was performed of data obtained from bibliometric analysis. An electronic search was conducted at the Scientific Information Institute of journals included in the Journal Citation Report (https://scijournal.org/) to obtain the Impact Factor and the Eigenfactor Score, in the SCImago Journal official web portal to access the SCImago Journal & Country Rank (https://www.scimagojr.com/) and in Journal Indicators (https://www.journalindicators.com/indicators) 2018 edition to obtain the Source Normalized Impact per Paper. Data were quantified with the statistical package STATA v.14.0. An analysis was done of the characteristics of the journals for each indicator, whereas correlation between the variables was estimated with Spearman's test. Results: A total 100 journals were examined, all of them indexed in the databases selected. Examination of the indicators studied revealed the following Spearman's correlation coefficients: Impact Factor and Eigenfactor Score = 0,246; Impact Factor and SCImago Journal & Country Rank = 0,758; Impact Factor and Source Normalized Impact per Paper = 0,680; Eigenfactor Score and SCImago Journal & Country Rank = 0,367, Eigenfactor Score and Source Normalized Impact per Paper = 0,264, and SCImago Journal & Country Rank and Source Normalized Impact per Paper = 0,541. They were all statistically significant (p < 0,05). Conclusions: A moderate to high and significant correlation was found between Impact Factor, Eigenfactor Score, SCImago Journal & Country Rank and Source Normalized Impact per Paper(AU)

Pharmacokinetics in Elderly Women of Benzyl Alcohol From an Oil Depot.

Pharmaceutical oil depots are meant to release active substances at a sustained rate. Most of these depots contain benzyl alcohol (BOH) to facilitate the production and administration. Because BOH changes the solubility of components in both the body fluid and the oil formulation, it is relevant to know the change in the BOH concentration in the oil over time. In this study, volunteers were subcutaneously injected with an oil depot that contained 10% BOH, nandrolone decanoate, and cholecalciferol. The aim of this study was to determine the pharmacokinetic profiles of BOH and its metabolites benzoic acid and hippuric acid simultaneously in serum to estimate the BOH release out of the depot. For this, an HPLC bioassay was developed and adequately validated. Hereafter, the bioassay was applied to serum samples obtained at several time points between 0 and 35 days. BOH appeared immediately in serum after injection. The pharmacokinetic profile revealed that all BOH was depleted from the depot within 52 h after injection. Thus, the partition coefficient of active substances between the oil formulation and the body tissue changes rapidly in the first days after injection but will remain constant hereafter.

Caco-2 cells permeability evaluation of nifuroxazide derivatives with potential activity against methicillin-resistant Staphylococcus aureus (MRSA).

Throughout the period of evaluation and selection in drug development, the assessment of the permeability potential of a compound to achieve an efficient refinement of the molecular structure has been widely appraised by the transport of substances across cell monolayers. This study aims to develop in vitro assays through Caco-2 cells in order to analyze the permeability of 5-nitro-heterocyclic compounds analogues to nifuroxazide with antimicrobial activity, especially showing promising activity against multidrug-resistant Staphylococcus aureus (MRSA). Caco-2 cell monolayers cultivated for 21 days in Transwell® plates were used for the in vitro permeability assays. The quantification of the nifuroxazide derivatives in the basolateral chambers was performed by a validated high performance liquid chromatography with UV (HPLC-UV) method. Apparent permeability values (Papp) show that these compounds can be considered as new drug candidates with the potential to present high absorption in vivo, according to the classifications of Yee and Biganzoli. The thiophenic derivatives showed permeability values higher than the furanic ones, being AminoTIO the compound with the greatest potential for the development of a new drug against MRSA, since it showed the best cytotoxicity, permeability and solubility ratio among all the derivatives.

Drug delivery design for intravenous route with integrated physicochemistry, pharmacokinetics and pharmacodynamics: illustration with the case of taxane therapeutics.

This review is aimed at combining the published data on taxane formulations into a generalized Drug Delivery approach, starting from the physicochemistry and assessing its relationships with the pharmacokinetics, the biodistribution and the pharmacodynamics. Owing to the number and variety of taxane formulation designs, we considered this class of cytotoxic anticancer agents of particular interest to illustrate the concepts attached to this approach. According to the history of taxane development, we propose a classification as (i) "surfactant-based formulations" first generation, (ii) "surfactant-free formulations" second generation and (iii) "modulated pharmacokinetics drug delivery systems" third generation. Since our objective was to make the link between (i) the physicochemistry of the drug and carrier and (ii) the efficacy and safety of the drug in preclinical animal models and (iii) in human, we focused on the drug delivery technologies that were tested in clinic.