Estimation of skin permeation by liquid chromatography

Dermal absorption is a key process in the drug delivery studies of the pharmaceutical and cosmetic industries, as well as in the fields of dermal toxicology, risk assessment, and the exposure of environmental pollutants. This process is typically described by the skin-water permeability coefficient. However, in vivo determination is laborious and expensive. Thus, in the last few years, the development of prediction models from structure descriptors or subrogation through physico-chemical measurements has gained interest. In the present work, a previous subrogation model based on the chromatographic retention on a common C18 column has been tested for a wide set of drugs with very different chemical nature and having a wide range of permeability values. A total of 65 compounds have been used to establish the correlation between skin permeation and the HPLC retention, corrected by the McGowan volume of the drug. Afterwards it was successfully validated in terms of robustness and prediction ability. Finally, the permeability coefficient was estimated for a set of 29 new drugs, and results compared to the ones obtained by other estimation methods, as well as the available in vitro measured values, with very good agreement

Evaluation of the Ability of PAMPA Membranes to Emulate Biological Processes through the Abraham Solvation Parameter Model

Two parallel artificial membrane permeability assay (PAMPA) systems intended for emulating skin permeability have been characterized through the solvation parameter model of Abraham using multilinear regression analysis. The coefficients of the obtained equations have been compared to the ones already established for other PAMPA membranes using statistical tools. The results indicate that both skin membranes are similar to each other in their physicochemical properties. However, they are different from other PAMPA membranes (e.g., intestinal absorption and blood– brain PAMPAs), mainly in terms of hydrophobicity and hydrogen bonding properties. Next, all PAMPA membranes have been compared to relevant biological processes also characterized through the solvation parameter model. The results highlight that skin-PAMPA membranes are a very good choice to emulate skin permeability

Suitability of skin-PAMPA and chromatographic systems to emulate skin permeation. Influence of pH on skin-PAMPA permeability

The skin permeation, Kp, of a chemical compound is a relevant parameter in fields such as toxicology, exposure to pollutants, or dermal studies of pharmaceutical and cosmetic interest. Nonetheless, its experimental determination is not a trivial task, and for this reason alternative methods to estimate Kp have been developed. This work evaluates the suitability of different methodologies to estimate skin permeation of neutral compounds. Three different approaches have been examined: estimation through the skin-PAMPA (Parallel Artificial Membrane Permeability Assay) permeability, Pe, estimation through the chromatographic retention factor combined with molecular volume, and finally estimation through a quantitative structure–property relationship (QSPR) based on the octanol–water partition coefficient, log Po/w, and molecular volume as descriptors. The three approaches have been tested with the same set of compounds and it has been observed that all of them can be used to estimate Kp with similar results, although the chromatographic method presents slightly improved statistics in addition to the facility of measurement. As many drugs are partially ionised at the pH of skin, the influence of pH in skin-PAMPA permeability has been also studied. To this end, the log Pe vs. pH profiles of a set of 25 compounds of different nature have been determined. As expected, the permeation of neutral forms is higher than the one of ionic forms, and permeation of neutral and ionic species are not governed by the same mechanisms

A PSICOMOTRICIDADE PROMOVENDO O DESENVOLVIMENTO DA CRIANÇA DE EDUCAÇÃO BÁSICA

Desde o nascimento a criança utiliza-se de seu corpo para se comunicar com o entorno, é por meio do choro, do gorjeio, do balbucio, da fala, da percepção tátil e de todas as formas de comunicação corporal que ela inicia as suas descobertas sobre o mundo. Assim, a psicomotricidade atrela a mente, a afetividade e a motricidade, visando o pleno desenvolvimento do indivíduo. Com isso, buscou-se aperfeiçoar o conhecimento sobre "A Psicomotricidade como promotora do Desenvolvimento da Criança de Educação Básica". Por meio desta pesquisa de ação, qualitativa e exploratória realizada no componente de Estágio Curricular Supervisionado em Pedagogia da Unoesc de Capinzal, com o objetivo de: analisar como a psicomotricidade auxilia no desenvolvimento da criança. Para tanto, primeiramente realizou-se uma observação no campo de estágio, seguido de busca teórica sobre o tema e construção do projeto de pesquisa. Após isso, foram observadas uma turma multiseriada da Educação Infantil, Grupo 3, 4 e 5 e outra do 3º ano, ambas da rede municipal de ensino do município de Piratuba. A partir do tema e dos conteúdos propostos, foi elaborado e aplicado o projeto de intervenção, visando vivenciar diariamente os aspectos psicomotores na sala de aula. Assim, observou-se ao longo das atividades, a importância de resgatar o trabalho psicomotor dentro do ambiente escolar, auxiliando na formação cognitiva, afetiva e motora, fundamentais para uma aprendizagem efetiva para o processo de expressão corporal, de aquisição da linguagem, da escrita e expressão gráfica.Palavras-chave: Psicomotricidade. Aprendizagem. Desenvolvimento. E-mails: [email protected]

Evaluation of log Po/w values of drugs from some molecular structure calculation software

Predictive software packages to estimate the lipophilicity of molecules have become key tools in the new drug design. Six different well-known computational programs including the classical BioByte-clogP and the GALAS algorithm offered by ACDlabs were evaluated through a set of 103 drugs with different structures and functionalities. To evaluate the predictions accuracy, reliable experimental log Po/w values for the whole testing set were carefully selected. The best estimations are performed by GALAS/logP based on the fragmental method, corrected according to the similarity with compounds included in the software training set

HIGH DOSE ORAL BUSULFAN and INTRAVENOUS MELPHALAN AS CONDITIONING THERAPY for AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANT (HSCT) for the TREATMENT of PEDIATRIC SOLID TUMORS

Universidade Federal de São Paulo, Inst Oncol Pediat, GRAACC, São Paulo, BrazilUniversidade Federal de São Paulo, Inst Oncol Pediat, GRAACC, São Paulo, BrazilWeb of Scienc

A system for accurate and automated injection of hyperpolarized substrate with minimal dead time and scalable volumes over a large range

Over recent years hyperpolarization by dissolution dynamic nuclear polarization has become an established technique for studying metabolism in vivo in animal models. Temporal signal plots obtained from the injected metabolite and daughter products, e.g. pyruvate and lactate, can be fitted to compartmental models to estimate kinetic rate constants. Modeling and physiological parameter estimation can be made more robust by consistent and reproducible injections through automation. An injection system previously developed by us was limited in the injectable volume to between 0.6 and 2.4 ml and injection was delayed due to a required syringe filling step. An improved MR-compatible injector system has been developed that measures the pH of injected substrate, uses flow control to reduce dead volume within the injection cannula and can be operated over a larger volume range. The delay time to injection has been minimized by removing the syringe filling step by use of a peristaltic pump. For 100 ll to 10.000 ml, the volume range typically used for mice to rabbits, the average delivered volume was 97.8% of the demand volume. The standard deviation of delivered volumes was 7 ll for 100 ll and 20 ll for 10.000 ml demand volumes (mean S.D. was 9 ul in this range). In three repeat injections through a fixed 0.96 mm O.D. tube the coefficient of variation for the area under the curve was 2%. For in vivo injections of hyperpolarized pyruvate in tumor-bearing rats, signal was first detected in the input femoral vein cannula at 3–4 s post-injection trigger signal and at 9–12 s in tumor tissue. The pH of the injected pyruvate was 7.1 ± 0.3 (mean ± S.D., n = 10). For small injection volumes, e.g. less than 100 ll, the internal diameter of the tubing contained within the peristaltic pump could be reduced to improve accuracy. Larger injection volumes are limited only by the size of the receiving vessel connected to the pump

ATLANTIC-PRIMATES: a dataset of communities and occurrences of primates in the Atlantic Forests of South America

Primates play an important role in ecosystem functioning and offer critical insights into human evolution, biology, behavior, and emerging infectious diseases. There are 26 primate species in the Atlantic Forests of South America, 19 of them endemic. We compiled a dataset of 5,472 georeferenced locations of 26 native and 1 introduced primate species, as hybrids in the genera Callithrix and Alouatta. The dataset includes 700 primate communities, 8,121 single species occurrences and 714 estimates of primate population sizes, covering most natural forest types of the tropical and subtropical Atlantic Forest of Brazil, Paraguay and Argentina and some other biomes. On average, primate communities of the Atlantic Forest harbor 2 ± 1 species (range = 1–6). However, about 40% of primate communities contain only one species. Alouatta guariba (N = 2,188 records) and Sapajus nigritus (N = 1,127) were the species with the most records. Callicebus barbarabrownae (N = 35), Leontopithecus caissara (N = 38), and Sapajus libidinosus (N = 41) were the species with the least records. Recorded primate densities varied from 0.004 individuals/km 2 (Alouatta guariba at Fragmento do Bugre, Paraná, Brazil) to 400 individuals/km 2 (Alouatta caraya in Santiago, Rio Grande do Sul, Brazil). Our dataset reflects disparity between the numerous primate census conducted in the Atlantic Forest, in contrast to the scarcity of estimates of population sizes and densities. With these data, researchers can develop different macroecological and regional level studies, focusing on communities, populations, species co-occurrence and distribution patterns. Moreover, the data can also be used to assess the consequences of fragmentation, defaunation, and disease outbreaks on different ecological processes, such as trophic cascades, species invasion or extinction, and community dynamics. There are no copyright restrictions. Please cite this Data Paper when the data are used in publications. We also request that researchers and teachers inform us of how they are using the data. © 2018 by the The Authors. Ecology © 2018 The Ecological Society of Americ

Sintesi, resolucio i estudi d'amines i amides aromatiques. Es com agents de solvatacio quiral en RMN. Estudi de les interaccions intermoleculars

Centro de Informacion y Documentacion Cientifica (CINDOC). C/Joaquin Costa, 22. 28002 Madrid. SPAIN / CINDOC - Centro de Informaciòn y Documentaciòn CientìficaSIGLEESSpai