Boas práticas de fabricação de medicamentos : uma análise sobre suas determinantes e o cenário brasileiro de cumprimento de seus requisitos

Tese (doutorado)—Universidade de Brasília, Faculdade de Ciências da Saúde, Programa de Pós-Graduação em Ciências da Saúde, 2018.Medicamentos com problemas de qualidade sempre demandaram trabalho e preocupação das autoridades sanitárias. Sua ocorrência está relacionada ao não cumprimento de um conjunto de regras a serem seguidas durante o processo fabril do medicamento, chamada de Boas Práticas de Fabricação (BPF). O presente estudo tem como objetivo analisar as BPF, procurando identificar as determinantes que interferem na sua evolução. Para isso, delinearam-se duas frentes de trabalho: i) investigar o processo de transformação das BPF e as suas motivações; e ii) identificar as possíveis dificuldades por parte das indústrias farmacêuticas em atender as BPF, analisando os problemas de qualidade encontrados nos medicamentos comercializados e discutindo suas relações com os requisitos das BPF, sempre adotando como lócus de trabalho o Brasil. Durante a coleta de dados, observou-se no mercado brasileiro a presença de uma grande quantidade de medicamentos falsificados, medicamentos em desacordo com o registro sanitário e medicamentos sem registro sanitário, o que resultou na ampliação do escopo desse trabalho. O estudo foi conduzido com base em todas as medidas cautelares aplicadas aos medicamentos e às indústrias farmacêuticas pela Agência Nacional de Vigilância Sanitária (Anvisa), no período de 2009 a 2016. Como resultado, evidenciou-se a importância da inovação tecnológica e das novas práticas da qualidade incorporadas pelo segmento fabril farmacêutico como determinantes para a evolução das BPF. Constatou-se ainda, que as indústrias farmacêuticas enfrentam dificuldades para cumprir determinados requisitos das BPF já bastante consolidados e, muitas vezes, de aparente simples cumprimento.Drugs with quality problems have always demanded work and concern from health authorities. The occurrence of this type of problem is related to the non-compliance of a set of rules to be followed during the manufacturing process of the drug, called Good Manufacturing Practices (GMP). This study aims to analyze the Good Manufacturing Practices (GMP), trying to identify the determinants that interfere with its development. For this, outlined up two lines of work: i) to investigate the GMP transformation process and its motivations; and; ii) to identify the possible difficulties faced by pharmaceutical companies in meeting GMP, analyzing the quality problems found in marketed drugs and discussing their relationship with GMP requirements, always adopting Brazil as a working locus. During the data collection, the brazilian market witnessed the presence of a large quantity of counterfeit drugs and unregistered/unlicensed drugs, which resulted in the expansion of the scope of this work. The study was conducted on the basis of all precautionary measures applied to drugs and pharmaceutical industries by the Brazilian Health Regulatory Agency (Anvisa), from 2009 to 2016. As a result, the importance of technological innovation and new practices of the quality incorporated by the pharmaceutical manufacturing segment as determinants for the evolution of GMP. It was also found that pharmaceutical companies face difficulties in complying with certain GMP requirements that are already well established and often of apparently simple compliance

Effect of breed on frequency of morphological defects in boar spermatozoa

The aim of this study was to assess an effect of breed on frequency of morphological changes in boar spermatozoa. A total of 1080 semen samples were used in this study. The samples were collected from January to December 2017 from 90 boars of the Duroc, Czech Large White and Czech Landrace breeds. Sperm cell abnormalities were evaluated microscopically from dyed smears of native semen on glass slides. Defects of spermatozoa were divided according to their impact on fertility of boars into categories of "major defects" (with a great negative effect on fertility) and "minor defects" (with a mild effect on fertility). The overall frequency of spermatozoa with morphological defects ranged from 11.62 % in Czech Landrace to 20.96 % in Duroc. Statistically significant differences were found in the frequencies of both major and minor defects among the breeds. The results of this study document that there are great inter-breed differences in the occurrence of morphologically defective spermatozoa that significantly affect fertility of boars.O

Phytoplankton of the Yacyretá Reservoir (Argentina-Paraguay) after a decade from its filling

Se estudió la estructura y dinámica del fitoplancton del embalse Yacyretá en relación con las principales variables limnológicas durante el periodo diciembre de 2004 a noviembre de 2005, a 10 años del llenado del embalse. Las muestras cualitativas y cuantitativas fueron recolectadas en 6 estaciones, previamente seleccionadas siguiendo un criterio de zonación longitudinal. Se analizó la densidad, composición, riqueza, diversidad específica, equitatividad y grupos taxonómicos dominantes. Durante el período de estudio, el embalse Yacyretá no presentó estratificación térmica y la concentración de oxígeno disuelto fue alta en toda la columna de agua. Se registraron 200 especies distribuidas en 9 clases. El número de especies por muestra osciló entre 14 y 45 taxa y la diversidad específica entre 1.55 y 4.61 bits. La densidad varió entre 66 y 10 060 ind/ml, con dominancia de Cryptophyceae y Bacillariophyceae en las distintas regiones del embalse. Al inicio del otoño y final de la primavera, se registró un aumento en la densidad de Cyanobacteria en las estaciones con mayor tiempo de residencia del agua. La composición y densidad del fitoplancton presentó una marcada variación espacial y temporal determinada principalmente, por las variaciones del régimen hidrosedimentológico del río Paraná.In this study, we analyzed the structure and dynamics of the phytoplankton of the Yacyretá Reservoir and its relationship with the main limnological variables between December 2004 and November 2005, 10 years after the filling of the reservoir. Qualitative and quantitative samples were collected at 6 sampling stations, following a longitudinal zonation criterion. Density, composition, specific richness, diversity, equitability and dominance were analyzed. During the studied period, the Yacyretá Reservoir did not present thermal stratification, and the dissolved oxygen concentration in the water column was high. Two hundred species in 9 algae classes were recorded. The number of species per sample varied between 14 and 45 taxa and the specific diversity between 1.55 y 4.61 bits. Density ranged among 66 and 10 060 ind/ml, with dominance of Cryptophyceae and Bacillariophyceae in different regions of the reservoir. An increase in the Cyanobacteria density at the begining of Autumn and at the end of Spring, mainly in the stations with longer time of permanence of water, was recorded. During the analysis period the composition and density of the phytoplankton presented a noticeable spatial and temporal variation, determined mainly by the hydrosedimentologic cycle variations.Fil: Meichtry de Zabrulín, Norma Rosa. Universidad Nacional de Misiones. Facultad de Ciencias Exactas, Químicas y Naturales; ArgentinaFil: Vogler, Roberto Eugenio. Universidad Nacional de la Plata. Facultad de Cs.naturales y Museo. Div.zoologia Invertebrados; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnológico La Plata; ArgentinaFil: Llano, Víctor Martín. Universidad Nacional de Misiones. Facultad de Ciencias Exactas, Químicas y Naturales; ArgentinaFil: Martens, Imgard Sandra Mabel. Universidad Nacional de Misiones. Facultad de Ciencias Exactas, Químicas y Naturales; Argentin

Introducing COSMOS: a Web Platform for Multimodal Game-Based Psychological Assessment Geared Towards Open Science Practice

We have established the COgnitive Science Metrics Online Survey (COSMOS) platform that contains a digital psychometrics toolset in the guise of applied games measuring a wide range of cognitive functions. Here, we are outlining this online research endeavor designed for automatized psychometric data collection and scalable assessment: once set up, the low costs and expenditure associated with individual psychometric testing allow substantially increased study cohorts and thus contribute to enhancing study outcome reliability. We are leveraging gamification of the data acquisition method to make the tests suitable for online administration. By putting a strong focus on entertainment and individually tailored feedback, we aim to maximize subjects’ incentives for repeated and continued participation. The objective of measuring repeatedly is obtaining more revealing multitrial average scores and measures from various operationalizations of the same psychological construct instead of relying on single-shot measurements. COSMOS is set up to acquire an automatically and continuously growing dataset that can be used to answer a wide variety of research questions. Following the principles of the open science movement, this data set will also be made accessible to other publicly funded researchers, given that all precautions for individual data protection are fulfilled. We have developed a secure hosting platform and a series of digital gamified testing instruments that can measure theory of mind, attention, working memory, episodic long- and short-term memory, spatial memory, reaction times, eye-hand coordination, impulsivity, humor appreciation, altruism, fairness, strategic thinking, decision-making, and risk-taking behavior. Furthermore, some of the game-based testing instruments also offer the possibility of using classical questionnaire items. A subset of these gamified tests is already implemented in the COSMOS platform, publicly accessible and currently undergoing evaluation and calibration as normative data is being collected. In summary, our approach can be used to accomplish a detailed and reliable psychometric characterization of thousands of individuals to supply various studies with large-scale neurocognitive phenotypes. Our game-based online testing strategy can also guide recruitment for studies as they allow very efficient screening and sample composition. Finally, this setup also allows to evaluate potential cognitive training effects and whether improvements are merely task specific or if generalization effects occur in or even across cognitive domains

Automated Analysis of MUTEX Algorithms with FASE

In this paper we study the liveness of several MUTEX solutions by representing them as processes in PAFAS s, a CCS-like process algebra with a specific operator for modelling non-blocking reading behaviours. Verification is carried out using the tool FASE, exploiting a correspondence between violations of the liveness property and a special kind of cycles (called catastrophic cycles) in some transition system. We also compare our approach with others in the literature. The aim of this paper is twofold: on the one hand, we want to demonstrate the applicability of FASE to some concrete, meaningful examples; on the other hand, we want to study the impact of introducing non-blocking behaviours in modelling concurrent systems.Comment: In Proceedings GandALF 2011, arXiv:1106.081

The volume densities of giant molecular clouds in M83

Using observed GALEX far-ultraviolet (FUV) fluxes and VLA images of the 21-cm HI column densities, along with estimates of the local dust abundances, we measure the volume densities of a sample of actively star-forming giant molecular clouds (GMCs) in the nearby spiral galaxy M83 on a typical resolution scale of 170 pc. Our approach is based on an equilibrium model for the cycle of molecular hydrogen formation on dust grains and photodissociation under the influence of the FUV radiation on the cloud surfaces of GMCs. We find a range of total volume densities on the surface of GMCs in M83, namely 0.1 - 400 cm-3 inside R25, 0.5 - 50 cm-3 outside R25 . Our data include a number of GMCs in the HI ring surrounding this galaxy. Finally, we discuss the effects of observational selection, which may bias our results.Comment: 9 pages, 11 figure

CPEB3 is Associated with Human Episodic Memory

Cytoplasmic polyadenylation element-binding (CPEB) proteins are crucial for synaptic plasticity and memory in model organisms. A highly conserved, mammalian-specific short intronic sequence within CPEB3 has been identified as a ribozyme with self-cleavage properties. In humans, the ribozyme sequence is polymorphic and harbors a single nucleotide polymorphism that influences cleavage activity of the ribozyme. Here we show that this variation is related to performance in an episodic memory task and that the effect of the variation depends on the emotional valence of the presented material. Our data suggest a role for human CPEB3 in human episodic memory

A powerful and rapid approach to human genome scanning in small quantities of genomic DNA

Dense maps of short-tandem-repeat polymorphisms (STRPs) have allowed genome-wide searches for genes involved in a great variety of diseases with genetic influences, including common complex diseases. Generally for this purpose, marker sets with a 10 cM spacing are genotyped in hundreds of individuals. We have performed power simulations to estimate the maximum possible intermarker distance that still allows for sufficient power. In this paper we further report on modifications of previously published protocols, resulting in a powerful screening set containing 229 STRPs with an average spacing of 18·3 cM. A complete genome scan using our protocol requires only 80 multiplex PCR reactions which are all carried out using one set of conditions and which do not contain overlapping marker allele sizes. The multiplex PCR reactions are grouped by sets of chromosomes, which enables on-line statistical analysis of a set of chromosomes, as sets of chromosomes are being genotyped. A genome scan following this modified protocol can be performed using a maximum amount of 2.5 μg of genomic DNA per individual, isolated from either blood or from mouth swabs.link_to_subscribed_fulltex

A multi-wavelength study of Supernova Remnants in six nearby galaxies. I: Detection of new X-ray selected Supernova Remnants with Chandra

We present results from a study of the Supernova Remnant (SNR) population in a sample of six nearby galaxies (NGC 2403, NGC 3077, NGC 4214, NGC 4449, NGC 4395 and NGC 5204) based on Chandra archival data. We have detected 244 discrete X-ray sources down to a limiting flux of 10^{-15} erg/s. We identify 37 X-ray selected thermal SNRs based on their X-ray colors or spectra, 30 of which are new discoveries. In many cases the X-ray classification is confirmed based on counterparts with SNRs identified in other wavelengths. Three of the galaxies in our sample (NGC 4214, NGC 4395 and NGC 5204) are studied for the first time, resulting in the discovery of 13 thermal SNRs. We discuss the properties (luminosity, temperature, density) of the X-ray detected SNRs in the galaxies of our sample in order to address their dependence on their environment. We find that X-ray selected SNRs in irregular galaxies appear to be more luminous than those in spirals. We attribute this to the lower metalicities and therefore more massive progenitor stars of irregular galaxies or the higher local densities of the ISM. We also discuss the X-ray selected SNR populations in the context of the Star Formation Rate of their host galaxies. A comparison of the numbers of observed luminous X-ray selected SNRs with those expected based on the luminosity functions of X-ray SNRs in the MCs and M33 suggest different luminosity distributions between the SNRs in spiral and irregular galaxies with the latter tending to have flatter distributions.Comment: 56 pages, 14 figures, 26 tables. Accepted for publication in Ap