Genotoxic and Cytotoxic Safety Evaluation of Papain (Carica papaya L.) Using In Vitro Assays

Papain, a phytotherapeutic agent, has been used in the treatment of eschars and as a debriding chemical agent to remove damaged or necrotic tissue of pressure ulcers and gangrene. Its benefits in these treatments are deemed effective, since more than 5000 patients, at the public university hospital at Rio de Janeiro, Brazil, have undergone papain treatment and presented satisfactory results. Despite its extensive use, there is little information about toxic and mutagenic properties of papain. This work evaluated the toxic and mutagenic potential of papain and its potential antioxidant activity against induced-H2O2 oxidative stress in Escherichia coli strains. Cytotoxicity assay, Growth inhibition test, WP2-Mutoxitest and Plasmid-DNA treatment, and agarose gel electrophoresis were used to investigate if papain would present any toxic or mutagenic potential as well as if papain would display antioxidant properties. Papain exhibited negative results for all tests. This agent presented an activity protecting cells against H2O2-induced mutagenesis

Antiophidian sera sterility control: topics in perspective

The aim of this work is to review the most important topics about the antiophidic sera sterility, including obtaining methods, sterilization procedures and clean room control using Vital Brazil Institute (VBI) as an example. Bibliographical research was performed through Medline, Lilacs, PubMed, ISI and the Fundação Oswaldo Cruz - RJ and VBI Libraries, from 1960 to 2009. The antiophidic sera for human use are immunobiologic products produced in Brazil by three national laboratories, including VBI. Due to the parenteral use, these products should be sterile and pyrogen-free, which demands the microbiological control during the whole fabrication process. The sterility and pyrogen tests are important steps to ensure the quality and safety of these immunobiological products. Thus, these tests are target for continue evaluation and improvement. The most interfering aspects in the consistency and analytical patterns include the proper method selection, sampling, culture conditions and validation criteria. As the national and international legal requirements are cautious with the assays validation and approval of sterile parenteral products; the intrinsic limitations for established assays still require more investigation aiming the continue improvement of the microorganism and contaminants detection methods and optimization of the analysis extent.O objetivo deste trabalho é revisar os tópicos mais relevantes para o controle da esterilidade de soros antiofídicos, abordando-se métodos de obtenção, procedimentos de esterilização e o controle de áreas limpas utilizando como exemplo os procedimentos adotados pelo Instituto Vital Brazil (IVB). Um levantamento bibliográfico foi realizado no Medline, ISI, Biblioteca da Fundação Oswaldo Cruz-RJ e IVB, no período de 1960 a 2009. Os soros antiofídicos para uso humano são produtos imunobiológicos fabricados no Brasil por três laboratórios nacionais, dentre eles o IVB. Por serem de administração parenteral, devem ser obrigatoriamente estéreis e apirogênicos, exigindo controle microbiológico durante todo o processo de fabricação. O teste de esterilidade e apirogenia são importantes instrumentos para garantir a qualidade e segurança microbiológica desses produtos, sendo alvo de avaliações constantes para seus aprimoramentos. Os aspectos que mais interferem na sua consistência e valor analítico incluem a escolha adequada do método, amostragem, condições de cultivo e critérios de validação. À medida que os requisitos legais nacionais e internacionais se mostram rigorosos na validação de ensaios e aprovação de produtos estéreis parenterais, limitações intrínsecas ao ensaio padronizado requisitam mais investigações, objetivando o aprimoramento contínuo nos métodos de detecção de microorganisms, contaminantes e otimização do tempo total de análise

Pharmaceutical care and suspended attention: compromise-formations between pharmacy and psychoanalysis

Submitted by Alexandre Sousa ([email protected]) on 2014-10-02T10:48:13Z No. of bitstreams: 1 Ciênc saúde coletiva_19_609-618.pdf: 97249 bytes, checksum: 981100c8e260dbb9672bdcc534d83a6a (MD5)Approved for entry into archive by Alexandre Sousa ([email protected]) on 2014-10-02T10:48:24Z (GMT) No. of bitstreams: 1 Ciênc saúde coletiva_19_609-618.pdf: 97249 bytes, checksum: 981100c8e260dbb9672bdcc534d83a6a (MD5)Made available in DSpace on 2014-10-02T11:10:56Z (GMT). No. of bitstreams: 1 Ciênc saúde coletiva_19_609-618.pdf: 97249 bytes, checksum: 981100c8e260dbb9672bdcc534d83a6a (MD5) Previous issue date: 2014Universidade Federal do Rio de Janeiro. Faculdade de Farmácia. Departamento de Análises Clínicas e Toxicológicas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Controle de Qualidade em Saúde. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Faculdade de Farmácia. Departamento de Fármacos e Medicamentos. Rio de Janeiro, RJ, Brasil.Círculo Psicanalítico do Rio de Janeiro. Rio de Janeiro, RJ, Brasil.Instituto Estadual de Hematologia Arthur de Siqueira Cavalcanti. Rio de Janeiro, RJ, Brasil.O presente trabalho apresenta uma visão interdisciplinar do uso racional do medicamento a partir de uma perspectiva metapsicológica. A necessidade de resgate da atuação do profissional farmacêutico junto ao paciente, através da Atenção Farmacêutica, demanda a intervenção de novos saberes que possam proporcionar uma revitalização desta relação humana. Neste sentido, através de uma compilação de passagens da obra freudiana, foram apresentados alguns dos principais conceitos metapsicológicos: aparelho psíquico, atenção flutuante e formações de compromisso. Tais conceitos foram então apresentados como ferramenta teórica articulável com análises qualitativas em Atenção Farmacêutica, mais particularmente com a observação participante. Assim, os objetivos principais foram de fornecer ao farmacêutico novas ferramentas de escuta e acolhimento que podem aprimorar a atuação profissional na relação com seu paciente, assim como na obtenção e interpretação de dados qualitativos relacionados às questões humanas envolvidas nas pesquisas em Atenção Farmacêutica.This paper presents an interdisciplinary overview of the rational use of medicine from a metapsychological standpoint. The need to reinstate the activity of the pharmaceutical professionals vis-à-vis their patients through pharmaceutical care demands the intervention of new know-how that can ensure a revitalization of this human relationship. In this sense, by means of a compilation of passages from the works of Freud, some of the most important metapsychological concepts were presented: psychic apparatus, evenly hovering attention and commitment formations. These concepts were then presented as an applicable theoretical tool for qualitative analysis in pharmaceutical care, though especially for participant observation. Thus, the main objective was to provide new tools for the pharmacists in terms of listening and receptivity, which can enhance their professional routine regarding the relationship with their patients, as well as in the gathering and interpretation of qualitative data concerning human issues involving pharmaceutical care

Synthesis and Antiplatelet Activity of Antithrombotic Thiourea Compounds: Biological and Structure-Activity Relationship Studies

The incidence of hematological disorders has increased steadily in Western countries despite the advances in drug development. The high expression of the multi-resistance protein 4 in patients with transitory aspirin resistance, points to the importance of finding new molecules, including those that are not affected by these proteins. In this work, we describe the synthesis and biological evaluation of a series of N,N'-disubstituted thioureas derivatives using in vitro and in silico approaches. New designed compounds inhibit the arachidonic acid pathway in human platelets. The most active thioureas (compounds 3d, 3i, 3m and 3p) displayed IC50 values ranging from 29 to 84 µM with direct influence over in vitro PGE2 and TXA2 formation. In silico evaluation of these compounds suggests that direct blockage of the tyrosyl-radical at the COX-1 active site is achieved by strong hydrophobic contacts as well as electrostatic interactions. A low toxicity profile of this series was observed through hemolytic, genotoxic and mutagenic assays. The most active thioureas were able to reduce both PGE2 and TXB2 production in human platelets, suggesting a direct inhibition of COX-1. These results reinforce their promising profile as lead antiplatelet agents for further in vivo experimental investigations

Cytotoxicity of Extracts from <i>Petiveria alliacea</i> Leaves on Yeast

Petiveria alliacea L. is a plant used in traditional medicine harboring pharmacological properties with anti-inflammatory, antinociceptive, hypoglycemiant and anesthetic activities. This study assessed the potential cytotoxic, genotoxic and mutagenic effects of ethanolic extract of P. alliacea on Saccharomyces cerevisiae strains. S. cerevisiae FF18733 (wild type) and CD138 (ogg1) strains were exposed to fractioned ethanolic extracts of P. alliacea in different concentrations. Three experimental assays were performed: cellular inactivation, mutagenesis (canavanine resistance system) and loss of mitochondrial function (petites colonies). The chemical analyses revealed a rich extract with phenolic compounds such as protocatechuic acid, cinnamic and catechin epicatechin. A decreased cell viability in wild-type and ogg1 strains was demonstrated. All fractions of the extract exerted a mutagenic effect on the ogg1 strain. Only ethyl acetate and n-butanol fractions increased the rate of petites colonies in the ogg1 strain, but not in the wild-type strain. The results indicate that fractions of mid-polarity of the ethanolic extract, at the studied concentrations, can induce mutagenicity mediated by oxidative lesions in the mitochondrial and genomic genomes of the ogg1-deficient S. cerevisiae strain. These findings indicate that the lesions caused by the fractions of P. alliacea ethanolic extract can be mediated by reactive oxygen species and can reach multiple molecular targets to exert their toxicity

Translational impact of novel widely pharmacological characterized mofezolac-derived COX-1 inhibitors combined with bortezomib on human multiple myeloma cell lines viability

A set of novel diarylisoxazoles has been projected using mofezolac (1) as a lead compound to investigate structure-inhibitory activity relationships of new compounds and the cyclooxygenases (COXs) catalytic activity. Mofezolac was chosen because is the most potent and selective reversible COX-1 inhibitor [COX-1 IC50 = 0.0079 μM and COX-2 IC50 &gt; 50 μM, with a selectivity index (SI) in favor of COX-1 higher than 6300]. Seventeen new compounds were synthesized in fair to good yields and evaluated for their COXs inhibitory activity and selectivity. SIs ranged between 1 and higher than 1190.3,4-Bis(4-methoxyphenyl)-5-vinylisoxazole (22) has the highest SI with COX-1 IC50 = 0.042 μM and COX-2 IC50 &gt; 50 μM. 1 and 22 were superior to aspirin in inhibiting platelet aggregation (IC50 = 0.45, 0.63 and 1.11 μM, respectively) in human platelet rich plasma (hPRP) assay. They did not induce blood coagulation and hemolysis, and are neither genotoxic nor mutagen. 1 and 22 slightly increase bortezomib cytotoxic effect on multiple myeloma (MM) cell lines (NCI-H929 and RPMI-8226) and affects MM cell cycle and apoptosis when co-administered with the proteasome inhibitor bortezomib, a drug clinically used to treat plasma cell neoplasms including MM. In addition, structure-based binding mode of 1 and 22, through Fingerprints for Ligands and Proteins (FLAG) calculation, allowed to explain the one order of magnitude difference between COX-1 IC50 values of the two compounds. Specifically, the higher inhibitory potency seems due to the formation of a H-bond between COX-1 S530 and the carboxyl, present in 1 and absent in 22