RESUMO: A mastite causa significativas perdas econômicas à indústria leiteira bovina. O presente estudo teve como objetivo avaliar as propriedades antibacterianas de 39 derivados heterocíclicos (1,3-tiazóis e 4-tiazolidinonas) contra isolados clínicos de mastite em vacas leiteiras. Amostras de leite foram coletadas de vacas com mastite clínica e as espécies bacterianas isoladas foram identificadas por PCR. A atividade antibacteriana foi avaliada pelo método de microdiluição em caldo. Primeiramente, os 39 compostos heterocíclicos foram testados contra quatro isolados bacterianos (Staphylococcus aureus, Streptococcus agalactiae, Corynebacterium bovis e Escherichia coli) escolhidos aleatoriamente dentre os recuperados das amostras de leite (Estudo 1). Posteriormente, compostos com atividade antibacteriana mais forte foram testados contra todos os isolados bacterianos recuperados das amostras de leite (Estudo 2). Os compostos 1,3-tiazóis apresentaram a maior atividade antibacteriana, principalmente os compostos 30 e 38, que também apresentaram propriedades bactericidas de acordo com seus valores de concentração inibitória mínima (CIM) e concentração bactericida mínima (CBM). Os isolados Corynebacterium spp. e Enterobacteriaceae foram os mais suscetíveis aos compostos 30 e 38. Os compostos 30 e 38 mostraram-se promissores como novos agentes antimicrobianos.

ABSTRACT: Mastitis causes significant economic losses to the dairy cattle industry. The present study aimed to evaluate the antibacterial properties of 39 heterocyclic derivatives (1,3-thiazoles and 4-thiazolidinones) against clinical mastitis isolates from dairy cows. Milk samples were collected from cows with clinical mastitis and the bacterial species were identified by PCR. Antibacterial activity was assessed using the broth microdilution method. First, 39 heterocyclic compounds were tested against four bacterial isolates (Staphylococcus aureus, Streptococcus agalactiae, Corynebacterium bovis and Escherichia coli) randomly chosen from those recovered from the milk samples (Study 1). Subsequently, the compounds with the strongest antibacterial activity were tested against all the bacterial isolates recovered from the milk samples (Study 2). 1,3-thiazoles showed the strongest antibacterial activity, specially compounds 30 and 38, which also showed bactericidal properties according to their minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) values. Corynebacterium spp. and Enterobacteriaceae isolates were the most susceptible to compounds 30 and 38. Compounds 30 and 38 are promising targets for new antimicrobial agents.

Abstract Fibrinolytic proteases are a promising alternative in the pharmaceutical industry, they are used in the treatment of cardiovascular diseases, especially thrombosis. Microorganisms are the most interesting source of fibrinolytic proteases. The aim of this study was the production of fibrinolytic protease from Streptomyces parvulus DPUA 1573, the recovery of the protease by aqueous two-phase system and partial biochemical characterization of the enzyme. The aqueous two-phase system was performed according to a 24-full factorial design using polyethylene glycol molar mass, polyethylene glycol concentration, citrate concentration and pH as independent variables. It was analyzed the effect of different ions, surfactants, inhibitors, pH and temperature on enzyme activity. The best conditions for purifying the enzyme were 17.5% polyethylene glycol 8,000, 15% Phosphate and pH 8.0, it was obtained a partition coefficient of 7.33, a yield of 57.49% and a purification factor of 2.10-fold. There was an increase in enzyme activity in the presence of Fe2+ and a decrease in the presence of $\beta$-Mercaptoethanol, phenylmethylsulfonyl fluoride and Iodoacetic acid. The optimum pH was 7.0 and the optimum temperature was 40 ºC. The purified protease exhibited a molecular mass of 41 kDa. The fibrinolytic protease from Streptomyces parvulus proved to be a viable option for the development of a possible drug with fibrinolytic action.

Onze derivados da ftalimida foram avaliados quanto a sua atividade antiproliferativa em células tumorais e normais e possíveis efeitos tóxicos. Avaliou-se a citotoxicidade contra tumores murinos (células de Sarcoma 180 e B-16/F-10) e células mononucleares do sangue perférico (CMSP) usando os ensaios de MTT e Alamar Blue. Em seguida, a investigação de citotoxicidade foi executada por citometria de fluxo e potencial antitumoral e toxicológico por meio de métodos in vivo. As moléculas 3b, 3c, 4 e 5 revelaram citotoxicidade in vitro contra Sarcoma 180, B-16/F-10 e PBMC. Uma vez que o composto 4 foi o derivado mais efetivo, ele foi escolhido para detalhar o mecanismo de ação após 24, 48 e 72h de exposição (22.5 e 45 µM). Células de Sarcoma 180 tratadas com o composto 4 mostraram desintegração de membrana, fragmentação de DNA e despolarização mitocondrial de maneira tempo e concentracão dependente. Os compostos 3c, 4 e 5 (50 mg/kg/dia) não inibiu o crescimento tumoral in vivo. Os animals tratados com o composto 4 exibiram aumento do total de leucócitos, linfócitos e no peso relativo do baço, diminuição de neutrófilos e hiperplasia da polpa branca esplênica. Os animais tratados apresentaram alterações histológicas reversíveis. A molécula 4 tem ação antiproliferativa in vitro provavelmente por ativação de apoptose, efeitos tóxicos reversíveis e exibiu propriedades imunoestimulantes que podem ser exploradas para atacar células neoplásicas.

Eleven phthalimide derivatives were evaluated with regards to their antiproliferative activity on tumor and normal cells and possible toxic effects. Cytotoxic analyses were performed against murine tumors (Sarcoma 180 and B-16/F-10 cells) and peripheral blood mononuclear cells (PBMC) using MTT and Alamar Blue assays. Following, the investigation of cytotoxicity was executed by flow cytometry analysis and antitumoral and toxicological potential by in vivo techniques. The molecules 3b, 3c, 4 and 5 revealed in vitro cytotoxicity against Sarcoma 180, B-16/F-10 and PBMC. Since compound 4 was the most effective derivative, it was chosen to detail the mechanism of action after 24, 48 and 72 h exposure (22.5 and 45 µM). Sarcoma 180 cells treated with compound 4 showed membrane disruption, DNA fragmentation and mitochondrial depolarization in a time- and dose-dependent way. Compounds 3c, 4 and 5 (50 mg/kg/day) did not inhibit in vivotumor growth. Compound 4-treated animals exhibited an increase in total leukocytes, lymphocytes and spleen relative weight, a decreasing in neutrophils and hyperplasia of spleen white pulp. Treated animals presented reversible histological changes. Molecule 4 had in vitro antiproliferative action possibly triggered by apoptosis, reversible toxic effects on kidneys, spleen and livers and exhibited immunostimulant properties that can be explored to attack neoplasic cells.

A dengue representa um importante problema de saúde no Brasil, portanto, a identificação de vacina ou tratamento eficaz é uma necessidade urgente. A neutralização do vírus da dengue, por anticorpo específico, tem potencial aplicação terapêutica. Descrevemos aqui, pela primeira vez, a preparação de imunoglobulina específica para o vírus da dengue (IgG anti-DENV), produzida a partir do plasma selecionado de doadores brasileiros. A produção foi realizada utilizando o método clássico de Cohn-Oncley com pequenas modificações. A IgG anti-DENV foi bioquimicamente e biofisicamente caracterizada e cumpriu os requisitos definidos pela Farmacopeia Europeia. O produto final foi capaz de neutralizar diferentes sorotipos do vírus (DENV-1, DENV-2 e DENV-3), enquanto que a IgG comercial, produzida a partir do plasma de doadores americanos, apresentou baixos títulos de anticorpos anti-dengue. No geral, esta IgG anti-DENV representa uma importante etapa para o estudo do potencial terapêutico e segurança da neutralização, por anticorpos específicos, do vírus da dengue em humanos.

Dengue represents an important health problem in Brazil and therefore there is a great need to develop a vaccine or treatment. The neutralization of the dengue virus by a specific antibody can potentially be applied to therapy. The present paper describes, for the first time, the preparation of Immunoglobulin specific for the dengue virus (anti-DENV IgG), collected from screened Brazilian blood-donations. Production was performed using the classic Cohn-Oncley process with minor modifications. The anti-DENV IgG was biochemically and biophysically characterized and fulfilled the requirements defined by the European Pharmacopoeia. The finished product was able to neutralize different virus serotypes (DENV-1, DENV-2, and DENV-3), while a commercial IgG collected from American blood donations was found to have low anti-dengue antibody titers. Overall, this anti-DENV IgG represents an important step in the study of the therapeutic potential and safety of a specific antibody that neutralizes the dengue virus in humans.

INTRODUÇÃO: Durante a gravidez, ocorrem intensas modificações no organismo materno, desencadeadas por alterações hormonais. À medida que a gestação progride, a ação hormonal em tecidos conjuntivos, associada a alterações biomecânicas para crescimento uterino podem causar o afastamento da musculatura abdominal (diástase dos músculos retos abdominais), que se estende no período pós-parto, sendo considerada diástase a separação maior que 3 cm. OBJETIVOS: O objetivo deste estudo foi confrontar a relação entre o valor das medidas da diástase dos abdominais com variáveis obstétricas em puérperas de maternidades públicas de João Pessoa. MATERIAIS E MÉTODOS: Foram selecionadas 100 puérperas de acordo com os critérios de inclusão: idade fértil, em puerpério imediato e que durante a internação não tenham recebido atendimento fisioterapêutico para correção da diástase. Fez-se o levantamento dos antecedentes obstétricos e clínicos por meio de um questionário. Posteriormente, avaliou-se a diástase com um paquímetro digital. Para analisar a correlação significativa entre o evento e as variáveis, foi aplicado o teste do qui-quadrado. RESULTADOS: As puérperas que apresentaram a diástase eram multíparas, multigestas, com idade entre 19 e 30 anos, tendo seus filhos por meio de partos normais, com intervalos curtos entre as gestações. Quanto à localização, houve maior incidência da diástase supraumbilical associada à separação umbilical. CONCLUSÃO: A diástase é uma condição expressiva, visto que 56 apresentaram-na. Assim, observa-se a necessidade de uma avaliação mais criteriosa das gestantes pelos profissionais de saúde para que haja intervenção precoce, por meio de um protocolo de atendimento, durante o pré-natal, já que traz risco para a mãe e para a futura gestação.

INTRODUCTION: During pregnancy, enormous changes occur in the mother, triggered by hormonal alterations. As the pregnancy progresses, the hormones action in tissues to biomechanical changes associated with intrauterine growth, may cause the separation of the abdominal muscles (diastasis of the rectus abdominis muscles), which extends into the postpartum period, being considered diastasis the separation greater than 3 cm. OBJECTIVES: The aim of this study was to compare the relationship between the value of measurements of diastasis of abdominal and obstetric variables among women in public maternity hospitals in João Pessoa. MATERIALS AND METHODS: 100 postpartum women were selected according to the following inclusion criteria: fertile age, being in early puerperium and not having received physical therapy to correct the diastasis during hospitalization. There was a survey of obstetric and clinic background via a questionnaire. Subsequently, we evaluated the diastasis with a caliper. To analyze the correlation between the event and the variables, we used the chi-quadrado. RESULTS: The women who had diastasis were multiparous, aged between 19 and 30 years old, and had their children through normal deliveries, with short intervals between pregnancies. Regarding the location, there was a higher incidence of diastasis associated with supra-umbilical cord separation. CONCLUSION: The diastasis is an expressive condition, since 56 women had it. Thus, there is a need for a more detailed assessment of pregnant women by health professionals so that there is an early intervention, through a protocol of care during the prenatal period, since it brings risk to the mother and future pregnancy.

Obteve-se concentrado de imunoglobulina G intravenosa IgGIV, altamente purificado, utilizando-se polietilenoglicol associado a uma única etapa de precipitação por etanol, em substituição ao tradicional método descrito por Cohn-Oncley, que emprega, em três etapas, o mesmo álcool resfriado, como agente precipitante. A purificação da fração bruta contendo mais de 95% de imunoglobulina G foi realizada utilizando-se cromatografia líquida com um trocador de cátion, a CM-Sepharose, como fase estacionária. Durante o processamento o produto foi submetido a dupla inativação viral sendo a primeira pela ação do caprilato de sódio, 30 mM a pH 5,1+/- 0,1 e a segunda por ação de mistura de solvente/detergente. O produto acabado foi formulado a 5% utilizando-se sucralose 10% como estabilizante. O rendimento da metodologia foi de 3,3g de IgG/litro de plasma. A análise do produto acabado demonstrou atividade anti-complementar inferior a 1CH50. O valor percentual de polímeros e agregados em cinco lotes realizados foi inferior a 3%. O estudo da capacidade de neutralização demonstrou a presença de anticorpos anti-bacterianos e anti-virais em concentração pelo menos três vezes maior que o plasma de origem. O produto acabado apresentou conformidade com todos os requisitos de pureza dispostos na farmacopéia européia IV edição.

Highly purified intravenous immunoglobulin G concentrate (IV IgG) was produced with the use of polyethylene glycol associated to a single-stage precipitation by ethanol, instead of the classic Cohn-Oncley process, which employs cold alcohol as the precipitating agent, in a three-stage process. Precipitation of crude fraction containing more than 95% of immunoglobulin G was performed by liquid chromatography with a cation exchanger, CM-Sepharose, as a stationary phase. During the process, the product was subjected to two-stage viral inactivation. The first stage was performed by the action of sodium caprylate, 30 mM at pH 5.1+/- 0.1, and the second stage was performed by the action of a solvent-detergent mixture. The finished product was formulated at 5% with 10% sucralose as the stabilizing agent. The process yields 3.3g of IgG/liter of plasma. The finished product analysis showed an anti-complementary activity lower than 1CH50. Polymer and aggregate percent levels were lower than 3% in the five batches studied. The analysis of neutralizing capacity showed the presence of antibacterial and antiviral antibodies in at least three times higher concentrations than the levels found in source plasma. The finished product fulfilled all purity requirements stated in the 4th edition of the European pharmacopeia.

The phytochemical investigation of ethanolic extracts from leaves, branches and stems of D. bipinnatum afforded the steroids β-sitosterol, stigmasterol, campesterol, sitostenone and sitosterol-3-O-β-D-glycopyranoside, along with two cycloartane triterpenes: cycloeucalenol and 24-methylenecycloartenol. The antimicrobial activity of the extracts was evaluated against Staphylococcus aureus (ATCC 25923), Escherichia coli (ATCC 25922), Bacillus subtilis (ATCC 6623), Pseudomonas aeruginosa (ATCC 15442), Micrococcus luteus (ATCC 9341) and Candida albicans (ATCC 10231). The extracts of the leaves and branches showed moderate activity against Candida albicans. The extract of the branches was active against Micrococcus luteus. This is the first report on the phytochemical study of D. bipinnatum.

Compostos β-amino-dicarbonilados constituem uma classe de ligantes promissores para a química de coordenação. Diante desta perspectiva, um método eficiente e fácil visando à síntese de compostos β-amino-dicarbonilados foi desenvolvido, explorando a reação de adição do tipo azo-Michael em meio aquoso. Com isso, uma série de dez dietil 2-(feniletil)malonatos dissubstituídos foram obtidos de uma maneira regiosseletiva e facilmente purificados, levando à rendimentos satisfatórios. As análises cristalográficas de dois destes compostos forneceram as informações apropriadas sobre a conformação e configuração dos mesmos. Por último, uma proposta complementar do mecanismo reacional para as reações de adição de Michael em meio aquoso foi também descrito.

β-Amino dicarbonyl compounds comprise a class of useful ligands on the coordination chemistry. In view of their importance, an efficient and facile method for the synthesis of β-amino dicarbonyl compounds has been developed, exploring the aza-Michael addition reactions in an aqueous medium. It was possible to achieve good to excellent yields, along with regioselectivity, the substituted diethyl 2-(phenylmethyl)malonates that were easily isolated without any chromatographic purification. The correct configuration of two of these β-amino dicarbonyl compounds were confirmed by X-ray crystallography. A complementary mechanism of this aza-Michael protocol is proposed to explain the results obtained.

Aborda a trajetória dos direitos femininos em saúde no Brasil, do período pós-guerra até os dias atuais com foco na saúde materna, por meio de levantamento histórico das iniciativas mais amplas do poder público no âmbito da saúde da mulher e da implantação de ações voltadas para assistência à gravidez, ao parto e puerpério, de estímulo à amamentação, e de medidas dirigidas às mulheres durante o período reprodutivo.

Focusing on maternal health care, the article explores the path of women's health rights in Brazil since World War II. It presents a historical survey of broader government initiatives in this arena and of the introduction of actions to provide prenatal, birth, and postpartum care, encourage breastfeeding, and establish measures aimed at women during their reproductive lives.

The beta-lapachone is a product obtained from the Ipê Roxo tree [Tabebuia avellandae], which has proved its excellent antineoplasic potential acting through a particular mechanism of apoptosis against various cancer types. This study aims at determining the identity card of beta-lapachone by means of physico-chemical and pharmaco-technical characterization. A purifying process has been performed, as well as the isolation of a contaminant, its isomer alpha-lapachone. A stability study was also performed, determining the ideal storing conditions for beta-lapachone, essential for the ongoing pre-formulation studies for obtaining the different classic pharmaceutical forms and modified release systems.

A series of heterocyclic compounds with a 4-thiazolidone nucleus and amino acyl moiety were synthesized by protection reaction of thiosemicarbazide using the symmetrical anhydride (Boc)2O and cyclization with chloroacetic acid under mild conditions. Trifluoroacetic acid was used to obtain 4-thiazolidone and the alpha-amino acid condensation reactions were carried out using strategies for peptide synthesis. The characterization of this new class of compounds was performed using IR and ¹H-NMR spectroscopy.

Droplet counter-current chromatography, rotation locular counter-current chromatography and high-speed counter-current chromatography were applied to the preparative separation of the alkaloid ricinine from the dichloromethane extracts of Ricinus communis leaves. The solvent system used was composed of dichloromethane-methanol-water (93:35:72 v/v/v) and all techniques led to the isolation of large amounts of the alkaloid. The best result was obtained through HSCCC, since the ricinine yield was respectively 50% and 30% higher than when using RLCCC or DCCC.