Developmental Exposure to the Flame Retardant Mixture Firemaster 550 Compromises Adult Bone Integrity in Male but not Female Rats.

Flame retardants (FRs) are used in a variety of common items from furniture to carpet to electronics to reduce flammability and combustion, but the potential toxicity of these compounds is raising health concerns globally. Organophosphate FRs (OPFRs) are becoming more prevalent as older, brominated FRs are phased out, but the toxicity of these compounds, and the FR mixtures that contain them, is poorly understood. Work in a variety of in vitro model systems has suggested that FRs may induce metabolic reprogramming such that bone density is compromised at the expense of increasing adiposity. To address this hypothesis, the present studies maternally exposed Wistar rat dams orally across gestation and lactation to 1000 µg daily of the FR mixture Firemaster 550 (FM 550) which contains a mixture of brominated FRs and OPFRs. At six months of age, the offspring of both sexes were examined for evidence of compromised bone composition. Bone density, composition, and marrow were all significantly affected, but only in males. The fact that the phenotype was observed months after exposure suggests that FM 550 altered some fundamental aspect of mesenchymal stem cell reprogramming. The severity of the phenotype and the human-relevance of the dose employed, affirm this is an adverse outcome meriting further exploration.

The Importance of Eculizumab in the Treatment of Atypical Hemolytic Uremic Syndrome.

In most cases, the atypical hemolytic uremic syndrome (aHUS) is a genetic disease resulting from defects in the regulation of the complement cascade, which conditions the development of thrombotic microangiopathy. Clinically, aHUS presents with acute kidney injury, thrombocytopenia, and microangiopathic hemolytic anemia, with frequent renal and extrarenal thrombotic phenomena. Early diagnosis and treatment are essential. Plasmapheresis is an alternative treatment being frequently used considering the high cost of eculizumab, despite its lower clinical efficacy. This article describes the clinical case of a patient admitted to intensive care with a personal history of aHUS diagnosed 10 years ago, with recurrent aHUS triggered by viral infection. The patient presented with acute kidney injury and thrombocytopenia. Despite the institution of admission of plasmapheresis, the clinical evolution was only favorable after the administration of eculizumab, highlighting the importance of early initiation of this therapy.

A Case of Paraganglioma-Induced Adrenergic Shock.

Paragangliomas (PGLs) are rare neuroendocrine tumors that, when functional, can release excessive catecholamines, causing health conditions ranging from asymptomatic arterial hypertension to life-threatening arrhythmias and cardiogenic shock. Early diagnosis of functional PGLs is extremely important as timely treatment can be curative and prevent vascular sequelae. We describe the clinical case of a 30-year-old woman with arterial hypertension under study, who was presented to the emergency department with a hypertensive crisis that progressed to adrenergic shock, in the context of a functional PGL.

Synthesis, Antileishmanial Activity and in silico Studies of Aminoguanidine Hydrazones (AGH) and Thiosemicarbazones (TSC) Against Leishmania chagasi Amastigotes.

BACKGROUND: Leishmaniasis is a worldwide health problem, highly endemic in developing countries. Among the four main clinical forms of the disease, visceral leishmaniasis is the most severe, fatal in 95% of cases. The undesired side-effects from first-line chemotherapy and the reported drug resistance search for effective drugs that can replace or supplement those currently used in an urgent need. Aminoguanidine hydrazones (AGH's) have been explored for exhibiting a diverse spectrum of biological activities, in particular the antileishmanial activity of MGBG. The bioisosteres thiosemicarbazones (TSC's) offer a similar biological activity diversity, including antiprotozoal effects against Leishmania species and Trypanosoma cruzi. OBJECTIVES: Considering the impact of leishmaniasis worldwide, this work aimed to design, synthesize, and perform a screening upon L. chagasi amastigotes and for the cytotoxicity of the small "inhouse" library of both AGH and TSC derivatives and their structurally-related compounds. METHODS: A set of AGH's (3-7), TSC's (9, 10), and semicarbazones (11) were initially synthesized. Subsequently, different semi-constrained analogs were designed and also prepared, including thiazolidines (12), dihydrothiazines (13), imidazolines (15), pyrimidines (16, 18) azines (19, 20), and benzotriazepinones (23-25). All intermediates and target compounds were obtained with satisfactory yields and exhibited spectral data consistent with their structures. All final compounds were evaluated against L. chagasi amastigotes and J774.A1 cell line. Molecular docking was performed towards trypanothione reductase using GOLD® software. RESULTS: The AGH's 3i, 4a, and 5d, and the TSC's 9i, 9k, and 9o were selected as valuable hits. These compounds presented antileishmanial activity compared with pentamidine, showing IC50 values ranged from 0.6 to 7.27 µM, maximal effects up to 55.3%, and satisfactory SI values (ranged from 11 to 87). On the other hand, most of the resulting semi-constrained analogs were found cytotoxic or presented reduced antileishmanial activity. In general, TSC class is more promising than its isosteric AGH analogs, and the beneficial aromatic substituent effects are not similar in both series. In silico studies have suggested that these hits are capable of inhibiting the trypanothione reductase from the amastigote forms. CONCLUSION: The promising antileishmanial activity of three AGH's and three TSC's was characterized. These compounds presented antileishmanial activity compared with PTD, showing IC50 values ranged from 0.6 to 7.27 µM, and satisfactory SI values. Further pharmacological assays involving other Leishmania strains are in progress, which will help choose the best hits for in vivo experiments.

Compatibility of Azospirillum brasilense with Pesticides Used for Treatment of Maize Seeds.

Seed treatment with chemical pesticides is commonly used as an initial plant protection procedure against pests and diseases. However, the use of such chemicals may impair the survival and performance of beneficial microorganisms introduced via inoculants, such as the plant growth-promoting bacterium Azospirillum brasilense. We assessed the compatibility between the most common pesticide used in Brazil for the treatment of maize seeds, composed of two fungicides, and one insecticide, with the commercial strains Ab-V5 and Ab-V6 of A. brasilense, and evaluated the impacts on initial plant development. The toxicity of the pesticide to A. brasilense was confirmed, with an increase in cell mortality after only 24 hours of exposure in vitro. Seed germination and seedling growth were not affected neither by the A. brasilense nor by the pesticide. However, under greenhouse conditions, the pesticide affected root volume and dry weight and root-hair incidence, but the toxicity was alleviated by the inoculation with A. brasilense for the root volume and root-hair incidence parameters. In maize seeds inoculated with A. brasilense, the pesticide negatively affected the number of branches, root-hair incidence, and root-hair length. Therefore, new inoculant formulations with cell protectors and the development of compatible pesticides should be searched to guarantee the benefits of inoculation with plant growth-promoting bacteria.

Structural studies and antileishmanial activity of 2-acetylpyridine and 2-benzoylpyridine nitroimidazole-derived hydrazones.

Three imidazole hydrazone compounds, namely 2-(4-nitro-1H-imidazol-1-yl)-N'-[1-(pyridin-2-yl)ethylidene]acetohydrazide, C12H12N6O3, (1), 2-(2-nitro-1H-imidazol-1-yl)-N'-[1-(pyridin-2-yl)ethylidene]acetohydrazide, C12H12N6O3, (2), and 2-(2-nitro-1H-imidazol-1-yl)-N'-[(phenyl)(pyridin-2-yl)methylidene]acetohydrazide, C17H14N6O3, (3), were obtained and fully characterized, including their crystal structure determinations. While all the compounds proved not to be cytotoxic to J774.A1 macrophage cells, (1) and (3) exhibited activity against Leishmania chagasi, whereas (2) was revealed to be inactive. Since both (1) and (3) exhibited antileishmanial effects, while (2) was devoid of activity, the presence of the acetyl or benzoyl groups was possibly not a determining factor in the observed antiprotozoal activity. In contrast, since (1) and (3) are 4-nitroimidazole derivatives and (2) is a 2-nitroimidazole-derived compound, the presence of the 4-nitro group probably favours antileishmanial activity over the 2-nitro group. The results suggested that further investigations on compounds (1) and (3) as bioreducible antileishmanial prodrug candidates are called for.

Polymorphisms in exons 6 and 7 of the ABO locus and their association with venous thrombosis in young Brazilian patients.

The A1 and B alleles of the ABO blood system have been associated with high levels of both factor VIII and von Willebrand factor and with a predisposition to venous thromboembolism (VTE). In this study, genotypes of the ABO system were determined by PCR-restriction fragment length polymorphism for 148 young VTE Brazilian patients and 233 unrelated control individuals. The blood group O was more frequent among the controls [odds ratio (OR), 0.21; 95% confidence interval (CI), 0.13-0.34; P = 0.000) and groups A and B (OR, 2.24; 95%, CI, 1.46-3.42; P = 0.000 and OR, 2.52; 95% CI, 1.42-4.48; P = 0.002, respectively) among patients. The patients' group was under Hardy-Weinberg equilibrium, whereas the control group was not (P < 0.0051), suggesting that natural selection might be acting in favor of carriers of the O blood group. When the allelic frequencies were compared through multivariate logistic regression analysis for adjustments of covariates, the alleles A1 (OR, 1.69; 95% CI, 1.17-2.45; P = 0.006), A2 (OR, 2.19; 95% CI, 1.24-3.87; P = 0.010), and B (OR, 2.65; 95% CI, 1.64-4.26; P = 0.000) were independently associated with VTE and may represent important risk factors to the development of VTE among young Brazilian patients. Thus, the inclusion of ABO blood group determination may be helpful to discriminate individuals with high risk for VTE allowing target intervention as well as to manage VTE in young patients.

Antinociceptive and anti-inflammatory activity of hydroalcoholic extracts and fractions from Erythrina mulungu

Erythrina mulungu Mart. ex Benth., Fabaceae, popularly known as mulungu, is used for the treatment of insomnia and disorders of the central nervous system. This study examined the antinociceptive effects of the hydroalcoholic extracts (HAE), the ethyl acetate and chloroformic fractions from E. mulungu in four experimental models of nociception using laboratory mice. The extracts and fractions were administered orally to mice at doses of 100 mg/kg. Inhibition of abdominal contractions were observed for all the extracts and fractions tested, as compared to controls. All extracts and fractions from E. mulungu reduced the nociception activity produced by formalin in the 2nd phase. In the hot plate test no significant effect was observed for any extract or fraction. In the peritonitis test induced by Zymosan, all of the tested extracts and the chloroformic fraction, except for the ethyl acetate phase, reduced cell migration of the peritoneal cavity. We concluded that E. mulungu shows antinociceptive effects, which are independent of the opioid system.

Avaliação de programas comunitários de promoção da atividade física: o caso de Curitiba, Paraná / Evaluation of community physical activity programs: the case of Curitiba, Brazil

O objetivo do estudo foi avaliar as intervenções para promoção de atividade física (AF) ofertadas pela prefeitura municipal de Curitiba, Paraná (PMC). Para tal, realizou-se um inquérito domiciliar com 120 adultos igualmente distribuídos entre os sexos, e residentes próximos a Centros de Esporte e Lazer (CEL) da cidade. A seleção dos CEL ocorreu de forma aleatória, e as residências foram abordadas de maneira sistemática. Entre os entrevistados, 76% já viram, 15% participaram/participam de algum programa, 48% realiza AF nos espaços disponibilizados pela PMC e 43% ouviu falar do Programa CuritibAtiva. Apenas 10% dos entrevistados relataram ter recebido algum folder do programa CuritibAtiva e uma proporção ainda menor (0,8%) disseram que participam/participaram das atividades promovidas pelo programa CuritibAtiva. Mais da metade dos usuários atribuiu boa/ótima avaliação aos itens dos programas. Desta forma os programas da PMC parecem ser abrangentes, bem difundidos e bem avaliados por seus usuários.

The aim of this study was to evaluate community physical activity (PA) programs offered by the Curitiba municipality administration. We carried out a household-based study including 120 adults (equally distributed by sex), living close to sports and leisure centers (CEL). CELs were randomly sampled, and households around each selected CEL were systematically approached. Out of the 120 interviewees, 76% saw, 15% participate/have participated of at least one of the programs offered by the municipality. Approximately half (48%) of the respondents practiced PA in the city public spaces, or heard about the CuritibAtiva program (43%). Only 10% and 0.8% of the subjects reported to have received a flyer or to participate/have participated of the CuritibAtiva program, respectively. More than half of the interviewees rated as good or excellent the items of the programs. We conclude that Curitiba programs seem to be widely known by the city population, as well as rated positively by the interviewees.