Aplicação de resíduos de construção e demolição como camada de reforço para fundações radier

Trabalho de conclusão de curso (graduação)—Universidade de Brasília, Faculdade de Tecnologia, Departamento de Engenharia Civil e Ambiental, 2016.Sustentabilidade na construção civil tornou-se um tópico importante nos últimos anos, o aumento na produção e os impactos ambientais causados pelo descarte inapropriado de resíduos de construção e demolição (RCD) gerou mais pesquisas envolvidas em utilizações alternativas do material. O presente trabalho tem como proposta analisar os efeitos benéficos da adição de RCD ao solo em obras geotécnicas, com foco principal para fundações rasas tipo radier. A pesquisa foi elaborada em duas etapas. Primeiramente foram realizados ensaios de prova de carga em placa em solo natural, inundado e com RCD, de modo a as curvas tensão x recalque e parâmetros de resistência do solo. Foi então utilizado o software de elementos finitos Plaxis 3D para simular as deformações e tensões causadas no solo, segundo um modelo linear elástico, por uma fundação radier referência, simulando o solo natural e solo reforçado com RCD, a fim de investigar a ocorrência de redução nas deformações e tensões nas camadas não reforçadas. Encontrou-se uma redução de recalques abaixo da fundação de 26%, e reduziu-se a tensão aplicada sobre o solo de 200 kN/m² para 62 kN/m², redução de 69%

Políticas de comunicação comparadas: comunicação e democracia na saúde em dois municípios em gestão plena

As ciências políticas e os estudos das democracias se referem frequentemente à liberdade de imprensa e à liberdade de expressão como variáveis a serem consideradas nos estudos das democracias contemporâneas, ou mesmo indicadores da existência de governos democráticos. No entanto, estas liberdades são muitas vezes tratadas como variáveis exógenas dos processos de construção e legitimação destas mesmas democracias e seus regimes de visibilidade e ausculta as demandas sociais (Pitta, 2004)

Cytotoxicity evaluation of haloperidol, clozapine and a new molecule with antipsychotic potential, PT-31, in NIH-3T3 cells

Schizophrenia is an illness that affects 26 million people worldwide. However, conventional antipsychotics present side effects and toxicity, highlighting the need for new antipsychotics. We aimed to evaluate the cytotoxicity of haloperidol (HAL), clozapine (CLO), and a new molecule with antipsychotic potential, PT-31, in NIH-3T3 cells. The neutral red uptake assay and the MTT assay were performed to evaluate cell viability and mitochondrial activity, morphological changes were assessed, and intracellular reactive oxygen species (ROS) detection was performed. HAL and CLO (0.1 μM) showed a decrease in cell viability in the neutral red uptake assay and in the MTT assay. In addition, cell detachment, content decrease, rounding and cell death were also observed at 0.1 μM for both antipsychotics. An increase in ROS was observed for HAL (0.001, 0.01 and 1 μM) and CLO (0.01 and 1 μM). PT-31 did not alter cell viability in any of the assays, although it increased ROS at 0.01 and 1 μM. HAL and CLO present cytotoxicity at 0.1 μM, possibly through apoptosis and necrosis. In contrast, PT-31 does not present cytotoxicity to NIH-3T3 cells. Further studies must be performed for a better understanding of these mechanisms and the potential risk of conventional antipsychotics

Hydroxychloroquine decreases Th17-related cytokines in systemic lupus erythematosus and rheumatoid arthritis patients

OBJECTIVES: Hydroxychloroquine is an antimalarial agent that has been used in systemic lupus erythematosus and rheumatoid arthritis treatment for many years. Recently, novel mechanisms of action have been proposed, thereby broadening the therapeutic perspective of this medication. The purpose of this study was to evaluate the immunomodulatory activity of hydroxychloroquine in T helper 17 (Th17) cytokines in healthy individuals and patients. METHODS: Eighteen female patients with systemic lupus erythematosus (mean age 39.0±12.9 years) and 13 female patients with rheumatoid arthritis (mean age 51.5±7.7 years) were recruited from Universidade Federal de Pernambuco-Brazil. The patients were included after fulfilling four classification criteria for systemic lupus erythematosus or rheumatoid arthritis from the American College of Rheumatology. After being stimulated with phorbol 12-myristate 13-acetate and ionomycin in the absence or presence of different concentrations of hydroxychloroquine, the interleukin 6, 17 and 22 levels were quantified with an enzyme-linked immunosorbent assay in culture supernatants of peripheral blood mononuclear cells from healthy individuals and patients. RESULTS: We demonstrated that in peripheral blood mononuclear cells from healthy volunteers and in systemic lupus erythematosus and rheumatoid arthritis patients, there was a significant reduction in the IL-6, IL-17 and IL-22 supernatant levels after adding hydroxychloroquine. CONCLUSIONS Our in vitro results demonstrated that hydroxychloroquine inhibits IL-6, IL-17 and IL-22 production and contributes to a better understanding of the mechanism of action of this medication

Synthesis and biological evaluation of novel imidazolidine derivatives as candidates to schistosomicidal agents

Introduction: Schistosomiasis is an infectious parasitic disease caused by trematodes of the genus Schistosoma, which threatens at least 258 million people worldwide and its control is dependent on a single drug, praziquantel. The aim of this study was to evaluate the anti-Schistosoma mansoni activity in vitro of novel imidazolidine derivatives. Material and methods: We synthesized two novel imidazolidine derivatives: (LPSF/PTS10) (Z)-1-(2-chloro-6-fluorobenzyl)-4-(4-dimethylaminobenzylidene)-5-thioxoimidazolidin-2-one and (LPSF/PTS23) (Z)-1-(2-chloro-6-fluoro-benzyl)-5-thioxo-4-(2,4,6-trimethoxy-benzylidene)-imidazolidin-2-one. The structures of two compounds were determined by spectroscopic methods. During the biological assays, parameters such as motility, oviposition, mortality and analysis by Scanning Electron Microscopy were performed. Results: LPSF/PTS10 and LPSF/PTS23 were considered to be active in the separation of coupled pairs, mortality and to decrease the motor activity. In addition, LPSF/PTS23 induced ultrastructural alterations in worms, after 24 h of contact, causing extensive erosion over the entire body of the worms. Conclusion: The imidazolidine derivatives containing the trimetoxy and benzylidene halogens showed promising in vitro schistosomicidal activity

GQ-16, a TZD-derived partial PPARγ agonist, induces the expression of thermogenesis- related genes in brown fat and visceral white fat and decreases visceral adiposity in obese and hyperglycemic mice

Background Beige adipocytes comprise a unique thermogenic cell type in the white adipose tissue (WAT) of rodents and humans, and play a critical role in energy homeostasis. In this scenario, recruitment of beige cells has been an important focus of interest for the development of novel therapeutic strategies to treat obesity. PPARγ activation by full agonists (thiazolidinediones, TZDs) drives the appearance of beige cells, a process so-called browning of WAT. However, this does not translate into increased energy expenditure, and TZDs are associated with weight gain. Partial PPARγ agonists, on the other hand, do not induce weight gain, but have not been shown to drive WAT browning. The present study was designed to investigate the effects of GQ-16 on BAT and on browning of WAT in obese mice. Methods Male Swiss mice with obesity and hyperglycemia induced by high fat diet were treated with vehicle, rosiglitazone (4 mg/kg/d) or the TZD-derived partial PPARγ agonist GQ-16 (40 mg/ kg/d) for 14 days. Fasting blood glucose, aspartate aminotransferase, alanine aminotransferase and lipid profile were measured. WAT and brown adipose tissue (BAT) depots were excised for determination of adiposity, relative expression of Ucp-1, Cidea, Prdm16, Cd40 and Tmem26 by RT-qPCR, histological analysis, and UCP-1 protein expression analysis by immunohistochemistry. Liver samples were also removed for histological analysis and determination of hepatic triglyceride content. Results GQ-16 treatment reduced high fat diet-induced weight gain in mice despite increasing energy intake. This was accompanied by reduced epididymal fat mass, reduced liver triglyceride content, morphological signs of increased BAT activity, increased expression of thermogenesis- related genes in interscapular BAT and epididymal WAT, and increased UCP-1 protein expression in interscapular BAT and in epididymal and inguinal WAT. Conclusion This study suggests for the first time that a partial PPARγ agonist may increase BAT activity and induce the expression of thermogenesis-related genes in visceral WAT. General Significance These findings suggest that PPARγ activity might be modulated by partial agonists to induce WAT browning and treat obesity

Drug repurposing clinical trials in the search for life-saving COVID-19 therapies; research targets and methodological and ethical issues

Introduction: So far, there is no vaccine, nor are there effective drugs to treat COVID-19, an emerging viral respiratory infection deadlier than influenza. Objective: To take a snapshot picture of planned and ongoing clinical research addressing drugs potentially useful for treating SAR-CoV-2 infections. Method: A search was conducted (20 April 2020) in an international registry of clinical studies (https://ClinicalTrials.gov, US NIH). After excluding observational studies and other interventions that fell outside the scope of this study, 294 research protocols (out of 516 retrieved protocols) were selected for analysis. Results: Of 294 included trials, 249 were Randomized Controlled Trials (RCT), 118 of which were double-, triple- or quadruple-blinded studies. The interventions (drug therapies) were compared with “standard-of-care” (SOC) or with the placebo plus SOC, or yet with presumed “active” comparators. RCT focused on the primary treatment of the disease (inhibitors of viral replication) or on the therapy for resolution of hyperinflammation in pneumonia/Acute Respiratory Distress Syndrome (ARDS) and thromboembolism associated with SARS-CoV-2. The trials found in the database involve existing antiviral compounds and drugs with multiple modes of antiviral action. Antiparasitic drugs, which inhibited viral replication in cell-culture assays, are being tested as well. Regarding the adjunctive immunomodulatory, anti-inflammatory and antithrombotic therapies, a number of drugs with distinct pharmacological targets are under investigation in trials enrolling patients with severe COVID-19. Conclusions: Although many clinical studies of drugs for COVID-19 are planned or in progress, only a minority of them are sufficiently large, randomized and placebo-controlled trials with masking and concealment of allocation. Owing to methodological limitations, only a few clinical trials found in the registry are likely to yield robust evidence of effectiveness and safety of drugs repurposable for COVID-19.TÍTULO PT: Ensaios clínicos para reposicionamento de medicamentos para COVID-19 na busca de terapias para salvar vidas; alvos de pesquisa, e questões metodológicas e éticas Introdução: Até agora, não há vacinas ou medicamentos eficazes para tratar COVID-19, uma infecção viral respiratória emergente mais letal do que a gripe. Objetivo: Desenhar um quadro das pesquisas planejadas e em curso sobre medicamentos potencialmente úteis para tratar infecções por SARS-CoV-2. Método: Um levantamento foi realizado (20 de abril de 2020) em um registro internacional de estudos clínicos (https://ClinicalTrials.gov, US NIH). Após excluir estudos observacionais e outras interveções fora do escopo deste estudo, 294 protocolos (de 516 identificados na busca) foram selecionados para análise. Resultados: De 294 ensaios incluídos, 249 eram Ensaios Controlados Randomizados (ECR), dos quais 118 eram estudos duplo-, triplo- ou quadruplo-cego. As intervenções (medicamentos testados) foram comparadas com o “tratamento padrão” (TP) ou com placebo mais TP, ou ainda com comparadores supostamente ativos. ECR abordaram o tratamento primário da doença (inibidores da replicação viral) ou a resolução da super-inflamação na pneumonia e Síndrome do Desconforto Respiratório Agudo (SDRA), e do tromboembolismo associados ao SARS-CoV-2. Os ensaios localizados no registro envolviam fármacos antivirais com múltiplos modos de ação e medicamentos anti-parasitários que inibem a replicação viral em cultura de células. Em relação às terapias imunomodulatória, antiinflamatória e antitrombótica adjuvantes, inúmeros medicamentos com alvos farmacológicos distintos também estão sendo investigados em ensaios envolvendo pacientes graves com COVID-19. Conclusões: Embora muitos ensaios clínicos de medicamentos para COVID-19 tenham sido planejados e estejam em andamento, apenas uma minoria deles são estudos suficientemente grandes, randomizados, controlados com placebo e com mascaramento, e ocultação da alocação. Em virtude das limitações metodológicas apontadas, provavelmente apenas uns poucos ensaios clínicos fornecerão evidências robustas da eficácia e segurança de medicamentos potencialmente redirecionáveis para COVID-19

Análise do Mercado de Oncológicos e Novas Substância Ativas para o Tratamento do Câncer / Oncology Market Analysis and New Active Substances for Cancer Treatment

O presente trabalho buscou analisar o comportamento do mercado farmacêutico de oncológicos e aspectos do planejamento de novos fármacos quimioterápicos para o tratamento do câncer aprovados pelo FDA no período 2015-2020. A análise do mercado de oncológicos demonstrou tendência de crescimento para os próximos anos e um aumento no lançamento de drogas órfãs.  Foram analisadas 50 Novas Substâncias Ativas obtidas a partir de síntese química, observando o tipo de câncer, alvo terapêutico, grupos heterocíclicos e aderência às regras de Lipinski. O principal alvo dos novos oncológicos foram as quinases (especialmente com atuação em tirosina quinases) e os principais grupos heterocíclicos foram anéis nitrogenados, com prevalência de piridinas e pirimidinas. A avaliação das regras de Lipinski demonstrou que 19 substâncias violaram ao menos uma das regras de Lipinski e três substâncias violam duas regras. A análise dos novos fármacos oncológicos demonstra a importância do desenvolvimento dos quimioterápicos e dos grupamentos heterocíclicos com a presença de nitrogênios. O estudo também oferece insumos que contribuem para o planejamento e desenvolvimento de novas moléculas que ofereçam opções seguras e eficazes para o tratamento do câncer

Evaluation of the potential toxicity of haloperidol, clozapine and a new putative antipsychotic molecule, PT-31, in an alternative toxicity model, C. elegans

Schizophrenia is a disabling mental illness that affects approximately 1% of the world population. The treatment of this disorder is based on two generations of substances, typical antipsychotics, such as haloperidol, and atypical antipsychotics, such as clozapine, which can cause severe adverse effects. Therefore, the development of novel molecules that are safe and efficacious to treat the disease is crucial. PT-31 is a putative α2-adrenoceptor agonist effective against schizophrenia positive and cognitive symptoms in mice. C. elegans is an alternative model that has been successfully used to investigate the toxicity of a variety of substances. The present study aimed to evaluate the potential toxicity of the new molecule PT-31 and the antipsychotics haloperidol and clozapine in C. elegans. The evaluation was carried out based on toxicity endpoint tests, survival, developmental and behavioral assays. The antipsychotics haloperidol and clozapine decreased nematode survival by 30 and 40%, respectively, exposing the potential toxicity of these substances whereas PT-31 was safer based on this parameter. Similar results were obtained in the nematode developmental assay: haloperidol and clozapine significantly reduced nematode body length and area, whereas PT-31 preserved the normal development of the nematodes. The behavioral assessment was based on the frequency of body bends; none of the antipsychotics affected the locomotion rate of the nematodes, and PT-31 also did not compromise this parameter, demonstrating the safety of this new compound and reinforcing the recognized toxicity of antipsychotics

Symptoms, Ca125 And He4 For The Preoperative Prediction Of Ovarian Malignancy In Brazilian Women With Ovarian Masses.

This manuscript evaluates whether specific symptoms, a symptom index (SI), CA125 and HE4 can help identify women with malignant tumors in the group of women with adnexal masses previously diagnosed with ultrasound. This was a cross-sectional study with data collection between January 2010 and January 2012. We invited 176 women with adnexal masses of suspected ovarian origin, attending the hospital of the Department of Obstetrics and Gynecology of the Unicamp School of Medicine. A control group of 150 healthy women was also enrolled. Symptoms were assessed with a questionnaire tested previously. Women with adnexal masses were interviewed before surgery to avoid recall bias. The Ward Agglomerative Method was used to define symptom clusters. Serum measurements of CA125 and HE4 were made. The Risk of Ovarian Malignancy Algorithm (ROMA) was calculated using standard formulae. Sixty women had ovarian cancer and 116 benign ovarian tumors. Six symptom clusters were formed and three specific symptoms (back pain, leg swelling and able to feel abdominal mass) did not agglomerate. A symptom index (SI) using clusters abdomen, pain and eating was formed. The sensitivity of the SI in discriminating women with malignant from those with benign ovarian tumors was 78.3%, with a specificity of 60.3%. Positive SI was more frequent in women with malignant than in women with benign tumors (OR 5.5; 95% CI 2.7 to 11.3). Elevated CA125 (OR 11.8; 95% CI 5.6 to 24.6) or HE4 (OR 7.6; 95% CI 3.7 to 15.6) or positive ROMA (OR 9.5; 95% CI 4.4 to 20.3) were found in women with malignant tumors compared with women with benign tumors. The AUC-ROC for CA125 was not different from that for HE4 or ROMA. The best specificity and negative predictive values were obtained using CA125 in women with negative SI. Women diagnosed with an adnexal mass could benefit from a short enquiry about presence, frequency and onset of six symptoms, and CA125 measurements. Primary care physicians can be thereby assisted in deciding as to whether or not reference the woman to often busy, congested specialized oncology centers.1342