Planejamento e síntese de seleno-diidropirimidinonas e avaliação como agentes multi-alvo para o tratamento da doença de Alzheimer

Tese (doutorado) - Universidade Federal de Santa Catarina, Centro de Ciências Físicas e Matemáticas, Programa de Pós-Graduação em Química, Florianópolis, 2014.Nesta tese de doutorado realizou-se a síntese de uma nova classe de compostos organoselênio bioativos, que são as selenodiidropirimidinonas. Para tanto, uma rota sintética curta e linear foi estabelecida para síntese destes compostos, e através desta foi possível obter as diidropirimidinonas com grande diversidade estrutural e funcionalizadas com grupamentos selenetos, disselenetos, selenocianatos, selenoesteres e calcogenouréias imidazólicas. A série dos selenocianatos derivados de diidropirimidinonas foi avaliada quanto a sua atividade como inibidores da enzima acetilcolinesterase, como quelantes do átomo de ferro (II) e também como antioxidantes através dos mecanismos da glutationa peroxidase, poder redutor e capacidade antioxidante total. Todos os compostos testados apresentaram atividade como inibidores da acetilcolinesterase próximo ao fármaco padrão galantamina, sendo que alguns compostos foram mais ativos que este. Todos os compostos também apresentaram atividade como miméticos da glutationa peroxidase e boa capacidade antioxidante através dos demais testes realizados. Com a metodologia proposta, foi possível sintetizar uma série de novas seleno-diidropirimidinonas e demonstrar sua ação como inibidores da acetilcolinesterase e como antioxidantes, bem como quelantes do átomo de ferro (II). Os compostos sintetizados apresentam um grande potencial como novos candidatos a fármacos multi-alvo para o tratamento da doença de Alzheimer.Abstract : In this thesis the synthesis of a new class of bioactive organoselenium compounds was performed, the seleno-dihydropyrimidinones. A short and linear synthetic route was optimized for the synthesis of the selenodihydropyrimidinones, and the dihydropyrimidinones were obtained with high structural diversity containing selenides, diselenides, selenocyanides, selenoesthers and imidazolic chalcogen ureas as substituents. The selenocyanides derived from dihydropyrimidinones were evaluated as acethylcolinesterase inhibitors, iron chelators and also as antioxidants through the glutathione peroxidase mechanism, reduction power and total antioxidant capacity, respectively. All tested compounds were as active as the standard as acethylcolinesterase inhibitors, being some compounds more active than the standard galanthamine. All compounds also presented glutathione peroxidase mimetic activity and showed good antioxidant properties by several mechanisms. Thus, a new series of seleno-dihydropyrimidinones was synthesized and demonstrated excellent acethylcholinesterase inhibition, as well as antioxidant and iron chelator properties. The synthesized compounds can be considered as a very promissor multi-targeted agents for the treatment of Alzheimer s disease

Estudo de caso: perfil de perda no beneficiamento da rocha Ornamental / Case study: profile of loss in the benefit of the Ornamental rock

O estado do Espírito Santo concentra o maior parque industrial de beneficiamento de rocha ornamental do Brasil. A pesquisa em questão foi realizada na cidade de Nova Venécia, ES conhecida como a capital nacional do granito. A metodologia consistiu em um estudo de caso do tipo exploratório. O estudo teve como objetivo analisar o percentual de perda de material no beneficiamento de diferentes tipos de rochas ornamentais na etapa de serragem/desdobramento do bloco. Os resultados foram correlacionados com as propriedades físicas e variáveis do processo, a fim de entender o comportamento de cada material no processo produtivo e traçar um perfil de perdas para diferentes tipologias das rochas processadas. Trata-se, portanto, de uma ferramenta de natureza pragmática que poderá ser utilizada no gerenciamento/planejamento das atividades de uma unidade industrial de beneficiamento de rochas ornamentais. 

Pentacloreto de nióbio (NbCl5) : um novo catalisador ácido de Lewis aplicado na síntese de 3,4-dihidropirimidinonas

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Desastre da Samarco no Brasil: desafios para a conservação da biodiversidade

On November 5, 2015, Brazil and the world noticed the environmental disaster caused by the disruption of Fundão dam (Samarco / Vale / BHP Billiton) in Mariana, Minas Gerais. The disaster's impact was not restricted to dam’s immediately downstream areas, where caused destruction of human settlements, but also impacted waterways, farmland, economic activities, drinking water supply to cities and biodiversity. The State Park of Rio Doce (PERD), the main remnant of the Atlantic Forest from Minas Gerais state faced a threat not predicted in his management plan. So, this article is dedicated to the history and importance of the PERD, to the Samarco/Vale/BHP disaster and to impacts on this Conservation Unit. Therefore, it discusses disaster impacts to human life and biodiversity, because ecological conditions even imply on opportunities and obstacles to Social Processes.No dia 5 de novembro de 2015, o Brasil e o mundo tomaram conhecimento do desastre ambiental provocado pelo rompimento da barragem de Fundão (Samarco/Vale/BHP Billiton), em Mariana-MG. O impacto do desastre não se restringiu às áreas imediatas à jusante do barramento, onde causou destruição de assentamentos humanos, mas impactou cursos d’água, terras agricultáveis, atividades econômicas, abastecimento de água potável para cidades e a biodiversidade. O Parque Estadual do Rio Doce (PERD), principal remanescente da Mata Atlântica do estado, se viu diante de uma ameaça não prevista em seu plano de manejo. Assim, este artigo é dedicado à história e importância do PERD, ao desastre da Samarco/Vale/BHP e aos impactos provocados nesta unidade de conservação. Discute-se impactos do desastre para a vida humana e biodiversidade, inclusive porque as condições ecológicas implicam em possibilidades e entraves para processos sociais

Development of copper hatch baskets and evaluation of the productive indexes of a commercial hatchery

Background: The dissemination of pathogenic microorganisms in hatcheries leads to a higher number of contaminated eggs, causing reduction in hatchability and increase of discarded chicks. Sanitation programs are crucial for maximum hatchability and chick quality. Efforts have been made to find alternative approaches to the conventional disinfectants, and surfaces with copper, which have antimicrobial properties, could assist in this process. However, the possible adverse effects of copper surfaces on chicks in hatcheries have not yet been evaluated. The present study aimed at developing hatch baskets composed of copper and evaluating the effect of these baskets on the productive indexes of a hatchery. Materials, Methods & Results: For this experiment, 3.15 kg hatch tray prototypes with 99.9% Cu (Cu11000) were developed to fit inside conventional polypropylene hatch baskets (580 × 755 × 83 mm). Six polypropylene hatch baskets (control group) and six polypropylene hatch baskets covered by 99.9% copper (Cu11000) hatch trays (test group) were evaluated during 5 hatchings. Hatched eggs and chicks remained in contact with the hatch basket surfaces for at least 72 h, corresponding to the entire period in which they were located in the hatcher. Cleaning and disinfection programs of the hatchery were not modified. The level of microbial contamination on the hatch baskets was evaluated at 6 different periods: 0 h (initial contamination after disinfection and egg transfer to the trays); 24 h, 30 h, 45 h and 60 h after the first sampling; and at the moment when chicks were removed from the hatching cabinet and transferred to the chick-holding room (> 60 h). Counting of total moulds and yeasts, mesophilic microorganisms, Enterobacteria and Escherichia coli colonies was performed. The number of hatched chicks, non-hatched eggs, and chicks discarded were registered for each hatching. Microbiologic analyses showed no growth on hatch baskets neither of the test group nor on those of the control group, regardless of the period evaluated. No significant difference was found between the two groups in the counts of hatched chicks, non-hatched eggs, and chicks discarded. Discussion: The antimicrobial efficacy of copper surfaces has been established for a variety of bacteria and fungi, including in the healthcare environment. In addition, antimicrobial resistance to copper is extremely rare because of copper’s multisite kill mechanism and other mostly nonspecific damage mechanisms. Several copper applications have been established; however, the potential adverse effects of using copper surfaces in hatcheries on chicks or on hatchery productive indexes had not yet been evaluated. The analyses performed in this study did not show microbiological growth. The results showed that the copper surface did not cause any significant adverse effects on chicks. The hatched chicks were visually healthy, and no significant difference was found between the numbers of chicks discarded in the control and test groups. Since the production parameters were not altered or impaired in the present study, it is possible to conclude that the use of copper surfaces in hatcheries can be an effective tool in the microbiological control of these environments. Nevertheless, copper alloys lend themselves to the creation of self-sanitizing surfaces that should be used as a complement and not as a substitute for standard cleaning and disinfection practices

Development of Copper Hatch Baskets and Evaluation of the Productive Indexes of a Commercial Hatchery

Background: The dissemination of pathogenic microorganisms in hatcheries leads to a higher number of contaminated eggs, causing reduction in hatchability and increase of discarded chicks. Sanitation programs are crucial for maximum hatchability and chick quality. Efforts have been made to find alternative approaches to the conventional disinfectants, and surfaces with copper, which have antimicrobial properties, could assist in this process. However, the possible adverse effects of copper surfaces on chicks in hatcheries have not yet been evaluated. The present study aimed at developing hatch baskets composed of copper and evaluating the effect of these baskets on the productive indexes of a hatchery.Materials, Methods and Results: For this experiment, 3.15 kg hatch tray prototypes with 99.9% Cu (Cu11000) were developed to fit inside conventional polypropylene hatch baskets (580 × 755 × 83 mm). Six polypropylene hatch baskets (control group) and 6 polypropylene hatch baskets covered by 99.9% copper (Cu11000) hatch trays (test group) were evaluated during 5 hatchings. Hatched eggs and chicks remained in contact with the hatch basket surfaces for at least 72 h, corresponding to the entire period in which they were located in the hatcher. Cleaning and disinfection programs of the hatchery were not modified. The level of microbial contamination on the hatch baskets was evaluated at 6 different periods: 0 h (initial contamination after disinfection and egg transfer to the trays); 24 h, 30 h, 45 h and 60 h after the first sampling; and at the moment when chicks were removed from the hatching cabinet and transferred to the chick-holding room (> 60 h). Counting of total moulds and yeasts, mesophilic microorganisms, Enterobacteria and Escherichia coli colonies was performed. The number of hatched chicks, non-hatched eggs, and chicks discarded were registered for each hatching. Microbiologic analyses showed no growth on hatch baskets neither of the test group nor on those of the control group, regardless of the period evaluated. No significant difference was found between the two groups in the counts of hatched chicks, non-hatched eggs, and chicks discarded. Discussion: The antimicrobial efficacy of copper surfaces has been established for a variety of bacteria and fungi, including in the healthcare environment. In addition, antimicrobial resistance to copper is extremely rare because of copper’s multisite kill mechanism and other mostly nonspecific damage mechanisms. Several copper applications have been established; however, the potential adverse effects of using copper surfaces in hatcheries on chicks or on hatchery productive indexes had not yet been evaluated. The analyses performed in this study did not show microbiological growth. The results showed that the copper surface did not cause any significant adverse effects on chicks. The hatched chicks were visually healthy, and no significant difference was found between the numbers of chicks discarded in the control and test groups. Since the production parameters were not altered or impaired in the present study, it is possible to conclude that the use of copper surfaces in hatcheries can be an effective tool in the microbiological control of these environments. Nevertheless, copper alloys lend themselves to the creation of self-sanitizing surfaces that should be used as a complement and not as a substitute for standard cleaning and disinfection practices

Clinical and epidemiological characteristics of patients with Amyotrophic Lateral Sclerosis (ALS) in central Brazil

Objective: This study aimed to evaluate the clinical-epidemiological characteristics of patients with Amyotrophic Lateral Sclerosis (ALS) in the State of Goiás, Brazil. Methods: We conducted a descriptive cross-sectional study to assess medical records of patients with ALS followed-up at the State Rehabilitation and Readaptation Medical Center Dr. Henrique Santillo, Goiânia, GO, Brazil, between 2005 and 2018. In addition, we registered and created a photographic panel with the main clinical findings of ALS cases. Results: From 224 investigated patients, 51.8% were male, and 67.4% manifested the classic form of the disease. Initial symptoms were more frequent in the lower limbs (37.9%), and complications resulted in 45.5% of tracheostomy, 60.3% of gastrostomy, and 49.1% of deaths. Most patients had a five-year survival from the onset of symptoms, and no significant association between the use of non-invasive ventilation and increased survival were found. The analysis of the clinical-epidemiological characteristics showed a more extended time between the first symptoms and the diagnosis of the disease was observed. Conclusion: In this study, the time between the first symptoms and diagnosis was longer than in the literature, resulting in late treatments. In addition, there was no satisfactory result regarding survival with the use of non-invasive ventilation. Therefore, clinical-epidemiological studies of the disease in Brazil, as well as public awareness and training of professionals in recognition of ALS clinical signs will assist in early and more efficient interventions.Objetivo: Este estudo teve como objetivo avaliar as características clínico-epidemiológicas de pacientes com Esclerose Lateral Amiotrófica (ELA) no Estado de Goiás, Brasil. Métodos: Foi realizado um estudo transversal descritivo para avaliação de prontuários de pacientes com ELA acompanhados no Centro Médico Estadual de Reabilitação e Readaptação Dr. Henrique Santillo, Goiânia, GO, Brasil, entre 2005 e 2018. Além disso, registramos e criamos um painel fotográfico com os principais achados clínicos dos casos de ELA. Resultados: Dos 224 pacientes investigados, 51,8% eram do sexo masculino e 67,4% manifestavam a forma clássica da doença. Os sintomas iniciais foram mais frequentes em membros inferiores (37,9%) e as complicações resultaram em 45,5% de traqueostomia, 60,3% de gastrostomia e 49,1% de óbitos. A maioria dos pacientes teve sobrevida de cinco anos desde o início dos sintomas, e nenhuma associação significativa entre o uso de ventilação não-invasiva e aumento da sobrevida foi encontrada. A análise das características clínico-epidemiológicas mostrou um tempo mais prolongado entre os primeiros sintomas e o diagnóstico da doença. Conclusão: Neste estudo, o tempo entre os primeiros sintomas e o diagnóstico foi maior quando comparado à literatura, resultando em tratamentos tardios. Além disso, não houve resultado satisfatório em termos de sobrevida com o uso da ventilação não-invasiva. Portanto, estudos clínico-epidemiológicos sobre a doença no Brasil, bem como a conscientização pública e o treinamento de profissionais para o reconhecimento dos sinais clínicos de ELA, auxiliarão em intervenções precoces e mais eficazes

Nascentes urbanas em São Sebastião do Paraíso - MG: uma análise como plataforma de planejamento / Urban springs in São Sebastião do Paraíso - MG: an analysis as a planning platform

O parcelamento e a ocupação do solo urbano estão integrados ao ordenamento territorial, conforme parâmetros previamente estabelecidos pelo plano diretor municipal e legislações afins. A ocorrência de Área de Preservação Permanente oriunda de afloramentos do lençol freático, pode resultar em restrições de uso na área objeto de urbanização. Amiúde ocorrem divergências na interpretação da legislação, identificação e classificação relativas às nascentes urbanas e as áreas de restrição de uso a elas inerentes. A elaboração de uma base de dados onde se evidenciam as nascentes urbanas e suas características tornou-se o objetivo principal desse estudo. A bacia hidrográfica foi utilizada como suporte no intuito e crença de sua importância, já consolidada, como unidade de planejamento.  Buscou-se a identificação e o mapeamento das nascentes do município de São Sebastião do Paraíso – MG, utilizando-se de ferramentas como sensoriamento remoto, geoprocessamento e software de SIG. Obteve-se o mapeamento de 1012 nascentes, sendo que o montante de 154, que são o objeto desse estudo, estão dispostas em cinco sub-bacias hidrográficas do perímetro urbano. Esta pesquisa subsidiará a tomada de decisão de órgãos gestores, profissionais envolvidos em planejamento urbano e na problemática ambiental, de forma a contribuir para consolidar estratégias de recuperação que favoreça a conservação e preservação desses ecossistemas tão biodiversos. O levantamento das nascentes urbanas e o primeiro olhar com relação a sua qualidade facilitarão a direção de estudos mais específicos sobre o tema