Patienters upplevelser av att leva med Amyotrofisk LateralSkleros, ALS

Syfte: Syftet med litteraturöversikten var att sammanställa aktuell forskning som beskriver hur det är att leva med Amyotrofisk Lateral Skleros (ALS). Metod: Vetenskapliga artiklar söktes i databaserna CINAHL och PubMed. Tolv artiklar med kvalitativ ansats valdes ut och kvalitetsgranskades enligt granskningsmall för kvalitativa studier. Huvudresultat: Resultatet visade att de som drabbades av ALS, en obotlig sjukdom, och deras närstående utsattes för stora psykologiska påfrestningar. Det fanns en rädsla och oro över att förlora kroppsfunktioner utan förvarning och detta medförde att patienter med ALS kände sig som fångar i den egna kroppen. Självförtroende och självkänsla rubbades negativt och bidrog till stunder av isolering, uppgivenhet och frustration. För att hantera sin livssituation använde sig patienter med ALS av olika strategier och livsstilsförändringar för att underlätta och möjliggöra ett oberoende i vardagen. Känslor av skuld och skam över familjens lidande i samband med sjukdomen ALS kunde bli en börda att bära för patienter med ALS och dessa känslor kunde generera till ett ökat kontrollbehov av omgivningen. Patienter med ALS hade kvar en känsla av hopp inför framtiden. Slutsats: Litteraturöversikten kan öka förståelsen hos sjuksköterskan och de närstående hur det är att leva med sjukdomen ALS och därmed skapa bättre individuella förutsättningar för god omvårdnad och god omsorg för patienter med ALS.

Internet share of advertising expenditure : growth drivers and inhibitors in the brazilian market

Os investimentos com publicidade na Internet como uma percentagem das despesas totais de publicidade variam significativamente de um país para outro. O número é tão baixo quanto 4,7% no mercado brasileiro e tão alto como 28,5% no mercado britânico (ZenithOptimedia, 2011b). Algumas razões explicam tal disparidade. No nível macro, a participação dos gastos com publicidade na Internet está fortemente ligada a variáveis como o produto interno bruto per capita e à penetração da Internet na população. No nível micro, uma pesquisa qualitativa foi feita para identificar os fatores que contribuem e inibem o crescimento da participação da publicidade online no mercado brasileiro. A vasta lista de inibidores parece ter profundo impacto sobre como os profissionais de mercado tomar decisões de alocação de investimento em publicidade por tipo de mídia. Devido à legislação, à auto-regulamentação e às dinâmicas da indústria, grande parte da tomada de decisão é realizada por agências de publicidade. Estas parecem ter fortes incentivos econômicos para selecionar outros tipos de mídia e não a Internet ao definir planos de mídia. Ao mesmo tempo, a legislação e a auto-regulamentação fornecem desincentivos para corretores de mídia a operar no mercado local. A falta de profissionais qualificados e a padronização limitada também desempenham papéis importante para inibir uma maior participação da Internet nos gastos com publicidade no Brasil. A convergência dos resultados quantitativos com os qualitativos indica possíveis motivos pelos quais a participação da publicidade online no Brasil é tão baixa. Em primeiro lugar, a participação é explicada pelo estágio de desenvolvimento dos países. Quanto mais rico e mais desenvolvido um país, maior a proporção de gastos com publicidade online tende a ser. Em segundo lugar, o estágio econômico emergente do Brasil potencialmente dá espaço para o aumento do ineficiências do mercado, tais como programas de descontos oferecidos de forma desproporcional para os principais decisores de alocação de investimentos de mídia. Este fato aparentemente produz um feedback negativo, contribuindo para manter a baixa participação da publicidade online no total dos investimentos publicitários.

Efeito do déficit hídrico na eficiência de herbicidas e nas características bioquímicas de picão-preto

The objective of this work was to evaluate conditions the effectiveness of acetolactate synthase (ALS) and protoporphyrinogen oxidase (PROTOX) inhibitors in the Bidens pilosa control under two water deficit conditions, as well as to determine the influence of water deficit under the contents of soluble carbohydrates and protein of weed. The experimental design was randomized completely design with the treatments, with four replications, setup in a factorial scheme 4x2, with four herbicides (fomesafen lactofen, chlorimuron-ethyl and imazethapyr), and two water conditions (-0.5 MPa and -0.01MPa). At 7, 14, 21 and 28 days after application (DAA), was assessed visually control efficiency of herbicides. For the determination of organic solutes plants were collected at 24, 48, 72 and 96 hours after application (HAA). Herbicides controlled efficiently plants of B. pilosa, except lactofen, whereas the water deficit affected the efficiency of control of all the herbicides. The soluble carbohydrate content increased with the imposition of water deficit, however, herbicides and water deficit further reduction of soluble proteins in plants of B. pilosa.

Seletividade de herbicidas aplicados em pós-emergência sobre capim-braquiária

O estudo foi conduzido com o objetivo de avaliar a seletividade de alguns herbicidas inibidores de ALS e FS II aplicados em pós-emergência em plantas de Brachiaria brizantha cv. Marandu e Brachiaria decumbens cv. Basilisk em condições de campo e seu efeito na qualidade das sementes. Os herbicidas testados (em g/ha) foram: imazethapyr a 100; chlorimuronethyl a 15; nicosulfuron a 50; bentazon a 720; e atrazine a 3.000, além de uma testemunha, sem aplicação de herbicidas. Dois experimentos em campo foram instalados em delineamento em blocos casualizados com quatro repetições e os ensaios de laboratório em delineamento inteiramente casualizado, com 16 repetições. Todos os herbicidas testados tiveram algum efeito de fitointoxicação visual aos cultivares avaliados. O nicosulfuron foi o herbicida que visualmente proporcionou os níveis mais elevados de injúrias às plantas de B. decumbens e B. brizantha. A produção de MS de B. brizantha nos estádios iniciais de crescimento foi reduzida pelos herbicidas nicosulfuron e atrazine, enquanto, em B. decumbens, apenas o herbicida nicosulfuron ocasionou redução da produção de MS. A qualidade das sementes de ambos os cultivares foi afetada pelo nicosulfuron, que induziu a dormência em sementes de B. decumbens, reduziu a porcentagem de sementes normais e, assim como o atrazine, aumentou a porcentagem de sementes mortas.

Diapocynin versus apocynin as pretranscriptional inhibitors of NADPH oxidase and cytokine production by peripheral blood mononuclear cells

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Variability and resistance mutations in the hepatitis C virus NS3 protease in patients not treated with protease inhibitors

The goal of treatment of chronic hepatitis C is to achieve a sustained virological response, which is defined as exhibiting undetectable hepatitis C virus (HCV) RNA levels in serum following therapy for at least six months. However, the current treatment is only effective in 50% of patients infected with HCV genotype 1, the most prevalent genotype in Brazil. Inhibitors of the serine protease non-structural protein 3 (NS3) have therefore been developed to improve the responses of HCV-infected patients. However, the emergence of drug-resistant variants has been the major obstacle to therapeutic success. The goal of this study was to evaluate the presence of resistance mutations and genetic polymorphisms in the NS3 genomic region of HCV from 37 patients infected with HCV genotype 1 had not been treated with protease inhibitors. Plasma viral RNA was used to amplify and sequence the HCV NS3 gene. The results indicate that the catalytic triad is conserved. A large number of substitutions were observed in codons 153, 40 and 91; the resistant variants T54A, T54S, V55A, R155K and A156T were also detected. This study shows that resistance mutations and genetic polymorphisms are present in the NS3 region of HCV in patients who have not been treated with protease inhibitors, data that are important in determining the efficiency of this new class of drugs in Brazil.

COX-2 Inhibitors for Cancer Treatment in Dogs

Cancer is one of the main causes of death in canines and felines, and this fact is probably related to the increase in the longevity of these species. The longer the animals live, the higher the exposure to carcinogenic agents will be. With the high incidence of cancer in companion animals, new studies are currently being performed with the aim of finding therapeutic options which make the complete inhibition of the development of neoplasms in animals possible in the future. The correlation of cyclooxygenase-2 (COX-2) whith the development of cancer opens the way for the use of new therapeutic approaches. This relationship has been suggested based on various studies which established an association between the chronic use of nonsteroidal anti-inflammatory drugs (NSAID) and a decrease in the incidence of colon carcinoma. As cancer progresses, COX-2 participates in the arachidonic acid metabolism by synthesizing prostaglandins which can mediate various mechanisms related to cancer development such as: increase in angiogenesis, inhibition of apoptosis, suppression of the immune response, acquisition of greater invasion capacity and metastasis. Accordingly, overexpression of this enzyme in tumors has been associated with the most aggressive, poor-prognosis cancer types, especially carcinomas. Therefore, treatments which use COX-2 inhibitors such as coxibs, whether administered as single agents or in combination with conventional antineoplastic chemotherapy, are an alternative for extending the survival of our cancer patients.

The Potential of p38 MAPK Inhibitors to Modulate Periodontal Infections

Periodontal disease initiation and progression occurs as a consequence of the host immune inflammatory response to oral pathogens. The innate and acquired immune systems are critical for the proper immune response. LPS, an outer membrane constituent of periodontal pathogenic bacteria, stimulates the production of inflammatory cytokines IL-1 beta TNF alpha IL-6 and RANKL either directly or indirectly. In LPS-stimulated cells, the induction of cytokine expression requires activation of several signaling pathways including the p38 MAPK pathway. This review will discuss the significance of the p38 MAPK pathway in periodontal disease progression and the potential therapeutic consequences of pharmacological antagonism of this pathway in the treatment of periodontal diseases.

Subfornical organ mediates pressor effect of angiotensin: Influence of nitric oxide synthase inhibitors, AT(1) and AT(2) angiotensin antagonist's receptors

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Crystallization and preliminary X-ray diffraction analysis of an acidic phospholipase A(2) complexed with p-bromophenacyl bromide and alpha-tocopherol inhibitors at 1.9-and 1.45-A resolution

An acidic phospholipase A(2) (PLA(2)) isolated from Bothrops jararacussu snake venom was crystallized with two inhibitors: alpha-tocopherol (vitamin E) and p-bromophenacyl bromide (BPB). The crystals diffracted at 1.45- and 1.85-Angstrom resolution, respectively, for the complexes with alpha-tocopherol and p-bromophenacyl bromide. The crystals are not isomorphous with those of the native protein, suggesting the inhibitors binding was successful and changes in the quaternary structure may have occurred. (C) 2004 Elsevier B.V. All rights reserved.

Snake venom phospholipase A(2) inhibitors: Medicinal chemistry and therapeutic potential

Phospholipases A(2) (PLA(2)s) are commonly found in snake venoms from Viperidae, Hydrophidae and Elaphidae families and have been extensively studied due to their pharmacological and physiopathological effects in living organisms. This article reports a review on natural and artificial inhibitors of enzymatic, toxic and pharmacological effects induced by snake venom PLA(2)s. These inhibitors act on PLA(2)S through different mechanisms, most of them still not completely understood, including binding to specific domains, denaturation, modification of specific amino acid residues and others. Several substances have been evaluated regarding their effects against snake venoms and isolated toxins, including plant extracts and compounds from marine animals, mammals and snakes serum plasma, in addition to poly or monoclonal antibodies and several synthetic molecules. Research involving these inhibitors may be useful to understand the mechanism of action of PLA(2)s and their role in envenomations caused by snake bite. Furthermore, the biotechnological potential of PLA(2) inhibitors may provide therapeutic molecular models with antiophidian activity to supplement the conventional serum therapy against these multifunctional enzymes.

Proteomic analysis reveals suppression of bark chitinases and proteinase inhibitors in citrus plants affected by the citrus sudden death disease

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The kinetic mechanism of human uridine phosphorylase 1: Towards the development of enzyme inhibitors for cancer chemotherapy

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Molecular models of tryptophan synthase from Mycobacterium tuberculosis complexed with inhibitors

The development of new therapies against infectious diseases is vital in developing countries. Among infectious diseases, tuberculosis is considered the leading cause of death. A target for development of new drugs is the tryptophan pathway. The last enzyme of this pathway, tryptophan synthase (TRPS), is responsible for conversion of the indole 3-glycerol phosphate into indol and the condensation of this molecule with serine-producing tryptophan. The present work describes the molecular models of TRPS from Mycobacterium tuberculosis (MtTRPS) complexed with six inhibitors, the indole 3-propanol phosphate and five arylthioalkyl-phosphonated analogs of substrate of the a-subunit. The molecular models of MtTRPS present good stereochemistry, and the binding of the inhibitors is favorable. Thus, the generated models can be used in the design of more specific drugs against tuberculosis and other infectious diseases.

Structural bioinformatics study of cyclin-dependent kinases complexed with inhibitors

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)