924 resultados para Cl Channel


Relevância:

20.00% 20.00%

Publicador:

Resumo:

Apresenta-se uma contextualização teórica sobre a Estratégia Saúde da Família (ESF) e se discutem suas possíveis fortalezas e fragilidades. O texto foi construído com base em uma revisão da literatura com estratégia de busca definida e reflexão crítica sobre os textos selecionados. Destaca-se como um ponto importante a tentativa de resposta ao desafio de reorientar o modelo de atenção à saúde – em sua dimensão político-operacional – que emergiu em 1994, quando o Ministério da Saúde implantou o Programa Saúde da Família (PSF), que, posteriormente, passou a ser considerado a estratégia estruturante dos sistemas municipais de saúde, a ESF. Alguns aspectos apontam um avanço alcançado com a implementação da ESF, destacando-se a reorganização da Atenção Primária à Saúde (APS), o espaço-tempo da visita domiciliar e a alteridade e a produção do acolhimento na APS. Apesar dos inegáveis avanços, seus princípios e práxis ainda não são uma completa realidade no cotidiano dos serviços de saúde, destacando-se especialmente o desafio de compreender e praticar a integralidade na APS, o desafio da valorização e da adequação do perfil dos profissionais/trabalhadores da ESF, a formação, a inserção e a práxis do agente comunitário de saúde, e a dificuldade de trabalho em equipe nas unidades da ESF.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

Strategic partnerships have become a key to competitive advantage and success in a dynamic, global business environment. Partnering provides a strategic response to complex offerings that need multiple sources of technology and knowledge, allowing companies to offer a wider range of services and solutions to meet their customers’ needs. Companies that collaborate with strategic partners in sales channels may significantly grow their business and improve their prospects of winning major contracts. As a consequence, companies are increasingly transforming their go-to-market strategies and sales channel structures to align with the need to create added value to customers together with a business partner. The research objective of this case study is to review and assess the success of an established sales channel partnership in IT services industry and to find ways how to develop it towards a strategic collaboration. The research consists of two main parts. The first part reviews the literature, concluding with the identification of the critical success factors for partnering. The second part sets out for the case findings, focusing on how the success of the established sales channel partnership is perceived by key executives within the partner organizations, and further what actions are required to make the sales channel partnership and joint go-to-market more strategic.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

Kalciumjonen reglerar flera processer i celler såsom transkribering av gener, celldelning, cellernas rörlighet och celldöd. Därför har cellerna utvecklat många mekanismer för att reglera den intracellulära kalciumkoncentrationen. Kalciumkanaler spelar en viktig roll i denna regleringsprocess. TRPC-kanalerna (eng. canonical transient receptor potential) är en familj av jonkanaler med sju medlemmar (TRPC1-7) vars regleringsmekanismer och fysiologiska roller är varierande. TRPC2-kanalens fysiologiska signifikans, samt hur kanalen regleras, är dåligt karakteriserad. För första gången, rapporterar vi närvaron av TRPC2 kanalen i råttans sköldkörtelceller samt primära sköldkörtelceller från råtta. Hos gnagare har TRPC2 antagits vara exklusivt uttryckt i det vomeronasala organet. För att undersöka den fysiologiska betydelsen av kanalen, har vi utvecklat stabila celler med nedreglerat TRPC2 (shTRPC2) m.h.a. shRNA-teknik. Nedreglering av TRPC2 resulterade i stora skillnader i flera viktiga cellulära funktioner och i regleringen av sköldkörtelcellernas cellsignalering. Nedreglering av TRPC2 orsakade minskad agonist-beroende frigivning av kalcium från det endoplasmatiska nätverket, samt minskat agonist-beroende inflöde av extracellulärt kalcium, men ökade det basala kalciuminflödet. Uttrycket av PKCβ1 och PKCδ, SERCA-aktiviteten och kalciumhalten i det endoplasmatiska nätverket minskade i shTRPC2 celler. Kommunikation mellan kalcium- och cAMP-signalering påvisades vara TRPC2-beroende, vilket visades reglera uttrycket av TSH-receptorn. Vi undersökte också betydelsen av TRPC2 kanalen i reglering av sköldkörtelcellers proliferation, migration, vidhäftning och invasion; processer som alla var dämpade i shTRPC2 celler. Samamnfattningsvis påvisade dessa resultat en ny och viktig fysiologisk betydelse för TRPC2 kanalerna.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

A VDAC é a proteína mais abundante na membrana mitocondrial externa. Exerce o controle da atividade desta organela através da regulação da troca de metabólitos e tem função crucial no mecanismo de apoptose. Em nosso caso, os estudos dos complexos protéicos, das interações entre a VDAC e outras proteínas presentes no interior do neurônio que auxiliam na manutenção das funções das organelas e da célula, fazem parte da chamada interactômica. O presente estudo determinou o interactoma do complexo protéico Hexoquinase-VDAC-ANT presente em cérebros murino, bovino e aviar. Nosso objetivo foi identificar se as expressões diferenciadas da VDAC1 e VDAC2 verificadas nos cérebros murino, aviar e bovino, estão associadas a diferenças nos interactomas dessas proteínas. Este estudo revelou que as espécies aviar e bovina apresentaram o maior número de complexos protéicos contendo VDACs (5) quando comparadas com os neurônios de rato (1), o que é indicativo de uma cinética diferencial de montagem ou desmontagem do complexo. Além disso, a VDAC mitocondrial neuronal aviar também interage com mais proteínas em relação à VDAC mitocondrial neuronal bovina, o que é resultado de uma composição de subunidades diferenciada. Tais resultados indicam diferenças significativas quanto ao metabolismo energético e apoptótico no cérebro aviar, bovino e murino, existindo interações diferenciais da VDAC no cérebro aviar.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

O controle das plantas daninhas, em geral, é realizado pelo uso de herbicidas, porém essa prática é limitada na cultura do girassol, por haver apenas dois produtos registrados para essa cultura (alachlor e trifluralin). Entretanto, o uso de novas tecnologias pode facilitar o controle das plantas daninhas com herbicidas que possuem amplo espectro de controle. Assim, o objetivo deste trabalho foi avaliar a eficácia e seletividade de herbicidas do grupo das imidazolinonas aplicados em pós-emergência de plantas daninhas monocotiledôneas na cultura do girassol Clearfield (CL). Para isso, foram instalados dois experimentos em campo. Os tratamentos e as respectivas doses em g ha-1 foram: trifluralin (1.800) aplicado em pré-emergência, fluazifop-p-butil (187) e imazapic+imazapyr nas doses de [36,75+12,25], [52,5+17,5], [12,25+36,75] e [17,5+52,5], aplicados em pós-emergência, além de duas testemunhas sem aplicação de herbicida, sendo uma sem capina e outra com capina. Foram realizadas avaliações de controle para Eleusine indica, Brachiaria plantaginea, Lolium multiflorum, Digitaria insularis, Cenchrus echinatus e Digitaria horizontalis, fitointoxicação do girassol Clearfield, estande e produtividade em kg ha-1. De acordo com os resultados, verificou-se que o uso do sistema CLmostrou-se uma ótima opção para áreas com infestação de plantas daninhas monocotiledôneas, pois possibilita a aplicação de herbicidas inibidores da enzima acetolactato sintase (ALS), obtendo excelente controle das plantas daninhas, além de não provocar injúrias visuais, mantendo o estande inicial, sem alterar a produtividade da cultura.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

The importance of after-sales service or service in general can be seen and experienced by customers every day with industrial as well as other non-industrial services or products. This dissertation, drawing on theory and experience, focuses on practical engineering implications, specifically the management of customer issues in the after-sales phase in the mobile phone arena. The main objective of this doctoral dissertation is to investigate customer after-sales issue management, specifically regarding mobile phones. The case studies focus on issue resolution time and the issue of corrective actions. This dissertation consists of a main body and four peer-reviewed journal articles and one manuscript currently under review by a peer-reviewed journal. The main body of this dissertation examines the elements of customer satisfaction, loyalty, and retention with respect to corrective actions to address customer issues and issue resolution time through literature and empirical studies. The five independent works are case studies supporting the thesis research questions. This study examines four questions: 1) What are the factors affecting corrective actions for customers? 2) How can customer issue resolution time be controlled? 3) What are the factors affecting processes in the service chain? and 4) How can communication be measured in a service chain? In this work, both quantitative and qualitative analysis methods are used. The main body of the thesis reviews the literature regarding the elements that bridge the five case studies. The case studies of the articles and surveys lean more toward the methodology of critical positivism and then apply the interpretive approach in interpreting the results. The case study articles employ various statistical methods to analyze and to interpret the empirical and survey data. The statistical methods were used to create a model that is useful for significantly optimizing issue resolution time. Moreover, it was found that samples for verifying issues provided by the customer neither improve the perceived quality of corrective actions nor the perceived quality of issue resolution time. The term “service” in this work is limited to the technical services that are provided by product manufacturers and after-sales authorized service vendors. On the basis of this research work, it has been observed that corrective actions and issue resolution time are associated with customer satisfaction and hence, according to induction theory, to customer loyalty and retention. This thesis utilizes knowledge of marketing and customer relationships to contribute to the existing body of knowledge concerning information and communication technology for after-sales service recovery of mobile terminals. The established models in the thesis contribute to the existing knowledge of the after-sales process of dealing with customer issues in the field of mobile phones. The findings suggest that process managers could focus more on communication and training provided to the staff as new technology evolves rapidly. The study also suggest the managers formulate strategies for how customers can be kept informed on a regular basis of the status of issues that have been escalated for corrective action. The findings also lay the foundation for the comprehensive objective to control the entire product development process, starting with conceptualization. This implies that robust design should be applied to the new products so that problems affecting customer service quality are not repeated. The objective will be achieved when the entire service chain from product development to the final user can be modeled and this model can be used to support the organization at all levels.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

The aim of this master’s thesis was to make a qualitative marketing research and on the basis of this to develop a distribution plan for the case company Finnish 3M Ltd.’s wound care products. The literature review includes three important parts: distribution channel planning, the buying behavior of seniors, and special characteristics of health care products’ marketing. The empirical part of this thesis comprises two different parts. The first part is a marketing research, in which the buying behavior of wound care products is studied in Espoo. The research aim was to examine, in which distribution channels the wound care patients under home care would most preferably buy wound care products during the time period, when municipalities will not yet provide the products for free. The data was collected through semi-structured phone interviews and regular interviews, and was treated qualitatively and anonymously. The study revealed that the recommendations of nurses and doctors influenced most the buying behavior of wound care customers. In the second part of the thesis a distribution channel plan for wound care products was made for the case company 3M Finland Ltd. based on the results. 3M Finland Ltd. should focus on pharmacies, online-stores and municipal health centers as their main distributors.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

Cystic fibrosis (CF) is a lethal autosomal recessive genetic disease caused by mutations in the CF transmembrane conductance regulator (CFTR). Mutations in the CFTR gene may result in a defective processing of its protein and alter the function and regulation of this channel. Mutations are associated with different symptoms, including pancreatic insufficiency, bile duct obstruction, infertility in males, high sweat Cl-, intestinal obstruction, nasal polyp formation, chronic sinusitis, mucus dehydration, and chronic Pseudomonas aeruginosa and Staphylococcus aureus lung infection, responsible for 90% of the mortality of CF patients. The gene responsible for the cellular defect in CF was cloned in 1989 and its protein product CFTR is activated by an increase of intracellular cAMP. The CFTR contains two membrane domains, each with six transmembrane domain segments, two nucleotide-binding domains (NBDs), and a cytoplasmic domain. In this review we discuss the studies that have correlated the role of each CFTR domain in the protein function as a chloride channel and as a regulator of the outwardly rectifying Cl- channels (ORCCs).

Relevância:

20.00% 20.00%

Publicador:

Resumo:

The vasorelaxant effects of SR 47063 (4-(2-cyanimino-1,2-dihydropyrid-1-yl)-2,2-dimethyl-6-nitrochromene), a new K+-channel opener structurally related to levcromakalim, were examined in isolated human saphenous vein (HSV) and rat aorta (RA). HSV or RA rings were precontracted with either KCl or noradrenaline and cumulative relaxant concentration-response curves were obtained for SR 47063 (0.1 nM to 1 µM) in the presence or absence of 3 µM glibenclamide. SR 47063 potently relaxed HSV and RA precontracted with 20 mM (but not 60 mM) KCl or 10 µM noradrenaline in a concentration-dependent manner, showing slightly greater activity in the aorta. The potency of the effect of SR 47063 on HSV and RA was 12- and 58-fold greater, respectively, than that reported for the structurally related K+-channel opener levcromakalim. The vasorelaxant action of SR 47063 in both blood vessels was strongly inhibited by 3 µM glibenclamide, consistent with a mechanism of action involving ATP-dependent K+-channels.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

Nephrolithiasis is one of the most common diseases in the Western world. The disease manifests itself with intensive pain, sporadic infections, and, sometimes, renal failure. The symptoms are due to the appearance of urinary stones (calculi) which are formed mainly by calcium salts. These calcium salts precipitate in the renal papillae and/or within the collecting ducts. Inherited forms of nephrolithiasis related to chromosome X (X-linked hypercalciuric nephrolithiasis or XLN) have been recently described. Hypercalciuria, nephrocalcinosis, and male predominance are the major characteristics of these diseases. The gene responsible for the XLN forms of kidney stones was cloned and characterized as a chloride channel called ClC-5. The ClC-5 chloride channel belongs to a superfamily of voltage-gated chloride channels, whose physiological roles are not completely understood. The objective of the present review is to identify recent advances in the molecular pathology of nephrolithiasis, with emphasis on XLN. We also try to establish a link between a chloride channel like ClC-5, hypercalciuria, failure in urine acidification and protein endocytosis, which could explain the symptoms exhibited by XLN patients.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

We examined some of the mechanisms by which the aspirin metabolite and the naturally occurring metabolite gentisic acid induced relaxation of the guinea pig trachea in vitro. In preparations with or without epithelium and contracted by histamine, gentisic acid caused concentration-dependent and reproducible relaxation, with mean EC50 values of 18 µM and Emax of 100% (N = 10) or 20 µM and Emax of 92% (N = 10), respectively. The relaxation caused by gentisic acid was of slow onset in comparison to that caused by norepinephrine, theophylline or vasoactive intestinal peptide (VIP). The relative rank order of potency was: salbutamol 7.9 > VIP 7.0 > gentisic acid 4.7 > theophylline 3.7. Gentisic acid-induced relaxation was markedly reduced (24 ± 7.0, 43 ± 3.9 and 78 ± 5.6%) in preparations with elevated potassium concentration in the medium (20, 40 or 80 mM, respectively). Tetraethylammonium (100 µM), a nonselective blocker of the potassium channels, partially inhibited the relaxation response to gentisic acid, while 4-AP (10 µM), a blocker of the voltage potassium channel, inhibited gentisic acid-induced relaxation by 41 ± 12%. Glibenclamide (1 or 3 µM), at a concentration which markedly inhibited the relaxation induced by the opener of ATP-sensitive K+ channels, levcromakalim, had no effect on the relaxation induced by gentisic acid. Charybdotoxin (0.1 or 0.3 µM), a selective blocker of the large-conductance Ca2+-activated K+ channels, caused rightward shifts (6- and 7-fold) of the gentisic acid concentration-relaxation curve. L-N G-nitroarginine (100 µM), a NO synthase inhibitor, had no effect on the relaxant effect of gentisic acid, and caused a slight displacement to the right in the relaxant effect of the gentisic acid curve at 300 µM, while methylene blue (10 or 30 µM) or ODQ (1 µM), the inhibitors of soluble guanylate cyclase, all failed to affect gentisic acid-induced relaxation. D-P-Cl-Phe6,Leu17[VIP] (0.1 µM), a VIP receptor antagonist, significantly inhibited (37 ± 7%) relaxation induced by gentisic acid, whereas CGRP (8-37) (0.1 µM), a CGRP antagonist, only slightly enhanced the action of gentisic acid. Taken together, these results provide functional evidence for the direct activation of voltage and large-conductance Ca+2-activated K+ channels, or indirect modulation of potassium channels induced by VIP receptors and accounts for the predominant relaxation response caused by gentisic acid in the guinea pig trachea.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

Ischemic pain occurs when there is insufficient blood flow for the metabolic needs of an organ. The pain of a heart attack is the prototypical example. Multiple compounds released from ischemic muscle likely contribute to this pain by acting on sensory neurons that innervate muscle. One such compound is lactic acid. Here, we show that ASIC3 (acid-sensing ion channel #3) has the appropriate expression pattern and physical properties to be the detector of this lactic acid. In rats, it is expressed only in sensory neurons and then only on a minority (~40%) of these. Nevertheless, it is expressed at extremely high levels on virtually all dorsal root ganglion sensory neurons that innervate the heart. It is extraordinarily sensitive to protons (Hill slope 4, half-activating pH 6.7), allowing it to readily respond to the small changes in extracellular pH (from 7.4 to 7.0) that occur during muscle ischemia. Moreover, both extracellular lactate and extracellular ATP increase the sensitivity of ASIC3 to protons. This final property makes ASIC3 a "coincidence detector" of three molecules that appear during ischemia, thereby allowing it to better detect acidosis caused by ischemia than other forms of systemic acidosis such as hypercapnia.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

We have shown that myocardial dysfunction induced by food restriction is related to calcium handling. Although cardiac function is depressed in food-restricted animals, there is limited information about the molecular mechanisms that lead to this abnormality. The present study evaluated the effects of food restriction on calcium cycling, focusing on sarcoplasmic Ca2+-ATPase (SERCA2), phospholamban (PLB), and ryanodine channel (RYR2) mRNA expressions in rat myocardium. Male Wistar-Kyoto rats, 60 days old, were submitted to ad libitum feeding (control rats) or 50% diet restriction for 90 days. The levels of left ventricle SERCA2, PLB, and RYR2 were measured using semi-quantitative RT-PCR. Body and ventricular weights were reduced in 50% food-restricted animals. RYR2 mRNA was significantly decreased in the left ventricle of the food-restricted group (control = 5.92 ± 0.48 vs food-restricted group = 4.84 ± 0.33, P < 0.01). The levels of SERCA2 and PLB mRNA were similar between groups (control = 8.38 ± 0.44 vs food-restricted group = 7.96 ± 0.45, and control = 1.52 ± 0.06 vs food-restricted group = 1.53 ± 0.10, respectively). Down-regulation of RYR2 mRNA expressions suggests that chronic food restriction promotes abnormalities in sarcoplasmic reticulum Ca2+ release.