Äldre och psykofarmaka : Några sjuksköterskors uppfattning

Nearly nine percent of the population in Sweden are 75 years or older. Still they consume more than a quarter of all medicines. This increased use, is specially noticeable in nursing home residents, where the elderly is using a average of 8-10 preparations per day. According to the National Board of Health and Welfare in Sweden, the number of drugs and specially psychotropic drugs, has proved to be a risk factor for drug-related problems among the elderly, such as drug interaction and side effects. Routines for regular and systematic follow-up of drug prescription and utilisation reviews were not extensively implemented. According to the National Board of Health and Welfare its important to start the work to reduce psychotropic drugs among the elderly in nursing homes. Aim: This studie examine nurses apprehension about psychotopic drugs among the elderly in nursing homes. Method: An questionnarie based survey whit 10 closed questions. The questionary was answered of 46 nurses who works in nursing homes. Result: A majority of the nurses, tought the elderly in nursing homes were using to musch psychotropic drugs. The nurses tought that psychotropic drugs often prescribes as a matter of routin, particullary hypnotics and sedeativs. Those drugs was not effectiv in long terms according to the nurses. They also tought that alternative mehtods should be considered before describing pscyhotropic drugs. The nurses tought as a occupational group, that they had a responsibility to follow up and evaluate the elderlys medication whit psychotropic drugs.

Malnutrition vid cytostatikabehandligen, sjuksköterskans förebyggande och lindrande omvårdnadsåtgärder : systematisk litteraturstudie

Syftet men denna systematiska litteraturstudie har varit att beskriva vilka komplikationer, som kunde leda till malnutrition hos cancerpatienter när de genomgått cytostatikabehandling. Studien syftar även till att beskriva vilka omvårdnadsåtgärder sjuksköterskan kunde vidta för att förebygga och lindra dessa komplikationer hos patienter med cancer. Artikelsökningen har skett via databaserna Elin@Dalarna, Blackwell Synergy och ScienceDirect (Elsevier). Sökorden som användes var cancer, constipation, fatigue, malnutrition, nutrition, nursing, pain, support, treatment, chemotherapy, side-effects, prevention, oral, complication, nausea, nutritional support, weight loss, BMR, oncology och care. Resultatet visade att komplikationerna som cancerpatienterna kunde drabbas av var fatigue, diareér, kräkningar, såriga slemhinnor och illamående. Dessa komplikationer kunde leda till malnutrition. Många patienter med cancer kunde dö av malnutrition istället för själva sjukdomen. Malnutrierade patienter med cancer kunde även få fler komplikationer av cytostatikabehandlingen än de patienter med cancer som var normalviktiga. Att följa upp nutritionsstatusen tidigt visade sig vara mycket viktigt för att förebygga och lindra komplikationerna och hjälpa patienter med cancer att motarbeta malnutritionen. Samarbetet med andra vårdgivare visade sig vara nödvändigt för att patienten med cancer skulle få en så bra omvårdnad som möjligt.

Evaluating Projects in a Dynamic Economy: Some New Envelope Results

This paper is concerned with the modern theory of social cost-benefit analysis in a dynamic economy. The theory emphasizes the role of a comprehensive, forward-looking, dynamic welfare index within the period of the project rather than that of a project's long-term consequences. However, what constitutes such a welfare index remains controversial in the recent literature. In this paper, we attempt to shed light on the issue by deriving three equivalent cost-benefit rules for evaluating a small project. In particular, we show that the direct change in net national product (NNP) qualifies as a convenient welfare index without involving any other induced side effects. The project evaluation criterion thus becomes the present discounted value of the direct changes in NNP over the project period. We also illustrate the application of this theory in a few stylized examples.

Acupuncture for labour pain

Background: Acupuncture involves puncturing the skin with thin sterile needles at defined acupuncture points. Previous studies are inconclusive regarding the effect of acupuncture on labour pain, but some studies have found a reduction in the use of pharmacological pain relief when acupuncture is administered. The appropriate dose of acupuncture treatment required to elicit a potential effect on labour pain has not been fully explored. The dose is determined by many different factors, including the number of needles used and the intensity of the stimulation. In Sweden, manual stimulation of the needles is common practice when acupuncture is used for labour pain, but electrical stimulation of the needles, which gives a higher dose, could possibly be more effective. The overall aim of this thesis was to evaluate the effectiveness of acupuncture with manual stimulation (MA) of the needles as well as acupuncture with a combination of manual and electrical stimulation (EA) in reducing labour pain, compared with standard care without any form of acupuncture (SC). Methods: The study was designed as a three-armed randomised controlled trial in which 303 nulliparous women with normal pregnancies were randomised to MA, EA, or SC. The primary outcome was labour pain, assessed using the Visual Analogue Scale (VAS). Secondary outcomes were relaxation during labour, use of obstetric pain relief, and associations between maternal characteristics and labour pain and use of epidural analgesia respectively. Also, labour and infant outcomes, recollection of labour pain, and maternal experiences, such as birth experience and experience of the midwife, were investigated two months after the birth. The sample size calculation was based on the potential to discover a difference of 15 mm on the VAS. Data were collected during labour before the interventions, the day after birth, and two months later. Besides using the VAS, information was collected by means of study specific protocol, questionnaires and medical records. Results: The mean VAS scores were 66.4 in the MA group, 68.5 in the EA group, and 69.0 in the SC group (mean differences: MA vs. SC 2.6 95% CI -1.7 to 6.9, and EA vs. SC 0.6 95% CI -3.6 to 4.8). Other methods of pain relief were used less frequently in the EA group, including epidural analgesia, MA 61.4%, EA 46%, and SC 69.9%. (EA vs. SC OR 0.4 95% CI 0.2 to 0.7). No statistically significant differences were found in the recollection of labour pain between the three groups two months after birth (mean VAS score: MA 69.3, EA 68.7 and SC 70.1). A few maternal characteristics were associated with labour pain (age, dysmenorrhea, and cervix dilatation), but none of the investigated characteristics predicted the outcome of the acupuncture treatment in MA or EA. Women in the EA group experienced acupuncture as being effective for labour pain to a higher extent than women who received MA, MA 44.4%, EA 67.1% (EA vs. MA OR 2.4 95% CI 1.2 to 4.8). Women in the EA group also spent less time in labour (mean 500 min) than those who received MA (mean 619 min) and SC (mean 615 min) (EA vs. MA HR 1.4 95% CI 1.0 to1.9, EA vs. SC HR 1.4, 95% CI 1.1 to 2.0), and had less blood loss than women receiving SC, (EA vs. SC OR 0.1 95% CI 0.3 to 0.7). The women’s assessment of the midwife as being supportive during labour (MA 77.2%, EA 83.5%, SC 80%), overall satisfaction with midwife care (MA 100%, EA 97.5%, SC 98.7%), and having an overall positive childbirth experience (MA 64.6%, EA 61.0%, SC 54.3%) did not differ statistically. No serious side effects of the acupuncture treatment were reported. Conclusion: Acupuncture, regardless of type of stimulation, did not differ from standard care without acupuncture in terms of reducing women’s experience of pain during labour, or their memory of pain and childbirth overall two months after the birth. However, other forms of obstetric pain relief were less frequent in women receiving a combination of manual and electrical stimulation, suggesting that this method could facilitate coping with labour pain.

Beröringens betydelse i vårdandet av cancerpatienter – en litteraturöversikt

Bakgrund: Beröringen är ett av människans grundläggande behov. Närhet och beröring har betydelse för välbefinnandet. Beröring är en central del i vårdandet, där den är förväntad och accepterad. Att leva med cancer innebär ett stort lidande. Både fysiskt, psykiskt, socialt och existentiellt. Många genomgår tuffa behandlingar med biverkningar, vilket skapar ett lidande för både patient och närstående. Syfte: Syftet med denna litteraturöversikt var att beskriva beröringens betydelse i vårdandet av cancerpatienter. Metod: En litteraturöversikt, där femton vårdvetenskapliga artiklar har använts, nio med kvantitativ metod och sex med kvalitativ metod. Resultat: Studiens resultat visade att beröring har betydelse i omvårdnaden av cancerpatienter, både i livets slut och hos de som genomgår tuffa behandlingar. Beröring dämpade svåra biverkningar såsom illamående, oro/ångest, smärta samt att lindra lidandet. Patienterna upplevde ökad livskvalitet. Beröringen hade även en positiv betydelse för patienternas relation med både sjuksköterskan och anhöriga. Slutsats: Att drabbas av cancer innebär ett stort lidande, både fysiskt, psykiskt, socialt och existentiellt. Litteraturöversikten visar att beröring som omvårdnadsåtgärd hjälper patienterna att öka sitt välbefinnande på alla dessa fyra plan. Genom att använda beröring inom vårdandet av cancerpatienter kan man öka deras livskvalité och välbefinnande.

Omvårdnadsåtgärders effekter påcytostatikarelaterade biverkningar

Syfte: Syftet var att utvärdera effekten av sjuksköterskans föreslagna omvårdnadsåtgärder på cytostatikarelaterade biverkningar hos cancerpatienter som genomgår cytostatikabehandling. Metod: Examensarbetet utfördes som en litteraturöversikt. Resultatet grundar sig på 13 stycken kvantitativa artiklar. För datainsamlingen användes databaserna PubMed och Cinahl. Resultat: Resultatet visade att sjuksköterskan kan utföra omvårdnadsåtgärder som minskar patienters upplevelse av cytostatikarelaterade biverkningar. Effekterna som framkom av sjuksköterskans omvårdnadsåtgärder presenteras under rubrikerna; oral kryoterapi vid oral mukosit, personcentrerad patientutbildning med underrubriken utbildning utifrån ett teoretiskt perspektiv, automatiserad och sjuksköterske- assisterad symtombehandling samt musikterapi, bildspråk och avslappning. Slutsats: Sjuksköterskan kan genom olika omvårdnadsåtgärder hjälpa patienter att lindra symtom från cytostatikarelaterade biverkningar.

Associação entre resposta clínica e eventos adversos ao metilfenidato e genes dopaminérgicos e serotoninérgicos em crianças e adolescentes com transtorno de déficit de atenção/hiperatividade

Introdução: Poucos estudos sobre a farmacogenética do Transtorno de Déficit de Atenção/Hiperatividade (TDAH) foram conduzidos até o momento, apesar da extensa literatura sobre a participação de genes na etiologia do TDAH. Os estudos farmacogenéticos podem auxiliar na identificação a priori dos indivíduos que se beneficiarão de determinados tratamentos e dos que possivelmente apresentarão intolerância aos agentes farmacológicos. A maior parte dos estudos, até o momento, avaliou genes do sistema dopaminérgico e resultou em achados tanto positivos quanto negativos. Métodos: em um estudo naturalístico avaliamos os efeitos dos polimorfismos dos genes candidatos dopaminérgicos (DRD4, DAT1) e serotoninérgicos (HTR1B, HTR2A e 5-HTT) na resposta ao tratamento em 111 pacientes para os quais foi prescrito metilfenidato. As medidas de desfecho (Swanson, Nolan, and Pelham scale - versão IV – anexo I, Children Global Assessment Scale – anexo II, Barkley’s Stimulants Side Effects Rating Scale – anexo III) foram aplicadas no momento de avaliação e um mês após a intervenção. Resultados: Participaram do estudo 111 famílias de crianças e adolescentes eurobrasileiros de ambos os sexos que apresentavam TDAH segundo o DSM-IV. Estes pacientes foram consecutivamente triados no Programa de Déficit de Atenção/Hiperatividade do Hospital de Clínicas de Porto Alegre entre janeiro de 2003 e maio de 2004. Não foi detectada associação significativa entre os polimorfismos dos genes dopaminérgicos e serotoninérgicos avaliados e a resposta ao metilfenidato ou presença de eventos adversos. Conclusão: Os achados deste estudo quanto aos genes dopaminérgicos são negativos, concordando com três outros estudos disponíveis na literatura. Este foi o primeiro estudo a avaliar o efeito dos genes serotoninérgicos isolados na resposta ao metilfenidato e na presença de eventos adversos. Não foi encontrada nenhuma associação significativa. Os resultados dos estudos existentes são de difícil comparação devido à grande variabilidade metodológica existente entre os estudos. Assim, ensaios controlados multicêntricos prospectivos com maiores tamanhos amostrais são necessários para desvendar o papel dos genes candidatos na resposta ao tratamento para o TDAH.

Ressuscitação hipertônica com salina/dextran em pacientes sépticos graves estáveis : um estudo randomizado

Objetivo: estudar os efeitos hemodinâmicos da solução salina hipertônica/dextran, comparada com solução salina normal, em pacientes com sepse grave. Modelo: ensaio clínico randomizado, prospectivo, duplo-cego, controlado. Local: Unidade de Terapia Intensiva de um hospital universitário. Pacientes: 29 pacientes com sepse grave, admitidos na UTI com pressão de oclusão da artéria pulmonar (POAP) menor que 12 mmHg. Intervenções: os pacientes foram randomizados para receber 250 ml da solução salina normal [NaCl 0,9%] (Grupo SS, n=16) ou solução salina hipertônica [NaCl 7,5%]/dextran 70 8% ( Grupo SSH, n=13). Medidas e resultados: para cada grupo foram coletadas medidas hemodinâmicas, gasometrias (arterial e venosa), lactato e sódio séricos nos tempos 0, 30 minutos, 60 minutos, 120 minutos e 180 minutos. Durante o período do estudo não foi permitida qualquer alteração na infusão tanto de fluidos quanto das drogas vasopressoras. A POAP foi maior no grupo SSH, com a diferença sendo maior em 30 minutos (10,7±3,2 mmHg vs. 6,8±3,2 mmHg) e 60 minutos (10,3±3 mmHg vs. 7,4±2,9 mmHg); p<0,05. O índice cardíaco aumentou apenas no grupo SSH, sendo que as diferenças foram maiores em 30 minutos (6,5±4,7 l min-1 m-2 vs. 3,8±3,4 l min-1 m-2), em 60 minutos (4,9±4,5 l min-1 m-2 vs. 3,7±3,3 l min-1 m-2) e em 120 minutos (5,0±4,3 l min-1 m-2 vs. 4,1±3,4 l min-1 m-2); p<0,05. O índice sistólico seguiu o mesmo padrão e foi maior em 30 minutos (53,6[39,2-62,8] ml m-2 vs. 35,6[31,2-49,2] ml m-2) e em 60 minutos (46,8[39,7-56,6] ml m-2 vs. 33,9[32,2-47,7] ml m-2); p<0,05. A resistência vascular sistêmica diminuiu no grupo SSH e foi menor nos tempos 30 minutos (824±277 dyne s-1 cm-5 m-2 vs. 1139±245 dyne s-1 cm-5 m-2), em 60 minutos (921±256 dyne s-1 cm-5 m-2 vs. 1246±308 dyne s-1 cm-5 m-2) e em 120 minutos (925±226 dyne s-1 cm-5 m-2 vs. 1269±494 dyne s-1 cm-5 m-2); p<0,05. O sódio sérico aumentou no grupo SSH e foi maior do que o grupo SS em 30 minutos (145±3 mEq l-1 vs. 137±7 mEq l-1), em 60 minutos (143±4 mEq l-1 vs. 136±77 mEq l-1), em 120 minutos (142±5 mEq l-1vs. 136±7 mEq l-1) e em 180 minutos (142±5 mEq l-1 vs. 136±87 mEq l-1); p<0,05. Conclusão: Solução salina hipertônica/dextran pode melhorar a performance cardiovascular na ressuscitação de pacientes com sepse grave. Os efeitos hemodinâmicos parecem estar relacionados tanto ao efeito no volume quanto a melhora da função cardíaca. A SSH/dextran podem ajudar a restaurar rapidamente a estabilidade hemodinâmica em pacientes sépticos, hipovolêmicos, sem apresentar efeitos indesejáveis significativos.

Pesquisa orientada a resultado : proposta de um método estruturado para disponibilizar uma nova tecnologia para o mercado : um caso aplicado ao projeto etanol de 2ª geração

Esta dissertação de mestrado teve como objetivo principal propor um método estruturado suportado for ferramentas gerenciais que permitisse orientar e sistematizar o desenvolvimento de um projeto de pesquisa na disponibilização de uma nova tecnologia para o mercado. O “Projeto Etanol de 2ª Geração”, etanol produzido a partir de biomassas lignocelulósicas, aqui selecionado para estudo de caso, foi extraído da carteira de projetos do Centro de Tecnologia Canavieira (CTC). O método estruturado sugerido é constituído, fundamentalmente, por oito requisitos arranjados de forma cronológica ao longo do desenvolvimento do projeto, que visam auxiliar na prospecção, entendimento, avaliação, valoração, priorização, planejamento e implantação de, por exemplo, uma tecnologia inovadora, otimizando tempo, capital e recursos humanos aplicados. Um dos principais pontos do método proposto refere-se à escolha adequada das ferramentas gerenciais a serem utilizadas em cada requisito (brainstorm, análise de patentes, painel de especialistas, análise SWOT, dentre outras). O êxito na aplicação do método requer o entendimento de todos os (potenciais) efeitos, inclusive os colaterais, no processo como um todo. Ou seja, uma vez que toda ferramenta gerencial apresenta pontos fortes e fracos, o importante é adaptá-las ao sistema de negócio e não vice-versa. A partir do gerenciamento do projeto por um gestor com domínio das ferramentas gerenciais, a escolha destas ocorre de forma dinâmica, onde a cada passo de avaliação novas ferramentas (simples e/ou complexas) podem ser incluídas ou excluídas da matriz do método. Neste trabalho ficou demonstrada a importância de se trabalhar com métodos estruturados e flexíveis, que permitem retroalimentação de informações geradas internamente durante o desenvolvimento da pesquisa ou advindas de fontes externas. O projeto Etanol de 2ª Geração do CTC vem aplicando o método proposto em seu desenvolvimento e obtendo grande êxito em seus resultados, uma vez que a equipe envolvida permanece focada no objetivo principal, obedecendo prazos e recursos inicialmente definidos, com constância do propósito do projeto, sem retrocesso ou recomeço.

Inimigos públicos: crimes corporativos e necrocorporações

As corporações estão presentes em todos os lugares e em quase todos os aspectos de nossas vidas, porém, elas podem ser perigosas para a sociedade, protagonizando ações com impactos negativos para consumidores, trabalhadores, meio ambiente e comunidades. Nesta tese, lançamos nosso olhar sobre o lado sombrio das corporações, explorando dois crimes corporativos cometidos no Brasil por duas corporações transnacionais da indústria química, uma indústria predominada por grandes corporações operando em forma de oligopólios, dentro de um setor altamente estratégico por produzir insumos para a produção da maioria dos bens de consumo. Nosso objetivo é compreender os crimes corporativos para além da perspectiva funcionalista predominante na literatura sobre o tema. Para tanto, realizamos uma pesquisa qualitativa, com base na perspectiva crítica, focalizando dois casos ocorridos há mais de quatro décadas, no Brasil. Para reunir material empírico, entrevistamos ex-trabalhadores e trabalhadores das corporações protagonistas dos crimes, ex-moradores da comunidade atingida pelos crimes e especialistas, como advogados e profissionais da saúde, que se envolveram nos casos. As entrevistas foram do tipo narrativa, tendo sido gravadas e, posteriormente, transcritas para análise. Além das entrevistas, reunimos diversos documentos sobre os casos, como a cobertura jornalística, relatórios técnicos, sentenças e acórdãos. Analisamos o material empírico buscando reconhecer que os crimes corporativos ocorreram como uma extensão das organizações e de seu modo de organizar, e não como infortúnio ou efeitos colaterais não intencionais. Como principais resultados, desenvolvemos os conceitos de necrocorporação e crimes corporativos contra a vida. Nossa análise estendeu-se sobre as articulações engendradas pelas corporações; a produção da morte; e o poder, o consentimento e a resistência. Em ambos os casos analisados, os crimes foram cometidos na busca pelos objetivos corporativos, provocando a morte e doenças, bem como outros danos irreversíveis ao meio ambiente e à comunidade. Nossos resultados apontam para a necessidade de uma mudança no modo de pensar quanto às relações entre governos, sociedade e corporações, iniciando-se pela dissolução desse modelo de organização de negócios.

Is what you say what you do? Analyzing and comparing the effect of buyer-supplier relationship in the Brazilian and Chinese supplier selection criteria

Choosing properly and efficiently a supplier has been challenging practitioners and academics since 1960’s. Since then, countless studies had been performed and relevant changes in the business scenario were considered such as global sourcing, quality-orientation, just-in-time practices. It is almost consensus that quality should be the selection driver, however, some polemical findings questioned this general agreement. Therefore, one of the objectives of the study was to identify the supplier selection criteria and bring this discussion back again. Moreover, Dickson (1966) suggested existing business relationship as selection criterion, then it was reviewed the importance of business relationship for the company and noted a set of potential negative effects that could rise from it. By considering these side effects of relationship, this research aimed to investigate how the relationship could influence the supplier selection and how its harmful effects could affect the selection process. The impact of this phenomenon was investigated cross-nationally. The research strategy adopted was a controlled experiment via vignette combined with discrete choice analysis. The data collections were performed in China and Brazil. By examining the results, it could be drawn five major findings. First, when purchasers were asked to declare their supplier selection priorities, quality was stated as the most important independently of country and relationship. This result was consistent with diverse studies since 60’s. However, when purchasers were exposed to a multi-criteria trade-off situation, their actual selection priorities deviate from what they had declared. In the actual decision-making without influence of buyer-supplier relationship, Brazilian purchasers focused on price and Chinese buyers prioritized delivery then price. This observation reinforced some controversial prior studies of Verma & Pullman (1998) and Hirakubo & Kublin (1998). Second, through the introduction of the buyer-supplier relationship (operationalized via relational capital) in the supplier selection process, this research extended the existing studies and found that Brazilian buyers still focused on price. The relationship became just another criterion for supplier selection such as quality and delivery. However, from the Chinese sample, the results suggested that quality was totally discarded and the decision was majorly made through price and relationship. The third finding suggested that relational capital could legitimate the quality and sustainability of the supplier and replaces these selection criteria and made the decisional task less complex. Additionally, with the relational capital, the decision-makings were associated to few biases such as availability cognition, commitment, confirmatory and perceived biases. By analyzing the purchasers’ behavior, relational capital inducted buyers of both countries to relax in their purchasing requirements (quality, delivery and sustainability) leading to potential negative effects. In the Brazilian sample, the phenomenon of willing to pay a higher price for a lower quality offer demonstrated to be a potential counterproductive and suboptimal decision. Finally, the last finding was associated to the cultural effect on the buyers’ decisions. From the outcome, it is possible to observe that if a purchaser’s cultural background is more relation-oriented, the more he will tend to use relational capital as a decision heuristic, thus, the purchaser will be more susceptible to the potential relationship’s side effects

Enzymatic inhibitory activity of hydroxycinnamates (HCs): in silico studies

Diabetes is a worldwide health issue that has been expanding mainly in developed countries. It is characterized by abnormal levels of blood sugar due to several factors. The most common are resistance to insulin and the production of defective insulin which exerts little or no effect. Its most common symptoms include tissue damage to several systems due to elevated levels of blood sugar. One of the key enzymes in hydrocarbon metabolism is α-glucosidase (EC 3.2.1.20). It catalyzes the breakdown of complex carbohydrates into their respective monomers (glucose) which allows them to be absorbed. In this work, caffeoyl quinic acids and their metabolites were analyzed as potential inhibitors for α-glucosidase. The search for the best inhibitor was conducted using molecular docking. The affinity of each compound was compared to the inhibitor present in the crystal structure of the protein. As no inhibitor with a similar affinity was´found, a new approach was used, in situ drug design. It was not possible to achieve an inhibitor capable of competing with the one present in the crystal structure of the enzyme, which is also its current commercial inhibitor. It is possible to draw some conclusions as to which functional groups interact best with certain residues of the active site. This work was divided into three main sections. The first section, Diabetes, serves as an introduction to what is Diabetes, its symptoms and/or side effects and how caffeoyl quinic acids could be used as a treatment. The second section, Caffeoylquinic acids and their metabolites as inhibitors for Alfa-glucosidase, corresponds to the search through molecular docking of caffeoyl quinic acids as inhibitors for α-glucosidase and what was possible to draw from this search. The last section, In situ design of an inhibitor for α-glucosidase (EC 3.2.1.20), corresponds to the in situ drug design study and what it achieved. The representation of each of the molecules used as a ligand can be found in the Annexes.

Cell-responsive nanogels for anticancer drug delivery

One of the main goals in Nanomedicine is to create innovative drug delivery systems (DDS) capable of delivering drugs into a specific location with high efficiency. In the development of DDS, some essential properties are desired, such as biocompatibility and biodegradability. Furthermore, an ideal DDS should be able to deliver a drug in a controlled manner and minimize its side effects. These two objectives are still a challenge for researchers all around the world. Nanogels are an excellent vehicle to use in drug delivery and several other applications due to their biocompatibility. They are polymer-based networks, chemically or physically crosslinked, with at least 80-90% water in their composition. Their properties can be tuned, like the nanogel size, multifunctionality and degradability. Nanogels are capable of carrying in their interior bioactive molecules and deliver them into cells. The main objective of this project was to produce nanogels for the delivery of anticancer drugs with the ability of responding to existent stimuli inside cells (cellresponsiveness nanogels) and/or of controlled drug delivery. The nanogels were mainly based on alginate (AG), a natural biopolymer, and prepared using emulsion approaches. After their synthesis, they were used to encapsulate doxorubicin (Dox) which was chosen as a model drug. In the first part of the experimental work, disulfide-linked AG nanogels were prepared and, as expected, were redox-sensitive to a reducing environment like the intracellular medium. In the second part, AG nanogels crosslinked with both calcium ions and cationic poly(amidoamine) dendrimers were developed with improved sustained drug delivery. The prepared nanogels were characterized in terms of size, chemical composition, morphology, and drug delivery behavior (under redox/pH stimuli). The in vitro cytotoxicity of the nanogels was also tested against CAL-72 cells (an osteosarcoma cell line).

Limiting glutamate transmission in a Vglut2-expressing subpopulation of the subthalamic nucleus is sufficient to cause hyperlocomotion

The subthalamic nucleus (STN) is a key area of the basal ganglia circuitry regulating movement. We identified a subpopulation of neurons within this structure that coexpresses Vglut2 and Pitx2, and by conditional targeting of this subpopulation we reduced Vglut2 expression levels in the STN by 40%, leaving Pitx2 expression intact. This reduction diminished, yet did not eliminate, glutamatergic transmission in the substantia nigra pars reticulata and entopeduncular nucleus, two major targets of the STN. The knock-out mice displayed hyperlocomotion and decreased latency in the initiation of movement while preserving normal gait and balance. Spatial cognition, social function, and level of impulsive choice also remained undisturbed. Furthermore, these mice showed reduced dopamine transporter binding and slower dopamine clearance in vivo, suggesting that Vglut2-expressing cells in the STN regulate dopaminergic transmission. Our results demonstrate that altering the contribution of a limited population within the STN is sufficient to achieve results similar to STN lesions and high-frequency stimulation, but with fewer side effects.

Avaliação do efeito do composto tipo heparina isolado do caranguejo Chaceon fenneri na hemostasia e na morte celular

Heparin is a pharmaceutical animal widely used in medicine due to its potent anticoagulant effect. Furthermore, it has the ability to inhibit the proliferation, invasion and adhesion of cancer cells to vascular endothelium. However, its clinical applicability can be compromised by side effects such as bleeding. Thus, the search for natural compounds with low bleeding risk and possible therapeutic applicability has been targeted by several research groups. From this perspective, this study aims to evaluate the hemorrhagic and anticoagulant activities and citotoxic effect for different tumor cell lines (HeLa, B16-F10, HepG2, HS-5,) and fibroblast cells (3T3) of the Heparin-like from the crab Chaceon fenneri (HEP-like). The HEP-like was purified after proteolysis, ion-exchange chromatography, fractionation with acetone and characterized by electrophoresis (agarose gel) and enzymatic degradation. Hep-like showed eletroforetic behavior similar to mammalian heparin, and high trisulfated /Nacetylated disaccharides ratio. In addition, HEP-like presented low in vitro anticoagulant activity using aPTT and a minor hemorrhagic effect when compared to mammalian heparin. Furthermore, the HEP-like showed significant cytotoxic effect (p<0.001) on HeLa, HepG2 and B16-F10 tumor cells with IC50 values of 1000 ug/mL, after incubation for 72 hours. To assess the influence of heparin-like on the cell cycle in HeLa cells, analysis was performed by flow cytometry. The results of this analysis showed that HEP-like influence on the cell cycle increasing S phase and decreasing phase G2. Thus, these properties of HEP-like make these compounds potential therapeutic agents