The diploma paper was prepared on: Alternative treatment of hypertension in the Czech Republic and its impact on nursing care. Hypertension is one of the most common diseases of the cardiovascular system and it is the most frequent cause of morbidity and mortality in the Czech Republic. High blood pressure occurs more and more often nowadays and it is frequently underestimated by patients. Therefore, its treatment as well as its prevention is important. A nurse should be able to guide patients with hypertension along the right path and to advise them, especially in relation to preventive precautions against hypertension origination, but also a nurse should be close during the treatment of high blood pressure using other methods. Two types of interviews were carried out with nurses and patients at the cardiology department of hospital Nemocnice České Budějovice, a.s, at the cardiology department of hospital Na Homolce, a.s. and at the department of internal medicine at hospital Nemocnice Klatovy, o.p.s. In both the interviews, we first focused on the identification data of the nurses and the patients, and then questions were directed at answering our research questions specified in advance. According to the results of the data obtained from the interviews with the nurses and the patients, it was found that there was no difference in the nursing care provided to patients treated pharmacologically and patients with non-pharmacological treatment. The individual variants of hypertension treatment therefore have no impact on nursing care. Research question 1 was: Are there any differences in nursing care between pharmacological hypertension treatment and alternative hypertension treatment? Research question 2 was: Do alternative hypertension treatment methods affect nursing care? Both of these research questions have been answered by the data obtained from the interviews with the nurses as well as with the patients. Research question 3 was: Do patients view alternative hypertension treatment as part of the treatment of this disease? This question was answered by the data obtained from the interviews with the patients. Since the survey found that there are not any differences in the nursing care provided to patients with pharmacological therapy or non-pharmacological treatment, and that alternative hypertension treatment methods have no effect on nursing care, the two groups of patients should be educated properly and checked for high blood pressure. An appropriate recommendation is to organize additional research to the problems of educating patients on regimen precautions during non-pharmacological treatment of arterial hypertension.

Submitted by Franciele Moreira (francielemoreyra@gmail.com) on 2018-04-04T13:31:58Z No. of bitstreams: 2 Dissertação - Elis Marra da Madeira Freitas - 2018.pdf: 2802710 bytes, checksum: af4f0f1765370b18bf1ff79378f6628e (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2018-04-05T12:52:52Z (GMT) No. of bitstreams: 2 Dissertação - Elis Marra da Madeira Freitas - 2018.pdf: 2802710 bytes, checksum: af4f0f1765370b18bf1ff79378f6628e (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2018-04-05T12:52:52Z (GMT). No. of bitstreams: 2 Dissertação - Elis Marra da Madeira Freitas - 2018.pdf: 2802710 bytes, checksum: af4f0f1765370b18bf1ff79378f6628e (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2018-03-09 / Pharmacological treatment for heart failure evolved in the last decades. Betablockers, angiotensin converting enzyme inhibitors, angiotensin II receptor blockers and aldosterone antagonists have been widely used, as they were proven to reduce morbi/mortality in heart failure. Patient adherence has been studied all over the world in the last years in acute and chronic heart failure. Many factors knownly can influence the patient adherence to treatment. This study purpose was to evaluate pharmacological treatment in patients diagnosed with heart failure in outpatient follow up in a university hospital. Different methods were used to get to this objective, comparing each other and also clustering patients in more adherent and less adherent to pharmacological treatment, furthermore, we described the factors influencing patient adherence to pharmacological treatment. Thereunto, the Morisky questionnaire was used. Also a questionnaire made by the author and a form to collect data in patient’s chart were applied. Data frequency was described and then hierarchic clusters analysis was performed. Adherence measured by the Morisky questionnaire resulted in 71% of patients more adherent to pharmacological treatment and 26% less adherent. A different result and with more expressive values was found in the self-report adherence to pharmacological treatment by the patient, where 90% of the patients considered themselves as more adherent to pharmacological treatment and 8% considered themselves as less adherent. When comparing treatment prescribed and treatment reported by the patients, the majority of patients (78%) reports at least one drug different from the prescription. When measured by different methods, adherence can show not uniform results. The clinical factors and factors related to the satisfaction with the service did not influence the patient adherence to pharmacological treatment. In the other hand, some sociodemographics factors, like age (p = 0,0476), employment condition (p = 0,0132), schooling (p = 0,0167), marriage status (p = 0,011), family income (p = 0,0123), and factors related to the use of medications, as having family help to the the medications (p = 0,006), use medication alone (p = 0,0186) and have medical orientation bout the use of medication (p = 0,0077) had influence in patient adherence to pharmacological treatment. Thus, it was observed that patients being followed up in the Heart Failure Clinic of Hospital das Clínicas da Universidade Federal de Goiás are well medicated and have satisfactory adherence to pharmacological treatment. / O tratamento medicamentoso da insuficiência cardíaca evoluiu nas últimas décadas. Os betabloqueadores (BB), inibidores da enzima conversora de angiotensina (IECA), bloqueadores dos receptores de angiotensina II (BRA) e antagonistas de aldosterona são classes fundamentais pois comprovadamente diminuem morbi/mortalidade na IC. A adesão ao tratamento vem sendo amplamente estudado em insuficiência cardíaca aguda como crônica. Vários são os fatores que podem influenciar a adesão. O objetivo deste estudo foi avaliar a adesão ao tratamento medicamentoso, em pacientes diagnosticados com Insuficiência Cardíaca em acompanhamento ambulatorial em um hospital universitário. Foram utilizados diferentes métodos para este fim, comparando-os entre si, assim como agrupou-se os pacientes em mais aderentes e menos aderentes, além de se descrever os fatores que influenciaram na adesão ao tratamento medicamentoso. Para isso, utillizou-se o teste de Morisky de quatro perguntas. Além dele, também foi utilizado um questionário confeccionado pela autora e um formulário de coleta de dados no prontuário. Descreveu-se a frequência dos dados e posteriormente, a análise hierárquica de clusters foi aplicada. A adesão medida por meio do teste de Morisky resultou em 71% dos pacientes mais aderentes e 26% menos aderentes. Um resultado diferente, e também com valores mais expressivos, foi encontrado no autorrelato de adesão ao tratamento medicamentoso pelo paciente, em que 90% dos pacientes se consideraram mais aderentes e 8% menos aderentes. Quando se compara os medicamentos prescritos e relatados, a maioria dos pacientes (78%) relata pelo menos um medicamento diferente da prescrição. Quando medida por métodos diferentes, a adesão pode apresentar resultados não uniformes. Os fatores clínicos e os relacionados à satisfação com o serviço não influenciam na adesão ao tratamento medicamentoso. Já alguns fatores sociodemográficos, como idade (p=0,0476), condições de emprego (p=0,0132), escolaridade (p=0,0167), estado marital (p=0,0110), renda familiar (p=0,0123) e fatores relacionados ao uso do medicamento, como ter ajuda da família para retirar os medicamentos (p=0,0060), utilizar os medicamentos sozinhos (p=0,0186) e ter orientação médica quanto aos medicamentos (p=0,0077), influenciam na adesão ao tratamento medicamentoso. Assim, observou-se que os pacientes atendidos no Ambulatório de Insuficiência Cardíaca do Hospital das Clínicas da Universidade Federal de Goiás (HC/UFG) possuem adesão satisfatória ao tratamento medicamentoso prescrito.

A obesidade é uma doença crônica que vêm alcançando proporções epidêmicas em todo o mundo. É um fator de risco para inúmeras desordens médicas, morbidade e mortalidade, além de estar também associada a um aumento dos custos socioeconômicos e com saúde. O tratamento a longo prazo, incluindo a farmacoterapia, mostra-se necessário para muitos pacientes obesos. Neste contexto, este trabalho teve a finalidade de avaliar a tolerabilidade e eficácia clínica da Fluoxetina, adjunta a uma dieta de 1.500 Kcal/dia, na redução de parâmetros antropométricos e metabólicos em mulheres obesas. Cloridrato de Fluoxetina (60 mg/dia), foi comparado ao placebo em 19 mulheres obesas, durante 90 dias de tratamento. O grupo Fluoxetina (n=9) apresentou uma redução estatisticamente significativa do peso (-9,24 vs -1,05 kg), IMC (-3,64 vs -0,45 Kg/m²) e circunferência abdominal (-12,3 vs -2,9 cm), em relação ao placebo (n=10). Observou-se ainda uma elevação estatisticamente significativa dos níveis séricos de HDL-colesterol (p< 0,01) no grupo tratado com o fármaco, e uma redução significativa dos níveis plasmáticos de triglicérides (-39,5 vs +18,7 mg/dL) quando comparado ao grupo placebo. As reações adversas mais comumente reportadas pelos pacientes foram insônia, náuseas e sonolência. Concluímos que a Fluoxetina demonstrou ser um fármaco bem tolerado e eficaz na redução de parâmetros antropométricos e metabólicos, prevenindo o desenvolvimento de fatores de risco cardiovasculares e diminuindo morbidade em mulheres obesas. / Obesity is a chronic condition that has been reaching epidemic proportions worldwide. It is a risk factor for numerous medical disorders and excessive mortality. Long-term treatment, including pharmacotherapy, may be necessary for many obese patients. This study aimed to assess the tolerability and clinical effectiveness of Fluoxetine, as an adjunct therapy to a 1.500 Kcal/day diet, in reducing anthropometric and metabolic parameters in obese women. Fluoxetine (60 mg/day), was compared to placebo in 19 obese females in a 90-day trial. Fluoxetine therapy (n=9) resulted in a statistically significant greater mean reduction in weight (-9,24 vs -1,05 kg), BMI (-3,64 vs -0,45 Kg/m²) and waist circumference (-12,3 vs -2,9 cm), than placebo group (n=10). There was also an elevation of HDL-cholesterol (p< 0,01) in Fluoxetine group and mean triglycerides levels was reduced (-39,5 vs +18,7 mg/dL) when compared to placebo. Side effects most commonly reported by the patients were insomnia, nausea and somnolence. We concluded that Fluoxetine may provide an effective and well tolerated possibility in reducing anthropometric and metabolic parameters, preventing the development of cardiovascular risk factors and reducing morbidity in obese women.

Excerpt: Interactions between chemotherapy and dietary or herbal supplements can compromise patient care.

Purpose: Cetuximab is a monoclonal antibody with a known risk of hypersensitivity reactions. Early studies showed hypersensitivity reaction rates of 3%, but there appears to be a higher incidence in the southeastern United States. To confirm the findings from nearby institutions that cetuximab-associated hypersensitivity reactions occur in approximately 20% of patients in the southeastern United States. Methods: A retrospective chart review was conducted at Johnson City Medical Center in Johnson City, Tennessee. Each patient’s first infusion was analyzed for hypersensitivity reaction, as well as for demographic information such as allergy and smoking history, pre-medications, and malignancy type. Results: Data from the first infusion of cetuximab were collected for a total of 71 patients with various malignancies. The overall rate of grade 3 or higher hypersensitivity reaction was 1.4%, and total rate of hypersensitivity reaction was 8.5%. These findings more closely correlate to the early clinical trials and package insert. Both severe (p = 0.001) and any-grade (p = 0.002) hypersensitivity reaction occurred less frequently in one Southeastern Appalachian medical center compared to academic medical centers directly to the east and west. Conclusions: Patients in southern Appalachia may be less likely to develop cetuximab hypersensitivity reactions compared to surrounding areas in the Southeastern U.S. These results lend support to the theory that exposure to lonestar ticks (Amblyomma americanum) may be responsible for the development of IgE antibodies to cetuximab that cause hypersensitivity reactions. The development of quick and reliable bedside predictors of cetuximab hypersensitivity reactions may aid clinicians considering the use of cetuximab.

The advent of effective oral, molecular-targeted drugs in oncology has changed many incurable malignancies such as chronic myeloid leukemia into chronic diseases similar to coronary artery disease and diabetes mellitus. Oral agents including monoclonal antibodies, kinase inhibitors and hormone receptor blockers offer cancer patients incremental improvements in both overall survival and quality of life. As it is imperative to recognize and manage side effects of platelet inhibitors, beta blockers, statins, HIV drugs, and fluoroquinolones by all healthcare providers, the same holds true for these newer targeted therapies, patients may present to their generalist or other subspecialist with drug-related symptoms. Cardiovascular adverse events are among the most frequent, and potentially serious, health issues in outpatient clinics, and among the most frequent side effects of targeted chemotherapy. Data support improved patient outcomes and satisfaction when primary care and other providers are cognizant of chemotherapy side effects, allowing for earlier intervention and reduction in morbidity and health care costs. With the implementation of accountable care and pay-for-performance, improved communication between generalists and subspecialists is essential to deliver cost-effective patient care.

Objective: To review the place in therapy of isavuconazole, the active metabolite of isavuconazonium sulfate, via a review of the available literature on drug chemistry, spectrum of activity, pharmacokinetic/pharmacodynamic profile and trials assessing clinical efficacy and safety. Methods: Relevant data, original research articles and reviews, were gathered primarily through the use of a PubMed database search. The search was conducted without date restrictions in order to collect both historical and recent data regarding isavuconazole. Key findings: Isavuconazole is a triazole currently approved not only for use in invasive aspergillosis and mucormycosis but also has demonstrable activity against Candida species and other common fungal pathogens. This drug has features which make it more clinically appealing compared to other azoles with similar indications. In specific, isavuconazole does not require a cyclodextrin vehicle due to its water solubility, and at present, does not require therapeutic drug monitoring. Moreover, isavuconazole has displayed improved safety and tolerability compared to voriconazole. Available data from Phase III clinical trials shows isavuconazole to be a possible therapeutic option to currently available therapies for which it is approved; however, clinical conclusions should be reserved until results have been published and more data from clinical use is reported. Conclusions: Isavuconazole is a new triazole with broad‐spectrum antifungal activity including invasive aspergillosis and mucormycosis.

Bakgrund: Personer med demens har en försämrad förmåga att förstå och kommunicera med omgivningen och därför kan det vara svårt och krävande att vårda personer med demens. Agitation är ett vanligt beteendeproblem vid demenssjukdom och är påfrestande för såväl personen med demens, som för vårdgivaren. Personer med demens behandlas främst farmakologiskt trots de biverkningar som läkemedelsbehandlingen orsakar och därför behövs andra behandlingsstrategier och omvårdnadsåtgärder för att öka välbefinnandet och minska deras lidande. Syfte: Att beskriva musikens inverkan på människor med demenssjukdom och deras vårdgivare. Metod: En systematisk litteraturöversikt av fjorton kvalitativa och kvantitativa vetenskapliga artiklar som sedan analyserades och sammanställdes i ett resultat. Resultat: Musik visade sig ha en övervägande positiv inverkan på personer med demenssjukdom och deras vårdgivare. De demenssjuka personernas agitation minskade, deras möjlighet att kommunicera förbättrades och de fick en ökad livskvalitet. Vårdgivarnas samarbete med den demenssjuka personen förbättrades och de blev mer närvarande i omvårdnaden. Slutsats: Musiken inverkade på ett övervägande positivt sätt i omvårdnaden av demenssjuka personer och gav även en positiv inverkan på de demenssjuka personernas vårdgivare. Resultatet visar att musik kan vara användbart för att förbättra vården av personer med demens och kan förmodligen fungera som en icke-farmakologisk behandling i omvårdnaden. / Background: People with dementia have an impaired ability to understand and communicate with their environment and it can be difficult and demanding to care for people with dementia. Agitation is a common behavior problem in dementia and this is stressful for both the person with dementia, as for the caregiver. People with dementia are treated primarily pharmacological despite the many side effects that drug therapy induced and therefore requires other treatments strategies and nursing interventions to improve wellbeing and to reduce their suffering. Aim: To describe the impact of music on people with dementia and their caregivers. Method: A systematic literature review of fourteen qualitative and quantitative research articles that then were analyzed and summarized in the result. Results: Music was found to have a predominantly positive impact on people with dementia and their caregivers. The dementia person’s agitation decreased, their ability to communicate improved and they had an improved quality of life. The caregiver’s cooperation with the dementia persons was improved and they became more present in the care. Conclusion: The music had a mainly positive impact in the care of persons with dementia and also gave a positive impact on the caregivers. The results show that music probably can be useful for improving the care of people with dementia and can act as a non-pharmacological treatment in the care.

Bakgrund: Hjärtsvikt är vanligt förekommande i den svenska befolkningen och är den vanligaste orsaken till sjukhusinläggning. Bristande följsamhet till den farmakologiska hjärtsviktbehandlingen är idag ett stort problem inom sjukvården. Detta bidrar till ökade sjukhusinläggningar samt ökad dödlighet hos hjärtsviktspatienterna. Icke-farmakologisk behandling har dock kunnat ses som ett komplement till den farmakologiska behandlingen. Syfte: Syftet med denna litteraturstudie var att beskriva patienters följsamhet till, samt beskrivningar och upplevelser av, att följa icke-farmakologiska riktlinjer i samband med hjärtsvikt. En granskning av kvaliteten beträffande de inkluderade studiernas undersökningsgrupp utfördes även. Metod: En beskrivande litteraturstudie där 12 vetenskapliga artiklar inkluderades.  Artiklarna söktes vid databaserna Pubmed och Cinahl. Delar från studiernas resultat plockades ut och analyserades. Dessa delades sedan upp under kategorier och underkategorier passande för att svara till litteraturstudiens frågeställningar. Resultat: Generellt var följsamheten till de icke-farmakologiska behandlingsriktlinjerna bristande. Flest antal hinder identifierades beträffande riktlinjer gällande saltrestriktioner. Törst, glömska, samt fysiska symtom var även de stora hinder till en följsam icke-farmakologisk behandling. De största fördelarna som identifierades till en följsam behandling var ökat välmående samt minskade sjukhusinläggningar. Slutsats: En generellt bristande följsamhet till de icke-farmakologiska behandlingsriktlinjerna gällande salt- och vätskerestriktioner, regelbunden vägning samt träning förekommer bland hjärtsviktspatienter. Många hinder till en följsam behandling identifierades, men även fördelar till att vara följsam till icke-farmakologiska behandlingsriktlinjer beskrevs i studierna. / Background: Heart failure is a common disease among the Swedish population today and it is also the number one cause of hospitalisation. A lack of compliance with the pharmacological treatment for heart failure is a big issue within the medical services today. This significantly contributes to increased hospitalisation as well as higher mortality rates among Heart failure patients. However, non-pharmacological treatments have been found to be a rather good complement to the pharmacological treatment.  Aim: The purpose of this literature study was to describe patients’ compliance with, as well as their experiences and accounts of, following non-pharmacological guidelines in connection to heart failure. An examination of the included studies’ focus groups and their quality was done as well. Method: A descriptive literature study where twelve scientific articles were included. The articles were found on the databases Pubmed and Cinahl. Parts of the study’s results were selected and analysed. These were then divided into categories and subcategories that suited the literature study’s research questions. Result: The compliance with the non-pharmacological treatment guidelines was generally inadequate. The most obstacles were found concerning the guidelines the patients got regarding the restrictions on salt. Thirst, forgetfulness, and physical symptoms were also big obstacles for complying with a non-pharmacological treatment. The biggest advantages of complying with the treatment that were identified were an increased sense of well-being and decreased hospitalisation. Conclusion: A general lack of compliance with the non-pharmacological treatment guidelines concerning the restrictions on salt and fluid, regular weigh-ins, and exercise occur among heart failure patients. Many obstacles to complying with treatment were identified, but the advantages of complying with non-pharmacological treatment guidelines were also described in the study.

Orientador: Kleber Gomes Franchini / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-11T04:16:59Z (GMT). No. of bitstreams: 1 Deckmann_AnaCarolina_D.pdf: 7310325 bytes, checksum: 97d12a5e15b0b17033701d84779632e1 (MD5) Previous issue date: 2008 / Resumo: O termo síndrome coronária aguda compreende a angina instável e o infarto do miocárdio, entidades clínicas freqüentes e potencialmente letais. Ambas as situações caracterizam-se por um desbalanço entre a oferta e a demanda de oxigênio no miocárdio, freqüentemente desencadeadas pela diminuição da perfusão resultante de estreitamento ou oclusão de artérias coronárias em conseqüência de aterosclerose. As elevadas taxas de morbidade e mortalidade destas condições são atribuídas, principalmente, à perda de massa miocárdica e instabilidades elétricas decorrentes não apenas da isquemia, mas também da reperfusão espontânea ou induzida de áreas do miocárdio isquêmico. Desta forma, é intensa a busca por estratégias e agentes farmacológicos que possam reduzir os danos miocárdicos provocados tanto pela isquemia como pela reperfusão. Evidências experimentais e algumas evidências clínicas indicam que a adenosina (Ado) administrada sistemicamente é capaz de proteger o miocárdio dos efeitos da isquemia/reperfusão. A proteção conferida pela Ado ocorre tanto aguda (1-6 horas) como tardiamente (1-3 dias) após a administração em dose única. Enquanto a proteção aguda depende da ativação de vias de sinalização que mobilizam efetores constitutivamente expressos nas células, a proteção tardia parece depender da alteração da expressão de genes envolvidos em múltiplas funções celulares. No entanto, algumas características da ação sistêmica da Ado, tais como a meia-vida curta e seus efeitos cardiovasculares (i.e. bradicardia e hipotensão), são barreiras importantes para seu uso clínico nas síndromes coronárias agudas. Uma das maneiras de evitar estes efeitos indesejáveis é utilizar agentes farmacológicos que aumentam a biodisponibilidade de Ado, como antagonistas de seus transportadores ou inibidores da adenosina quinase, uma enzima-chave no metabolismo de purinas que fosforila a adenosina em AMP através de hidrólise do ATP. Neste contexto, demonstramos anteriormente que compostos derivados de anilinoquinazolinas são inibidores de adenosina quinase e induzem a proteção miocárdica tanto aguda como tardia em modelo de coração isolado. Tendo em vista que a proteção tardia depende da expressão diferencial de genes, o presente estudo foi planejado para investigar as respostas transcricionais envolvidas na cardioproteção induzida tardiamente após a administração do composto quinazolínico líder inibidor de adenosina quinase, DMA. Para tanto, foram utilizados lâminas de oligonucleotídeos contendo as sequências referentes a todos os genes de camundongo (~35 mil genes). As sondas de RNA foram sintetizadas a partir de corações de camundongos tratados com dose única de DMA O termo síndrome coronária aguda compreende a angina instável e o infarto do miocárdio, entidades clínicas freqüentes e potencialmente letais. Ambas as situações caracterizam-se por um desbalanço entre a oferta e a demanda de oxigênio no miocárdio, freqüentemente desencadeadas pela diminuição da perfusão resultante de estreitamento ou oclusão de artérias coronárias em conseqüência de aterosclerose. As elevadas taxas de morbidade e mortalidade destas condições são atribuídas, principalmente, à perda de massa miocárdica e instabilidades elétricas decorrentes não apenas da isquemia, mas também da reperfusão espontânea ou induzida de áreas do miocárdio isquêmico. Desta forma, é intensa a busca por estratégias e agentes farmacológicos que possam reduzir os danos miocárdicos provocados tanto pela isquemia como pela reperfusão. Evidências experimentais e algumas evidências clínicas indicam que a adenosina (Ado) administrada sistemicamente é capaz de proteger o miocárdio dos efeitos da isquemia/reperfusão. A proteção conferida pela Ado ocorre tanto aguda (1-6 horas) como tardiamente (1-3 dias) após a administração em dose única. Enquanto a proteção aguda depende da ativação de vias de sinalização que mobilizam efetores constitutivamente expressos nas células, a proteção tardia parece depender da alteração da expressão de genes envolvidos em múltiplas funções celulares. No entanto, algumas características da ação sistêmica da Ado, tais como a meia-vida curta e seus efeitos cardiovasculares (i.e. bradicardia e hipotensão), são barreiras importantes para seu uso clínico nas síndromes coronárias agudas. Uma das maneiras de evitar estes efeitos indesejáveis é utilizar agentes farmacológicos que aumentam a biodisponibilidade de Ado, como antagonistas de seus transportadores ou inibidores da adenosina quinase, uma enzima-chave no metabolismo de purinas que fosforila a adenosina em AMP através de hidrólise do ATP. Neste contexto, demonstramos anteriormente que compostos derivados de anilinoquinazolinas são inibidores de adenosina quinase e induzem a proteção miocárdica tanto aguda como tardia em modelo de coração isolado. Tendo em vista que a proteção tardia depende da expressão diferencial de genes, o presente estudo foi planejado para investigar as respostas transcricionais envolvidas na cardioproteção induzida tardiamente após a administração do composto quinazolínico líder inibidor de adenosina quinase, DMA. Para tanto, foram utilizados lâminas de oligonucleotídeos contendo as sequências referentes a todos os genes de camundongo (~35 mil genes). As sondas de RNA foram sintetizadas a partir de corações de camundongos tratados com dose única de DMA / Abstract: The term acute coronary syndrome includes unstable angina and myocardial infarction, which are frequent and potentially lethal clinical entities. Both situations are characterized by an imbalance between myocardial oxygen supply and demand, often triggered by the reduced perfusion caused by narrowing or occlusion of coronary arteries due to atherosclerosis. The high morbidity and mortality rates determined by these conditions are attributed mainly to loss of myocardial and electrical instabilities, arising not only from ischemia, but also from spontaneous or induced reperfusion of the ischemic regions. Thus, there is much interest in the development of strategies and pharmacological agents able to minimize the injuries caused not only by myocardial ischemia but also by reperfusion. Experimental and clinical data indicate that systemically administered adenosine (Ado) is able to protect the myocardium from ischemia/reperfusion injuries. The protection induced by Ado occurs in two phases, an acute (1-6 hours) and a late (1-3 days) phase after a single dose administration. While acute protection depends on activation of signaling pathways that mobilize end-effectors constitutively expressed in the cells, the late protection depends on the alterations of the expression of genes involved in multiple cellular functions. However, some characteristics of the systemic action of Ado, such as its short half-life and cardiovascular side effects (i.e. bradycardia and hypotension), are major barriers to its clinical use in acute coronary syndromes. One way to circumvent these undesirable effects is to use pharmacological agents that increase Ado bioavailability, as antagonists of its transporters or adenosine kinase (ADK) inhibitors. ADK is a key enzyme in the metabolism of purines that phosphorilates adenosine to AMP by ATP hydrolysis. In this context, we have previously demonstrated that derivatives of anilinoquinazolines are potent inhibitors of adenosine kinase and induce both acute and late phases of cardioprotection, as showed in isolated heart model. The present study was designed to investigate the transcriptional responses involved in late cardioprotection induced by administration of the anilinoquinazoline DMA. We used oligonucleotide microarrays containing representative sequences of all genes from mouse genome (~35 thousand genes). The RNA probes were synthesized from hearts of mice treated with DMA (30 mg/kg, single dose) ou vehicle (DMSO), 24 and 48 hours prior to tissue excision. We considered differentially expressed (fold change>[2.0], p<0.1) a total of 1061 genes in 24-hour and 844 genes in 48-hour groups, in comparison to vehicle treated samples. Most of these transcripts were unknown genes (ESTs-Expressed Sequence Tags; 63% at 24 hours, 76% in 48 hours). In 24h transcriptome, most of the genes (75% of the known genes and 62% of ESTs) were upregulated, while in 48h transcriptome 56% of the known genes and 58% of ESTs were upregulated. The functional analysis of known genes showed large representation of classes associated with cell adhesion, signaling, transport and metabolism in 24 hours, and cell adhesion, development of multicellular organism and metabolism in 48 hours. The analysis of gene identities revealed few coincidences between the two transcriptomes, and clustering analysis performed to study the gene profile transition from 24 to 48h revealed that most genes presents transitory regulation of its expression (i.e., tendency of upregulation at 24h followed by downregulation at 48h and vice-versa). Analysis of differentially expressed genes in terms of metabolic and signaling pathways in which they are inserted allowed us to assess a putative metabolome of myocardial cells treated by the quinazoline DMA. Results indicated that the most affected pathways are glucose and lipids metabolism, PPAR-? and adipocytokines, angiogenic responses, among others. Among these results, we confirmed experimentally the angiogenic effect of DMA and also the expression of genes and proteins associated with modifications in cardiac energy metabolism. Our results indicate that various cellular responses, including the energetic metabolism, ion homeostasis and changes in cell osmolarity, must cooperate to induce the cardioprotection phenotype after DMA administration. Studies focusing the mechanistic modifications of these groups of genes will contribute to elucidate their involvement in the protection induced by treatment with quinazolines, and will provide clues to comprehend myocardial protection phenomenon. Keywords: cardioprotection, quinazolinic compounds, gene expression, oligonucleotide microarrays, Mus musculus / Doutorado / Medicina Experimental / Doutor em Clínica Médica