No / Objective The objective of this study was to evaluate adherence and causes for non-adherence to antihypertensive therapy in Austrian patients. A special focus was placed on social parameters and behavioural theories. Methods Patients were invited via advertisements in community pharmacies in Austria to complete an online survey. Inclusion criteria were an age of 18 years or older, a diagnosis of arterial hypertension and a current prescription of antihypertensive medication. Adherence was measured by the four-item Morisky scale. Non-adherence was defined by at least one point in the Morisky scale. Several demographic, social and behavioural parameters were analysed as potential co-variables associated with adherence. Results A total of 323 patients completed the online survey, of which 109 (33.7 %) met the criteria for nonadherence. In a multivariable model, self-efficacy and age were associated with adherence, whereas intention and barriers were linked to non-adherence; 56 patients (17.3 %) were classified as intentionally non-adherent. Conclusion This study demonstrates that non-adherence affects an important proportion of patients in the treatment of arterial hypertension. Young age was a particularly important risk factor for non-adherence, and this patient population is, therefore, in need of special attention. Modifiable risk factors were identified that could help improving the treatment of arterial hypertension and potentially other chronic conditions. / European Union’s Seventh Framework Programme FP7/2007–2013 ‘Ascertaining Barriers to Compliance (ABC) project’ under grant agreement number 223477.

Title: Analysis of Pharmacotherapy by patients with diagnosis of arterial hypertension Student: Vasiliki Kontou Tutor: Prof. RNDr. Jiri Vlcek, CSs Department of Social and Clinical Pharmacy, Charles University of Prague, Faculty of Pharmacy in Hradec Kralove Introduction: Arterial Hypertension (AH) is characterized by elevated blood pressure, which often leads to increased morbidity and mortality. AH divided into primary and secondary. Aim: In the theoretical part the aim is to analyse the etiopathogenesis, methods of diagnosis and the treatment strategies of arterial hypertension in the recent literature. In the experimental part the aim is to analyse the provisions of the above diagnosis of arterial hypertension. Method: During a six month period were collected 58 prescriptions with the diagnosis of arterial hypertension from a pharmacy that provided pharmaceutical care in the Greek village, Mytikas. Only one prescription for one patient was analysed. In the prescriptions were collected data on drugs, patients and physicians. Results: The pilot study included 58 prescriptions. Most patients were elderly, over 65 years old and 30% were in age 71 - 80 years. General practitioners prescribed 65% of the medical prescriptions. Most frequently prescribed ARBs with hydrochlorothiazide drugs (27%) and...

Mon projet porte d'une part sur le rôle de la voie TGF-b/Alk1 dans l’hypertension artérielle (HTAP) humaine et expérimentale. Le but est d’évaluer in vitro (i) l’expression du TGF-b et de ses récepteurs ALK1/Endogline dans les cellules endothéliales d’artères pulmonaires (CE-AP) de patients atteints d’HTAP idiopathique (HTAPi), (ii) les conséquence de l’activation de la voie TGF-b/ALK1 des CE-AP dans la synthèse de facteurs capables d’induire la prolifération des cellules musculaires lisses d’artères pulmonaires (CML-AP), (iii) identifier par une analyse protéomique différentielle la nature de ses facteurs paracrines, (iv) évaluer chez la souris la conséquence de la déficience en Endogline, co-récepteur de ALK1 sur le développement de l’hypertension artérielle pulmonaire. / My project relates to the role of the TGF-b/Alk1 pathway in human and experimental pulmobnary arterial hypertension (PAH). The goal is to evaluate in vitro (I) the expression of TGF-b and its receptors ALK1/Endoglin in pulmonary arterial endothelial (P-EC) of patients reached of idiopathic PAH (iPAH), (II) the consequence of the activation of the TGF-b/ALK1 pathway on the P-EC in the synthesis of factors able to induce the proliferation of the pulmonary arterial smooth muscle cell (PA-SMC), (III) to identify by a differential proteomic analysis the nature of its factors paracrines, (iv) to evaluate in the mouse the consequence of deficiency in Endoglin (co-receptor of ALK1) on the development of PAH.

Die Arterielle Hypertonie zählt neben Hypercholesterinämie, Diabetes mellitus, Übergewicht, Rauchen und Bewegungsmangel als Risikofaktor für Erkrankungen des Kreislaufsystems. Die in vielen Leitlinien geforderte Behandlungsqualität bei arterieller Hypertonie soll sowohl in der hausärztlichen und fachärztlichen Praxis als auch in der stationären Behandlung optimal erreicht werden. In der vorliegenden Arbeit wird untersucht, ob der Anteil der stationär behandelten Patienten, die insgesamt einen Zielblutdruck unterhalb von 140 mmHg erreichen, höher ist als der Anteil derselben Patienten in der hausärztlichen Versorgung. Durch die retrospektive Auswertung der Daten von Patienten mit Hypertonie in der Abteilung Nephrologie und Rheumatologie der Medizinischen Fakultät der Georg-August-Universität Göttingen wurden die Informationen für die Analyse erfasst und statistisch ausgewertet. Es wird die Frage erörtert, inwiefern die medikamentöse Behandlung im stationären Aufenthalt zu einer signifikanten Verbesserung der Blutdruckwerte, insbesondere bei Patienten mit manifesten Vorerkrankungen und mit Vormedikation gegen Bluthochdruck, führt. Darüber hinaus wurde dem Problem nachgegangen, inwieweit die medikamentöse Behandlung nach dem Krankenhausaufenthalt fortgesetzt wird. Hierzu wurde zunächst ein Fragebogen entwickelt, um folgende Kategorien aus den Krankenakten der ausgewählten Patienten einheitlich erfassen zu können: persönliche Daten, Vorerkrankungen, Familien¬anamnese, Risikofaktoren, Vormedikation, Anamnese am Tag der Aufnahme, Nachmedi-kation, Diagnostik während des stationären Aufenthalts, Daten am Tag der Entlassung. Diese Informationen wurden im Anschluss statistisch ausgewertet und zur Einschätzung der aufgestellten Hypothesen herangezogen. Die Untersuchungen belegen, dass in der stationären Behandlung insgesamt für mehr Patienten Erfolge bezüglich der medikamentösen Therapie erzielt wurden. Die Ergebnisse dokumentieren eine Gleichberechtigung der von der Deutschen Hochdruckliga empfohlenen Therapieformen, sei es die Monotherapie oder die primäre Kombinationstherapie. Alle durchgeführten Medikationen führen gleichermaßen zu signifikanten Verbesserungen der Blutdruckwerte.

Pulmonary arterial hypertension (PAH) is a lethal disease characterized by excessive proliferation of pulmonary vascular cells, such as endothelial cells (ECs). Hereditary (H) PAH is mainly caused by ―loss-of-function‖ mutations in the gene coding for the bone morphogenetic protein type II receptor (BMPR2). However, the mechanisms by which these mutations cause PAH remain unclear. The hypothesis of this thesis was that BMPR2 mutations produce an imbalance in EC protein expression and/or activity that is integrally related to the development of abnormalities in lung vascular function and structure in HPAH. Patient-specific blood-outgrowth endothelial cells (BOECs) expanded ex vivo from peripheral blood mononuclear cells from patients with HPAH and healthy subjects were used to examine the consequences of BMPR2 mutations on the BOEC protein expression profile as well as on their functionality. Functional analyses of the BOECs revealed that HPAH-derived BOECs are more susceptible to apoptosis and more proliferative compared with healthy controls. Protein isolates of BOECs from patients with HPAH and from healthy subjects were subjected to 2-D gel electrophoresis and stained for total proteins and phosphoproteins, and to a quantitative computerassisted analysis. Differentially regulated proteins were identified by mass spectrometry (LC-MS/MS). Of the 416 total proteins detected under basal conditions, 11 were significantly downregulated in HPAH-derived BOECs and 11, including the translationally controlled tumor protein (TCTP), were upregulated. TCTP has previously been shown to be involved in systemic arteriolar remodeling, inflammation and growth. Therefore, the potential role of TCTP in PAH was studied in vivo in the SU5416 rat model of severe angioproliferative PAH. Immunofluorescence staining revealed high expression of TCTP in arteriolar ECs of PAH lungs tightly localized to proliferating cells within occlusive intimal lesions; whereas, only minimal TCTP expression was seen in vascular ECs of normal lungs. Similarly, abundant TCTP immunostaining was also seen in human PAH lung sections, again associated with complex vascular lesions. In BOECs, TCTP was found to participate in cell growth and survival. These data suggest that TCTP could play an important role in PAH by mediating pro-survival and growth signaling in vascular cells, contributing to occlusive pulmonary vascular remodeling triggered by EC apoptosis.

Pulmonary arterial hypertension (PAH) is a lethal disease characterized by excessive proliferation of pulmonary vascular cells, such as endothelial cells (ECs). Hereditary (H) PAH is mainly caused by ―loss-of-function‖ mutations in the gene coding for the bone morphogenetic protein type II receptor (BMPR2). However, the mechanisms by which these mutations cause PAH remain unclear. The hypothesis of this thesis was that BMPR2 mutations produce an imbalance in EC protein expression and/or activity that is integrally related to the development of abnormalities in lung vascular function and structure in HPAH. Patient-specific blood-outgrowth endothelial cells (BOECs) expanded ex vivo from peripheral blood mononuclear cells from patients with HPAH and healthy subjects were used to examine the consequences of BMPR2 mutations on the BOEC protein expression profile as well as on their functionality. Functional analyses of the BOECs revealed that HPAH-derived BOECs are more susceptible to apoptosis and more proliferative compared with healthy controls. Protein isolates of BOECs from patients with HPAH and from healthy subjects were subjected to 2-D gel electrophoresis and stained for total proteins and phosphoproteins, and to a quantitative computerassisted analysis. Differentially regulated proteins were identified by mass spectrometry (LC-MS/MS). Of the 416 total proteins detected under basal conditions, 11 were significantly downregulated in HPAH-derived BOECs and 11, including the translationally controlled tumor protein (TCTP), were upregulated. TCTP has previously been shown to be involved in systemic arteriolar remodeling, inflammation and growth. Therefore, the potential role of TCTP in PAH was studied in vivo in the SU5416 rat model of severe angioproliferative PAH. Immunofluorescence staining revealed high expression of TCTP in arteriolar ECs of PAH lungs tightly localized to proliferating cells within occlusive intimal lesions; whereas, only minimal TCTP expression was seen in vascular ECs of normal lungs. Similarly, abundant TCTP immunostaining was also seen in human PAH lung sections, again associated with complex vascular lesions. In BOECs, TCTP was found to participate in cell growth and survival. These data suggest that TCTP could play an important role in PAH by mediating pro-survival and growth signaling in vascular cells, contributing to occlusive pulmonary vascular remodeling triggered by EC apoptosis.

Background: Pulmonary arterial hypertension (PAH) is a multifaceted disease characterized by elevated pulmonary arterial pressure, right ventricular hypertrophy, and a poor prognosis. Pathological hallmarks of PAH include pulmonary vascular remodelling, pre-capillary arterial obliteration, and plexiform lesions. Over the past 15 years, pulmonary endothelial cell (EC) apoptosis has been repeatedly implicated as a key trigger of occlusive arterial remodelling in PAH. While it has been hypothesized that pulmonary EC apoptosis gives rise to the emergence of growth-dysregulated, apoptosis- resistant ECs involved in arterial remodelling, the molecular mechanisms linking these two events has not yet been fully elucidated. Recently, our lab identified translationally controlled tumour protein (TCTP) as one of several significantly dysregulated proteins in culture-derived blood-outgrowth endothelial cells (BOECs) isolated from hereditable PAH (HPAH) patients harbouring mutations in the gene encoding for bone morphogenetic protein receptor type 2. Immunohistological analyses indicated that TCTP expression was associated with intra-luminal pulmonary ECs and inflammatory cells in the remodelled vessels of both human PAH patients and SU5416 rats. Furthermore, TCTP silencing abrogated excessive HPAH BOEC proliferation and promoted apoptosis in vitro. Hypothesis: We hypothesized that TCTP represents a central molecular mechanism linking pulmonary arterial EC damage and apoptosis to the emergence of growth- dysregulated lung vascular cells and complex arterial remodelling in PAH.Purpose: The purpose of the present thesis was to examine the effects TCTP inhibition on EC survival and TCTP abundance in vitro as well as on pulmonary hemodynamic changes and arterial remodelling in vivo using a well-validated rat model of severe PAH. Methods: Inhibition of TCTP was accomplished using two TCTP small molecule inhibitors, sertraline and thioridazine. In vitro, rat lung microvascular ECs (RLMVECs) were exposed to thioridazine and assayed for TCTP abundance, survival, and markers of apoptosis. In vivo, PAH was induced in male Sprague Dawley rats using SU5416 combined with 3 weeks of chronic hypoxia (SU/CH). After 4 weeks, right ventricle systolic pressure (RVSP) was measured by direct catheterization and osmotic pumps containing either thioridazine or sertraline were implanted subcutaneously. Following 3 weeks of small molecule delivery, RVSP was re-evaluated, cardiac function/structure was determined using transthoracic echocardiography, and histological analyses of vascular remodelling and inflammation were performed. Results: Our in vitro experiments demonstrated that thioridazine was able to significantly down-regulate TCTP levels and induce an apoptotic phenotype in RLMVECs. In the SU/CH rat model of severe PAH, both thioridazine and sertraline failed to have any effect on pulmonary hemodynamics, right ventricle structure/function, or vascular remodelling. Moreover, neither small molecule was able to detectably down-regulate TCTP levels in the lungs of SU/CH rats. Immunofluorescence staining revealed that TCTP expression occasionally corresponded with the expression of macrophage/monocyte marker CD68 in the lungs of SU/CH rats, consistent with its expression by inflammatory cells; however, no significant differences were found in adventitial cell clearance in the presence or absence of the inhibitors. Conclusions: Our findings support previous reports that thioridazine is able to significantly down-regulate TCTP and induce apoptosis in vitro. In contrast, both small molecule inhibitors failed to down-regulate lung TCTP levels or have any beneficial effects on the progression of PAH in SU/CH rats.

Yes / Pulmonary arterial hypertension (PAH) is a rare cardiovascular disorder caused by narrowing of blood vessels in the lung and in the absence of therapy leads to right heart failure and death. No cure for this devastating disorder is known. The major objective of the current treatments is to improve symptoms and these therapies were developed prior to the discovery that this disease has substantial genetic components. In this review, we discuss molecular genetic basis of PAH together with pathobiology, current and future therapeutic interventions.

No description available.

Introdução: Nas últimas décadas os óbitos por DCNT aumentaram três vezes nos estados brasileiros. Assim, o objetivo do estudo foi identificar a prevalência da obesidade e da hipertensão arterial na população de crianças e adolescentes estudantes da rede estadual de ensino de Ribeirão Preto/SP. Métodos: Foi conduzido um estudo transversal com 505 crianças/adolescentes, da faixa etária de 10 a 16 anos, que frequentavam as escolas estaduais de Ribeirão Preto. A coleta de dados, foi realizada através de pesquisa de campo com visitas às escolas e entrevista dos alunos selecionados ao longo dos anos de 2013 e 2014. Medidas antropométricas (peso, altura, cintura, quadril), e os níveis de pressão arterial foram aferidos em todos os participantes. Resultados: Aproximadamente 53% (n=265) dos estudantes eram do gênero masculino e 47% (n=240) do gênero feminino, com média de idade de 12,74 anos. Verificou-se alteração do peso corporal em 30,9% da população estudada, sendo 18,22% com sobrepeso e 12,67% com obesidade, sem diferença estatística entre os gêneros. Quanto aos níveis de pressão arterial, verificou-se alteração em 8,71% da população total, sendo mais frequente no grupo feminino (4,95%). As crianças com níveis de PA normal admitem passar menos tempo livre sem gasto energético quando comparadas com as de PA alterada [RP 0,92 (IC95% 0,88 0,97)]. Encontrou-se associação significativa [RP 2,02 (IC95% 1,28;3,2)] para o IMC alterado e menarca antes dos 10 anos de idade. A análise de regressão linear simples mostrou associação positiva entre IMC e níveis de PA tanto sistólica (R² = 0,2244; y= 61,1770 + 1,8228x; p<0,001) quanto diastólica (R² = 0,3450; y = 35,2008 + 1,0726 x; p <0,0001). Para as demais variáveis comportamentais e de hábitos alimentares, não foram encontradas associações entre obesidade ou níveis de PA. Conclusão: Observou-se alta prevalência de obesidade e hipertensão arterial na população estudada. Foi encontrada associação positiva entre IMC e HAS. Para as variáveis comportamentais e alimentares poucas foram as associações. Houve associação para a ocorrência da menarca antes dos 10 anos e o IMC alterado. Houve associação também para o aumento dos níveis pressóricos e o tempo livre sem gasto energético. Não foram encontradas associações significativas entre consumo elevado de doces, refrigerantes e a prática de atividade física foi menor que a recomendação feita pela OMS. Ressalta-se a importância do desenvolvimento de estratégias de intervenção com a participação de equipe multiprofissional e familiares para prevenção e controle da obesidade e da hipertensão arterial nas crianças e adolescentes. / Introduction: In recent decades, deaths from CDNT increased three times in the Brazilian county. The objective of the study was to identify the prevalence of obesity and high blood pressure in the population of children and adolescents students of the county school of Ribeirão Preto/SP. Methods: A cross-sectional study was conducted with 505 children / adolescents, the age group 10-16 years who attended state schools in Ribeirão Preto/SP. Data collection was conducted through field research with visits to schools and interviews of selected students over the years 2013 and 2014. Anthropometric measurements (weight, height, waist, and hip) and blood pressure levels were measured for all participants. Results: Approximately 53% (n=265) of the students were male and 47 % (n 240) were female, with a mean age of 12.74 years. There was change in body weight in 30.9 % of the study population, and 18.22 % were overweight and 12.67 % were obese, with no statistical difference between genders. As for blood pressure levels, there was change to 8.71 % of the total population, being more frequent in the female group (4.95%). Children with normal BP levels admit spend less time off without energy expenditure compared with the amended BP [RP 0.92 (95% CI from 0.88 to 0.97)]. Found a significant association [RP 2.02(95% CI 1.28, 3.2)] BMI changed and menarche before 10 years of age. Simple linear regression analysis showed a positive association between BMI and both systolic BP levels (R² = 0.2244, y = 61.1770 + 1,8228x; p < 0.001) and diastolic (R² = 0.3450, y = 35 2008 x + 1.0726; p <0.0001). For the other behavioral and eating habits variables, there were no associations between obesity and BP levels. Conclusion: There was a high prevalence of obesity and hypertension in this population. There was a positive association between BMI and SAH. For behavioral and dietary variables were few associations. There was an association for the occurrence of menarche before age 10 and the changed BMI. Was associated also to increased blood pressure and the free time without energy expenditure. Significant associations between high consumption of sweets, soft drinks and physical activity lower than recommended were found. It emphasizes the importance of developing intervention strategies with the participation of multidisciplinary team, including schools and family for the prevention and control of obesity and high blood pressure in children and adolescents.