Smelter workers who were exposed to air-borne arsenic for a mean of 23 years, and age-matched referents, were examined with clinical, physiological, and neurophysiological methods. Exposure to arsenic in workroom air was estimated to have been around the Swedish occupational limits, which were 500 yg/m before 1975 and 50 yg/ra thereafter. An increased preval ence of Raynaud's phenomenon and a reduced finger systolic blood pressure (FSP) during local and general cooling were found in the smelter workers. Slight, but significant sub-clinical neuropathy, in the form of slightly reduced nerve conduction velocity (NCV) in two or more peripheral nerves, was more common among the arsenic workers than among the referents. There were positive correlations between cumulative exposure to arsenic, reduced NCV in three peripheral motor nerves, and decrease in FSP during cooling. Arsenic levels in urine were 1 ymole/1 (75 yg/1) in the arsenic workers and 0.1 ymole/1 in the referents. In 21 arsenic workers with no or very low exposure to vibra ting hand tools, the FSP during cooling had increased significantly after 3 years wit h the lower arsenic exposure. There was no change in FSP during the summer vacation, whereas urinary levels of arsenic decreased to normal values. Thus there seems to be a slow improvement of finger blood circ ulation which is independent of short-term fluctuations in the exposure to arsenic. No seasonal variation was found in FSP during cooling with the standardized method used. When the NCV-measurements were repeated five years later the difference between arsenic workers and referents had increased, despite the fact that 14 of the 47 arsenic workers had had no exposure to arsenic during the last 1-5 years. These observations indicate, that in subjects with long term exposure to arsenic, sub-clinical neuropathy is not reversible. Ten milligrams of Ketanserin, a serotonin receptor antagonist, was given intravenously to five arsenic workers with cold-induced vasospasm. Skin temperature and FSP during cooling increased significantly with Ketanserin as compared wit h saline solution. After oral treatment, 2 x 40 mg /day for four weeks, no significant increase of FSP during cooling or rise in skin temperature was found in six arsenic workers and eleven patients with Raynaud's phenomenon. The decrease of vasospastic tendency after intravenous injection of Ketanserin indicated that similar mechanisms might operate in arsenic-induced and other types of Raynaud's phenomenon. A general co nclusion from the five studies in this dissertation is that long-term occupational exposure to arsenic has had adverse effects on the peripheral circulation and nerve conduction. The tendency to vasospasm, but not the sub-clinical neuropathy, seemed to be reversible with decreasing exposure. / <p>S. 1-54: sammanfattning, s. 55-112: 5 uppsatser</p> / digitalisering@umu

Pulmonary arterial hypertension (PAH) is a lethal disease, characterized by functional or structural abnormalities involving distal pulmonary arterioles that result in increased pulmonary vascular resistance (PVR) and ultimately right heart failure. Our objective is to establish a conditional transgenic system in mice, to test the hypothesis that lung EC apoptosis at the level of distal pulmonary arterioles is necessary and sufficient to cause a PAH phenotype. In a pilot study, the Fas-Induced Apoptosis (FIA) construct was expressed under the control of endothelial-specific Tie2 promoter in transgenic mice (i.e. EFIA mice). Administration of a small molecule dimerizing agent, AP20187, resulted in lung modest dose-dependent PAH, which was associated with proliferative vascular lesions localized to distal lung arterioles in a small proportion of mice. Due to the low level of transgene expression in preliminary EFIA lines, we re-designed the transgenic vector by incorporating a more robust endothelial promoter (superTie2). The new construct was transfected into HUVEC and BAEC and analyzed by monitoring immunofluorescence (DsRed). Data from the EFIA model suggests that EC apoptosis may be sufficient to induce a PAH phenotype with the characteristic lung vascular lesions. The EFIA model will allow us to better explore the mechanism that links distal lung EC apoptosis with reactive vascular cell proliferation in the pathogenesis of this devastating disease.

Pulmonary arterial hypertension (PAH) is a lethal disease, characterized by functional or structural abnormalities involving distal pulmonary arterioles that result in increased pulmonary vascular resistance (PVR) and ultimately right heart failure. Our objective is to establish a conditional transgenic system in mice, to test the hypothesis that lung EC apoptosis at the level of distal pulmonary arterioles is necessary and sufficient to cause a PAH phenotype. In a pilot study, the Fas-Induced Apoptosis (FIA) construct was expressed under the control of endothelial-specific Tie2 promoter in transgenic mice (i.e. EFIA mice). Administration of a small molecule dimerizing agent, AP20187, resulted in lung modest dose-dependent PAH, which was associated with proliferative vascular lesions localized to distal lung arterioles in a small proportion of mice. Due to the low level of transgene expression in preliminary EFIA lines, we re-designed the transgenic vector by incorporating a more robust endothelial promoter (superTie2). The new construct was transfected into HUVEC and BAEC and analyzed by monitoring immunofluorescence (DsRed). Data from the EFIA model suggests that EC apoptosis may be sufficient to induce a PAH phenotype with the characteristic lung vascular lesions. The EFIA model will allow us to better explore the mechanism that links distal lung EC apoptosis with reactive vascular cell proliferation in the pathogenesis of this devastating disease.

Made available in DSpace on 2016-01-26T12:51:40Z (GMT). No. of bitstreams: 1 erosdamotadias_dissert.pdf: 1356790 bytes, checksum: 1ece28a3152d142febf47e53f4b83f1e (MD5) Previous issue date: 2012-07-25 / Introduction- The role of hypertension in the loss of cognitive function is controversial. Relationships of hypertension with increases in cerebral vascular resistance, diffused lesions and multiple lacunars infarct of the white matter are well known. Objectives- To evaluate the relationship between hypertension and cognitive deficiency (CD), identify risk factors associated with the development of CD and determine the association between markers of early vascular disease and CD in hypertensive individuals. Methods- One hundred and ninety eight individuals aged between 40 and 80 years old were evaluated. Forty eight participants were normotensive (NT). The remaining 150 hypertensive patients were subdivided into two groups, those with CD (HCD) and those without CD (HNCD). All participants underwent clinical evaluations and complete physical examinations and biochemical blood tests were performed. CD was investigated using the Mini Mental State Examination (MMSE) following the guidelines for its use in Brazil. The impact of hypertension on the arterial bed was assessed by identifying and measuring changes in the intima-media thickness (IMT) by vascular ultrasonography of the carotid arteries and analyses of the central blood pressure and Augmentation Index by applanation tonometry of the radial artery. Results- There were no significant differences in the plasma concentrations of total cholesterol, high density lipoprotein cholesterol and triglycerides of the three groups. The serum creatinine and estimated glomerular filtration rate where within normal ranges for all three groups. However, significantly higher values were found for the HCD and HNCD Groups compared to the NT Group (p-value < 0.05). A significantly lower MMSE score was recorded for the HCD Group compared to the HA and NT Groups (p-value < 0.05). The IMT was significantly different between the HNCD and HCD Groups (p-value = 0.0124). A significant difference in the IMT was also observed between hypertensive patients and the NT Group (p-value < 0.0001). The central systolic pressure was significantly higher in the HCD and HNCD Groups compared to NT Group (p-value < 0.0001). There were no significant differences in the Augmentation Index (corrected for heart rate) between the three groups (HNCD, HCD and NT). Conclusions- Hypertensive patients with CD have changes in the vascular morphology characterized by an increased carotid IMT and hemodynamic functional impairment manifested by elevated central systolic blood pressure. / Introdução- O papel da Hipertensão Arterial Sistêmica (HAS) no desenvolvimento de disfunção cognitiva é controverso. Reconhece-se sua relação com o aumento da resistência vascular cerebral e com lesões difusas e infartos lacunares múltiplos na substância branca. Objetivos- Avaliar a relação entre HAS e Déficit Cognitivo (DC), identificar fatores de risco associados a DC e identificar marcadores precoces de doença vascular e DC em hipertensos. Casuística e métodos- Foram avaliados 198 indivíduos com idades entre 40 e 80 anos, dos quais 150 eram hipertensos subdivididos em dois grupos, Hipertensos com DC (HA-DC) e Hipertensos sem DC (HA) e 48 indivíduos normotensos (NT). Todos foram submetidos à avaliação clínica, exame físico completo e exames bioquímicos de sangue. O DC foi investigado mediante o Mini Exame do Estado Metal (MEEM) segundo os critérios cujo uso é recomendado no Brasil. A repercussão da HAS no leito arterial foi rastreada por meio da identificação e quantificação de alteração na Espessura Íntima Média (EIMc) das carótidas com Ultrassonografia Vascular Digital e análise da Pressão Arterial Central (PSC) e do Augmentation Index (AI) mediante Tonometria por Aplanação (TA) da artéria radial. Resultados- As concentrações plasmáticas do colesterol total, colesterol de lipoproteína de alta densidade (HDL) e triglicérides (TG) nos três grupos estudados não mostraram diferenças significantes. Os valores de creatinina sérica e a Taxa de Filtração Glomerular estimada (TFGe) encontram-se dentro da faixa de normalidade nos três grupos. Entretanto valores maiores foram observados nos grupos HA-DC e HA, quando comparados ao grupo NT (p < 0,05). O grupo HA-DC confirmou redução significante do escore do MEEM quando comparado aos grupos HA e NT ( p <0,05). Avaliação da EIMc mostrou diferença significante entre os grupos HA e HA-DC (p=0,0124). Por outro lado, também observamos diferença significante para EIMc entre hipertensos e controles (p < 0,0001). Os grupos HA-DC e HA evidenciaram aumento significante da pressão sistólica central (PSC), quando comparados ao grupo NT (p < 0,0001). Os resultados do Augmentation Index 75 (corrigido para FC), avaliados nos três grupos (HA, HA-DC e NT) não apresentaram diferença significante. Os resultados do presente estudo mostraram: presença de alterações morfológicas caracterizadas por aumento da espessura íntima média das carótidas e alterações funcionais qualificadas como elevação da pressão sistólica central no grupo de hipertensos com DC. Entre os fatores de risco para o desenvolvimento de DC apenas a idade foi associada com déficit do escore do MEEM. Conclusões- Hipertensos com DC apresentam alterações morfológicas vasculares caracterizadas por aumento da espessura íntima média das carótidas e comprometimento hemodinâmico funcional manifesto por elevação de pressão sistólica central.

Doctor Pharmaceuticae - DPharm / An aqueous extract prepared from the leaves and smaller stems of Leonotis leonurus was used to investigate the potential effects on certain cardiovascular parameters, such as left ventricular systolic pressure, end-diastolic pressure, developed pressure, heart rate, cardiac work and coronary perfusion pressure in isolated rat hearts. Hearts were perfused at constant flow for 3min using the modified Langendorf! perfused model of the heart. Effects of adrenaline and digoxin solutions on the isolated heart were compared to that of the plant extract. Adrenaline produced both positive inotropic and chronotropic effects. Adrenaline increased (p<O.Ol) the left ventricular systolic pressure and hence the left ventricular developed pressure by 40.6% and 43.9% at peak, and 24.3% and 31.9%, after 3min, respectively. Simultaneously, the heart rate and the cardiac work were increased (p<0.01) by 22.5% and 89.4% at peak, and 24.6% and 63%, after 3rnin, respectively. There were no significant effects on the left ventricular diastolic pressure and the coronary perfusion pressure. Digoxin solution (2.5ng/ml) significantly (p<O.Ol) increased the left ventricular systolic pressure by 5.1% after 3min and the left ventricular diastolic pressure by 9.7% at peak and 5.3% after 3min. The heart rate was significantly (p<O.OI) decreased by 3.7% at peak. The cardiac work was increased by 4.5% after 3rnin. Digoxin did not significantly affect the left end diastolic pressure and the coronary perfusion pressure. The extract of Leonons leonurus at O.lmg/ml increased (p<O.OI) the left ventricular systolic pressure and hence the left ventricular diastolic pressure by 9.7% and 10.7% at peak, and 5.4% and 5.5% after 3rnin, respectively. The cardiac work was increased (p<O.Ol) by 10.1% at peak. Leonotis leonurus (0.1mg/ml) did not significantly affect the left ventricular end diastolic pressure, the heart rate and the coronary perfusion pressure. At 0.5mg/ml, the left ventricular systolic pressure and hence the left ventricular diastolic pressure were increased (p<0.01) by 14.8% and 15.4% at peak and 7.4% and 7.8% after 3rnin, respectively with a corresponding decrease (p<O.OI) in the coronary perfusion pressure of 8.5% at peak and 4.4% after 3rnin. The cardiac work was increased (p<O.OI) by 13.6% at peak and 5.2% after 3rnin. The extract at 1.0mg/ml increased (p<O.Ol) the left ventricular systolic pressure and hence the left ventricular diastolic pressure by 25.4% and 29.4% at Peak, and 23.1% and 26.3% after 3rnin, respectively. The heart rate was reduced (p<O.OI) by 34.7% at peak and 28.3% after 3min. The cardiac work and the coronary perfusion pressure were decreased (p<O.OI) by 15.9% and 12.1% at Peak and 3.3% and 11.4% after 3rnin. However, at 2.0mg/ml, the left ventricular systolic pressure and the left ventricular diastolic pressure were increased (p<O.OI) by 14.9% at peak. The left ventricular diastolic pressure was decreased (p<O.OI)by 9.8% over the 3rnin. The heart rate was drastically decreased (p<O.OI) by 42.7% after 3rnin. The cardiac work was reduced (p<O.Ol) by 48.8% over the 3min period. Also, the coronary perfusion pressure was decreased (p<0.01) by 16.9% at peak. Thus, Leonatis leonurus produced both positive inotropic and negative chronotropic effects after 3min perfusion, accompanied by a decreased coronary perfusion pressure. Thus, it appears that the extract seemed to contain certain constituents associated with positive inotropic and negative chronotropic agents as wel! as constituents associated with coronary vasodilation. However, at the higher concentration, it seemed to contain some constituents associated with toxic effects on the isolated heart. Therefore, further studies are needed to isolate the various constituents and examine their possible pharmacological effects on the heart individually before it could be considered safe to recommend this plant for its use in the treatment of cardiovascular disease.

In my master's tehsis I'm dealin with the methods used for non-invasive blood pressure measurement. For realization of a virtual blood pressure meter in LabVEW I have chosen the oscillometric method. Algorithm determining systolic and diastolic blood pressure is based on the relatively easy detection of maximum amplitude oscillations (corresponds with a mean arterial pressure), when thelimiting valuesof blood pressure are in a specific ratio with a maximum amplitude of oscillation. In LabVIEW was solved loading of signal from the measure card and processing pressure curve into a form suitable for the detection of the peak oscillations. The program calculates the limits of arterial pressure and mean heart rate too. Linking the virtual device with the blood pressure sensor Vernier BPS-BTA then makes up komplex for capturing the blood pressure via oscillatory method.

Yes / This study investigated the relationship of ethnicity to the differences between blood pressure (BP) measured in a clinic setting and by ambulatory blood pressure monitoring (ABPM) in individuals with a previous diagnosis of hypertension (HT) and without a previous diagnosis of hypertension (NHT). A cross-sectional comparison of BP measurement was performed in 770 participants (white British (WB, 39%), South Asian (SA, 31%), and African Caribbean (AC, 30%)) in 28 primary care clinics in West Midlands, United Kingdom. Mean differences between daytime ABPM, standardized clinic (mean of 3 occasions), casual clinic (first reading on first occasion), and last routine BP taken at the general practitioner practice were compared in HT and NHT individuals. Daytime systolic and diastolic ABPM readings were similar to standardized clinic BP (systolic: 128 (SE 0.9) vs. 125 (SE 0.9) mm Hg (NHT) and 132 (SE 0.7) vs. 131 (SE 0.7) mm Hg (HT)) and were not associated with ethnicity to a clinically important extent. When BP was taken less carefully, differences emerged: casual clinic readings were higher than ABPM, particularly in the HT group where the systolic differences approached clinical relevance (131 (SE 1.2) vs. 129 (SE 1.0) mm Hg (NHT) and 139 (SE 0.9) vs. 133 (SE 0.7) mm Hg (HT)) and were larger in SA and AC hypertensive individuals (136 (SE 1.5) vs. 133 (SE 1.2) mm Hg (WB), 141 (SE 1.7) vs. 133 (SE 1.4) mm Hg (SA), and 142 (SE 1.6) vs. 134 (SE 1.3) mm Hg (AC); mean differences: 3 (0-7), P = 0.03 and 4 (1-7), P = 0.01, respectively). Differences were also observed for the last practice reading in SA and ACs. BP differences between ethnic groups where BP is carefully measured on multiple occasions are small and unlikely to alter clinical management. When BP is measured casually on a single occasion or in routine care, differences appear that could approach clinical relevance.