| 1. |
- Björck, Hanna, et al.
(författare)
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Gender-specific association of the plasminogen activator inhibitor-1 4G/5G polymorphism with central arterial blood pressure
- 2011
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Ingår i: American Journal of Hypertension. - New York, USA : Nature Publishing Group. - 0895-7061 .- 1941-7225. ; 24:7, s. 802-8
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Tidskriftsartikel (refereegranskat)abstract
- Background: The functional plasminogen activator inhibitor-1 (PAI-1) 4G/5G polymorphism has previously been associated with hypertension. In recent years, central blood pressure, rather than brachial has been argued a better measure of cardiovascular damage and clinical outcome. The aim of this study was to investigate the possible influence of the 4G/5G polymorphism on central arterial blood pressure in a cohort of elderly individuals.Methods: We studied 410 individuals, 216 men and 194 women, aged 70-88. Central pressures and pulse waveforms were calculated from the radial artery pressure waveform by the use of the SphygmoCor system and a generalized transfer function. Brachial pressure was recorded using oscillometric technique (Dinamap, Critikon, Tampa, FL). PAI-1 antigen was determined in plasma.Results: The results showed that central pressures were higher in women carrying the PAI-1 4G/4G genotype compared to female carriers of the 5G/5G genotype, (P = 0.025, P = 0.002, and P = 0.002 for central systolic-, diastolic-, and mean arterial pressure, respectively). The association remained after adjustment for potentially confounding factors related to hypertension. No association of the PAI-1 genotype with blood pressure was found in men. Multiple regression analysis revealed an association between PAI-1 genotype and plasma PAI-1 levels (P = 0.048).Conclusions: Our findings show a gender-specific association of the PAI-1 4G/5G polymorphism with central arterial blood pressure. The genotype effect was independent of other risk factors related to hypertension, suggesting that impaired fibrinolytic potential may play an important role in the development of central hypertension in women.
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| 2. |
- Garkavij, Michael, et al.
(författare)
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Lu-177-[DOTA0,Tyr3] Octreotate Therapy in Patients With Disseminated Neuroendocrine Tumors: Analysis of Dosimetry With Impact on Future Therapeutic Strategy
- 2010
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Ingår i: Cancer. - : Wiley. - 1097-0142 .- 0008-543X. ; 116:4, s. 1084-1092
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Lu-177-(DOTAO,Tyr3) octreotate is a new treatment modality for disseminated neuroendocrine tumors. According to a consensus protocol, the calculated maximally tolerated absorbed dose to the kidney should not exceed 27 Gy. In commonly used dosimetry methods, planar imaging is used for determination of the residence time, whereas the kidney mass is determined from a computed tomography (CT) scan. METHODS: Three different quantification methods were used to evaluate the absorbed dose to the kidneys. The first method involved common planar activity imaging, and the absorbed dose was calculated using the medical internal radiation dose (MIRD) formalism, using CT scan-based kidney masses. For this method, 2 region of interest locations for the background correction were investigated. The second method also included single-photon emission computed tomography (SPECT) data, which were used to scale the amplitude of the time-activity curve obtained from planar images. The absorbed dose was calculated as in the planar method. The third method used quantitative SPECT images converted to absorbed dose rate images, where the median absorbed dose rate in the kidneys was calculated in a volume of interest defined over the renal cortex. RESULTS: For some patients, the results showed a large difference in calculated kidney-absorbed doses, depending on the dosimetry method. The 2 SPECT-based methods generally gave consistent values, although the calculations were based on different assumptions. Dosimetry using the baseline planar method gave higher absorbed doses in all patients. The values obtained from planar imaging with a background region of interest placed adjacent to the kidneys were more consistent with dosimetry also including SPECT. For the accumulated tumor absorbed dose, the first 2 of the 4 planned therapy cycles made the major contribution. CONCLUSIONS: The results suggested that patients evaluated according to the conventional planar-based dosimetry method may have been undertreated compared with the other methods. Hematology and creatinine did not indicate any restriction for a more aggressive approach, which would be especially useful in patients with more aggressive tumors where there is not time for more protracted therapy. Cancer 2010;116(4 suppl):1084-92. (C) 2010 American Cancer Society.
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| 3. |
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| 4. |
- Ljungberg, Liza, 1980-
(författare)
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Angiotensin-converting enzyme in cardiovascular function and dysfunction
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Angiotensin-converting enzyme (ACE) is a key enzyme in the renin-angiotensin system, converting angiotensin I to the vasoactive peptide angiotensin II, and degrading bradykinin. Angiotensin II is a multifunctional peptide, acting on a number of different tissues. A common genetic variation in the gene encoding ACE; ACE I/D polymorphism influences the level of ACE in the circulation, and has been linked to increased risk for cardiovascular disease. This thesis aimed to explore the connection between ACE and cardiovascular function and dysfunction.The impact of nicotine and nicotine metabolites on ACE in cultured human endothelial cells was studied. Nicotine as well as nicotine metabolites induced increased ACE activity in cultured human endothelial cells. In elderly men a higher ACE level was seen in smokers compared to non-smokers. Furthermore, diabetes was associated with higher circulating ACE. Increased ACE level may represent a cellular mechanism which contributes to vascular damage.Elderly men carrying the ACE D allele had higher abdominal aortic stiffness compared to men carrying the I/I genotype. Our data suggest that the mechanism by which the ACE D allele modulates aortic wall mechanics is independent of circulating ACE levels. Previous studies have indicated a link between the D allele and abdominal aortic aneurysm. Increased aortic stiffness suggests impaired vessel wall integrity, which combined with local hemodynamic and/or inflammatory factors may have a role in aneurysm formation.Subjects with left ventricular dysfunction had higher levels of circulating ACE compared to those with normal left ventricular function, while there was no association between ACE and central hemodynamics. ACE might play a role in the pathogenesis of left ventricular dysfunction and our findings suggest a direct effect on the heart rather than affecting central blood pressure.
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| 5. |
- Ljungberg, Liza, et al.
(författare)
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Circulating angiotensin-converting enzyme levels are associated with left ventricular dysfunction, but not with central aortic blood pressure, aortic augmentation or pulse pressure amplification
- 2011
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Aim: This study aimed to explore the link between angiotensin-converting enzyme (ACE), and left ventricular (LV) function and central hemodynamics. Methods and Results: The study population consisted of 672 subjects (322 men and 350 women) aged 69-87 years. LV function was evaluated semi-quantitatively by visual estimation using echocardiography. Central aortic blood pressure, aortic augmentation and pulse pressure amplification were determined in a sub-group of 422 subjects by the use of the SphygmoCor system. ACE genotype was determined by PCR and circulating ACE levels were analysed using enzyme-linked immunosorbent assay (ELISA). LV dysfunction was associated with higher levels of circulating ACE compared to subjects with normal LV function (p=0.007). This association remained after adjustment for factors previously shown to affect circulating ACE (ACE-genotype, age, diabetes and smoking) (p=0.036). There was a significant association between ACE level and degree of LV dysfunction (p=0.019). However, there was no association of ACE genotype or circulating ACE with central aortic blood pressure, aortic augmentation or pulse pressure amplification. Conclusion: Subjects with LV dysfunction have higher levels of circulating ACE compared to subjects with normal LV function. ACE might play a role in the pathogenesis of LV dysfunction and our data indicates a direct effect on the heart rather than affecting central blood pressure.
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| 6. |
- Ljungberg, Liza, et al.
(författare)
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Effects of nicotine, its metabolites and tobacco extracts on human platelet function in vitro
- 2013
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Ingår i: Toxicology in Vitro. - Oxford, United Kingdom : Elsevier. - 0887-2333 .- 1879-3177. ; 27:2, s. 932-938
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Tidskriftsartikel (refereegranskat)abstract
- Cigarette smoking is a leading cause of cardiovascular disease. The cardiovascular effects of smoking are probably multifactorial, including effects on platelets. Previous reports investigating the effects of nicotine and tobacco on platelet function are inconsistent.The present study investigated in vitro effects of nicotine, its major metabolites, tobacco extracts and extract of tobacco-free snuff on human platelets.None of the metabolites cotinine, cotinine-N-oxide, nicotine-1′-N-oxide or trans-3′-hydroxycotinine (0.1–10 μM) affected platelet aggregation or P-selectin expression. Nicotine (10 μM) weakly increased platelet aggregation, whereas trans-3′-hydroxycotinine (0.1 μM) and nicotine-1′-N-oxide (1–10 μM) weakly inhibited adhesion to fibrinogen. To elucidate the influence of other tobacco compounds, we investigated the impact of moist tobacco and smoke extracts on platelet function. Filtered extracts of oral snuff, cigarette smoke and tobacco free snuff inhibited platelet adhesion concentration-dependently. The inhibitory effects of tobacco extracts on platelet adhesion were independent of nicotine content and the nitric-oxide-pathway and not mediated through a platelet-nicotine-receptor.Taken together, tobacco extracts inhibit platelet activation during short-term in vitro challenge. As only limited effects of nicotine and nicotine metabolites were seen, the tobacco-induced platelet inhibition are likely induced by other compounds present in tobacco and tobacco free snuff.
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| 7. |
- Ljungberg, Liza, et al.
(författare)
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The association between circulating angiotensin-converting enzyme and cardiovascular risk in the elderly : A cross-sectional study.
- 2011
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Ingår i: jraas. Journal of the renin-angiotensin-aldosterone system. - London, United Kingdom : SAGE. - 1470-3203 .- 1752-8976. ; 12:3, s. 281-289
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: A polymorphism in the angiotensin-converting enzyme gene (ACE I/D polymorphism) has been associated with increased risk for cardiovascular disease (CVD). This polymorphism affects the level of circulating ACE, but there is great individual variation, even between those with the same genotype. Few previous studies have investigated the link between circulating ACE and cardiovascular risk. The aim of this study was to investigate this association, and to examine the relationship between ACE level, ACE genotype and CVD. MATERIALS AND METHODS: The study population consisted of 322 men and 350 women aged 69-87. Plasma ACE level was determined using enzyme-linked immunosorbent assay (ELISA), and ACE genotype was analysed using PCR followed by gel electrophoresis. RESULTS: In men, ACE levels increased with increasing number of cardiovascular risk factors (p = 0.003). There was a significant association in men between increased ACE level and both diabetes (p = 0.007) and smoking (p = 0.037). CONCLUSIONS: This study shows that cardiovascular risk factors (such as smoking and diabetes) are associated with higher levels of circulating ACE in men. High ACE levels may represent one of the cellular mechanisms involved in producing the vascular damage associated with cardiovascular risk factors.
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| 8. |
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| 9. |
- Ljungberg, Liza U., 1980-, et al.
(författare)
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Impaired abdominal aortic wall integrity in elderly men carrying the angiotensin-converting enzyme D allele
- 2011
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Ingår i: European Journal of Vascular and Endovascular Surgery. - London, United Kingdom : W. B. Saunders Co. Ltd.. - 1078-5884 .- 1532-2165. ; 42:3, s. 309-16
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Tidskriftsartikel (refereegranskat)abstract
- Objective: A polymorphism in the angiotensin-converting-enzyme gene (ACE I/D) has been associated with abdominal aortic aneurysm and a link between aortic aneurysm and aortic stiffness has been suggested. This study aimed to explore the links between ACE I/D polymorphism, circulating ACE and abdominal aortic wall integrity as reflected by abdominal aortic wall stiffness.Material: A total of 212 men and 194 women, aged 70-88 years, were studied.Methods: Mechanical properties of the abdominal aorta were determined using the Wall Track System, ACE genotype using the polymerase chain reaction (PCR) and circulating ACE level by enzyme-linked immunosorbent assay (ELISA).Results: In men, pulsatile diameter change differed between genotypes (II 0.70, ID 0.55 and DD 0.60 mm, P = 0.048), whereas a tendency was seen for distensibility coefficient (DC) (II 10.38, ID 7.68 and ID 8.79, P = 0.058). Using a dominant model (II vs. ID/DD), men carrying the ACE D allele had lower pulsatile diameter change (P = 0.014) and DC (P = 0.017) than II carriers. Multiple regression analyses showed additional associations between the D allele and increased stiffness β, and reduced compliance coefficient.Conclusion: Men carrying the ACE D allele have stiffer abdominal aortas compared with II carriers. Deranged abdominal aortic stiffness indicates impaired vessel wall integrity, which, along with other local predisposing factors, may be important in aneurysmal disease.
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| 10. |
- Minarik, David, et al.
(författare)
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90Y Bremsstrahlung Imaging for Absorbed-Dose Assessment in High-Dose Radioimmunotherapy.
- 2010
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Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 2159-662X. ; 51:12, s. 1974-1978
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Tidskriftsartikel (refereegranskat)abstract
- This feasibility study demonstrates (90)Y quantitative bremsstrahlung imaging of patients undergoing high-dose myeloablative (90)Y-ibritumomab treatment. METHODS: The study includes pretherapy (111)In SPECT/CT and planar whole-body (WB) imaging at 7 d and therapy (90)Y SPECT/CT at 6 d and (90)Y WB imaging at 1 d. Time-activity curves and organ-absorbed doses derived from (90)Y SPECT images were compared with pretherapy (111)In estimates. Organ activities derived from (90)Y WB images at the first day were compared with corresponding pretherapy estimates. RESULTS: Pretherapy (111)In images from 3 patients were similar to the (90)Y images. Differences between absorbed-dose estimates from pretherapy (111)In and (90)Y therapy were within 25%, except for the lungs. Corresponding activity differences derived from WB images were within 25%. Differences were ascribed to incomplete compensation methods and real differences in pharmacokinetics between pretherapy and therapy. CONCLUSION: Quantitative bremsstrahlung imaging to estimate organ activities and absorbed doses is feasible.
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