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- Becriovic-Agic, Mediha
(författare)
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Susceptibility to Acute Decompensated Heart Failure in Two Common Mouse Strains
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Heart failure is a clinical syndrome characterized by an inability of the heart to meet oxygen demands of the body. During the initial stage of heart failure development compensatory mechanisms are activated to help the heart sustain proper function. Over time these compensatory mechanisms become inadequate resulting in decompensation. Acute decompensated heart failure is characterized by rapidly escalating heart failure symptoms, such as dyspnea and congestion, which require urgent treatment. The pathophysiology of decompensation and role of genetic background on this process is not completely understood. The aim of this thesis was to investigate the role of genetic background on susceptibility to develop acute decompensated heart failure.Balb/CJ and C57BL/6J mice are two common mouse strains that we found have different susceptibility to angiotensin II and high-salt diet (AngII+Salt) induced decompensation. Balb/CJ treated with AngII+Salt develop massive edema associated with anuria and high mortality within 4-6 days of treatment, while C57BL/6J mice do not. Due to the clinical symptoms of heart failure we hypothesized that Balb/CJ develop acute decompensated heart failure, and that the genetic background of this strain is responsible for the increased susceptibility to heart failure. AngII+Salt increased pulmonary and systemic vascular resistance, reduced left ventricle filling, and increased sodium and water retention in Balb/CJ mice. Increased pulmonary vascular resistance correlated with a higher angiotensin II response in isolated pulmonary arteries from Balb/CJ compared to C57BL/6J. Cardiac output was lower in Balb/CJ than C57BL/6J during AngII+Salt treatment even though they retained more sodium and water. This indicated that AngII+Salt impairs cardiac function in Balb/CJ mice. Oxidative stress was shown to play a role in AngII+Salt induced acute decompensation since treatment with an antioxidant reduced oxidative stress but impaired cardiac function and increased mortality in both strains. A linkage study was performed to reveal genes that are with high probability related to AngII+Salt induced decompensation in Balb/CJ mice. Quantative trait loci (QTLs) on chromosome 3 and 12 were linked to cardiac dysfunction and QTLs on chromosome 2 and 3 were linked to sodium and fluid balance. Foxo1 was found to be one of candidate genes for further study.Taken together, the data in this thesis shows that genetic background does play a large role in the development of acute decompensated heart failure. It reveals several candidate genes that could be studied in the setting of acute decompensated heart failure. Finally, it describes a new mouse model that could potentially be used for studying the pathophysiology of decompensation and identifying new drug targets.
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- Sampogna, F, et al.
(författare)
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The impact of skin diseases on patients : comparing dermatologists' opinions with research data collected on their patients.
- 2003
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Ingår i: British Journal of Dermatology. - : John Wiley & Sons. - 0007-0963 .- 1365-2133. ; 148:5, s. 989-95
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Research data suggest that the detection of psychiatric disorders by dermatologists is not completely satisfactory, and that patients and dermatologists often assess patients' quality of life differently. Given that expectations influence perception and cognitia, these discrepancies might at least in part descend from conceptual models of skin disease that are prevalent among dermatologists.OBJECTIVES: We explored to what degree dermatologists' opinions about quality of life and prevalence of psychiatric disorders in several dermatological conditions corresponded to the actual data collected on their patients.METHODS: All dermatologists working in a large institution were asked to express on a five-point scale their opinion about the quality of life and the prevalence of depressive and anxiety disorders in different skin conditions. Physicians' opinions were then compared with the results of a large research project on quality of life and psychological well-being in dermatological out-patients performed in their institution some months before.RESULTS: Forty-six dermatologists (82%) agreed to participate and completed the research questionnaire. We observed a fairly good concordance between dermatologists' opinion about the impact of the various skin conditions on patients' lives and survey data on quality of life impairment. With regard to psychiatric morbidity, we found that dermatologists believe that psychiatric disorders are substantially less frequent than they actually are in many skin conditions.CONCLUSIONS: The belief that psychiatric morbidity is rare in patients with certain skin conditions might hamper, at least in part, the recognition of psychiatric disorders in these patients. Dermatologists probably should be more alert to the question of psychiatric morbidity in their patients. Allocating more space to this issue in training programmes for dermatologists might favour a shift in their conceptual models of skin disease.
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