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- Andersson, Kristina E
(författare)
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Cholesterol-lowering and anti-atherogenic effects of oats in mice
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The cholesterol-lowering effect of oats is well established, but the crucial properties eliciting this effect need to be further investigated to optimize the use of oats as functional foods. Furthermore, there are almost no reports investigating the effect of oats on atherosclerosis development. This thesis describes our work with finding suitable mouse models to study cholesterol-lowering and anti-atherogenic effects of oats, the mechanism behind, and how processing of oat foods might interfere with these beneficial effects. We found that supplementation of oat bran to an atherogenic diet significantly reduced plasma cholesterol and LDL+VLDL concentrations in C57BL/6 mice. The responsiveness to oats did however differ between two substrain of mice. Oat intake resulted in reduced plasma cholesterol, increased faecal excretion of bile acids and cholesterol, and increased expression of the bile acid producing enzyme CYP7A1 in the C57BL/6NCrl substrain. None of these parameters were altered in the C57BL/6JBomTac mice. The different expression of CYP7A1 in the two substrains of C57BL/6 strongly supports the importance of increased bile acid excretion, together with increase of bile acid synthesis from cholesterol, for oats to reduce levels of cholesterol in plasma. To address how processing of oats might interfere with its cholesterol-lowering properties, oat beta-glucans were enzymatically digested to different molecular weights and then fed to C57BL/6NCrl mice. Reducing the molecular weight of the beta-glucans affected its viscous properties in vitro. It also affected the production of short chain fatty acids in caecal contents of the mice, but did not influence the cholesterol-lowering properties. Thus molecular weight and viscous properties of beta-glucans do not seem to be crucial parameters for the cholesterol-lowering properties of oats in the C57BL/6 mice. When studying effects of oats on atherogenesis and inflammation we used a mouse model developing more pronounced hypercholesterolaemia, the LDL-receptor deficient mice. Oats reduced plasma cholesterol and levels of LDL+VLDL in this model too, and also reduced plasma concentrations of the inflammation markers fibrinogen and soluble vascular adhesion molecule-1 (sVCAM-1). Most importantly oat bran in the diet reduced incidence of atherosclerotic lesions in both the aortic root and the descending aorta. These findings demonstrate that oats have anti-atherogenic properties, and support health claims that oats can reduce risk of cardiovascular disease.
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| 2. |
- Ekdahl, Christer, 1962-
(författare)
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Infective Endocarditis : aspects of pathophysiology, epidemiology, management and prognosis
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Infective endocarditis (IE) is a rare but complex disease that is fatal if untreated. With a modern combination of antimicrobial therapy and heart valve surgery, mortality is still 10-20 %. The structure of the endocarditis vegetation impedes the penetration of phagocytic cells such as monocytes and granulocytes. This leads to high bacterial counts inside the vegetation and the need for long treatment courses with a combination of intravenously administered bactericidal antibiotics.The aim of this thesis was to study the changes in epidemiology, management, and mortality at our hospital between 1980 and 2001, and to identify prognostic factors associated with mortality. To assess the issue of referral bias, differences between referred episodes and episodes from our local community were studied. Additional aims were to study the occurrence of the pro-chemotactic cytokines IL-8 and TNF-α in heart valves and vegetations during the active phase of IE, and to study the effect of the glycopeptide antibiotic vancomycin in dense staphylococcal cultures in vitro. As it is a rare and complex disease, management of IE is usually complicated for non-specialists. For this reason a computerised decision support system for IE was developed and evaluated.Between 1980 and 2001, the occurrence of Staphylococcus aureus IE and the use of early heart valve surgery increased significantly, regardless of whether the episodes were referred or of local origin. Glycopeptide antibiotics, mainly vancomycin, were used more frequently, especially among referred patients. Referred patients were younger, predominantly male, had more complications, and received surgical treatment more often than patients from our local community. The reason for the lower frequency of female patients in the referral cohort cannot be explained by more comorbidity or fewer complications. The differences between referred and local episodes seen in our study highlight the need for assessment and adjustment for referral bias in IE studies (Paper I).In six patients who needed early heart valve surgery, the largest numbers of IL-8-containing cells, and the greatest amount of inflammation, were seen in patients with short preoperative antimicrobial treatment courses. No such relationships were seen with respect to TNF-α-containing cells. The IL-8-containing cells and the inflammatory cells were predominantly scattered in the heart valve stroma or in the margin of the vegetation (Paper II). The primary effect of IL-8 is to stimulate chemotaxis of polymorphonuclear neutrophil granulocytes. This indicates that there is no deficiency of IL-8 in the area close to the vegetation as a cause of the localised agranulocytosis often present inside the vegetation.Our study revealed a need for computerised decision support systems (DSSs) in the field of IE, but to be used in clinical practice these DSSs need be part of knowledge bases covering larger domains (Paper IV). Some of our initial ideas described in Paper III, especially the use of Internet technology and the combination of rule-based advice and explanatory hypertext, will probably be included in these knowledge bases.In vitro, there is a rapid reduction of free vancomycin in broth containing dense staphylococcal cultures. Consequently, there is a simultaneous increase in broth MICs, particularly in high inocula, which is not caused by a development of resistance (Paper V). These findings need further evaluation in vivo, but indicate that the dosing regimen of vancomycin is of particular importance in staphylococcal infections with dense inocula, e.g. infective endocarditis.Diabetes mellitus and moderate to severe heart failure were independent risk factors for 6-month mortality in left-sided, Duke definite IE episodes, regardless of referral or local origin of the episodes. Early heart valve surgery had a positive impact on the 6-month mortality in the referral cohort of episodes, which may be due to referral bias (Paper VI).
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| 3. |
- Lindroos, Hillevi Lina, 1976-
(författare)
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Studies of Genome Diversity in Bartonella Populations : A journey through cats, mice, men and lice
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Bacteria of the genus Bartonella inhabit the red blood cells of many mammals, including humans, and are transmitted by blood-sucking arthropod vectors. Different species of Bartonella are associated with different mammalian host species, to which they have adapted and normally do not cause any symptoms. Incidental infection of other hosts is however often followed by various disease symptoms, and several Bartonella species are considered as emerging human pathogens.In this work, I have studied the genomic diversity within and between different Bartonella species, with focus on the feline-associated human pathogen B. henselae and its close relatives, the similarly feline-associated B. koehlerae and the trench-fever agent B. quintana which is restricted to humans.In B. henselae, the overall variability in sequence and genome content was modest and well correlated, suggesting low levels of intra-species recombination in the core genome. The variably present genes were located in the prophage and the genomic islands, which are also absent from B. quintana and B. koehlerae, indicating multiple independent excision events. In contrast, diversity of genome structures was immense and probably associated with rearrangements between the repeated genomic islands located around the terminus of replication, possibly to avoid the host’s immune system. In both B. henselae and the mouse-associated species B. grahamii a large portion of the chromosome was manifold amplified in long-time cultures and packaged into phage particles, allowing for different recombination rates for different chromosomal regions.In B. quintana, diversity was studied by sequencing non-coding spacers. The low variability might be due to the recent emergence of this species. Surprisingly, also this species displayed high variability in genome structures, despite its lack of repeated sequences.The results indicate that genome rearrangements and gain or loss of mobile elements are major mechanisms of evolution in Bartonella.
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