The vascular system transports components essential to the survival of the individual and acts as a barrier to substances that may injure the organism. Atherosclerosis is a dynamic, lesion producing disease of the arterial system that compromises the functioning of the organ by occlusive and thrombogenic processes. This investigation was undertaken to elucidate some of the normal biochemical processes related to the development of atherosclerosis. A significant part of the investigation was directed toward developing and combining methods and protocols to obtain the data in a concerted manner. A postmitochondnal supernatant of bovine aorta, using mevalonate-2-�����C as the substrate, was employed in the investigation. Methods included paper, thin layer, and silica gel chromatography; gel filtration, high performance liquid chromatography (HPLC), and mass spectrometry. This current research demonstrated direct incorporation of mevalonate-2- �����C into the trans-methyiglutaconic shunt intermediates. The aorta also contains alcohol dehydrogenase activity, which converts dimethylallyl alcohol and isopentenol to dimethylacrylic acid, a constituent of the trans-methylgiutaconate Small, radioactive peptides, named Nketewa as a group, were biosynthesized using mevalonate-2-�����C as the substrate. They were shown to pass through a 1000 D membrane. Acid hydrolysis and dabsyl-HPLC analysis defined the composition of the Nketewa peptides. One such peptide, Nketewa 1, had a molecular weight of 1038 and a sequence of his-gly-val-cys-phe-ala-ser-met (HGVCFASM), with a farnesyl group linked via thioether linkage to the cysteine residue. Methods were developed for the concerted investigation of the trans-methylglutaconate shunt, the isolation of mevalonate-2-�����C labeled peptides, and characteristics of neutral and acidic metabolites of mevalonate. The question as to whether or not mevalonate was the direct precursor was answered in the affirmative. These results contribute to the understanding of the biochemistry of the vessel wall and the associated atherogenic processes. Mevalonate-derived volatile and acidic compounds may represent an alternate metabolic pathway. The prenylated Nicetewa peptide may be, as are other prenylated peptides, participants in the intracellular signaling process, release of cytokines, expansion of extracellular matrix, and calcium release. / Graduation date: 2001

Thesis (M. Med. Sc.)--University of Hong Kong, 2001. / Includes bibliographical references (leaves 44-50).

published_or_final_version / Pharmacology and Pharmacy / Doctoral / Doctor of Philosophy

No description available.

Bakgrund: Bukaortaaneurysm (AAA) har under de senaste tjugo åren blivit allt vanligare både när det gäller förekomst och diagnostisk upptäckt. Oftast är sjukdomen symtomfri och upptäcks ofta först när det rupturerar. AAA behandlas med antingen endovaskulär aortaaneurysm reparation (EVAR), öppen kirurgi av aorta (ÖA), farmakologiskt eller inte alls. Syfte: Syftet var att se hur mortaliteten och komplikationerna ser ut efter EVAR jämfört med ÖA och vilka olika kort- respektive långsiktiga för- och nackdelar som finns med de olika metoderna. Metod: Sökning av artiklar gjordes i databasen PubMed. Totalt valdes 10 artiklar ut som var baserade på 6 olika studier. Resultat: Majoriteten av dödsfallen som skedde inom 30 dagar hos ÖA-patienterna var aneurysmrelaterade och fler än inom EVAR. Efter 2-3 år syntes inte längre någon signifikant skillnad mellan de två patientgrupperna. Under operationen hade ÖA-patienter högre blodförlust, mer blodtransfusion samt längre tid i respirator efter operationen än patienterna i EVAR-gruppen. Implantatrelaterade komplikationer var vanligare vid EVAR, medan ärrbråck var vanligt hos ÖA-patienter. Konklusion: Under de första 30 dagarna efter operation och upp till ett år efter är mortalitets- och komplikationsrisken signifikant lägre hos EVAR-patienterna. Komplikationer och risk för endoläckage, ruptur trots operation och reinterventioner blir dock vanligare hos EVAR-patienterna med tiden.

Thesis (M.Med.Sc.)--University of Hong Kong, 2001. / Includes bibliographical references (leaves 44-50) Also available in print.

Thesis (M. Med. Sc.)--University of Hong Kong, 2004. / Also available in print.

Thesis--University of Tampere, 1987. / Includes bibliographical references.

Thesis (doctoral)--Lund University, 1998. / Added t.p. with thesis statement inserted.

Thesis (doctoral)--Lund University, 1998. / Added t.p. with thesis statement inserted.