Adhesion of bacteria is a key event in biofilm formation and is mediated by bacterial adhesins recognising host or bacterial partner receptors. In oral biofilm formation, primary Actinomyces and Streptococcus colonizers adhere to salivary pellicle proteins such as proline-rich proteins (PRPs) as well as to mucosal surfaces. Subsequently, Actinomyces and Streptococcus strains and other bacteria, such as Veillonella, Fusobacterium and Porphyromonas, adhere to each other. The nature of this community is highly important for the health or disease status, although specific pathogenic species may also have been implicated. The aim of this thesis was to study key players in early oral colonisation, Actinomyces and Streptococcus species, and more specifically the nature of their adhesins and ligands. A further aim was to study the function of the salivary PRP proteins and an innate peptide derived thereof on bacterial adhesion, proliferation and regulation of pH, i.e. key factors in biofilm formation. In paper I and II, adhesion, proliferation and pH affecting features of the RGRPQ (arginine-glycine-arginine-proline-glutamine) peptide, derived from PRP-1, were demonstrated. By use of an alanine-scan (I), motifs for adhesion inhibition and desorption of Actinomyces naeslundii, and proliferation stimulation, ammonia production and inhibition of sucrose induced pH drop by Streptococcus gordonii were indicated. The RGRPQ peptide also stimulated S. gordonii colonisation in vivo. In paper II, a more sophisticated quantitative structure-activity relationship (QSAR) study, using statistical molecular design (SMD) and multivariate modelling (partial least squares projections to latent structures, PLS), further narrowed down the RGRPQ peptide motifs. The R and Q amino acids were crucial for activity. For proliferation a hydrophobic and large size third position amino acid was crucial, while adhesion inhibition and desorption needed a small hydrophilic second position amino acid. All functions depended on a low polarity hydrophobic fourth position. Accordingly, activities could be optimized separately, with decreased function in the others. In paper III and IV, focus was on the bacterial adhesins and their binding epitopes. The genes for FimA major subunit proteins of type-2 fimbriae were sequenced from A. naeslundii genospecies 1 and 2 and Actinomyces odontolyticus, each with unique carbohydrate binding specificities (III). Three major subtypes of FimA proteins were found that correlated with binding specificity, including a novel fimA gene in A. odontolyticus. All subtypes contained a pilin, LPXTG and E box motif. In paper IV, multiple PRP binding patterns for Actinomyces and Streptococcus strains were mapped using a hybrid peptide construct. The two most deviating binding groups deviated in type-1 fimbriae mediated binding to milk and saliva protein ligands. In conclusion, differences in bacterial adhesins and their ability to utilise salivary proteins may render bacteria tropism for different niches. Peptides derived from protein receptors, such as RGRPQ, may be important modulators of biofilm formation, giving commensal bacteria a competitive edge in the bacterial community.

<p><strong>Introduktion</strong>: Karies är en av de infektionssjukdomar som är mest spridda över världen. I världen sker det stora förflyttningar av människor, orsaker till förflyttningar varierar. Munhälsan påverkas ofta vid påfrestande situationer för både vuxna och barn. De vanor och den kultur som människor har med sig från sin barndom lever kvar bland annat avseende kost och munhygien. Familjer som invandrat är ofta mer socioekonomiskt utsatta än de som är födda och etablerade i det nya hemlandet, vilket är ännu en riskfaktor för karies. <strong>Syfte</strong>: Att beskriva kariesförekomsten hos barn och ungdomar med invandrarbakgrund i Norden samt hos barn och ungdomar födda i Norden. <strong>Frågeställningar</strong>: Vilken kariesprevalens föreligger bland små barn (0-5 år) med invandrarbakgrund i Norden respektive födda i Norden? Vilken kariesprevalens föreligger bland skolbarn (6-12 år) med invandrarbakgrund i Norden respektive födda i Norden? Vilken kariesprevalens föreligger bland ungdomar (13-19 år) med invandrarbakgrund i Norden respektive födda i Norden? <strong>Metod</strong>: Systematisk litteraturstudie. <strong>Resultat</strong>: Kariesprevalensen är högre bland barn och ungdomar i Norden med invandrarbakgrund jämfört med barn och ungdomar som har nordiskt ursprung. Skillnaderna följer samma mönster i alla åldrar genom barn- och ungdomsåren. <strong>Slutsats</strong>: Tandvårdspersonal bör uppmärksamma att barn och ungdomar med invandrarbakgrund i Norden kan behöva mer stöd i form av förebyggande åtgärder för att uppnå och bibehålla en god oral hälsa.</p>

Heart valve dysfunction is a relatively common condition in the population, whereas significant heart valve disease is more unusual. The cause of different types of heart valve disease depends on which valve is concerned. Rheumatic heart valve disease, has for a long time been considered to constitute a post-inflammatory condition. During the 1990s it was also shown that the so-called non-rheumatic or degenerative tricuspid aortic stenosis, comprised signs of inflammation. In this study, 118 patients (the VOCIN study group) referred to the University Hospital for preoperative investigation due to significant heart valve disease, were examined regarding signs of inflammation. Twenty-nine aortic valves from patients with significant aortic stenosis were divided into tricuspid and bicuspid aortic valves. The bicuspid aortic stenotic valves revealed signs of inflammation to a similar extent as the tricuspid valves. However, the tricuspid and bicuspid valves differed regarding distribution of calcification. In contrast, inflammation was not a predominant feature in 15 aortic and mitral valves from patients with significant heart valve regurgitation. Gross valvular pathology consistent with rheumatic aortic stenosis was found in 10 patients. These valves revealed a somewhat lower degree of inflammatory cell infiltration, but on the whole, there were no substantial differences when compared to non-rheumatic aortic stenotic valves. They did, however, reveal a similar distribution of calcification as the bicuspid, non-rheumatic aortic valves. The VOCIN study group was compared to an age- and gender matched control group with regard to history and signs of rheumatic disease. There was not any increased prevalence of clinical manifestations of non-cardiac inflammatory disease in patients with significant heart valve disease, when compared to healthy control subjects. However, patients with heart valve disease had significantly increased serum levels of inflammatory markers compared to controls. The increase in inflammatory markers remained significant even in the subgroup of non-rheumatic aortic stenosis devoid of coronary artery disease. These results indicate that a systemic inflammatory component is associated with stenotic, non-rheumatic heart valve disease. The similarities between different forms of calcific aortic valve disease indicate a similar pathogenesis. The question is raised whether aortic stenosis is one disease, mainly caused by a general and non-specific response to dynamic tissue stress due to an underlying malformation of the valve.

Infectious diseases e.g. gastric ulcer, caries and perodontitis, are caused by bacteria in a biofilm. Adhesion of bacteria to host ligands e.g. proteins, polypeptides and glycoproteins, is a key event in biofilm formation and colonization of surfaces such as mucosa and tooth tissues. Thus, host ligands could contribute to the susceptibility to infectious diseases. The general aim of this doctoral thesis was to study the effect of phosphorylated polypeptides and gp-340 in saliva and milk on oral bacterial adhesion and aggregation. Statherin is a non-glycosylated, phosphorylated polypeptide in saliva. The polypeptide inhibits precipitation and crystal growth of calcium phosphate and mediates adhesion of microorganisms. By using a hybrid peptide construct, the domain for adhesion of Actinomyces isolated from human infections and from rodents was found to reside in the C-terminal end, and the adhesion was inhibitable. With alanine substitution the peptide recognition epitope in the C-terminal end was delineated to Q and TF, where QAATF was an optimal inhibitory peptide. In contrast, human commensal Actinomyces bound to the middle region in a non-inhibitable fashion. Gp-340 is another protein in saliva, and it is a large, multifunctional glycoprotein. Four novel size variants (I-IV) of salivary gp-340 were distinguished within individuals, and their glycoforms were characterized. All four size variants were identical in the N-terminal amino acid sequence and shared core carbohydrates. Low-glyco lung gp-340, high-glyco saliva gp-340, and size variants I-III aggregated bacteria differently. Human milk, which shares many traits with saliva, could inhibit adhesion of Streptococcus mutans to saliva-coated hydroxyapatite (s-HA), a model for teeth, in an individually varying fashion. Human milk caseins, lactoferrin, secretory IgA, and IgG inhibited the binding avidly. By using synthetic peptides the inhibitory epitope in b-casein was mapped to a C-terminal stretch of 30 amino acids. Inhibition by human milk, secretory IgA and the b-casein-derived inhibitory peptide was universal among a panel of mutans streptococci. The main conclusions are: (i) statherin mediates differential binding of commensal versus infectious Actinomyces strains with small conformation-dependent binding epitopes, (ii) salivary gp-340 has individual polymorphisms that at least affect binding of bacteria, (iii) human milk inhibits S. mutans adhesion to s-HA in an individually varying fashion, and the C-terminal end of human milk β-casein is one inhibitory component. Together these results suggest that the studied host ligands can influence the composition of the oral biofilm. Statherin may protect the host from colonization of bacteria associated with infections. Gp-340 size variants may affect functions related to host innate immune defences such as interactions with a wide array of bacteria, and human milk may have a protective effect in infants from colonization of mutans streptococci.

Introduktion: Karies är en av de infektionssjukdomar som är mest spridda över världen. I världen sker det stora förflyttningar av människor, orsaker till förflyttningar varierar. Munhälsan påverkas ofta vid påfrestande situationer för både vuxna och barn. De vanor och den kultur som människor har med sig från sin barndom lever kvar bland annat avseende kost och munhygien. Familjer som invandrat är ofta mer socioekonomiskt utsatta än de som är födda och etablerade i det nya hemlandet, vilket är ännu en riskfaktor för karies. Syfte: Att beskriva kariesförekomsten hos barn och ungdomar med invandrarbakgrund i Norden samt hos barn och ungdomar födda i Norden. Frågeställningar: Vilken kariesprevalens föreligger bland små barn (0-5 år) med invandrarbakgrund i Norden respektive födda i Norden? Vilken kariesprevalens föreligger bland skolbarn (6-12 år) med invandrarbakgrund i Norden respektive födda i Norden? Vilken kariesprevalens föreligger bland ungdomar (13-19 år) med invandrarbakgrund i Norden respektive födda i Norden? Metod: Systematisk litteraturstudie. Resultat: Kariesprevalensen är högre bland barn och ungdomar i Norden med invandrarbakgrund jämfört med barn och ungdomar som har nordiskt ursprung. Skillnaderna följer samma mönster i alla åldrar genom barn- och ungdomsåren. Slutsats: Tandvårdspersonal bör uppmärksamma att barn och ungdomar med invandrarbakgrund i Norden kan behöva mer stöd i form av förebyggande åtgärder för att uppnå och bibehålla en god oral hälsa.

Eftersom medellivslängden ökar och de egna tänderna behålls högre upp i åldrarna finns det en ökad kariesrisk hos de äldre. Syftet med litteraturstudien var att redogöra för riskfaktorer som påverkar kariessituationen hos äldre personer. Ytterligare ett syfte var att ta reda på vilka tänder och tandytor som främst drabbas av karies. Studien genomfördes som en allmän litteraturstudie. Databaserna PubMed och Cinahl användes. Artiklar publicerade år 2000-2010 inkluderades. Total ingick 15 artiklar i resultatet. Resultatet visade att kost, mediciner, saliv, bakterier, gingivala retraktioner, egenvård, rökning, avtagbara proteser, protetiska kronor och antalet kvarvarande tänder var riskfaktorer som kunde orsaka både kron- och rotytekaries hos äldre. Rotytan, ocklusalytan och lingualytan samt de ytor som var belägna i direkt relation med lagningar var de ytor som främst drabbades av karies. De mest utsatta tänderna för kariesangrepp var molarerna, premolarerna samt caninerna. Många olika faktorer bidrar till en ökad kariesrisk hos äldre. Flertalet studier redovisade ett samband mellan gingivala retraktioner och rotytekaries. Majoriteten av det granskade materialet visade att rotytan var känslig för kariesangrepp. Framförallt var molarerna utsatta för kariesrisk hos äldre. / As life expectancy increases and our teeth are retained to a higher age, there is an increased risk of caries in the elderly. The purpose was to describe risk factors that affect the caries situation in the elderly. Another purpose was to find out which teeth and tooth surfaces are mainly affected. This study was carried out as a general literature review; PubMed and Cinahl were used. Articles published 2000-2010 were used. A total of 15 articles were included. The results show that diet, medications, saliva, bacteria, gingival recession, self-care, smoking, removable prostheses, prosthetic crowns and the number of remaining teeth are various risk factors that can cause both crown and root surface caries in the elderly. Those surfaces that were mainly affected by caries were root surface, the occlusal surface and the lingual surface, as well as the surfaces that are directly related to fillings. The teeth most vulnerable to caries were the molars, premolars and canines. Several studies showed a relationship between gingival recession and root surfaces caries. The majority of the reviewed articles showed that the root surfaces were susceptible to caries. It was primarily molars that were exposed to caries in the elderly.