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  • Sarkonen, Nanna (Helsingin yliopisto, 2007)
    The genus Actinomyces consists of a heterogeneous group of gram-positive, mainly facultatively anaerobic or microaerobic rods showing various degrees of branching. In the oral cavity, streptococci and Actinomyces form a fundamental component of the indigenous microbiota, being among initial colonizers in polymicrobial biofilms. The significance of the genus Actinomyces is based on the capability of species to adhere to surfaces such as on teeth and to co-aggregate with other bacteria. Identification of Actinomyces species has mainly been based on only a few biochemical characteristics, such as pigmentation and catalase production, or on the use of a single commercial kit. The limited identification of oral Actinomyces isolates to species level has hampered knowledge of their role both in health and disease. In recent years, Actinomyces and related organisms have attracted the attention of clinical microbiologists because of a growing awareness of their presence in clinical specimens and their association with disease. This series of studies aimed to amplify the identification methods for Actinomyces species. With the newly developed identification scheme, the age-related occurrence of Actinomyces in healthy mouths of infants and their distribution in failed dental implants was investigated. Adhesion of Actinomyces species to titanium surfaces processed in various ways was studied in vitro. The results of phenotypic identification methods indicated a relatively low applicability of commercially available test kits for reliable identification within the genus Actinomyces. However, in the study of conventional phenotypic methods, it was possible to develop an identification scheme that resulted in accurate differentiation of Actinomyces and closely related species, using various different test methods. Genotypic methods based on 16S rRNA sequence analysis of Actinomyces proved to be a useful method for genus level identification and further clarified the species level identification with phenotypic methods. The results of the study of infants showed that the isolation frequency of salivary Actinomyces species increased according to age: thirty-one percent of the infants at 2 months but 97% at 2 years of age were positive for Actinomyces. A. odontolyticus was the most prominent Actinomyces colonizer during the study period followed in frequency by A. naeslundii and A. viscosus. In the study of explanted dental implants, Actinomyces was the most prevalent bacterial genus, colonizing 94% of the fixtures. Also in the implants A. odontolyticus was revealed as the most common Actinomyces species. It was present in 84% of Actinomyces -positive fixtures followed in frequency by A. naeslundii, A. viscosus and A. israelii. In an in vitro study of titanium surfaces, different Actinomyces species showed variation regarding their adhesion to titanium. Surface roughness as well as albumin coating of titanium had significant effects on adhesion. The use of improved phenotypic and molecular diagnostic methods increased the accuracy of the identification of the Actinomyces to species level. This facilitated an investigation of their occurrence and distribution in oral specimens in both health and disease.
  • Ahmed Haji Omar, Abdirisak (Helsingin yliopisto, 2015)
    Oral (OSCC) and cutaneous (CSCC) squamous cell carcinomas are epithelial neoplasms, which are both derived from keratinocyte cells. However, the etiology and prognosis of OSCC and CSCC are different. Main etiological factors behind OSCC are tobacco smoke and alcohol consumption, and for CSCC the UV-radiation. OSCC has poorer prognosis than CSCC. In order to be invasive, cancer cells have to pass various barriers. They have to disrupt cell-to-cell junctions, penetrate basement membrane, and invade connective tissue. The pattern of invasion of tumors varies strikingly. Some invade in large border fronts while others invade in single cell manner. Expression of transmembrane proteins E-cadherin and Syndecan-1 in cell membrane are lost during tumor invasion, and therefore loosening cell adhesion. Matrix metalloproteinases (MMP) are tissue proteinases, which have proteolytic role in various physiological events and during tumor progression MMPs are capable of degrading extracellular matrix (ECM) proteins but have also immunomodulatory role. Toll-like receptors (TLRs) are part of innate immunity and can recognize exogenous pathogen associated molecular patterns or endogenous damage associated molecular patterns. Cancer cells may use TLRs to induce tumor promoting inflammation. The aim of the study was to examine possible cellular and molecular differences between OSCC and CSCC explaining their different behaviors as cancers despite cellular similarities. The study included 36 OSCC and 27 CSCCs from patients with early stage tumors. The over-all and disease-specific survival was retrospectively evaluated with histological risk assessment (HRA) model and histological risk assessment score (HRS). We performed immunohistochemical staining for E-cadherin, Snail (Snail1), Syndecans (1 and 2), MMPs (7, 8 and 9) and TLRs (4 and 5). In vitro, with oral and cutaneous cell lines the effect of TLR-5 ligand flagellin on proliferation, migration and invasion was studied. OSCC patients had worse disease-specific survival than CSCC patients and it correlated with invasion depths of the OSCC tumors. OSCC had more severe histological pattern of invasion than CSCC. E-cadherin and Syndecan-1 expression decreased in the invasive front of OSCCs and CSCCs. Syndecan-1 expression in the tumor stroma was higher in OSCC than in CSCC in tumors with invasion depth over 4 mm. MMP-7 was mainly expressed in the invasive front of OSCC and CSCC and was stronger in OSCC than in CSCC. MMP-8 and MMP-9 were mainly expressed in the peritumoral inflammatory cells. TLR-5 expression was stronger in OSCC than in CSCC. In vitro, TLR-5 ligand flagellin increased proliferation, migration and invasion of less aggressive oral and cutaneous cell lines, but failed to do so with the most aggressive oral cancer cell line. As a conclusion, OSCC patients of this study had poorer disease specific survival than CSCC patients. Increased stromal syndecan-1 expression in OSCC, MMP-7 expression in the invasive front of tumor, and MMP-9 expression in inflammatory cells could partly explain the difference in survival between OSCC and CSCC.
  • Saarela, Riitta (Helsingin yliopisto, 2014)
    ABSTRACT This study formed part of a developmental project in the Helsinki Metropolitan Area of Finland during 2003 2011 that aimed to develop nutritional care in long-term care facilities. The aim of this study was to assess tooth brushing/denture cleaning habits, dentition, chewing problems, and swallowing difficulties and their associations with nutritional status and eating habits. Furthermore, the aim was to explore the prognostic value of dentition, chewing problems and swallowing difficulties in relation to mortality. In addition, the adequacy of the dietary intake of energy, protein, and other nutrients was examined. Of all the residents in assisted living facilities (N = 2188) in the cities of Helsinki and Espoo, 67% (1475) participated in this study in 2007. Trained registered nurses familiar with the residents assessed each participant and collected demographic data, the medical history, information on the functional and cognitive status, tooth brushing/dentition cleaning habits, dentition, oral symptoms, eating habits and diets. The nutritional status was assessed with the Mini Nutritional Assessment (MNA). In addition, 343 volunteer residents provided one-day food diaries. Their energy, protein, and nutrient intakes were calculated from these detailed food diaries and compared with the recommendations of the Finnish National Nutrition Council as a measure of dietary adequacy. Information on three-year mortality was retrieved from central registers on 6 July 2010. The mean age of the residents was 83 years and 79% of them were women. The educational level was low; 56% of the residents had a primary school level of education or less. In activities of daily living, most residents (84%) required at least prompting or assistance in dressing, hygiene and the keeping of personal effects, or required considerable help with personal care, often involving incontinence. Over half of the residents (55%) had cognitive impairment. Edentulousness was common; more than half of the residents (52%) had lost all their teeth, while 7% (n = 94) were totally edentulous without prosthesis. Of the residents, 17% did not clean or had not cleaned their teeth/dentures daily. According to the MNA, 13% were malnourished, 65% were at risk of malnutrition and 22% were well nourished. Edentulousness without prostheses and infrequent tooth brushing were associated with malnutrition, oral symptoms and infrequent use of oral health care services. Residents with chewing problems (n = 287) were older, had more comorbidities and were more likely to be malnourished according to the MNA, to be dependent in activities of daily living (ADL) and to have poorer subjective health than those without chewing problems. In logistic regression analysis including age, sex, MNA class and the Charlson´s Comorbidity Index as covariates, chewing problems still independently predicted mortality (OR = 1.46, 95% CI = 1.10 1.93). Of the residents, 12% (n = 173) had swallowing difficulties and they were more likely to be malnourished that those residents without swallowing difficulties. Swallowing difficulties also had an independent predictive value for mortality (OR = 1.49, 95% Cl = 1.04-2.12). Large proportions of volunteer participants in the subsample that provided one-day food diaries received less than the recommended amounts of energy, protein or micronutrients. The dietary intake of protein was significantly lower among edentulous subjects without dentures than those with natural teeth. In the adjusted (age, gender and Charlson s comorbidity index) logistic regression model, being in Group 1 (edentulous participants without dentures) and Group 2 (edentulous participants with some removable dentures in one or both jaws) predicted a poorer protein intake (less than 60 g/day; OR 2.4, 95% CI 1.0 5.7, p = 0.042 and OR 1.6, 95% CI 1.0 2.6, p = 0.045, respectively) compared with the reference Group 3 (dentulous participants all or some natural teeth and with or without removable dentures in one or both jaws; OR = 1). Oral problems were common among frail older residents in assisted living facilities and they were associated with nutritional problems. These findings suggest the need for co-operation between nursing staff and oral care personnel.
  • Helenius, L Miia J (Helsingin yliopisto, 2005)
  • Sargeran, Katayoun (Helsingin yliopisto, 2008)
    Oral Cancer in Tehran, Iran: An approach for understanding disease burden. The present study investigated the burden of oral cancer in Tehran, Iran in terms of patient and tumour characteristics, survival rate, and delay in diagnosis, with the main focus on oral cavity cancers. For exploring the characteristics of malignant oral tumours, data were obtained from records of 1042 patients diagnosed with invasive oral cancers during 1993-2003 in 30 major hospitals in Tehran, and analysed in three groups: tumours of the lips, oral cavity, and major salivary glands. For survival analysis, 470 primary oral cavity and 82 lip cancer patients diagnosed during 1996-2003 were followed from the date of diagnosis to late 2005. To assess the time elapsed between patients’ first awareness of symptoms and the final diagnosis (diagnostic delay) 100 consecutive patients with primary squamous cell carcinoma (SCC) of the oral cavity who were referred to three university hospitals in Tehran during September 2004 to September 2006 were studied. Diagnostic delay was analysed in two phases: 1) time from onset of symptoms to the patient’s first professional visit (patient delay) and 2) time from the first professional visit to the final diagnosis (professional delay). At the time of diagnosis, most oral cavity cancer patients were at advanced stages. The overall five-year survival rates of patients with oral cavity and lip cancer were 30% and 62%, lower than rates reported from western countries. Oral cancer patients’ survival was negatively associated with the tumour stage at diagnosis. The findings of this study revealed that the mean diagnostic delay was high (7.2 months, SD 7.5), in particular, higher than that reported from developed countries. In general, “patient delay” constitutes a substantial part of the total time elapsed between the onset of symptoms and diagnosis. Based on the findings of this study, developing preventive programmes that focus on raising public awareness about the signs and symptoms of oral cancer is essential in promoting earlier diagnosis. In addition, health care professionals, especially dentists and oral hygienists, should be empowered to improve early diagnosis and gain better treatment outcomes for oral cancer patients in Tehran, Iran.
  • Patinen, Pertti (Helsingin yliopisto, 2004)
  • Saied-Moallemi, Zahra (Helsingin yliopisto, 2010)
    The present study assessed oral health and its determinants among Iranian preadolescents, and evaluated a school-based health education programme aimed to promote their oral health. The target population of this study comprised a random sample of the third-grade school children (n = 459) of all public primary schools in 19 areas of Tehran city. The data came from a clinical examination of the children and two self-administered questionnaires: one for children, and one for mothers. The clinical dental examination was performed for recording children's oral health. The mothers' questionnaires covered background factors, oral self-care (OSC) behaviours and oral health-related knowledge and attitude statements. After baseline data collection, a community trial was designed as a 3-month school-based intervention study. For the intervention trial, the third-grade classes as the clusters were randomly assigned to the intervention and control groups. Three kinds of intervention were implemented, one in class, one via the parents, and one as a combination of these. One group served as controls with no intervention. The outcome measures of the study were changes in plaque and bleeding scores recorded. The results showed that mean dmft was 3.75 (SD = 2.8) for the primary teeth and mean DMFT was 0.4 (SD = 0.9) for the permanent teeth. All children had plaque on at least one index tooth and bleeding on probing in at least one index tooth occurred in 81%. About one-third (34%) of the children reported favourable OSC and less than half (46%) of the children reported brushing their teeth at least twice daily. Girls reported favourable OSC (OR = 2.0), had decay-free teeth (OR = 1.8) and treated permanent teeth (OR = 3.3) more than did boys. Mother's oral health-related aspects, i.e., mother's favourable OSC, high knowledge levels of and positive attitudes towards oral health, and active supervision of the child's tooth brushing had a positive effect on all aspects of children's oral health status and behaviours (ORs from 1.3 to 1.9). After the intervention, the results showed a strong intervention effect on healthy gingiva in both groups where parents were involved: the parental-aid group (OR = 7.7, 95% CI 2.2-27.7) and combined group (OR = 6.6, 95% CI 2.0-22.1). To improve children's oral health, community school-based oral health educational programmes should be established to include all primary schools. These programmes should benefit from the common risk factor approach and a multi-sectored approach to employ for communication between the community, the school, and the family. Oral health interventions should empower the parents' ability to improve their own oral health behaviour and then to transfer that healthy behaviour to their children.
  • Hessari, Hossein (Helsingin yliopisto, 2009)
    The aim of the present study was to assess oral health and treatment needs among adult Iranians according to socio-demographic status, smoking, and oral hygiene, and to investigate the relationships between these determinants and oral health. Data for 4448 young adult (aged 18) and 8301 middle-aged (aged 35 to 44) Iranians were collected in 2002 as part of a national survey using the World Health Organization (WHO) criteria for sampling and clinical diagnoses, across 28 provinces by 33 calibrated examiners. Gender, age, place of residence, and level of education served as socio-demographic information, smoking as behavioural and modified plaque index (PI) as the biological risk indicator for oral hygiene. Number of teeth, decayed teeth (DT), filled teeth (FT), decayed, missing, filled teeth (DMFT), community periodontal index (CPI), and prosthodontic rehabilitation served as outcome variables of oral health. Mean number of DMFT was 4.3 (Standard deviation (SD) = 3.7) in young adults and 11.0 (SD = 6.4) among middle-aged individuals. Among young adults the D-component (DT = 70%), and among middle-aged individuals the M-component (60%) dominated in the DMFT index. Among young adults, visible plaque was found in nearly all subjects. Maximum (max) PI was associated with higher mean number of DT, and higher periodontal treatment needs. A healthy periodontium was a rare condition, with 8% of young adults and 1% of middle-aged individuals having a max CPI = 0. The majority of the CPI findings among young adults consisted of calculus (48%) and deepened periodontal pockets (21%). Respective values for middle-aged individuals were 40% and 53%. Having a deep pocket (max CPI = 4) was more likely among young adults with a low level of education (Odds ratio (OR) = 2.7, 95% Confidence interval (CI) = 1.9–4.0) than it was among well-educated individuals. Among middle-aged individuals, having calculus or a periodontal pocket was more likely in men (OR = 1.8, 95% CI = 1.6–2.0) and in illiterate subjects (OR = 6.3, 95% CI = 5.1–7.8) than it was for their counterparts. Among young adults, having 28 teeth was more (p < 0.05) prevalent among men (72% vs. 68% for women), urban residents (71% vs. 67% for rural residents), and those with a high level of education (73% vs. 60% for those with a low level). Among middle-aged individuals, having a functional dentition was associated with younger age (OR = 2.0, 95% CI = 1.7−2.5) and higher level of education (OR = 1.8, 95% CI = 1.6−2.1). Of middle-aged individuals, 2% of 35- to 39-year-olds and 5% of those aged 40 to 44 were edentulous. Among the dentate subjects (n = 7,925), prosthodontic rehabilitation was more prevalent (p < 0.001) among women, urban residents, and those with a high level of education than it was among their counterparts. Among those having 1 to 19 teeth, a removable denture was the most common type of prosthodontic rehabilitation. Middle-aged individuals lacking a functional dentition were more likely (OR = 6.0, 95% CI = 4.8−7.6) to have prosthodontic rehabilitation than were those having a functional dentition. In total, 81% of all reported being non-smokers, and 32% of men and 5% of women were current smokers. Heavy smokers were the most likely to have deepened periodontal pockets (max CPI ≥ 3, OR = 2.9, 95% CI = 1.8−4.7) and to have less than 20 teeth (OR = 2.3, 95% CI = 1.5−3.6). The findings indicate impaired oral health status in adult Iranians, particularly those of low socio-economic status and educational level. The high prevalence of dental plaque and calculus and considerable unmet treatment needs call for a preventive population strategy with special emphasis on the improvement of oral self-care and smoking cessation to tackle the underlying risk factors for oral diseases in the Iranian adult population.
  • Vesterinen, Maarit (Helsingin yliopisto, 2011)
    Chronic kidney disease (CKD) is a worldwide health problem, with adverse outcomes of cardiovascular disease and premature death. The ageing of populations along with the growing prevalence of chronic diseases such as diabetes and hypertension is leading to worldwide increase in the number of CKD patients. It has become evident that inflammation plays an important role in the pathogenesis of atherosclerosis complications. CKD patients also have an increased risk of atherosclerosis complications (including myocardial infarction, sudden death to cardiac arrhythmia, cerebrovascular accidents, and peripheral vascular disease). In line with this, oral and dental problems can be an important source of systemic inflammation. A decline in oral health may potentially act as an early marker of systemic disease progression. This series of studies examined oral health of CKD patients from predialysis, to dialysis and kidney transplantation in a 10-year follow-up study and in a cross-sectional study of predialysis CKD patients. Patients had clinical and radiographic oral and dental examination, resting and stimulated saliva flow rates were measured, whilst the biochemical and microbiological composition of saliva was analyzed. Lifestyle and oral symptoms were recorded using a questionnaire, and blood parameters were collected from the hospital records. The hypothesis was that the oral health status, symptoms, sensations, salivary flow rates and salivary composition vary in different renal failure stages and depend on the etiology of the kidney disease. No statistically significant difference were seen in the longitudinal study in the clinical parameters. However, some saliva parameters after renal transplantation were significantly improved compared to levels at the predialysis stage. The urea concentration of saliva was high in all stages. The salivary and plasma urea concentrations followed a similar trend, showing the lowest values in kidney transplant patients. Levels of immunoglobulin (Ig) A, G and M all decreased significantly after kidney transplantation. Increased concentrations of IgA, IgG and IgM may reflect disintegration of the oral epithelium and are usually markers of poor general oral condition. In the cross-sectional investigation of predialysis CKD patients we compared oral health findings of diabetic nephropathy patients to those with other kidney disease than diabetes. The results showed eg. more dental caries and lower stimulated salivary flow rates in the diabetic patients. HbA1C values of the diabetic patients were significantly higher than those in the other kidney disease group. A statistically significant difference was observed in the number of drugs used daily in the diabetic nephropathy group than in the other kidney disease group. In the logistic regression analyses, age was the principal explanatory factor for high salivary total protein concentration, and for low unstimulated salivary flow. Poor dental health, severity of periodontal disease seemed to be an explanatory factor for high salivary albumin concentrations. Salivary urea levels were significantly linked with diabetic nephropathy and with serum urea concentrations. Contrary to our expectation, however, diabetic nephropathy did not seem to affect periodontal health more severely than the other kidney diseases. Although diabetes is known to associate with xerostomia and other oral symptoms, it did not seem to increase the prevalence of oral discomfort. In summary, this series of studies has provided new information regarding the oral health of CKD patients. As expected, the commencement of renal disease reflects in oral symptoms and signs. Diabetic nephropathy, in particular, appears to impart a requirement for special attention in the oral health care of patients suffering from this disease.
  • Tarkkila, Laura (Helsingin yliopisto, 2011)
    Hormone therapy (HT) is widely used to relieve climacteric symptoms in order to increase the well-being of the women. The benefits as well as side-effects of HT are well documented. The principal menopausal oral symptoms are dry mouth (DM) and sensation of painful mouth (PM) due to various causes. Profile studies have indicated that HT users are more health-conscious than non-users. The hypothesis of the present study was that there are differences in oral health between woman using HT and those not using HT. A questionnaire study of 3173 women of menopausal age (50-58 years old) was done to investigate the prevalence of self-assessed sensations of PM and DM. Of those women participating in the questionnaire study, a random sample of 400 (200 using, 200 not using HT) was examined clinically in a 2-year follow-up study. Oral status was recorded according to WHO methods using DMFT and CPITN indices. The saliva flows were measured, salivary total protein, albumin and immunoglobulin concentrations and selected periodontal micro-organisms were analysed, and panoramic tomography of the jaws was taken. The patients filled in a structured questionnaire on their systemic health, medication and health habits. According to our questionnaire study there was no significant difference in the occurrence of self- assessed PM or DM between the HT users and non-users. According to logistic regression analyses, climacteric complaints significantly correlated with the occurrence of PM (p=0.000) and DM (p=0.000) irrespective of the use of HT, indicating that PM and DM are associated with climacteric symptoms in general. There was no difference between the groups in DMFT index values at follow up. The number of filled teeth (FT) showed a significant (p<0.05) increase in the HT group at follow-up. Periodontitis was diagnosed in 79% of HT users at baseline and in 71% at the follow-up. The values for non-HT users were 80% vs. 76%, respectively (Ns.). The mean numbers of ≥ 6 mm deep periodontal pockets were 0.9 ± 1.7 at baseline vs. 1.1 ± 2.1 two years later in the HT group, and 1.0 ± 1.7 vs. 1.2 ± 1.9, respectively, in the non-HT group. In a large Finnish national health survey, the prevalence of peridontitis of women of this age group was lower, but the prevalence of severe periodontitis seemed to be higher than in our study. Salivary albumin, IgG and IgM concentrations decreased in the HT group during the 2-year follow up (p<0.05), possibly indicating an improvement in epithelial integrity. No difference was found in any other salivary parameters or in the prevalence of the periodontal bacteria between or within the groups. In conclusion, the present findings showed that 50 to 58 year old women living in Helsinki have fairly good oral and dental health. The occurrence of PM and DM seemed to be associated with climacteric symptoms in general, and the use of HT did not affect the oral symptoms studied.
  • Vysniauskaite, Sonata (Helsingin yliopisto, 2009)
    The present cross-sectional study aimed to assess oral health behaviour, dental and periodontal conditions, dental care, and their relationships among elderly dentate patients in Lithuania. The target population in the study were dentate patients aged 60 and older attending public dental services in Kedainiai, Lithuania. The data collection took place between the autumn of 1999 and the winter of 2001. Data were collected by means of a self-administered questionnaire for all (n=174) and a clinical examination targeting about half of the subjects (n=100). The questionnaire inquired about oral health behaviour, the life-first and also the most recent dental treatments, sources on and self-assessed knowledge of oral self-care, a self-reported number of teeth, and socio-demographic information. The clinical examination included basic dental and periodontal conditions. A total of 82 women and 92 men completed the questionnaire; their mean age was 69.2 and their average number of teeth was 16.2 (CI 95% 15.4-17.1). In all, 25% had 21 or more teeth and 32% indicated wearing removable dentures. The oral health behaviour, the participants reported, was poor: 30% reported twice daily toothbrushing, 57% responded that they always use fluoride toothpaste, 19% indicated daily interdental cleaning, nearly all said they take sugar in their coffee and tea, and 30% indicated going for check-ups. As the main source of information on oral self-care, the subjects indicated health professionals (82%), followed by social contacts (72%), broadcasted media (58%), and printed media (42%). A total of 34% assessed their knowledge of oral self-care as good, and their self-assessed knowledge correlated (r=0.52) with professional guidance they had received about oral self-care. In their most recent treatment, conservative (39%) and non-conservative (34%) treatments dominated, and preventive ones were the least reported (7%). Regarding guidance in oral self-care, 54% reported having received such about toothbrushing, 32% about interdental cleaning, and 33% had been given visual information. Clinical examinations revealed the presence of plaque, calculus, bleeding on probing and deepened pockets in all of the subjects; 70% of the subjects were diagnosed with pockets of 6mm and deeper, 94% with caries, and 73% with overhangs of restorations. Those subjects assessing their knowledge of oral self-care as good and reporting a higher intensity of guidance in oral self-care as received, indicated practicing the recommended oral self-care more frequently. Twice daily toothbrushing was associated with good self-assessed knowledge of oral self-care (OR 4.1, p<0.001) and a university education (OR 5.6, p<0.001). Those subjects with better oral health behaviour had a greater number of teeth. Having 21 or more teeth was associated with good self-assessed knowledge of oral self-care (OR 4.1, p=0.03). Better periodontal conditions were associated with a higher frequency of toothbrushing. The presence of periodontal pockets of 6mm and deeper was associated with the level of self-assessed knowledge of oral self-care being below good (OR=3.0, p=0.04) and the level of dental cleanliness being poor (OR=2.7, p=0.02). To conclude, oral health behaviour and conditions call for improvement in elderly subjects in Lithuania. To improve the oral health of their elderly dentate patients, dentists should apply all the available tools of chair-side prevention and active guidance. The latter would be an effective means of updating the knowledge of oral self-care and supporting recommended oral health behaviour. A preventive approach should be strongly emphasized in countries with limited resources for oral health care, such as Lithuania. Author’s address: Sonata Vyšniauskaite, Department of Oral Public Health, Institute of Dentistry, University of Helsinki, P.O.Box 41, FI-00014 Helsinki, Finland. E-mail:
  • Venkata, Shyama Sundari Maddi (Helsingin yliopisto, 2004)
  • Helenius-Hietala, Jaana (Helsingin yliopisto, 2013)
    Liver transplantation (LT) is the treatment of choice for patients with severe liver disease. Quality of life of patients after LT may be comparable to that of the general population, but permanent immunosuppression poses a high risk for infections. Highly prevalent dental diseases not promptly treated may compromise LT outcome. All possible infectious foci, including dental infections, should thus be treated prior to LT. This thesis aimed to investigate how liver diseases and long-term immunosuppression after LT affect oral health and whether dental infections are associated with liver disease progression or with LT outcome. The study design was retrospective, cross-sectional, and observational. The study comprised 263 adult recipients of a LT between 2000 and 2006 at the Helsinki University Central Hospital, Finland. Of these patients, 212 (81%) had chronic liver disease, and all underwent dental examinations and treatment prior to LT. The study investigated the effect of differing liver disease etiology and severity on oral health status; the effect of dental infections on the progression of liver cirrhosis was further studied in a subgroup of 116 cirrhotic patients awaiting LT. Of the study patients, 51 (19%) had acute or subacute liver failure; these were further stratified by whether or not they received pretransplant dental treatment. Post-transplant systemic infectious complications were evaluated from the Finnish Liver Transplant Registry. After a minimum 2-year follow-up (median follow-up 6 years, range 2-11), all 84 eligible LT recipients were recruited for a new oral health examination according to a fixed protocol. A structured questionnaire was used to assess dry-mouth-related symptoms, with oral Candida cultivated, and salivary flow rates measured. The results were compared with those of 252 matched controls from a national health survey. Subjects were grouped according to liver disease etiology and type of immunosuppression. Dental health status of LT candidates varied depending on the etiology and severity of their liver disease. Alcohol cirrhosis patients (n=37) had significantly more tooth extractions before LT than did primary sclerosing cholangitis patients (n=54) (6 vs. 3, P less than 0.005). Poor liver function, as observed in higher Model for End-Stage Liver Disease (MELD) scores, associated with fewer teeth (21 vs. 25, 95%CI: -6.7-(-)1.4, P less than 0.005) and more tooth extractions (5 vs. 2, 95%CI: 1.6-4.2, P less than 0.001). Tooth extractions were often associated with severe complications such as bleeding. Several dental infections in cirrhotic patients associated with worsening of the liver disease as seen in the shorter time between diagnosis and LT operation. Post-transplant infection risk, especially sepsis, was higher in those acute liver disease patients who received no dental treatment before LT due to their more urgent need for LT compared with that of patients who had received dental treatment (OR=8.54, 95%CI: 1.82 40.1, P less than 0.05). This risk was independent of age, gender, etiology of acute liver failure, waiting-list time, MELD score, or level of immunosuppression. Compared with controls, chronic LT recipients had significantly more caries (1.2 vs. 0.5, P less than 0.005) and a higher prevalence of dysphagia (23% vs. 12%, P less than 0.05). They also had lower unstimulated salivary flow rates than did the acute LT recipients (0.3 ml/min vs. 0.6 ml/min, P less than 0.05). Oral mucosal lesions were significantly more frequent in LT recipients than in controls (43% vs. 15%, P less than 0.001). Drug-induced gingival overgrowth was the most common type of oral lesion, and its prevalence was significantly higher in chronic LT recipients than in their controls (16% vs. 1%, P less than 0.001). Simultaneous use of cyclosporine-A and calcium- channel blockers increased the overgrowth prevalence even further compared with the tacrolimus group (47% vs. 8%, P less than 0.05). Precancerous oral mucosal lesions occurred twice as often in chronic LT recipients as in controls (13% vs. 6%, Ns). Oral Candida count was positive in more than half the LT patients; use of steroids raised its prevalence to 70%. The need for dental treatment hence was high before the LT operation with differences in oral health between groups differing in liver disease etiology and severity. Among cirrhotic patients, several dental infections were reflected in the liver disease progression. Those patients who lacked dental treatment before LT showed an 8-fold risk for systemic infections after transplantation. Compared to controls, immunosuppressive and other xerogenic medications predisposed especially the chronic LT recipients to more dry-mouth-related symptoms and caries, and led to a higher risk for oral mucosal lesions, of which some were precancerous. Thus, both pre- and post-transplant dental treatments are highly important for these patients.
  • Heimonen, Aura (Helsingin yliopisto, 2012)
    Preterm birth (PTB) causes 75% of perinatal morbidity and mortality and is an important social and health problem. Infections have been shown to associate with PTB and other pregnancy outcomes, such as miscarriage (MC), pre-eclampsia, and gestational diabetes mellitus (GDM). Periodontal disease has been linked to PTB, as well as with MC and pre-eclampsia. However, the results have been inconclusive, and the majority of previous studies on oral health and adverse pregnancy outcomes have been carried out among women with a low socioeconomic status and a multi-ethnic background. Thus, we set up to investigate the association between oral health and pregnancy complications in a group of Finnish women with homogeneous ethnicity and high socioeconomic status. The study hypothesis was that pregnancy complications are reflected in the women s oral health and that markers of oral health differ between risk and non-risk parturient women. We examined 328 Finnish women with singleton births in this cross-sectional study. Within 2 days postpartum, the women were examined clinically and by taking microbiological and saliva samples for biochemical analyses. The women completed a questionnaire about their health- and lifestyle-related behaviour and oral symptoms. Information about demographic factors, prenatal care, and medical and obstetrical history was obtained from medical records. Chronic diseases, medications, and the number of previous pregnancies, including adverse pregnancy outcomes, were recorded. In our cohort, dental health was uniformly good, and no association was found between any specific periodontal parameter and adverse pregnancy outcome. However, oral inflammatory burden index (OIBI), a combination of multiple oral infections, was significantly associated with PTB. Oral healthcare patterns also seemed to affect birth outcomes in this cohort. Urgency-based dental treatment was associated with history of miscarriage, while preventive dental care patterns were associated with a lower probability of history of miscarriage. Self-reported poor oral health showed a significant association with MC. Salivary immunglobulin A (sIgA) was associated with GDM and type 1 diabetes mellitus (T1DM) independent of C-reactive protein, but when T1DM women were excluded, sIgA level lost its significance. In conclusion, the combined effects of multiple oral infections may exceed the threshold for an effect on birth outcome, even in women without evident oral health problems. Based on the findings of this study, all women planning a pregnancy and who already are pregnant should be referred to oral examination and treatment and counselled for preventive oral self-care.
  • Heikkinen, Anna Maria Kaarina (Helsingin yliopisto, 2011)
    The present cross-sectional study examined the effect of smoking on oral health in a birth cohort of 15 to 16-year-old Finnish adolescents. The hypothesis was that oral health parameters were poorer among smoking than non-smoking subjects and that a tobacco intervention program could be effective among the adolescents. The study was conducted in the Kotka Health Center, Kotka, Finland. Altogether 501 out of 545 subjects (15- to 16-year-old boys [n = 258] and girls [n = 243]) were clinically examined in 2004 and 2005. The sample frame was a birth cohort of all subjects in 1989 and 1990, living in Kotka. A structured questionnaire was also filled in by the participants to record their general health and health habits, such as smoking, tooth brushing, and medication used. The participants were classified into nonsmokers, current smokers, and former smokers. Subgingival pooled plaque samples were taken and stimulated salivary samples were also collected. The subjects were asked from which of seven professional groups (doctors, school nurses, dental nurses, general nurses, dentists, teachers and media professionals) they would prefer to receive information about tobacco. The two most popular groups they picked up were dentists and school nurses. Current smokers (n=127) were then randomly assigned into three groups: the dentist group (n =44), the school-nurse group (n =42), and the control group (n =39). The intervention was based on a national recommendation of evidence based guidelines by The Finnish Medical Society Duodecim ( 5A counseling system). Two months after the intervention, a second questionnaire was sent to the smokers in the intervention groups. Smoking cessation, smoking quantity per week, and self-rated addiction for smoking (SRA) were recorded. The results were analyzed using the R-statistical program. The results showed that 15% of the subjects had periodontitis. Smokers (25%) had more periodontitis than non-smokers (66%) (p < 0.001). Smoking boys (24%) also had more caries lesions than non-smokers (69%) (p < 0.001), and they brushed their teeth less frequently than non-smokers. Smoking significantly impaired periodontal health of the subjects, even when the confounding effects of plaque and tooth brushing were adjusted. Smoking pack-years, intensified the effects of smoking. Periodontal bacteria Prevotella nigrescens, Prevotella intermedia, Tannerella forsythia and Treponema denticola were more frequently detected among the smokers than non-smokers, especially among smoking girls. Smoking significantly decreased the values of both the salivary periodontal biomarkers MMP-8 (p=0.04) and PMN elastase (p=0.02) in boys. The effect was strengthened by pack years of smoking (MMP-8 p=0.04; elastase p0.01). Of those who participated in the intervention, 19 % quit smoking. The key factors associated with smoking cessation were best friend`s influence, nicotine dependence and diurnal type. When the best friend was not a smoker, the risk ratio (RR) of quit smoking after the intervention was 7.0 (Cl 95% 4.6 10.7). Of the diurnal types, the morning people seemed to be more likely to quit (RR 2.2 [Cl 95% 1.4 3.6]). Nicotine dependence also elicited an opposite effect: those who scored between 3 and 5 dependence scores were less likely to quit. In conclusion, smoking appears to be a major etiological risk factor for oral health. However, the early signs of periodontal disease were mild in the subjects studied. Based on the opinions of the adolescent s, dental professionals may have a key position in their smoking cessation. The harmful effects of smoking on oral health could be used in counselling. Best friend`s influence, nicotine dependence and diurnal type, all factors associated with smoking cessation, should be taken more carefully into account in the prevention programs for adolescents.
  • Musrati, Ahmed S Ali (Helsingin yliopisto, 2008)
    Candida yeast species are widespread opportunistic microbes, which are usually innocent opportunists unless the systemic or local defense system of the host becomes compromised. When they adhere on a fertile substrate such as moist and warm, protein-rich human mucosal membrane or biomaterial surface, they become activated and start to grow pseudo and real hyphae. Their growth is intricately guided by their ability to detect surface defects (providing secure hiding , thigmotropism) and nutrients (source of energy, chemotropism). The hypothesis of this work was that body mobilizes both non-specific and specific host defense against invading candidal cells and that these interactions involve resident epithelial cells, rapidly responding non-specific protector neutrophils and mast cells as well as the antigen presenting and responding den-dritic cell lymphocyte plasma cell system. It is supposed that Candida albicans, as a result of dar-winistic pressure, has developed or is utilizing strategies to evade these host defense reactions by e.g. adhering to biomaterial surfaces and biofilms. The aim of the study was to assess the host defense by taking such key molecules of the anti-candidal defense into focus, which are also more or less characteristic for the main cellular players in candida-host cell interactions. As a model for candidal-host interaction, sections of chronic hyperplastic candidosis were used and compared with sections of non-infected leukoplakia and healthy tissue. In this thesis work, neutrophil-derived anti-candidal α-defensin was found in the epithelium, not only diffusely all over in the epithelium, but as a strong α-defensin-rich superficial front probably able to slow down or prevent penetration of candida into the epithelium. Neutrophil represents the main host defence cell in the epithelium, to which it can rapidly transmigrate from the circulation and where it forms organized multicellular units known as microabscesses (study I). Neutrophil chemotactic inter-leukin-8 (IL-8) and its receptor (IL-8R) were studied and were surprisingly also found in the candidal cells, probably helping the candida to keep away from IL-8- and neutrophil-rich danger zones (study IV). Both leukocytes and resident epithelial cells contained TLR2, TLR4 and TLR6 receptors able to recognize candidal structures via utilization of receptors similar to the Toll of the banana fly. It seems that candida can avoid host defence via stimulation of the candida permissive TLR2 instead of the can-dida injurious TLR4 (study V). TLR also provides the danger signal to the immune system without which it will not be activated to specifically respond against candidal antigens. Indeed, diseased sites contained receptor activator of nuclear factor kappa B ligand (RANKL; II study), which is important for the antigen capturing, processing and presenting dendritic cells and for the T lymphocyte activation (study III). Chronic hyperplastic candidosis provides a disease model that is very useful to study local and sys-temic host factors, which under normal circumstances restrain C. albicans to a harmless commensal state, but failure of which in e.g. HIV infection, cancer and aging may lead to chronic infection.
  • Lammi, Johanna (Helsingin yliopisto, 2008)
    Nurr1, NGFI-B and Nor1 (NR4A2, NR4A1 and NR4A3, respectively) belong to the NR4A subfamily of nuclear receptors. The NR4A receptors are orphan nuclear receptors which means that activating or repressing ligands for these receptors have not been found. NR4A expression is rapidly induced in response to various stimuli including growth factors and the parathyroid hormone (PTH). The studies concerning the NR4A receptors in the central nervous system have demonstrated that they have a major role in the development and function of the dopaminergic neurons of the midbrain and in regulating hypothalamus-pituitary-adrenal-axis. However, the peripheral functions of the NR4A family are largely unknown. Cultured mouse primary osteoblasts, a preosteoblastic cell line and several osteoblastic cell lines were used to investigate the role of NR4A receptors in osteoblasts. NR4A receptors were shown to directly bind to and activate the promoter of the osteopontin gene (OPN) in osteoblastic cells, thus regulating its expression. OPN is a major bone matrix protein expressed throughout the differentiation of preosteoblastic cells into osteoblasts. The activation of the OPN promoter was shown to be dependent on the activation function-1 located in the N-terminal part of Nurr1 and to occur in both monomeric and RXR heterodimeric forms of NR4A receptors. Furthermore, PTH was shown to upregulate OPN expression through the NR4A family. It was also demonstrated that the fibroblast growth factor-8b (FGF-8b) induces the expression of NR4A receptors in osteoblasts as immediate early genes. This induction involved phosphatidylinositol-3 kinase, protein kinase C, and mitogen activated protein kinase, which are all major pathways of FGF signalling. Nurr1 and NGFI-B were shown to induce the proliferation of preosteoblastic cells and to reduce their apoptosis. FGF-8b was shown to stimulate the proliferation of osteoblastic cells through the NR4A receptors. These results suggest that NR4A receptors have a role both in the differentiation of osteoblasts and in the proliferation and apoptosis of preosteoblast. The NR4A receptors were found to bind to the same response element on OPN as the members of the NR3B family of orphan receptors do. Mutual repression was observed between the NR4A receptors and the NR3B receptors. This repression was shown to be dependent on the DNA-binding domains of both receptor families, but to result neither from the competition of DNA binding nor from the competition for coactivators. As the repression was dependent on the relative expression levels of the NR4As and NR3Bs, it seems likely that the ratio of the receptors mediates their activity on their response elements. Rapid induction of the NR4As in response to various stimuli and differential expression of the NR3Bs can effectively control the gene activation by the NR4A receptors. NR4A receptors can bind DNA as monomers, and Nurr1 and NGFI-B can form permissive heterodimers with the retinoid X receptor (RXR). Permissive heterodimers can be activated with RXR agonists, unlike non-permissive heterodimers, which are formed by RXR and retinoic acid receptor or thyroid hormone receptor (RAR and TR, respectively). Non-permissive heterodimers can only be activated by the agonists of the heterodimerizing partner. The mechanisms behind differential response to RXR agonists have remained unresolved. As there are no activating or repressing ligands for the NR4A receptors, it would be important to find out, how they are regulated. Permissiviness of Nurr1/RXR heterodimers was linked to the N-terminal part of Nurr1 ligand-binding domain. This region has previously been shown to mediate the interaction between NRs and corepressors. Non-permissive RAR and TR, permissive Nurr1 and NGFI-B, and RXR were overexpressed with corepressors silencing mediator for retinoic acid and thyroid hormone receptors (SMRT), and with nuclear receptor corepressor in several cell lines. Nurr1 and NGFI-B were found to be repressed by SMRT. The interaction of RXR heterodimers with corepressors was weak in permissive heterodimers and much stronger in non-permissive heterodimers. Non-permissive heterodimers also released corepressors only in response to the agonist of the heterodimeric partner of RXR. In the permissive Nurr1/RXR heterodimer, however, SMRT was released following the treatment with RXR agonists. Corepressor release in response to ligands was found to differentiate permissive heterodimers from non-permissive ones. Corepressors were thus connected to the regulation of NR4A functions. In summary, the studies presented here linked the NR4A family of orphan nuclear receptors to the regulation of osteoblasts. Nurr1 and NGFI-B were found to control the proliferation and apoptosis of preosteoblasts. The studies also demonstrated that cross-talk with the NR3B receptors controls the activity of these orphan receptors. The results clarified the mechanism of permissiviness of RXR-heterodimers. New information was obtained on the regulation and functions of NR4A receptors, for which the ligands are unknown.