Association of obesity and weight gain with alveolar bone loss: Results of the Northern Finland Birth Cohort 1966 study.

AIM: To investigate whether long-term obesity, long-term central obesity and weight gain are associated with alveolar bone loss. MATERIALS AND METHODS: A sub-population (n = 1318) of the Northern Finland Birth Cohort 1966 was categorized based on body mass index (BMI: normal weight, overweight and obesity) and waist circumference (WC: no central obesity, central obesity) at ages 31 and 46. These categories were combined to define whether the participants stayed in the same categories or passed on to a higher category (weight gain). Alveolar bone level (BL) data were collected at age 46. RESULTS: The associations of long-term obesity and weight gain with BL ≥ 5 mm were stronger in smokers than in the total population and in never smokers. Males who passed on to higher BMI and WC categories showed a higher likelihood for BL ≥ 5 mm (range in relative risks [RRs] 1.3-2.2) than males who stayed in the same categories (range in RRs 0.7-1.1). The associations with BL ≥ 5 mm were weak or non-existent in females. CONCLUSIONS: The relation between obesity and periodontal diseases seems more complex than previously presumed. The role of gender and smoking should be taken into account in future studies.

Deregulated hepsin protease activity confers oncogenicity by concomitantly augmenting HGF/MET signalling and disrupting epithelial cohesion.

Hepsin belongs to a family of cell-surface serine proteases, which have sparked interest as therapeutic targets because of the accessibility of extracellular protease domain for inhibitors. Hepsin is frequently amplified and/or overexpressed in epithelial cancers, but it is not clear how enhanced hepsin expression confers a potential for oncogenicity. We show that hepsin is consistently overexpressed in more than 40% of examined breast cancers, including all major biological subtypes. The effects of doxycycline-induced hepsin overexpression were examined in mammary epithelial organoids, and we found that induced hepsin acutely downmodulates its cognate inhibitor, hepatocyte growth factor (HGF) activator inhibitor type 1 (HAI-1). Hepsin-induced depletion of cellular HAI-1 led to a sharp increase in pericellular serine protease activity. The derepressed hepsin proteolytically activated downstream serine proteases, augmented HGF/MET signalling and caused deterioration of desmosomes and hemidesmosomes; structures important for cell cohesion and cell-basement membrane interaction. Moreover, chronic induction of hepsin considerably shortened the latency of Myc-dependent tumourigenesis in the mouse mammary gland. The serine protease and uPA system inhibitor WX-UK1, identified as a micromolar range hepsin inhibitor, prevented hepsin from augmenting HGF/MET signalling and disrupting desmosomes and hemidesmosomes. The findings suggest that the oncogenic activity of hepsin arises not only from elevated expression level but also from depletion of HAI-1, events which together trigger gain-of-function activity impacting HGF/MET signalling and epithelial cohesion. Thus, hepsin overexpression is a major oncogenic conferrer to a serine protease activity involved in breast cancer dissemination.

Par6G suppresses cell proliferation and is targeted by loss-of-function mutations in multiple cancers.

Differentiated epithelial structure communicates with individual constituent epithelial cells to suppress their proliferation activity. However, the pathways linking epithelial structure to cessation of the cell proliferation machinery or to unscheduled proliferation in the context of tumorigenesis are not well defined. Here we demonstrate the strong impact of compromised epithelial integrity on normal and oncogenic Myc-driven proliferation in three-dimensional mammary epithelial organoid culture. Systematic silencing of 34 human homologs of Drosophila genes, with previously established functions in control of epithelial integrity, demonstrates a role for human genes of apico-basal polarity, Wnt and Hippo pathways and actin dynamics in regulation of the size, integrity and cell proliferation in organoids. Perturbation of these pathways leads to diverse functional interactions with Myc: manifested as a RhoA-dependent synthetic lethality and Par6-dependent effects on the cell cycle. Furthermore, we show a role for Par6G as a negative regulator of the phosphatidylinositol 3'-kinase/phosphoinositide-dependent protein kinase 1/Akt pathway and epithelial cell proliferation and evidence for frequent inactivation of Par6G gene in epithelial cancers. The findings demonstrate that determinants of epithelial structure regulate the cell proliferation activity via conserved and cancer-relevant regulatory circuitries, which are important for epithelial cell cycle restriction and may provide new targets for therapeutic intervention.

Low serum level of 1,25(OH)2 D is associated with chronic periodontitis.

BACKGROUND AND OBJECTIVES: Vitamin D has been studied primarily for its involvement in calcium and phosphate absorption and bone metabolism. The active form of vitamin D-1,25(OH)2 D-has also been investigated for its immune modulatory properties. We explored associations between serum levels of 25(OH)D and 1,25(OH)2 D and periodontal health. SUBJECTS AND METHODS: This case-control study included 55 subjects with chronic periodontitis (cases) and 30 periodontally healthy subjects (controls). Their serum levels of 25(OH)D, 1,25(OH)2 D, ultrasensitive C-reactive protein and high-density lipoprotein cholesterol were determined. Associations between vitamin D and periodontal health status were studied using logistic regression analysis. RESULTS: A statistically significant association was found between serum 1,25(OH)2 D level and periodontal health status; in that subjects with a low 1,25(OH)2 D were more likely to belong to the periodontitis group (OR = 0.97, 95% CI = 0.95-1.00). There was practically no association between 25(OH)D level and periodontal health status. CONCLUSION: In this case-control study low serum 1,25(OH)2 D level appeared to be associated with periodontitis, which was in line with the previously reported associations between serum 1,25(OH)2 D levels and other inflammatory diseases. Whether this association is causal in nature, remains to be confirmed in future studies.

Serum sCD14, polymorphism of CD14(-260) and periodontal infection.

BACKGROUND AND AIMS: CD14 is a co-receptor involved in the recognition of Gram-negative and positive bacteria. Infections are known to influence serum sCD14 levels, and CD14 gene promoter polymorphism (CD14 C-260T) has been reported to be associated with many infectious diseases. Our aim was to investigate whether serum sCD14 concentration is associated with periodontal infection and the CD14(-260) genotype. SUBJECTS AND METHODS: The periodontal status of 56 subjects with chronic periodontitis and 28 controls was clinically examined. Serum sCD14 concentration was analyzed using ELISA and CD14(-260) genotype using polymerase chain reaction (PCR). RESULTS: The mean concentration of sCD14 in serum was significantly higher in subjects with periodontitis than in control subjects (4.9 microg ml(-1)vs 3.8 microg ml(-1), P < 0.001). Serum sCD14 concentration associated significantly with the extent of advanced periodontal disease. In a regression analysis including both subject groups, the CD14(-260) genotype was a significant determinant for serum sCD14 concentration. After stratification by periodontal health status (periodontitis vs controls), the influence of the CD14(-260) genotype on serum sCD14 concentration was seen only in the control group. CONCLUSIONS: Periodontal infection is associated with the serum concentration of sCD14. Moderate to severe periodontal infection overshadows the influence of the genotype on serum sCD14 concentration.

Periodontal health status and treatment needs among the elderly.

The numbers of dentate elderly are growing rapidly in all industrialized countries, and epidemiological information about their oral health is urgently needed. Our study is part of the population-based Helsinki Ageing Study (HAS), and this paper describes the periodontal health status as well as the need for periodontal treatment among the dentate elderly born in 1904, 1909, and 1914 and living in January, 1989, in Helsinki, Finland (n = 175). The dental examinations were carried out during 1990 and 1991 at the Institute of Dentistry, University of Helsinki, Finland. The subjects' periodontal health was recorded by the CPITN (Community Periodontal Index of Treatment Needs) method. The mean number of remaining teeth was 15.1 among men and 14.0 among women, with the mean number of remaining sextants 3.7 and 3.5, respectively. Healthy periodontal tissues (CPI = 0) were found in 7% of the subjects. Bleeding on probing (CPI = 1) was recorded in 6%, and calculus and/or overhanging margins of restorations (CPI = 2) in 41% of the subjects, as the worst finding. Altogether, 46% of the subjects had deep periodontal pockets, 35% with at least one 4- to 5-mm pocket (CPI = 3), and 11% with at least one > or = 6-mm pocket (CPI = 4). Overall, 93% of the subjects required oral hygiene instruction, 87% scaling and root planing, and 11% complex periodontal treatment. The periodontal treatment need was significantly higher in men than in women; however, no significant differences were observed among the three age cohorts. The need for complex periodontal treatment was unexpectedly low, probably explained by the fact that there were many missing teeth, especially molars, perhaps lost due to poor periodontal health.

Alveolar bone loss in type 1 diabetic subjects.

UNLABELLED: AIM, BACKGROUND: The aim of this study was to assess the degree of marginal alveolar bone loss in a group of young subjects with type 1 diabetes mellitus (DM) (n=35, age range 24-36 years) and age-matched non-diabetic control subjects (n=10). METHOD: The diabetic group was divided into 3 subgroups (D1, D2, D3) according to the severity of the diabetic state. The level of alveolar bone was measured on panoramic radiographs of maxillary and mandibular molars as the % of the distance between the cemento-enamel junction (CEJ) and the bone crest along the total length of the root. All mesial and distal sites with a distance of > 15% (BL>15%) were picked, and calculations were performed using the individual %s of sites with BL> 15%. RESULTS: Based on the present findings, we conclude that type 1 DM has a modifying effect on marginal loss of alveolar bone. A clear trend towards increased marginal bone loss was seen in the subjects with complicated DM (D3). The subjects with good metabolic control and no complications of DM (D1) are no more susceptible to marginal bone loss than non-diabetic controls of the same age. CONCLUSIONS: The present findings confirm our previous results on increased loss of periodontal support in subjects with complicated DM already at an early age.

Periodontal disease related to diabetic status. A pilot study of the response to periodontal therapy in type 1 diabetes.

Variation in the periodontal health status and the response to oral hygiene education, scaling and root planing were studied in 36 subjects with type-1 diabetes mellitus (DM) and in 10 non-diabetic control subjects. The age range of the subjects was 24-36 years. The diabetic group was divided into 3 subgroups based on the levels of glycosylated hemoglobin (HbAlc) over a 3 year period and the presence of diabetic complications as follows: (D1) subjects with good metabolic control and no complications (n=13), (D2) subjects with varying metabolic control with/without retinopathy (n=15) and (D3) subjects with severe diabetes, i.e., with poor long-term control and/or multiple complications (n= 8). Clinical measurements (plaque, subgingival calculus, probing pocket depth, bleeding after probing and clinical attachment level) were performed at the baseline and 4 weeks and 6 and 12 months after periodontal therapy. The between-group comparisons were made using the Student t-test and ANOVA. Based on the plaque scores, the oral hygiene status was similar in all groups during the whole study. No statistically-significant differences in the periodontal health status could be found between the diabetic group as a whole and the non-diabetic controls at any examination. The level of periodontal health of the diabetics with good control and no complications (D1) and those with moderate control with/without retinopathy (D2) was on the same level with that seen in the non-diabetic controls. Our findings of the significantly higher extent of al > or =2 mm at the baseline and the fast recurrence of pd > or =4 mm during the longitudinal study in diabetic subjects with poor metabolic control and/or multiple complications (D3) indicate increased periodontal breakdown as a complication of DM in these subjects. To be able to assess the periodontal prognosis and the need for periodontal therapy on an individual basis,the clinical practitioner should be well aware of the diabetic status of his/her patients.

Adult diabetic and nondiabetic subjects as users of dental services. A longitudinal study.

Utilization of dental services by 30 diabetic and 30 nondiabetic subjects was assessed by longitudinal monitoring over a period of 3 years. All subjects were examined clinically three times, and their treatment consisted mainly of cariologic and periodontal treatment. The treatment was delivered by a dentist and an expanded-duty dental hygienist. The study groups were similar with regard to the total number of dental visits needed. However, the treatment of diabetic subjects was more demanding in that more dentist's workload was needed for the diabetic group. They also missed more appointments without cancellation and therefore more office time had to be reserved for them.

Prevalence of periodontal pathogens with varying metabolic control of diabetes mellitus.

The purpose of this study was to determine the prevalence of 5 periodontal pathogens in individuals with diabetes mellitus. Subjects (n = 107) 20-70 years of age with type 1 (n = 60) or 2 (n = 47) diabetes mellitus were studied for the occurrence of the periodontal pathogens A. actinomycetemcomitans, F. nucleatum, E. corrodens, P. gingivalis and P. intermedia. Subgingival plaque was sampled in each subject from a single site exhibiting the greatest inflammation. The evaluation of selected periodontal bacterial pathogens was based on an immunoassay utilizing bacterial specific monoclonal antibodies. 35% of the sites harbored P. gingivalis, 28% F. nucleatum and 21% E. corrodens. A. actinomycetemcomitans and P. intermedia were found in less than 10% of the sites. Subjects for whom the probing depth at the sampled site was > or = 4 mm were more often found to have detectable pathogens than those with a probing depth < or = 3 mm. Diabetic factors such as duration, type and metabolic control of the disease had no statistically significant effect on the prevalence of these bacteria.

Diabetes--a risk factor for periodontitis in adults?

With the increasing number of diabetics in an aging population and controversial research reports on the relationship of diabetes to periodontitis, clarification of diabetes as a risk factor for periodontitis would be helpful. This review notes variations in type, metabolic control, and duration of diabetes and highlights the results of studies that have considered these variations. Diabetics who maintained reasonably good metabolic control had not lost more teeth or experienced more periodontal attachment loss than non-diabetics, although they had more periodontal pockets. Poorly-controlled diabetics with extensive calculus on their teeth had more periodontitis and tooth loss than well-controlled diabetics or non-diabetics. Long-duration diabetics were also at greater risk for periodontitis. Mechanisms by which diabetes may contribute to periodontitis include vascular changes, neutrophil dysfunction, altered collagen synthesis, and genetic predisposition. Minimizing plaque and calculus in the oral cavity through careful self-care and regular professional care is important to reduce the risk of periodontitis in diabetics.

Periodontitis and tooth loss: comparing diabetics with the general population.

People with diabetes may be at increased risk for periodontal disease. This study compared the periodontal health of diabetic and employed adults. While tooth loss and gingival attachment was similar for both groups, diabetics had a greater prevalence and extent of periodontal pockets. Diabetics with poor metabolic control and calculus also had more periodontitis.

Long-term control of diabetes mellitus and periodontitis.

The purpose of this study was to evaluate the association between long-term control of diabetes mellitus (DM) and periodontitis. A total of 75 diabetics (Type I or II) aged 20-70 years with long-term records of their diabetic control were selected for the study. The following periodontal variables were recorded in a randomized half-mouth examination: plaque, calculus (+/-), probing depth (pd) and attachment loss (al). The mean of glycosylated hemoglobin measurements (HbAlc) over the past 2-5 years was used to indicate the long-term control of DM. The study participants were divided into well-, moderately- and poorly-controlled diabetics. An increase in the prevalence, severity and extent of periodontitis with poorer control of diabetes was observed. The extent of calculus also increased with poorer control. In a multiple regression analysis, calculus and long-term control of diabetes were significant variables when pd > or = 4 mm was used as the dependent variable. Age was a significant predictor for al > or = 3 mm but not for pd > or = 4 mm. Sex, duration and type of DM were not significant variables in the regression models. Less than 2% of sites with no calculus demonstrated pd > or = 4 mm. When calculus was present, the frequency of pd > or = 4 mm increased from 6% in the well-controlled diabetics to 16% in the poorly-controlled ones. We conclude that periodontitis in diabetics is associated with long-term metabolic control and presence of calculus.(ABSTRACT TRUNCATED AT 250 WORDS)

Enzyme activity in crevicular fluid in relation to metabolic control of diabetes and other periodontal risk factors.

Diabetics are generally considered at higher risk for periodontitis than non-diabetics. Among diabetics, those with poorer metabolic control have often been found to have more periodontitis. This study investigated the relationship between two crevicular fluid enzymes, beta-glucuronidase (beta G) and lactic dehydrogenase (LDH), and metabolic control in 93 adults with type 1 or 2 diabetes. Metabolic control was evaluated by glycosylated hemoglobin (HbA1c) levels. The most visibly inflamed site was sampled for crevicular fluid enzymes and plaque for microbial assessment. Plaque, calculus, and probing depth were also recorded. Beta-glucuronidase was found at significantly higher levels in patients with poorer diabetic control while LDH levels were not related to control. Using multiple regression analysis, good metabolic control was the only predicting variable for beta-glucuronidase when considered with microbes, probing depth, plaque, calculus, age, duration, and type of diabetes. If beta-glucuronidase is a predictor of periodontal disease activity, diabetics with poor metabolic control are at higher risk for periodontitis.

Increment of caries in diabetic adults. A two-year longitudinal study.

The increment of caries was monitored for two years in 30 adult diabetic and 30 healthy subjects, who received regular preventive and reparative treatment during this time. No significant differences in caries increment were found between the diabetic and control subjects, but there was a tendency for a greater increment on lingual surfaces of the teeth in the diabetic group than in the healthy subjects (P less than 0.09).

Risk factors associated with abundant dental caries and periodontal pocketing.

An adult population of 1275 subjects aged 25, 35, 50, and 65 yr were examined clinically with respect to their periodontal and caries situation. An interview and questionnaire were used to chart the following variables: dietary and oral hygiene habits, social factors, appreciation of natural teeth, and use and availability of dental services. The associations between the risk factors and the probability of periodontal pocketing (greater than or equal to 4 mm) or abundant dental caries (greater than or equal to 7 lesions) among the dentate population were examined using a logistic regression model. The final model correctly classified periodontal pocketing in 65% of the cases and abundant caries in 76%. In addition to social variables, behavioral factors were found to be significantly associated with periodontal pocketing and abundant untreated dental caries.

Immediate response to nonsurgical periodontal treatment in subjects with diabetes mellitus.

The short-term response (3-4 months) to non-surgical periodontal treatment, i.e., oral hygiene instruction, scaling and root planing, was determined in 34 diabetic and 45 control subjects. Measurements of probing pocket depth and gingival bleeding (%) were used for evaluation. No significant difference could be observed in the response to non-surgical periodontal treatment between the diabetics and controls.

Awareness of dental disorders and discrepancy between "objective" and "subjective" dental treatment needs.

A dental health survey including an interview, a questionnaire and a clinical examination was conducted among adults aged 25, 35, 50, and 65 yr in Ostrobothnia, Finland. A total of 1275 subjects, 80% of the sample, participated in the clinical examination. 40% of the subjects with at least one dentate sextant had noticed gingival bleeding, 16% gingival inflammation, 20% "gum disease", and 70% at least one decayed tooth. When objectively assessed, a total of 98% had a maximum CPITN code 1-4, 38% a maximum CPITN code 3-4 and 76% were deemed to be in need of fillings. Dentures were objectively non-acceptable in 64% of wearers and subjectively so in 42%. A need for replacing missing teeth was expressed by 14% of the total sample, whereas according to "objective" assessment, 23% had such a need. It is concluded that people tend to underestimate their dental treatment needs, the discrepancy being most distinct in the field of periodontology. Sufficient emphasis should thus be given to improving people's awareness and knowledge of their own dental disorders.

Prevalence of signs and symptoms of mandibular dysfunction among adults aged 25, 35, 50 and 65 years in Ostrobothnia, Finland.

The prevalence of objective signs and subjectively perceived symptoms of mandibular dysfunction were studied in a sample comprising 1600 subjects, 400 each aged 25, 35, 50 and 65 years. Eighty per cent of the subjects were examined clinically. The prevalence figures were higher among the females than among the males, and a slight tendency for higher frequencies of clinical signs was observed with increasing age. In view of the severity of clinical signs preference should be given for a total of 27% of the subjects when considering the need of treatment. The number of remaining teeth in subjects with natural teeth and no additional removable dentures had no marked influence on the prevalence of mandibular dysfunction, but subjects with complete dentures had signs and symptoms of dysfunction more often than those with natural dentition. The sex and age differences can partly be explained by the higher frequency of complete dentures in females than in males and in the older age groups.