Localization of plasminogen activators and plasminogen-activator inhibitors in human gingival tissues demonstrated by immunohistochemistry and in situ hybridization.

The plasminogen-activating system plays an important part in tissue proteolysis in physiological as well as pathological processes. Plasminogen activators u-PA (urokinase) and t-PA (tissue) as well as the inhibitors PAI-1 and PAI-2 are present in gingival crevicular fluid in concentrations significantly greater than in plasma. This fact, and the finding that the concentrations of t-PA and PAI-2 are higher in areas with gingival inflammation, indicate local production of these components. The present study describes, by means of in situ hybridization and immunohistochemistry, the localization of the plasminogen activators and their inhibitors in gingival tissues from patients undergoing periodontal surgery. t-PA mRNA and t-PA antigen were primarily found in the epithelial tissues, predominantly in the sulcular and junctional regions, although occasionally in the oral epithelium and in blood vessels of the connective tissue. u-PA and u-PA-receptor signals were seen in single cells within the junctional and sulcular epithelia and adjacent to blood vessels close to the junctional epithelium, but rarely in the oral epithelium. Similar to t-PA, the predominant location of PAI-2 mRNA was the gingival epithelia. In the junctional and sulcular epithelia, PAI-2 mRNA was seen throughout the thickness, while in the oral epithelium the strongest signals were seen in stratum granulosum and stratum spinosum. PAI-1 mRNA was invariably found in the connective tissue associated with blood vessels. The present study confirms earlier indications of local production of plasminogen activators and their inhibitors in gingival tissues. In addition, the results demonstrate that t-PA and PAI-2 in these patients are produced predominantly in the epithelial tissues. Furthermore, the presence of t-PA and PAI-2 seems to be most pronounced in the areas likely to be subjected to bacterial assault.

Main sensory neuropeptides, but not VIP and NPY, are involved in bone remodeling during orthodontic tooth movement in the rat.

During orthodontic tooth movement (OTM) a remodeling of the periodontal ligament (PDL) and the alveolar bone occurs. We have recently observed that the expression of CGRP and substance P (SP) increases in the PDL and dental pulp in response to buccally directed OTM of the upper first molar in the rat. We have now examined whether there is also an involvement of VIP and NPY in this type of OTM. A sectional arch wire cemented to the upper incisors exerted an orthodontic force, mediated by a coil on the lingual side of the tooth, for 24 hours. It was observed that the blood vessels in the periodontal ligament were supplied with VIP- and NPY-immunoreactive (IR) nerve fibers, whereas VIP-IR nerve fibers in contrast to NPY-IR fibers were only occasionally observed in the dental pulp. No significant changes were observed in response to OTM. The observations suggest that VIP and NPY, in contrast to the main sensory neuropeptides CGRP and SP, are not involved in the tissue processes that occur in the remodeling of PDL and alveolar bone during orthodontic tooth movement.

Glycerol kinase deficiency in two brothers with and without clinical manifestations.

We report two brothers with glycerol kinase deficiency (GKD). The older brother had serious clinical symptoms, mental and growth retardation, abnormal skeleton, spontaneous fractures and premature loss of abnormal teeth. He and his mother had low serum phosphate levels. He had elevated serum and urine glycerol levels and GKD was found in cultured fibroblasts. Prenatal diagnosis was performed in the second pregnancy. Glycerol kinase activity was considered normal in a chorionic villus sample of the foetus. After birth, it was found that the boy had elevated serum and urine glycerol levels. Enzymatic analysis in cultured fibroblasts revealed that this boy also had GKD, in spite of having no expression of the disease. Chromosomal analyses in the parents and both boys were normal. Major rearrangements or deletions were not detected in molecular studies of DNA from the two brothers. The hybridisation pattern was normal and no allelic loss was observed.

Hypophosphatasia affecting the permanent dentition.

Reports on dental abnormalities in connection with hypophosphatasia almost exclusively describe changes in primary teeth. A 23-year-old man with hypophosphatasia, first diagnosed at the age of 8 months, is described; histologically and radiographically verified signs of the condition were present in the permanent dentition. The findings included a reduced level of the marginal alveolar bone supporting the upper central incisors, which had to be extracted. The molars displayed large coronal pulp chambers. Histologically, the upper incisors demonstrated abnormal root cementum, with areas of dentin resorption, as well as disturbances of the mineralization of the coronal dentin. The patient also had signs of abnormal root resorption of molars. The potential involvement of permanent teeth puts children with hypophosphatasia at risk of developing oral complications during adolescent and adult life.

Aggravation of gingival inflammatory symptoms during pregnancy associated with the concentration of plasminogen activator inhibitor type 2 (PAI-2) in gingival fluid.

Gingival inflammatory symptoms are aggravated during pregnancy. In vitro studies suggest a hormonal influence on the plasminogen activator inhibitor type 2 (PAI-2), and a disturbed balance of the fibrinolytic system could help to explain pregnancy gingivitis. Gingival crevicular fluid (GCF) was sampled in 14 women in pregnant and post-pregnant states. The gingival condition was assessed by the gingival index of Løe & Silness (GI) and the amount of bacterial plaque by the plaque index of Silness & Løe (PI). The ratio of sites with gingivitis to sites with bacterial plaque was calculated (G/P-ratio). Antigen levels of tissue plasminogen activator (t-PA), urokinase-type plasminogen activator (u-PA), plasminogen activator inhibitors type 1 (PAI-1) and PAI-2 in GCF were determined with ELISAs and 17 beta-oestradiol and progesterone in serum with radioimmunoassays. For each individual the differences (delta) in hormone levels and PAs and PAIs between pregnancy and post-pregnancy were calculated. Based on differences in G/P-ratio between pregnancy and post-pregnancy, subgrouping was done into a high-reacting and a low-reacting group. For the total group, the mean G/P-ratio was 2.0 during and 1.2 after pregnancy (p = 0.064). A statistically significant correlation between delta progesterone and delta PAI-2 was noted: the higher delta progesterone, the lower delta PAI-2. No other significant correlations between hormone levels and components of the fibrinolytic system were found. For the total group of women, the concentrations of PAI-2, PAI-1 and t-PA were significantly higher during than after pregnancy. The individuals in the high-reacting group, however, showed a lower or unchanged production of PAI-2 during pregnancy, while those in the low-reacting group showed a greatly increased production. The lower inhibitory capacity in terms of a low production of PAI-2 during pregnancy in women with a higher inflammatory reaction indicates that the components of the fibrinolytic system may be involved in the development of pregnancy gingivitis and implies that PAI-2 serves as an inhibitor of importance for tissue proteolysis. The present finding contributes to the explanation of pregnancy gingivitis.

Oral findings in a group of newborn Swedish children.

Oral examinations were performed of 1021 newborn Swedish children, of whom 101 were re-examined after 2-3 or 4-5 months. The most common findings, registered in 74.9% of the children, were of oral mucosal cysts situated either palatally or on the alveolar ridges. The majority of the palatal cysts disappeared shortly after birth, and some alveolar cysts appeared after birth. Ankyloglossia was found in 2.5% of the children, and Fordyce spots in 1.0%. No natal teeth were found. The upper labial frenum was attached to the crest of the alveolar ridge in 76.7% of the children, palatally in 16.7% and buccally in 6.7%. The relationship of the alveolar ridges was recorded: the anterior segment of the mandibular ridge was distal to the maxillary in 99% of cases, and, posteriorly, the mandibular ridges were lingual to the maxillary in 97.6%. An open bite was found in 39.8% of the children.

Histologic characteristics of the gingiva associated with the primary and permanent teeth of children.

The severity of the gingival inflammatory response to dental plaque increases with age, and it has been suggested that this phenomenon may be related to histological characteristics of the gingiva. The objective of this study was to compare the histological characteristics of the gingival tissues of primary teeth with that of permanent teeth in children. Prior to extraction, children were subjected to a period of thorough oral hygiene. Histological sections prepared from gingival biopsies were examined using the light microscope. One biopsy from each of seven primary and seven permanent teeth of 14 children, whose mean ages were 11.0 +/- 0.9 and 12.9 +/- 0.9 years respectively, was obtained. All sections exhibited clear signs of inflammation. Apical migration of the junctional epithelium onto the root surface was associated only with the primary teeth. Compared with the permanent teeth, the primary teeth were associated with a thicker junctional epithelium (P < 0.05), higher numbers of leukocytes in the connective tissue adjacent to the apical end of the junctional epithelium (P < 0.05), and a higher density of collagen fibers in the suboral epithelial connective tissue (P < 0.01). No significant differences were noted in the width of the free gingiva, thickness of the oral epithelium, or its keratinized layer. In conclusion, this study indicates significant differences in the microanatomy of the gingival tissues between primary and permanent teeth in children.

Proximal attachment loss in Swedish adolescents.

The present study describes periodontal conditions in 22 adolescents with proximal attachment loss greater than or equal to 2 mm (AL) and 22 matched referents without AL, all identified in a cross-sectional study of 570 16- and 18-year-old. The cases were followed for 3 years and the referents for 1 year while they were in the care of an organized dental health system. With the exception of 1 case with Morbus Hodgkin, the case and referent groups had a similar background with respect to general health and participation in the dental health program. Bleeding on probing was found at AL sites in 12 of the cases and at corresponding sites in 4 referents. 2 cases had a history of eruption disorders at the AL sites, 1 case had experienced a defective filling and 1 had a root fissure at the AL sites. At re-examinations after 1 and 3 years, 10 out of 21 earlier identified AL cases did not meet the criterion of 1 or more sites with AL greater than or equal to 2 mm. None of the cases showed progression greater than or equal to 2 mm of the lesions. In 1 case, the number of AL sites increased during the period. 4 of the cases harboured Actinobacillus actinomycetemcomitans (A.a.) at AL sites in year 1 and 3 in year 3. 8 of the cases and 4 referents had antibodies specific for A.a.-leukotoxin. The 2 most severe cases, in terms of number of sites with AL, showed bleeding at 1 or more of the AL sites, harboured A.a. at these sites and had serum titers against A.a.-leukotoxin.

Periodontal conditions in a group of Swedish adolescents. (I). A descriptive epidemiologic study.

The aim of the present study was to describe, clinically and radiographically, the periodontal conditions in 16- and 18-year-old adolescents from Northern Sweden. The studied samples comprised 287 16-year-olds and 283 18-year-olds. The clinical examination included recording of presence of plaque, bleeding on probing and calculus, and measurements of attachment level and pocket depth. Alveolar bone level was measured on bite-wing radiographs. A history was taken of the individual's occupation, oral hygiene habits and tobacco use, health, medication and previous orthodontic treatment. The prevalence of attachment loss (AL) was 9.4% in the 16-year-olds and 19.4% in the 18-year-olds. Proximal AL was found in 2.8% and 4.9%, respectively, and proximal bone loss in 1% in both groups. With only a few exceptions (3 individuals out of 82), the individuals with AL had their loss either at buccal/lingual surfaces or at proximal surfaces. Calculus was present in 32.7% of the 16-year-olds and in 44.9% of the 18-year-olds. Pocket greater than 3 mm were found in 4%. No significant differences concerning the periodontal status or presence of plaque and calculus were detected between urban and rural groups or between sexes. Toothbrushing 2 or more times/day was performed by 84.3% of the 16-year-olds and by 83.7% of the 18-year-olds.

Periodontal health at first permanent molars adjacent to primary molar stainless steel crowns.

The present investigation was designed to study the effect of stainless steel crowns (SSC), placed on second primary molars, on the periodontal tissues of neighbouring first permanent molars. 36 children (9-12 years old) with an SSC on a second primary molar on one side of the mouth only, were selected for the study. A clinical and radiographic examination was performed at the mesial surface of the first permanent molar, adjacent to the SSC, and at the corresponding area on the contralateral side of the mouth. The clinical examination included gingival and plaque index scores and probing depth measurements. In the radiographic examination, the marginal bone level was assessed. No statistically significant differences in plaque index scores, gingival index scores and probing pocket depth were noted between the mesial surface of first permanent molars and the contralateral control area. Nor were any significant differences in bone level seen. The present findings suggest that the presence of a well-adapted SSC on a second permanent molar does not affect the periodontal health of the neighbouring first permanent molar.

Oral mucosal lesions in patients with acute leukemia and related disorders during cytotoxic therapy.

This study reports the presence of oral mucosal lesions in 26 patients with acute leukemia during the initial weeks of treatment (induction period). For comparison, three groups of patients without malignant disorders (acute disorders, long-term hospitalization, antibiotic treatment) were included. All patients were treated at the University Hospital of Umeå, Sweden. During the period of hospitalization hemorrhages were seen in 14 of the 26 patients with leukemia. No specific location was found. A correlation between presence of hemorrhages and low platelet counts was noted. Eighteen of the patients revealed ulcerations during the period. Ulcerations were predominantly found on the buccal mucosa, the lips, and the tongue. A tendency to an increase in the number and severity of ulcers was noted during the period of induction therapy. A correlation between presence of ulcers and low granulocyte counts was found. Candidiasis-like changes were seen in eight of the patients with leukemia. Compared with the patients with leukemia the patients in the reference groups showed a low prevalence of oral mucosal lesions.

Histologic characteristics of experimental gingivitis in the juvenile and adult beagle dog.

An earlier study (Matsson & Attström 1979) revealed an unexplained difference between juvenile and adult dogs in the propensity to develop clinical signs of gingivitis. The aims of the present investigation were to depict the structural composition of clinically normal gingiva and to analyze the histologic changes in the gingiva during plaque development in juvenile and adult dogs. Six beagle dogs were used. Two periods of discontinued oral hygiene were studied, the first at 3 and the second at 12 months of age. Biopsies were sampled on days 0, 4, 7, 14, 21 and 28 of each period. Sections from the biopsies were analyzed at two levels of magnification. Compared to adult dog gingiva, juvenile gingiva seemed to display: 1) a thicker keratinized layer of the oral epithelium, 2) a junctional epithelium that structurally resembles the oral epithelium, 3) a cuticular structure at the surface of the junctional epithelium, 4) a limited mononuclear inflammatory cell response during experimental gingivitis, and 5) a delayed establishment of an infiltrated connective tissue portion during experimental gingivitis. In addition, during experimental gingivitis, subgingival plaque formed along the tooth surfaces to a lesser extent in the juvenile stage compared to adult dogs.