Serum and Saliva MMP-3 in Patients with OLP and Oral SCC.

BACKGROUND: Matrix metalloproteinase-3 (MMP-3) plays a key role in development of cancer. The purpose of this study was to assess MMP-3 in the serum and saliva of patients with oral lichen planus (OLP) and oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: Thirty patients with OLP (8 reticular and 22 erosive forms), and 20 patients with OSCC (6 in low stage and 14 in advanced stage), were enrolled in this study, conducted at the Cancer Department, Clinic of Oral Medicine, Tehran University of Medical Sciences. The serum and saliva MMP-3 was assayed by ELISA method. Statistical analysis of the Student's t-test, ANOVA and Pearson correlation coefficient was performed. The mean saliva and serum levels of MMP-3 were significantly higher in patients with OSCC compared with OLP. RESULTS: The serum and saliva MMP-3 concentrations increased from reticular form of OLP to erosive form of OLP, and increased further to low stage of OSCC and advanced stage of OSCC. Serum MMP-3 correlated significantly with unstimulated (r = 0.310, p = 0.038) and stimulated (r = 0.365, p < 0.026) saliva MMP-3. CONCLUSION: Serum and saliva MMP-3 levels appear associated with OLP and OSCC.

Plasma cell granuloma in cyclosporine-induced gingival overgrowth: a report of two cases with immunohistochemical positivity of interleukin-6 and phospholipase C-gamma1.

We report two cases of gingival plasma cell granuloma in a 34-yr-old and 40-yr-old two male renal transplant recipients with cyclosporine A (CsA)-induced gingival overgrowth (GO). Histologically, these lesions were composed of mature plasma cells, showing polyclonality for both lambda and kappa light chains and fibrovascular connective tissue stroma. In addition to the fact that CsA-induced plasma cell granuloma is rare, the salient features of our cases were the secretion of interleukin-6 and overexpression of phospholipase C- gamma 1 of the tumor cells, which may explain the mechanisms of CsA- induced GO.

Expression of Tie-2, angiopoietin-1, angiopoietin-2, ephrinB2 and EphB4 in pyogenic granuloma of human gingiva implicates their roles in inflammatory angiogenesis.

Tie-2, angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), ephrin-B2 and Eph-B4 are all important vascular morphogenesis factors which exhibit their functions in angiogenesis and blood vessel remodeling in embryonic stage. However, their roles in post-natal inflammatory angiogenesis are still unclear. Pyogenic granuloma is a benign inflammatory lesion that mostly occurs on the gingiva of females with high levels of steroid hormones. Prominent capillary growth in hyperplastic granulation tissue is characteristic histopathologically in pyogenic granuloma. The purpose of this study was to detect and compare the expressions of Tie-2, Ang-1, Ang-2, ephrin-B2 and Eph-B4 among pyogenic granuloma on human gingiva, gingiva diagnosed with periodontitis and healthy gingiva by immunohistochemistry. The immunostaining revealed that all of the endothelial cells and some mesenchymal cells expressed Tie-2. The cells which expressed Ang-1 and Ang-2 were mainly macrophage- or monocyte-like mesenchymal cells and smooth muscle cells surrounding blood vessels. The expression of ephrin-B2 and Eph-B4 was not exclusively limited to the endothelial cells of arteries and veins, respectively, as in mice embryo. Eph-B4 was expressed in the endothelial cells of newly budding capillaries and venules while ephrin-B2 was expressed in macrophage-like mesenchymal cells. Some of the ephrin-B2 positive cells were in direct contact with endothelial cells. The statistical analysis demonstrated that all of the five factors were upregulated in pyogenic granuloma compared to healthy gingiva. In conclusion, the 5 polypeptides mentioned above may play important roles in the process of adult inflammatory neovascularization, especially in pyogenic granuloma. It is highly plausible that most of the new capillaries in inflammatory angiogenesis originated from venules instead of arterioles.

First case of surgical treatment of Farber's disease.

Farber's disease (Farber's lipogranulomatosis), which is inherited as an autosomal recessive trait, was first reported by Farber in 1952. We report a case of Farber's disease in a 12-year-old female. Her younger brother was affected with Farber's disease and died of it at 2 years of age. When she first presented, our patient's main clinical features were a shrill voice; subcutaneous nodules; contracture of the joints throughout the body; and granulomas of the oral cavity, the pharynx, and the upper and lower eyelids. Serial radiographs disclosed deformation of the joints throughout the body. Due to the granulomas in her oral cavity, she could take little food orally and therefore was malnourished. We performed a granulectomy under general anesthesia, and her difficulty with feeding and upper airway obstruction improved. There is no specific treatment for Farber's disease, and most patients reported have died by 2 years of age. This is the first reported patient with Farber's disease who has been surgically treated.

Immunohistochemical study of linear gingival erythema from HIV-positive patients.

Severe forms of periodontal disease are frequent in patients with acquired immunodeficiency syndrome (AIDS). Linear gingival erythema (LGE) is a progressive disease described in HIV-positive patients and is considered to be an early stage of necrotizing periodontitis. Although clinical and microbiological differences are reported in LGE and non-specific gingivitis (NSG), a comparative immunopathological approach of both has not been performed yet. The purpose of this study was to compare relative populations of T-lymphocytes, B-lymphocytes, neutrophils, macrophages and IgG bearing plasma cells in gingival biopsies from sites exhibiting LGE and from sites exhibiting NSG. A biotin-streptavidin amplified system was used for identification of the following antigens: CD3 (T-lymphocytes), CD20 (B-lymphocytes), elastase (neutrophils), CD68 (macrophages) and IgG (plasma cell's secretors of IgG). The results have demonstrated decrease proportions of T-lymphocytes, macrophages and high percentage of neutrophils and IgG bearing plasma cells in LGE. In contrast with NSG, many neutrophils cells in LGE were found inside oral gingival epithelium. Our results highlight the idea that progressive periodontal disease is not only characterized by increased tissue inflammation, but, in addition, by significant changes in the proportion of specific inflammatory cells. The high number of neutrophils along the gingival epithelium is probably associated with the severe gingival necrosis reported in AIDS patients.

Interleukin-1: the principal osteolytic cytokine produced by keratocysts.

Fragments of keratocysts removed at operation were maintained in explant culture and the media were assayed for the biological activity of the potent osteolytic cytokines--interleukin (IL)-1, interleukin (IL)-6 and tumour necrosis factor (TNF). Media were also assayed for their ability to stimulate bone resorption. All six cysts examined released IL-1 and IL-6 bioactivity but TNF bioactivity was unmeasurable. Dialysed cyst media stimulated bone resorption and this could be completely inhibited by a monospecific antibody which neutralized IL-1 alpha and IL-1 beta. Immunohistochemical staining of cryostat sections of keratocysts revealed the presence of IL-1 alpha and IL-6 in cyst epithelial cells but not in other cell types. Sections did not react with antibodies to IL-1 beta or TNF. It is therefore proposed that IL-1 alpha is the major osteolytic cytokine produced by keratocysts and that IL-6 and IL-1 may contribute to keratocyst growth by promoting epithelial cell proliferation and bone resorption, respectively.

Transamidase and collagenase activity in healthy and diseased human gingival tissues.

Transamidases are a class of calcium-dependent mammalian enzymes which cross-link proteins by catalyzing the formation of (gamma-glutamyl)-epsilon-lysine bonds. It is possible that these enzymes play an important anabolic role in tissue healing. This study was to quantitate transamidase activity in human gingival tissue and examine the relation between transmidase activity and degree of inflammation. Forty-four out of a total 120 collected human gingival specimens from healthy and diseased patients were selected based on histometric and microbiologic criteria. Specimens were minced and homogenized in 10 mM CaCl2 and then extracted for 30 min, in 50 mM tris-HCl buffer (pH 7.5) containing 100 mM CaCl2. Following low speed centrifugation at 4 degrees C, the supernatant solution was assayed for both transamidase and collagenase activities by radioactive amine incorporation, and digestion of tritiated collagen, respectively. Appreciable levels of transamidase and collagenase activities in healthy gingivae were found. These enzyme activities were significantly elevated in the diseased and healing tissues. Unlike other transamidases, calcium was required in the enzyme extraction process.

Human collagenases: comparative and immunolocalization studies.

Four human collagenases derived from different tissues or cells were shown to have different physicochemical properties with regard to molecular size and protein charge. Such differences have been used to demonstrate that the collagenase activity of rheumatoid synovial fluids is of granulocytic origin. Immunolocalization studies have demonstrated that immunoreactive collagenase is present in a variety of human tissues. Its production by cells in normal tissues suggests a role in collagen remodelling processes, whereas its more frequent occurrence in diseased tissues suggests an important role in pathological collagen resorption. In nearly all the positive specimens examined the enzyme was restricted to a single cell or small groups of cells, or collagenous elements, suggesting microenvironmental rather than widespread collagenolytic activity.

Study of CoQ10-enzymes in gingiva from patients with periodontal disease and evidence for a deficiency of coenzyme Q10.

The specific activities of both the succinate dehydrogenase-coenzyme Q(10) reductase and the DPNH-cytochrome c reductase [NADH:(acceptor)oxidoreductase, EC 1.6.99.3] were determined in mitochondria from 40 diseased gingival biopsies from patients with periodontal disease and from 24 control biopsies from nondiseased areas (clinically evaluated) of gingival tissues from the same mouths of the patients from whom the diseased gingival tissues were taken. The control tissue was taken during normal surgical procedures, such as for gingival recontouring and tuberosity removal. The diseased gingival biopsies showed a mean specific activity for the succinate dehydrogenase-coenzyme Q(10) reductase which was higher (P < 0.02) than that of the control biopsies, and which increased (P < 0.01) when the assays utilized exogenous coenzyme Q(3), and corresponded to an average deficiency of coenzyme Q(10)-enzyme activity of 35%. About 60% of the 40 diseased gingival tissues showed a deficiency of coenzyme Q(10) at its site in this succinate-coenzyme Q(10) enzyme. Of the 24 control tissues, 20% showed deficiencies of coenzyme Q(10). As a group, the control tissues showed no deficiency of coenzyme Q(10). No deficiency of coenzyme Q(10) at its site in DPNH-cytochrome c reductase was observed for either the control or diseased gingival tissues, as groups or individually.