IL-10 and TGF-ß1 gene polymorphisms in Greek patients with recurrent aphthous stomatitis.

BACKGROUND: Recurrent aphthous stomatitis (RAS) is one of the most frequent inflammatory disorders of the oral mucosa. Cytokines, which play an important role in RAS pathogenesis, participate directly or indirectly in normal, immunological and inflammatory processes and are secreted from cells belonging to innate and adaptive immunity as a consequence of microbial and antigenic stimuli. Gene polymorphisms in specific cytokines may predispose to RAS development. The aim of this study was the investigation and association of IL-10 and TGF-ß1 gene polymorphisms with RAS. MATERIAL AND METHODS: Study's cohort consisted of 60 Greek patients diagnosed with RAS, including 40 patients with minor, 10 patients with major and 10 with herpetiform aphthous ulcers. Forty age- and sex-matched control subjects were included in this study. DNA was extracted from whole blood samples of all patients and sequence-specific primers (SSP)-based polymerase chain reaction (PCR) was used for genotyping. Gene polymorphisms for cytokines IL-10 at loci -592 and -819 and for TGF-ß1 at codon 10 were detected. RESULTS: Significant differences between patients with minor RAS and healthy controls were recorded for IL-10 genotypes distribution at position -592 (p=0.042) and -819 (p=0.045) with predominance of C/A and C/T genotypes in RAS patients, respectively. Also, in patients with minor and herpetiform aphthous ulcerations, heterozygous TGF-ß1 genotype C/T at codon 10 was associated with increased risk of RAS (p=0.044 and p=0.020, respectively). CONCLUSIONS: These data provide evidence that genetic predisposition for RAS and possibly its specific clinical variants is related with the presence of gene polymorphisms for specific cytokines, including IL-10 and TGF-ß1, which, in turn, may vary according to geographic origin and genetic background.

Finite element simulation of friction and adhesion attributed contact of bio-inspired gecko-mimetic PDMS micro-flaps with SiO2spherical surface.

The remarkable tribological attributes of the gecko feet have grown much interest in the field of biomimetic tribology over the past two decades. It has been shown that the complexity of friction and adhesion phenomena made it difficult to transfer these exceptional properties into fully functional smart, dry, micro patterned adhesives. The latter, combined with the relative lack of literature on computational oriented studies on these phenomena, is the motive of the current work. Here, a 2D time-dependent finite element model of friction and adhesion attributed contact of polydimethysiloxane (PDMS) micro flaps with a smooth SiO2spherical surface is presented. The model is tested through simulations concerning changes in the disc curvature, the flap density, as well as different disc mounting heights, representing the effect of preload. Furthermore, the effect of tribological parameters of adhesion and friction coefficient is discussed. Finally, the effect of the use of two hyperelastic material models was examined.

Diamond grinding wheels production study with the use of the finite element method.

Research results on 3D modeling of the diamond grain and its bearing layer when sintering diamond grinding wheels are provided in this paper. The influence of the main characteristics of the wheel materials and the wheel production process, namely the quantity of metallic phase within diamond grain, coefficient of thermal expansion of the metallic phase, the modulus of elasticity of bond material and sintering temperature, on the internal stresses arising in grains is investigated. The results indicate that the stresses in the grains are higher in the areas around the metallic phase. Additionally, sintering temperature has the greatest impact on the stresses of the grain-metallic phase-bond system regardless of the type of the bond. Furthermore, by employing factorial design for the carried out finite element model, a mathematical model that reflects the impact of these factors on the deflected mode of the diamond grain-metallic phase-bond material system is obtained. The results of the analysis allow for the identification of optimal conditions for the efficient production of improved diamond grinding wheels. More specifically, the smallest stresses are observed when using the metal bond with modulus of elasticity 204 GPa, the quantity of metallic phase in diamond grain of not higher than 7% and coefficient of thermal expansion of 1.32 × 10-5 1/K or lower. The results obtained from the proposed 3D model can lead to the increase in the diamond grains utilization and improve the overall efficiency of diamond grinding.

Detection and typing of human papillomaviruses (HPV) in malignant, dysplastic, nondysplastic and normal oral epithelium by nested polymerase chain reaction, immunohistochemistry and transitional electron microscopy in patients of northern Greece.

OBJECTIVES: To evaluate the role of HPV in oral carcinogenesis, we examined the prevalence of HPV in malignant, potentially malignant and normal oral epithelium and studied the relation of HPV prevalence with other factors obtained from the patient's records. MATERIALS AND METHODS: Our material consisted of 291 tissue specimens from 258 individuals. From every individual formalin fixed and paraffin embedded tissues were examined by nested Polymerase Chain Reaction (NPCR) for the detection of HPV DNA and by immunohistochemistry (IHC) for the in situ detection of HPV L1 protein. Positive PCR products were sequenced in order to type HPVs. Also 33 fresh tissues were obtained, fixed and used to detect HPV particles by transitional electron microscopy (TEM). RESULTS: HPV was detected in 32.9% of the tissue specimens by NPCR, in 4.7% by immunohistochemistry and in 28.1% by TEM. In detail, by nested PCR HPV L1 DNA was detected in 40% of normal tissues, 40% of fibromas, 35.8% of non-dysplastic leukoplakias, 31.6% of dysplastic leukoplakias and 22.2% of oral squamous cell carcinomas. The HPV viral load of 96.5% of the samples was very low (1 viral copy per 10(2)-10(4) cells). HPV16 prevails in all histological groups in 89-100%. CONCLUSION: We conclude that HPV does not seem, from the specific sample examined, to play a substantial role in oral carcinogenesis. However, it cannot be excluded that HPV could be involved in oral carcinogenesis only in cases with high viral load or at early stages of carcinogenesis possibly through the hit-and-run mechanism.

Minor salivary glands of the lips: a novel, easily accessible source of potential stem/progenitor cells.

OBJECTIVES: Cells with stem/progenitor properties have been detected in major salivary glands, but no data are available on their presence within minor salivary glands (MSGs). This study aimed to isolate and characterize potential stem/progenitor cells from human MSGs. MATERIALS AND METHODS: MSGs of the lower lip were surgically obtained during biopsy for Sjogren's syndrome investigation that finally proved to be histologically normal. The established MSG cultures were assessed for morphology, proliferation, colony-forming-unit efficiency, multipotentiality, and immunophenotypic characteristics. RESULTS: A mixed population of fibroblast-like and a few flat-shaped epithelial-like cells was obtained. These cells were capable for osteogenic, adipogenic, and neurogenic differentiation. Evidence for strong stem cell potency was observed by the detection of early stem cell markers, like Nanog, Oct-3/4, and SSEA-3. These cells also expressed characteristic mesenchymal stem cell markers, including CD90-Thy1, CD105, CD49f, CD81, nestin, CD146, and Stro-1, but were negative for CD117/C-KIT, CD45, and CD271/NFG. In addition, positivity for keratins 7/8 in part of the population was indicative of an epithelial phenotype, whereas these cells were negative for aquaporin-1 expressed in acinar/myoepithelial cells during development. CONCLUSIONS: Based on these data, a cell population with stem/progenitor characteristics was primarily isolated from labial MSGs. The morphologic and immunophenotypic features indicated that this population is mixed with mesenchymal (mainly) and epithelial characteristics. CLINICAL RELEVANCE: Due to their large number and superficial distribution in labial mucosa, MSGs may be proposed as a potential easily accessible source of adult stem/progenitor cells for regenerative therapies of glandular organs with parenchymal pathology.

Expression of N-cadherin in salivary gland tumors.

OBJECTIVE: To detect immunohistochemically the N-cadherin expression in different types of benign and malignant salivary gland tumors in an attempt to note any possible correlation to their development, stage and invasive properties. MATERIALS AND METHODS: N-cadherin expression was examined in tissue specimens from 49 salivary gland tumors including: pleomorphic adenomas (4), Warthin's tumors (10), and myoepitheliomas (4) (benign tumors), as well as adenoid cystic carcinomas (14), mucoepidermoid carcinomas (4), polymorphous low-grade adenocarcinomas (6), and adenocarcinomas not otherwise specified (5) (malignant tumors). Twelve specimens of normal salivary glands were used as control. The perineural invasion and stage of malignant salivary gland tumors were evaluated. Immunohistochemical procedure was performed automatically using the Bond Polymer Refine Detection Kit. RESULTS: N-cadherin expression was not found in normal salivary glands. In benign salivary gland tumors, N-cadherin along membranes of neoplastic cells as well as in centrocytes of lymphoid germinal centers was seen in 1 and 4 cases of Warthin's tumors, respectively. Varied degree of N-cadherin expression was found in 13 (45%) cases of malignant salivary gland tumors. N-cadherin expression was significantly correlated with perineural invasion (χ(2) = 11.7, p < 0.0001), but not with stage of malignant salivary gland tumors. CONCLUSION: N-cadherin expression was observed in malignant salivary gland tumors and could be an indicator of potentially aggressive behavior. N-cadherin expression by tumor cells could be attributed to perineural invasion.

VEGF expression from human dysplastic or malignant oral epithelium may be related to mast cell density and the subsequent angiogenetic phenomena.

Vascular endothelial growth factor (VEGF) is an angiogenic cytokine and mast cells play a role in neoangiogenesis in various malignancies. The aim of the present study was to elucidate the role of VEGF and mast cells in the early stages of tumorigenesis in oral squamous cell carcinoma (OSCC). Immunohistochemistry was conducted to study VEGF expression and microvessel density (MVD) in 49 tissue samples, 31 OSCCs, 13 leukoplakias (8 with and 5 without dysplasia) and 5 samples from normal oral tissue. Counterstaining with tolouidine blue was conducted to reveal mast cells. The number of microvessels and mast cells were counted at the same optical field. A gradually increased VEGF expression was observed from normal oral epithelium to leukoplakia and OSCC. MVD was found to increase significantly between normal oral tissue and OSCC (p=0.000). The number of mast cells was found to increase significantly between normal oral tissue, dysplasia (p=0.012) and OSCC (p=0.000). In the early stages of tumorigenesis in OSCC, VEGF, which is secreted by the epithelium, is gradually increased immediately affecting the population of mast cells, which are then related to the increase of microvessels.

HLA alleles and fissured tongue.

The aim of this study was to investigate the linkage between HLA and fissured tongue. Sixty- nine individuals with fissured tongue and 125 healthy volunteers were typed for HLA-DRB1*. The results showed increased frequency of HLA-DRB1*08 (P < 0.001), HLA-DRB1*14 (P < 0.01), HLA-DRB1*11 (P < 0.05) and HLA-DRB1*16 (P < 0.05), while HLA-DRB1*03 and HLA-DRB1*07 frequency was decreased (P < 0.05).

Coexistence of mucous retention cyst and basal cell adenoma arising from the lining epithelium of the cyst. Report of two cases.

OBJECTIVE: To report 2 cases of coexisting mucous retention cyst and basal cell adenoma arising from the lining epithelium of the cyst. CLINICAL PRESENTATION AND INTERVENTION: Two cases of painless swellings, well-demarcated, soft to palpation, and located in the submucosa of the upper lip were clinically examined with the provisional diagnosis of mucocele or salivary gland tumor. Histological examination showed the presence of a large unilocular cystic cavity in many parts surrounded by single or bilayered lining epithelium composed of flattened to cuboidal cells, and in other parts surrounded by projections of cells arranged in a trabecular pattern far into the cystic cavity. The trabeculae were composed of basal and low columnar cells that sometimes formed small duct-like structures. Immunohistochemistry showed that the lining epithelium of the cystic cavity and the cells of the projections expressed cytokeratin 7 and high-molecular-weight cytokeratins. The cells of the projections were weakly positive for S-100 protein and negative for vimentin and alpha-smooth muscle actin. Based on the results, a diagnosis of coexisting mucous retention cysts and basal cell adenomas arising from the lining epithelium of cysts was made. CONCLUSION: The coexistence of mucous retention cysts and basal cell adenomas arising from the lining epithelium of the cyst is reported.

HLA haplotypes in recurrent aphthous stomatitis: a mode of inheritance?

The aim of this study was to investigate the genetic association between recurrent aphthous stomatitis (RAS) and human leucocyte antigen (HLA) class I and II alleles and HLA haplotypes. Families selected had at least one child suffering from recurrent aphthous stomatitis in addition to one or both of the parents. HLA-A, -B and -DR alleles were typed in 29 families, 27 nuclear and two extended (121 subjects). HLA haplotypes of all family members with RAS were compared with those who were RAS negative. Although major histocompatibility complex class I and II gene analysis failed to demonstrate any significant association between RAS and HLA antigens, the study of HLA haplotypes revealed a significant association between HLA haplotypes and susceptibility to RAS. The results indicate that susceptibility to RAS segregates in families in association with HLA haplotypes.

Mast cells and angiogenesis in oral malignant and premalignant lesions.

UNLABELLED: Mast cell contribution to neoangiogenesis during tumorigenesis in oral squamous cell carcinoma is not determined yet. OBJECTIVES: To associate numerical mast cell density (MCD) to numerical microvessel density (MVD) during the progression of oral leukoplakia without dysplasia and leukoplakia with dysplasia to squamous cell carcinoma (OSCC). MATERIALS AND METHODS: MVD was analysed immunohistochemically (mouse monoclonal anti-human CD34) in 49 paraffin-embedded specimens, 35 OSCCs, 9 leukoplakias and 5 normal oral tissues. Toluidine blue counterstaining revealed mast cells. MCD and MVD were assessed at the same optical field. RESULTS: MVD increased between: normal oral mucosa, dysplasia (p=0.004), OSCC (p=0.001), leukoplakia and OSCC (p=0.041). MCD increased between: normal oral mucosa, dysplasia (p=0.003), OSCC (p=0.000), leukoplakia and OSCC (p=0.007). MVD was found to depend on MCD (p=0.000) in a percent 28.3% (power curve fit model). CONCLUSIONS: Mast cells are attracted at the lesion site and may turn on an angiogenic switch during tumorigenesis in OSCC.

Detection of T cells secreting type 1 and type 2 cytokines in the peripheral blood of patients with oral lichen planus.

OBJECTIVE: The purpose of this study was to detect and enumerate T cells secreting type 1 and 2 cytokines in the peripheral blood of patients with oral lichen planus (OLP) and in healthy controls. SUBJECTS AND METHODS: The study group consisted of 80 OLP patients and 80 healthy individuals. Cytokine secreting T cells were detected using ELISPOT assay. RESULTS: There was a statistically significant decrease (p<0.05) in the number of IFN- and IL-12 secreting cells in the peripheral blood of patients with OLP compared to the controls. No statistical difference was observed in the number of IL-2 and TNF-a secreting cells between OLP patients and controls (p>0.05). Also there was no significant difference in the numbers of IFN-gamma, IL-12, IL-2 and TNF-a secreting cells between reticular and erosive forms of OLP (p>0.05). As regards type 2 cytokines, the number of IL-5 and IL-10 secreting cells was significantly decreased in OLP patients compared to the healthy control group (p<0.05). No statistical difference was observed in the number of IL-6 secreting cells between OLP patients and control group (p>0.05). Similarly, no statistical difference was observed in the number of IL-4 secreting cells between OLP patients and controls (p>0.05). No significant difference was also found in the numbers of IL-4, IL-5, IL-10 and IL-6 secreting cells between reticular and erosive OLP group. CONCLUSION: These data suggest decreased type 1 and type 2 cytokine production (except IL-4) in OLP patients.

Bilateral aplasia of parotid glands correlated with accessory parotid tissue.

Congenital absence of major salivary glands, especially the parotid gland, is a rare entity. It is usually monolateral and is not correlated with accessory salivary gland tissue. Aplasia of parotid gland may occur alone or in association with abnormalities of other salivary glands, first branchial arch developmental disturbances or other congenital anomalies.We report an interesting case of bilateral aplasia of the parotid glands together with bilateral accessory parotid tissue, without other congenital or developmental anomalies, and we describe the clinical and radiological findings.

Outcome following treatment for Helicobacter pylori in patients with recurrent aphthous stomatitis.

OBJECTIVE: The aim of the current study was to investigate any association of Helicobacter Pylori (HP) in recurrent aphthous stomatitis (RAS) and the effect of eradication of the microorganism in the clinical course of the disease. STUDY DESIGN: Forty-eight patients with RAS were included in the study. Twenty-six were women and 22 men, of average age 41.3 +/- 2.44. Thirty-four out of these 48 patients were HP positive and the rest 14 who were negative were used as a control group. The diagnosis of HP infection was based on the detection of specific immunoglobulin G (IgG), and immunoglubulin A (IgA) antibodies using the enzyme-linked immunoabsorbent assay technique in the serum and the saliva of the patients. In all HP carriers an eradication therapy was administered. After a 2-month period the patients were checked for HP status, using 13C-UBT. The follow up period was 6-12 months following the eradication therapy. RESULTS: At entry patients with HP infection suffered from more severe symptoms compared with HP negative patients (P < 0.05). After the administration of HP eradication therapy, patients who had become negative showed a remarkable improvement (62.5%) with reference to recurrence of RAS as well as to symptom intensity. In 29.2% of patients symptoms had disappeared and in 33.3% of patients there was a decrease in both the frequency of recurrence and the intensity of symptoms. After the eradication treatment, the periods between recurrence of RAS in patients who had become negative were statistically significantly longer compared with those before treatment (P < 0.001). Another important observation was that patients who became negative after eradication therapy were of comparable clinical status with those who were HP negative from the beginning of the study (P > 0.05). CONCLUSIONS: These findings support the concept of a potential association between RAS and HP.

Actinic cheilitis: clinical and pathologic characteristics in 65 cases.

OBJECTIVE: The purpose of this study was to determine the clinical and histopathologic presentation of actinic cheilitis. STUDY DESIGN: A retrospective study on 65 patients attending an Oral Medicine clinic in Greece over a 10 year period. For each case the demographic, clinical and histopathologic information were evaluated. RESULTS: The mean age at the time of diagnosis was 53.1 +/- 11.4 years. Thirty-nine patients (60%) used tobacco in any form. An outdoor occupation was indicated for 43 (66.2%) patients. The location of the lesions of actinic cheilitis was in all cases on the lower lip. Actinic cheilitis appeared in three forms; white non-ulcerated lesions (29%), erosions or ulcers of the lip (48%), mixed white and erosive (23%). The histopathologic characteristics included increased thickness of keratin layer, alterations of the thickness of spinous cell layer, epithelial dysplasia, connective tissue changes, perivascular inflammation and basophilic changes of connective tissue. In 11 cases (16.9%) the presence of squamous cell carcinoma was observed. CONCLUSIONS: This case-series highlights varied clinical presentation of actinic cheilitis among whom a high proportion developed squamous cell carcinoma.

Epidermal growth factor in saliva and serum of patients with cyclosporin-induced gingival overgrowth.

The purpose of this study was to investigate the presence of epidermal growth factor (EGF) in patients receiving cyclosporin therapy who had gingival overgrowth and to determine whether there were any differences between these patients and normal healthy controls. Seventeen patients with cyclosporin-induced gingival overgrowth and seventeen age- and sex-matched controls who were taking cyclosporin but had healthy gingiva were used for this study. Unstimulated whole saliva was collected from all individuals by expectoration. Gingival crevicular fluid (GCF) was also collected from all individuals. Blood was additionally collected from all subjects and serum was separated by keeping the samples overnight at 4 degrees C. EGF levels in all cases were measured by an ELISA assay. EGF concentrations were found to be significantly higher in the saliva of patients with cyclosporin-induced gingival overgrowth compared to the control group (401.2 +/- 31.1 pg/ml and 144.3 +/- 31.4 pg/ml, respectively), whereas the results were reversed in the serum (67.0 +/- 15.6 pg/ml and 141.6 +/- 17.7 pg/ml, respectively). EGF was not detected in the samples of GCF in either group. This study thus demonstrated an increase in EGF levels in the saliva and a decrease of EGF in the serum of patients with cyclosporin-induced gingival overgrowth.

Benign tumors of adipose tissue of the oral cavity: a clinicopathologic study of 13 cases.

PURPOSE: The purpose of this study was to determine the clinical and histologic features of 9 simple lipomas, 2 fibrolipomas, and 2 infiltrating lipomas of the oral cavity. In addition, 10 cases of infiltrating lipoma of the oral cavity previously reported in the literature were reviewed. MATERIALS AND METHODS: All cases were retrieved from the archives of the Department of Oral Medicine/Pathology of the University of Thessaloniki, Greece. Data on age, sex, location, clinical appearance, duration, recurrence, and histologic appearance were evaluated. RESULTS: This study showed that the sex distribution of the simple lipomas was approximately equal, and the mean age of patients was 60.2 years. The buccal mucosa was the most frequent location of the tumors. Their size ranged from 0.2 to 1.5 cm, with an average rate 0.8 cm. In 3 cases, the tumor was not encapsulated. The sex distribution of the infiltrating lipomas was equal, and the mean age of the patients was 36.8 years. The most frequent location was the tongue. CONCLUSIONS: Tumors of adipose tissue represent rare neoplasms of the oral cavity. The diagnosis is based on both the clinical and histologic characteristics. Caution is required during their surgical excision to avoid recurrence, especially with infiltrating lipomas.

Immunohistochemical detection of insulin-like growth factor-I in the labial salivary glands of patients with Sjögren's syndrome.

OBJECTIVE: The purpose of the present study was to investigate the presence of insulin-like growth factor-I (IGF-I) in the labial salivary glands of patients with Sjögren's syndrome and healthy controls and to determine if there are any differences between these two groups. DESIGN: An immunohistochemical study. SUBJECTS AND METHODS: Twenty-five patients with Sjögren's syndrome, 20 healthy controls and 20 patients with mucoceles of the lip were used in this study. All individuals underwent a systemic evaluation and a lip biopsy. Sections from the lip biopsies were stained with haematoxylin and eosin (H&E). Immunohistochemical staining was also performed using a three-step indirect immunoperoxidase for IGF-I. RESULTS: The light microscopic examination revealed the presence of a mononuclear infiltration in the labial salivary glands of patients with Sjögren's syndrome. Most of the infiltrates were lymphocytes. Immunohistochemically an intense staining result was apparent in the same group. In contrast sections of labial salivary glands of healthy individuals and of patients with mucoceles revealed very weak staining. CONCLUSIONS: The above findings and the fact that both lymphocytic infiltration and IGF-I were predominantly seen in ductal regions, suggest that IGF-I may be a target of autoimmunity in Sjögren's syndrome.

Prevalence of oral lichen planus in diabetes mellitus according to the type of diabetes.

OBJECTIVE: The purpose of the present study was to determine the prevalence of oral lichen planus (OLP) in a population of patients with diabetes mellitus (DM) as compared with a control population. DESIGN: A clinicopathologic study. SUBJECTS AND METHODS: One hundred and thirty-nine patients with type I DM, 353 patients with type II DM and 274 controls were examined for clinical evidence of OLP. The clinical evidence of OLP in the diabetic and control patients was confirmed by histopathological examination. RESULTS: The prevalence of OLP in type I diabetic patients was 5.76%, in type II 2.83%, and 1.82% in the controls. The prevalence of OLP was significantly higher in patients with type I DM and slightly higher in patients with type II DM in comparison to the prevalence in the control sample. CONCLUSIONS: The above findings and the fact that type I diabetes and OLP are characterized by autoimmune phenomena and T cell immune responses respectively, suggest that the immune system may play a critical role in the appearance of OLP in patients with type I DM.