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.

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.

Myofibroma of the oral mucosa: a case report.

OBJECTIVE: To report a case of coexisting irritation fibroma and myofibroma in oral mucosa. CLINICAL PRESENTATION AND INTERVENTION: One case with two painless, nodular masses, adjacent to each other in the buccal mucosa, was clinically examined with a provisional diagnosis of irritation fibroma, salivary gland tumors, neurofibroma and schwannoma. Histological examination of the smaller swelling showed features of irritation fibroma, while the features of the other mass were compatible with myofibroma or leiomyoma. Additional immunohistochemical examination established the diagnosis of myofibroma. CONCLUSION: This was a case of a myofibroma that was clinically similar to an adjacent irritation fibroma, which highlights the possibility of misdiagnosis of a myofibroblastic tumor and underlines the importance of histologic examination together with immunohistochemical and/or histochemical analysis if necessary to establish the accurate diagnosis.

Immunohistochemical detection of E-cadherin in certain types of salivary gland tumours.

OBJECTIVES: To investigate the topography of E-cadherin and its possible correlation with the histological phenotype of salivary gland tumours. MATERIAL AND METHODS: Archival formalin-fixed, paraffin-embedded sections of 54 benign and 56 malignant tumours and 24 samples of normal and inflamed salivary gland tissue were studied immunohistochemically using an Envision/horseraddish peroxidase (HRP) technique. RESULTS: In normal and inflamed salivary gland samples, E-cadherin was expressed at the membrane of acinar, myoepithelial and ductal cells located at cell-cell contact points. Reduction and/or absence of E-cadherin was only observed in pleomorphic adenoma at the peripheral cells of the duct-like or island structures, or in the cells exhibiting plasmacytoid or stromal differentiation. Neoplastic epithelium in Warthin's tumours and in myoepithelial and oncocytic adenomas was strongly positive. Furthermore, a weak to moderate loss of expression which was related to tissue tumour subtype was seen in malignant tumours such as: adenoid cystic carcinomas; polymorphous low-grade adenocarcinomas; acinic cell carcinomas; and mucoepidermoid low-grade, epithelial-myoepithelial, lymphoepithelial and squamous low-grade carcinomas. Moderate to extreme loss or alternative cytoplasmic non-functional expression were observed in cases of salivary ductal carcinoma, carcinosarcoma, myoepithelial carcinoma, oncocytic adenocarcinoma, unspecified adenocarcinoma and squamous high-grade carcinomas. CONCLUSION: This study suggests a direct association of E-cadherin expression with neoplastic histologic phenotype, which is lost in the more undifferentiated and invasive epithelial salivary gland tumours.

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.

Oral Candida isolates in patients undergoing radiotherapy for head and neck cancer: prevalence, azole susceptibility profiles and response to antifungal treatment.

Oral pseudomembranous candidiasis and mucositis were assessed in 39 patients receiving a total dose of 39-70 Gy radiotherapy for head and neck cancer. Mucositis was scored using the Radiation Therapy Oncology Group criteria, and oral candidiasis was diagnosed on the basis of clinical evaluation and quantitative laboratory findings. Radiation-induced mucositis was observed in 9/39 patients. Only 3/39 patients discontinued radiotherapy due to acute severe mucosal effects. Candidiasis (colony-forming units 35 to > or = 60/lesion) associated with mucositis was diagnosed in 30/39 patients: the most frequent aetiology of the infection was Candida albicans (n = 23), followed by Candida glabrata (n = 3), Candida krusei (n = 2), Candida tropicalis (n = 1) and Candida kefyr (n = 1). Patients with confirmed oral pseudomembranous candidiasis were treated with either fluconazole 200 mg/day or itraconazole 200 mg/day for 2 weeks. Clinical improvement and concomitant negative Candida cultures (mycologic cure) were the criteria determining a response to antifungal treatment. Etest revealed very low voriconazole MICs (0.004-0.125 microg/ml) for all isolates, and fluconazole resistance for eight C. albicans strains (MIC > 64 microg/ml) and for the C. krusei isolates (MIC > 32 microg/ml). The same strains showed itraconazole susceptibility dose dependence (MIC 0.5 microg/ml). Despite the itraconazole susceptible dose dependent MIC readings, all patients with oral pseudomembranous candidiasis caused by these strains responded to antifungal treatment with 200 mg/day itraconazole. Oral mycologic surveillance of patients undergoing radiotherapy for head and neck malignancies and susceptibility testing of isolates may be indicated in cases with mucositis-associated confirmed oral pseudomembranous candidiasis to ensure prompt administration of targeted antifungal treatment. On the basis of the low MIC values found, clinical evaluation of voriconazole is indicated for management of oral pseudomembranous candidiasis refractory to other azoles.

Inheritance of behavioural differences between two interfertile, sympatric species, Drosophila silvestris and D. heteroneura.

The Hawaiian fly species, Drosophila silvestris and D. heteroneura, are sympatric and interfertile but show strong behavioural isolation and major differences in male aggressive behaviour and the associated morphology. As a first step in elucidating the genetic control of the differences between these species, we examined the mating and aggressive behaviour of their reciprocal F1 hybrids. The latency to the first wing vibration and the latency to copulate did not differ significantly between the parental species. However, D. heteroneura females had a very low tendency to copulate with D. silvestris males, rarely mating during the observation period. The duration of copulation also differed significantly; same-species pairs of D. silvestris had copulations that lasted about 50% longer than those of same-species pairs of D. heteroneura. The hybrids were intermediate between the parental species for both the tendency to copulate with D. silvestris males and the duration of copulation, suggesting codominance or polygenic inheritance for those traits. The aggression traits that we scored were the leg posture and wing extension during early aggression, and the leg posture and head position during escalated aggression. The parental species showed clear differences for each of these traits. The F1 hybrids resembled one parent or the other, without showing intermediate values, suggesting single-gene dominance or threshold expression of many genes for those traits. None of the courtship or aggressive traits showed X-chromosomal effects, although the head shape of hybrids is influenced by genes on the X chromosome. It is difficult to reconcile the patterns of inheritance of aggressive behaviour and the lack of an X-chromosomal effect with the hypothesis that these traits are influenced by a coadapted gene complex.

Comparison of the effects of salmeterol and ipratropium bromide on exercise performance and breathlessness in patients with stable chronic obstructive pulmonary disease.

To compare the effects of salmeterol, an adrenergic drug, and ipratropium bromide, an anticholinergic drug, on breathlessness and gas exchange during exercise in patients with chronic obstructive lung disease (COPD), we performed a progressive treadmill exercise test on 15 patients on 3 days (24 h apart), after inhalation placebo, ipratropium bromide (120 micrograms) or salmeterol (50 micrograms) in a randomized fashion. Dyspnoea during exercise was evaluated from the regression slope between Borg scale (BS) scores and distance walked each minute on the treadmill. The regression was expressed as the distance walked at BS score 5, the threshold load of dyspnoea (TLD) and breakpoint load of dyspnoea. During and after the exercise, oxygen saturation was monitored by pulse oxymeter and we measured the lower SaO2 during exercise and the recovery time of SaO2 after exercise. In comparison to placebo inhalation we found the same small but significant improvement in airflow limitation after salmeterol or ipratropium inhalation, also the distance walked on treadmill increased after bronchodilators. After bronchodilators the magnitude of oxyhaemoglobin desaturation with exercise was similar to that observed after placebo but the duration of the recovery from sustained SaO2 desaturation after exercise was shorter to the same extent as after ipratropium or salmeterol. Dyspnoeic sensation, when assessed by the TLD and by the distance walked at BS score 5, was decreased after salmeterol and after ipratropium bromide to a similar extent. We conclude that the salmeterol, when given in conventional doses, produces significant improvement in the airway obstruction in the recovery of postexercise HbO2 desaturation and in dyspnoeic sensation in patients with COPD, effects which were similar to those observed after inhalation of the anticholinergic agent ipratropium bromide.

Is sexual selection and species recognition a continuum? Mating behavior of the stalk-eyed fly Drosophila heteroneura.

If behavioral isolation between species can evolve as a consequence of sexual selection within a species, then traits that are both sexually selected and used as a criterion of species recognition by females should be identifiable. The broad male head of the Hawaiian picture-winged fly Drosophila heteroneura is a novel sexual dimorphism that may be sexually selected and involved in behavioral isolation from D. silvestris. We found that males with broad heads are more successful in sexual selection, both through female mate choice and through aggressive interactions. However, female D. heteroneura do not discriminate against hybrids on the basis of their head width. Thus, this novel trait is sexually selected but is not a major contributor to species recognition. Our methods should be applicable to other species in which behavioral isolation is a factor.

The effect of cellular glucoprivation on skin temperature regulation in the rat.

Studies were undertaken to determine the effects of cellular glucoprivation on temperature responses in morphine-addicted and placebo-treated rats and to compare these responses to those observed during naloxone-precipitated morphine withdrawal. Naloxone caused a tail skin temperature (TST) response of 5.7 +/- 0.5 degrees C in morphine-dependent rats. Intraperitoneal administration 2-deoxyglucose (2DG) caused TST responses in placebo-treated and morphine-dependent rats of 4.8 +/- 0.6 and 6.2 +/- 0.5 degrees C, respectively. These data indicate that the activation of the sympathetic nervous system by cellular glucoprivation causes a TST response which is equivalent in magnitude to that induced by precipitating withdrawal with naloxone. This effect of 2DG appears to be mediated by the brain, since icy administration of 2DG caused a TST response, similar to that induced by naloxone treatment of morphine-dependent rats. Collectively, these data suggest that a TST increase is a component of the response of rats to local brain glucoprivation induced by 2DG.