The Merkel cell-neurite complex initiates the perception of touch and mediates Ab slowly adapting type I responses. Lichen planus is a chronic inflammatory autoimmune disease with T-cell-mediated inflammation, whereas hyperkeratosis is characterized with or without epithelial dysplasia in the oral mucosa. To determine the effects of lichen planus and hyperkeratosis on the Merkel cell-neurite complex, healthy oral mucosal epithelium and lesional oral mucosal epithelium of lichen planus and hyperkeratosis patients were stained by immunohistochemistry (the avidin-biotin-peroxidase complex and double immunofluorescence methods) using pan cytokeratin, 20 (K20, a Merkel cell marker), and neurofilament 200 (NF200, a myelinated Ab- and Ad-nerve fibre marker) antibodies. NF200-immunoreactive (ir) nerve fibres in healthy tissues and in the lesional oralmucosa epitheliumof lichen planus and hyperkeratosis were counted and statistically analysed. In the healthy oral mucosa, K20-positive Merkel cells with and without close association to the intraepithelial NF200-ir nerve fibres were detected. In the lesional oral mucosa of lichen planus and hyperkeratosis patients, extremely rare NF200-ir nerve fibres were detected only in the lamina propria. Compared with healthy tissues, lichen planus and hyperkeratosis tissues had significantly decreased numbers of NF200-ir nerve fibres in the oral mucosal epithelium. Lichen planus and hyperkeratosis were associated with the absence of Ab-nerve endings in the oral mucosal epithelium. Thus, we conclude that mechanosensation mediated by the Merkel cell-neurite complex in the oral mucosal epithelium is impaired in lichen planus and hyperkeratosis.

AIMNitric oxide (NO)-mediated smooth muscle relaxation causes penile erections. The endothelial NO synthase (eNOS) coenzyme tetrahydrobiopterin (BH4) converts eNOS-mediated catalytic activity from oxygen radical to NO production, improving endothelial function and vascular smooth muscle relaxation.

METHODSUsing quantitative immunohistochemistry, 8-isoprostane and nitrotyrosine concentrations were compared in cavernosal tissue from 17 potent and 7 impotent men, and the effect of single oral doses of BH4 on penile rigidity and tumescence was investigated. The pharmacodynamic effect of single oral doses of BH4 on penile rigidity and tumescence was investigated in a randomized, placebo-controlled, double-blind cross-over fashion in 18 patients with erectile dysfunction (ED) while receiving visual sexual stimulation.

RESULTS8-Isoprostane content in endothelium and smooth muscle was significantly higher in impotent patient samples; the level of nitrotyrosine was unchanged in ED patients. Relative to placebo, a single dose of 200 mg BH4 led to a mean increase in duration of > 60% penile rigidity (33.5 min [95% confidence interval (CI): 13.1-49.3] at base and 29.4 min [95% CI: 8.9-42.2] at tip). A 500-mg dose increased the relative duration of > 60% penile rigidity by 36.1 min (95% CI: 16.3-51.8) at the base and 33.7 min (95% CI: 11.4-43.9) at the tip. Treatments were well tolerated.

CONCLUSIONBH4 treatment is suggested to switch eNOS catalytic activity from super-oxide to NO formation, leading to a reduced formation of free radical reaction product 8-isoprostane without alteration of nitrotyrosine. The observed results make BH4 a suitable candidate as an ED treatment through reconstitution of altered catalytic activity of the eNOS.

Adolescent ; Adult ; Aged ; Biopterin ; analogs & derivatives ; therapeutic use ; Cross-Over Studies ; Dinoprost ; analogs & derivatives ; analysis ; Double-Blind Method ; Erectile Dysfunction ; drug therapy ; Humans ; Immunohistochemistry ; In Vitro Techniques ; Male ; Middle Aged ; Muscle, Smooth, Vascular ; chemistry ; drug effects ; Nitric Oxide ; physiology ; Penile Erection ; physiology ; Penis ; chemistry ; drug effects ; Tyrosine ; analogs & derivatives ; analysis

OBJECTIVETo study the significance by analyzing the expression of angiopoietin-1 (Ang-1) and Angiopoietin-2 (Ang-2) in the tissues of squamous cell carcinoma (SCC) of the head and neck areas and in normal mucosa tissues.

METHODSThe expression of Ang-1 and Ang-2 in 45 tumor samples and 7 normal mucosa tissues were determined by the immunohistochemical method with avidin-biotin-peroxidase complex technique. The results were scored by two independent observers and analyzed statistically.

RESULTSThe positive expression of Ang-1 and Ang-2 existed in the endothelial cells, epithelial cells and also in SCC cells. The positive expression rates of Ang-1 in tumor samples was 78% in the endothelial cells, and 87% in SCC cells. The positive expression rates of Ang-2 in tumor samples was 69% in the endothelial cells, and 76% in SCC cells. The scores of positive expression of Ang-1 and Ang-2 were higher in endothelial cells and in SCC cells of tumor tissues than that of normal mucosa tissues (rank sum test, P < 0. 05). There was positive correlation between the expression of Ang-1 and Ang-2 in the endothelial cells and also in SCC cells (Chi-square test with contingency table, P < 0.05). Ang-1 expression in endothelial cells of tumor tissues was higher in clinical stage III-IV than that in clinical stage I-II (rank sum test, P < 0.05). Ang-2 expression in both endothelial cells and SCC cells, were higher in clinical stage II-IV than that in clinical stage I-II (rank sum test, P < 0.05). There was no statistical significance for degrees of Ang-1 and Ang-2 expression in different histological grades (P > 0.05).

CONCLUSIONSThe expressions of Ang-1 and Ang-2 in advanced SCC were remarkable. Ang-1 and Ang-2 may play a critical role during the progress of SCC of head and neck areas.

Adult ; Aged ; Angiopoietin-1 ; metabolism ; Angiopoietin-2 ; metabolism ; Carcinoma, Squamous Cell ; metabolism ; pathology ; Female ; Head and Neck Neoplasms ; metabolism ; pathology ; Humans ; Male ; Middle Aged ; Mouth Mucosa ; metabolism ; Neoplasm Staging ; Vascular Endothelial Growth Factor A ; metabolism