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Background: Anti-cancer effects of cyclooxygenase (COX)-2 inhibitors have been reported, but not fully investigated in skin and oral diseases. 5-aminolaevulinic acid (ALA)-based photodynamic therapy (PDT) for treating those patients with skin and oral lesions is a highly sophisticated procedure, but the incidence of disease recurrence after treatment is rather significant., Objective: To confirm that COX-2 could be a molecular target in adjunctive therapy to ALA-based PDT, we investigated (i) COX-2 expression in various skin and oral diseases, and (ii) the inhibitory effects on cellular growth of COX-2 selective inhibitor (nimesulide), ALA-based PDT and their combination on human oral squamous cell carcinoma (SCC) cell lines., Methods: A total of 129 biopsy samples from the skin and oral mucosal lesions were tested immunohistochemically for COX-2 expression. Then the in vitro effects of nimesulide, ALA-based PDT, and their combination were determined on two SCC cell lines, HSC-2 and HSC-4. Three different methods (MTT assay, double-staining for annexin V and propidium iodide, caspase-3/CPP32 fluorometric protease assay) were applied for evaluation of their inhibitory effects on these two cell lines., Results: Among the skin diseases, a considerable number of COX-2 high expressers were found in actinic keratosis (15 of 25, 60%), Bowen's disease (13 of 17, 76%) and extramammary Paget's disease (15 of 15, 100%). In contrast, only one of 33 (3%) basal cell carcinoma tumours was a COX-2 high expresser. Among the oral mucosal biopsies, the proportion of COX-2 high expressers increased gradually from hyperplasia (one of six, 17%) through mild dysplasia (five of eight, 63%) and moderate dysplasia (20 of 23, 87%) to severe dysplasia (two of two, 100%). Nimesulide had an inhibitory effect in vitro on HSC-2 (proven to be a COX-2 high expresser), but not on HSC-4 (a COX-2 non-expresser). While ALA-based PDT showed an inhibitory effect on both HSC-2 and HSC-4, most importantly the combination of nimesulide and ALA-based PDT demonstrated a significant synergistic effect on the cellular growth inhibition of only HSC-2, but not of HSC-4., Conclusions: Our study strongly suggests that COX-2 can be one of the molecular targets in treating various skin and oral diseases. The results from our in vitro experiments also prompt us to develop a new protocol with a combination of COX-2 selective inhibitor and ALA-based PDT for more effective treatment of those diseases.

The participation of apoptotic cell death of neutrophils in the development of skin lesions of patients with anaphylactoid purpura was examined by the in situ specific labeling of fragmented DNA. In the early stage of the skin lesions, there were few positively stained nuclei in infiltrating cells. The number of positive cells increased markedly in the fully developed stage of the lesions. A number of neutrophils were stained positively. Finally, a few fragmented nuclei were still positive in the late stage of the lesions. It was therefore suggested that fragmentation of neutrophils in the skin lesions from the patients might be due to apoptosis. Inducible nitric oxide synthase and nitrotyrosine were detected in infiltrates, and interleukin-8 was also detected in vascular endothelial cells in those skin lesions. The roles of nitric oxide and interleukin-8 in the apoptosis of neutrophils are discussed.

We investigated the role of apoptotic cell death in the production of skin lesions in patients with acquired zinc deficiency. Nuclear condensation of keratinocytes was observed at an early stage of skin lesions in patients with zinc deficiency, especially around vesicular lesions. Nuclei of keratinocytes in perivesicular lesions of the epidermis were positively stained by the nick-end labeling specific for fragmented DNA. Lewis Y antigen was also expressed on perivesicular lesions. On the other hand, there were no such positively stained cells in hyperkeratotic skin lesions of the patients. Therefore, it was suggested that apoptotic cell death might play a role in the formation of vesicular skin lesions in patients with zinc deficiency, but not in the formation of hyperkeratotic skin lesions.

Background/purpose: Topical 5-aminolevulinic acid (ALA)-based photodynamic therapy (PDT) is effective for actinic keratosis (AK); few studies have examined Oriental patients. The aim of this study is to assess the efficacy of PDT for the treatment of Japanese AK patients classified by lesion size and histological severity. Methods: Thirty patients with solitary AK lesions were divided into two groups according to diameter: a small lesion group (SL), diameter ≤10 mm and a larger lesion group (LL), diameter >10 mm, and histological severity: Group I (mild and moderate) and Group II (severe). After application of 20% ALA for 4 h, exposure to an excimer-dye laser at 630 nm was performed at a dose of 50 J/cm2 three times at an interval of 7 days. Therapeutic effects were assessed and followed for 12 months. Results: In all 10 SL patients, atypical cells disappeared after PDT and did not recur for 12 months. However, for the 20 LL patients, recurrence was seen in 2 of the 14 Group I patients, while 4 of 6 Group II patients showed residual tumor cells after the first PDT session. Conclusion: The present study demonstrated that ALA-PDT might be useful for treatment of Japanese AK. The therapeutic outcome might depend on the lesion size and the histopathological severity. [ABSTRACT FROM AUTHOR]

Pitted keratolysis (PK) has been reported to be more common among bare-footed people living in tropical regions. It is now known that the disease is not limited to the tropics but has a world-wide distribution. However, no study has previously been performed analysing the clinical manifestations of the disease in temperate countries. A survey of 53 patients revealed several distinctive clinical features. Hyperhidrosis is the most frequently observed symptom of this condition. Malodour and sliminess of the skin are also distinctive features, evident in 88.7% and 69.8% of the cases. respectively. The most common sites of onset of PK are the pressure-bearing areas, such as the ventral aspect of the toe. the ball of the loot and the heel. The next most common site is a friction area, the interface of the toes. Lesions are rarely seen on the non-pressure-bearing locations. Some of the primary lesions originate as a small defect along the plantar furrow. which gradually grows into the characteristic crateriform pit. Several clinical features arc helpful in diagnosing PK. [ABSTRACT FROM AUTHOR]

Describes a case of dermatitis herpetiformis Duhring (DH) with palmoplantar keratosis in a Japanese man. Symptoms; Diagnosis; Clinical pathology; Patient's adherence to a gluten-free diet for two weeks; Treatment.

The article discusses a case study of a 43-year-old Japanese female patient with rheumatoid arthritis who developed pemphigus vulgaris (PV) during treatment with antirheumatic agent bucillamine. Topics discussed include the appearance of erythematous macules with vesiculated or erosive lesions on the patient's body, the frequent development of pemphigus in patients being treated with drugs containing thiol compounds, and the use of the oral drug prednisolone to treat the PV in this case.