The onset risk of carcinoma in patients continuing tacrolimus topical treatment for oral lichen planus: a case report.

Oral lichen planus is a chronic inflammatory mucocutaneous disease. Topical use of steroids and other immuno-modulating therapies have been tried for this intractable condition. Nowadays, tacrolimus ointment is used more commonly as a choice for treatment. However, a number of discussions have taken place after tacrolimus was reported to be carcinogenic. This report describes a patient who applied tacrolimus ointment to the lower lip after being diagnosed with oral lichen planus in 2008, and whose lesion developed squamous cell carcinoma in 2010. Since the relationship between tacrolimus and cancer development has been reported in only a few cases, including this case report, the clinician must be careful selecting tacrolimus as a second-line treatment for oral lichen planus.

Evaluation of postextraction bleeding incidence to compare patients receiving and not receiving warfarin therapy: a cross-sectional, multicentre, observational study.

OBJECTIVES: We investigated incidence and risk factors for postextraction bleeding in patients receiving warfarin and those not receiving anticoagulation therapy. DESIGN: Cross-sectional, multicentre, observational study. SETTING: 26 hospitals where an oral surgeon is available. PARTICIPANTS: Data on 2817 teeth (from 496 patients receiving warfarin, 2321 patients not receiving warfarin; mean age (SD): 62.2 (17.6)) extracted between 1 November 2008 and 31 March 2010, were collected. Warfarin-receiving patients were eligible when prothrombin time-international normalised ratio (PT-INR) measured within 7 days prior to the extraction was less than 3.0. INTERVENTIONS: Simple dental extraction was performed, and incidence of postextraction bleeding and comorbidities were recorded. PRIMARY AND SECONDARY OUTCOME MEASURES: Postextraction bleeding not controlled by basic haemostasis procedure was clinically significant. RESULTS: Bleeding events were reported for 35 (7.1%) and 49 (2.1%) teeth, of which 18 (3.6%) and 9 (0.4%) teeth were considered clinically significant, in warfarin and non-warfarin groups, respectively, the difference between which was 3.24% (CI 1.58% to 4.90%). The incidence rates by patients were 2.77% and 0.39%, in warfarin and non-warfarin groups, respectively (incidence difference 2.38%, CI 0.65% to 4/10%). Univariate analyses showed that age (OR 0.197, p=0.001), PT-INR (OR 3.635, p=0.003), mandibular foramen conduction anaesthesia (OR 4.854, p=0.050) and formation of abnormal granulation tissue in extraction socket (OR 2.900, p=0.031) significantly correlate with bleeding incidence. Multivariate analysis revealed that age (OR 0.126, p=0.001), antiplatelet drugs (OR 0.100, p=0.049), PT-INR (OR 7.797, p=0.001) and history of acute inflammation at extraction site (OR 3.722, p=0.037) were significant risk factors for postextraction bleeding. CONCLUSIONS: Our results suggest that there is slight but significant increase in the incidences of postextraction bleeding in patients receiving warfarin. Although absolute incidence was low in both groups, the bleeding risk is not negligible.

Histological analysis of the sublingual gland in rats with streptozotocin-induced diabetes.

This study was designed to examine whether the sublingual gland parenchyma is influenced by the development of insulin-dependent diabetes mellitus. The sublingual glands of rats with streptozotocin-induced diabetes were examined by light and electron microscopy. In order to define the limiting membrane of mucous granules in more detail, samples processed by rapid freezing following by freeze-substitution in addition to chemical fixation were also prepared for electron microscopy. Light and electron microscopy showed vacuole-like structures considered to be lipid droplets in the cytoplasm of serous demilune cells, the largest reaching 4 microm in diameter. Electron microscopy of the chemically fixed samples revealed granule-like structures in addition to the mucous granules proper in the mucous cell cytoplasm. However, electron microscopy of the freeze-substitution fixed samples demonstrated no limiting membrane on the surface of the granule-like structures, although this was clearly observed on the surface of the mucous granules. Accordingly, the granule-like structures present in the mucous cell cytoplasm appeared to be lipid droplets. These findings suggest that the sublingual gland mucous cells become dysfunctional during the development of insulin-dependent diabetes mellitus, although to a slighter degree than the serous demilune cells.

Expression and regulation of WISP2 in rheumatoid arthritic synovium.

Numbers of growth factors expressed in the synovium deeply impact on the pathology of rheumatoid arthritis (RA). The WISP family was identified as growth factors, which are upregulated by WNT signaling. In the present study, we investigated expression pattern and regulatory mechanisms of WISPs in the synovium in patients with RA and osteoarthritis (OA). Among three members of WISP family, WISP2 mRNA was only preferentially detected in RA synovium by RT-PCR. WISP2 expression was immunohistochemically identified in RA fibroblasts in an extensive fibrotic area. WNT signaling-activated (s/abeta-catenin-expressing) synovial fibroblasts upregulated WISP2 at 2.9-fold, but -inactivated (Deltabeta-catenin-expressing) cells downregulated the expression. Quantitative RT-PCR demonstrated that WISP2 expression was increased upon 17-beta-estradiol stimulation and synergistically enhanced by WNT signaling. These data demonstrate that the expression of WISP2 is synergistically upregulated in RA synovial fibroblasts by estrogen and WNT pathways, and suggest an involvement in the pathology of the disease.

Lymphocyte changes in peripheral blood, spleen, and liver in DMBA-induced squamous cell carcinoma of mouse cheek skin.

The peripheral blood, spleen, and liver lymphocyte subsets of mice with experimental cheek skin carcinoma were determined. The carcinoma was induced by the topical application of 2% (w/v) 9,10-dimethyl-1,2-benzanthracene (DMBA) to cheek skin twice a week for 12 weeks, and it was examined macroscopically and histopathologically. The composition of lymphocyte subsets (T cells, B cells, CD4+ single-positive [SP] T cells, and CD8+SP T cells) in peripheral blood, spleen, and liver was determined by flow cytometry at 3-week intervals for up to 24 weeks. Spleens and livers were assessed by determining their content of natural killer (NK)T cells. The results showed histopathological progression of the skin lesions from papilloma to squamous cell carcinoma at week 12. Body weight was significantly reduced from weeks 15 to 24, and spleen weight was significantly increased at weeks 21 and 24, but liver weight was not significantly different from the control. The lymphocyte subset composition of peripheral blood showed significant elevation of T cells at weeks 6 and 9, followed by reduced levels at weeks 21 and 24, with significant reduction of B cells at weeks 6 and 9, followed by elevation at weeks 21 and 24. CD4+SP T-cell content was elevated at weeks 6, 9, and 12, and reduced at weeks 21 and 24. CD8+SP T-cell content was significantly reduced at weeks 6, 9, and 12, and elevated at weeks 21 and 24. The composition of the lymphocyte subsets in the spleen was similar to their composition in peripheral blood. The composition of both T and B cells in the liver was significantly different from that in the corresponding control group, but no significant differences were found in either CD4+SP or CD8+SP T cells. These findings revealed that the DMBA-induced cheek skin carcinoma in mice affected not only the lymphocyte subsets in peripheral blood, but the cells in the spleen and liver as well.

Effect of streptozotocin-induced diabetes mellitus on alveolar bone deposition in the rat.

Effects of diabetes on alveolar bone remodelling were assessed by quantitative histology and a chronological lead-labelling technique. Experimental diabetes was induced by a single dose of 40 mg/kg of streptozotocin. Remodelling of the alveolar wall surrounding the root of mandibular first molar was studied in control rats fed ad libitum, and in diabetic and insulin-treated diabetic rats 24 days after the induction of diabetes. The volumes of bone formation on the mesial side of the alveolar wall were evaluated over a 10-day period by chronological lead-labelling and computer image analysis. For a histometric measure of bone-resorption, the number of osteoclasts along the distal surface of the alveolar wall was counted. The volume of bone formed and the number of osteoclasts were significantly lower in the diabetic rats than in the controls, but insulin treatment of diabetic rats normalised these histomorphometric measures of bone turnover. These results demonstrate that streptozotocin-induced diabetes mellitus reduces the rate of bone turnover in the alveolar wall surrounding the root, which reduction is corrected by treatment with insulin.