A low-risk ZnT-8 allele (W325) for post-transplantation diabetes mellitus is protective against cyclosporin A-induced impairment of insulin secretion.

SLC30A8 encodes the ß-cell-specific zinc transporter-8 (ZnT-8) expressed in insulin secretory granules. The single-nucleotide polymorphism rs13266634 of SLC30A8 is associated with susceptibility to post-transplantation diabetes mellitus (PTDM). We tested the hypothesis that the polymorphic residue at position 325 of ZnT-8 determines the susceptibility to cyclosporin A (CsA) suppression of insulin secretion. INS (insulinoma)-1E cells expressing the W325 variant showed enhanced glucose-stimulated insulin secretion (GSIS) and were less sensitive to CsA suppression of GSIS. A reduced number of insulin granule fusion events accompanied the decrease in insulin secretion in CsA-treated cells expressing ZnT-8 R325; however, ZnT-8 W325-expressing cells exhibited resistance to the dampening of insulin granule fusion by CsA, and transported zinc ions into secretory vesicles more efficiently. Both tacrolimus and rapamycin caused similar suppression of GSIS in cells expressing ZnT-8 R325. However, cells expressing ZnT-8 W325 were resistant to tacrolimus, but not to rapamycin. The Down's syndrome candidate region-1 (DSCR1), an endogenous calcineurin inhibitor, overexpression and subsequent calcineurin inhibition significantly reduced GSIS in cells expressing the R325 but not the W325 variant, suggesting that differing susceptibility to CsA may be due to different interactions with calcineurin. These data suggest that the ZnT-8 W325 variant is protective against CsA-induced suppression of insulin secretion. Tolerance of ZnT-8 W325 to calcineurin activity may account for its protective effect in PTDM.

Comparison of higher dose and lower dose ganciclovir for cytomegalovirus prophylaxis in seropositive heart transplant recipients.

BACKGROUND: We performed a retrospective historical cohort study to compare the efficacy of higher dose (HD, 10 mg/kg/day for 2 weeks, followed by 5 mg/kg/day intravenously for 2 weeks) and lower dose (LD, 5 mg/kg/day for 4 weeks) ganciclovir (GCV) for cytomegalovirus (CMV) prophylaxis in seropositive heart transplant recipients. METHODS: All consecutive patients undergoing heart transplantation (HT) between June 1999 and January 2008 at our institution were enrolled. All recipients were seropositive for CMV before HT. Before October 2005, 72 patients received the HD regimen and after October 2005, 36 patients received the LD regimen. We followed up all patients for 1 year. RESULTS: In the HD group 43 of 72 patients (60%) developed CMV infections vs. 21 of 36 patients (58%) in the LD group (P=0.89). CMV diseases occurred in 4 patients of the HD group (6%) and 4 patients of the LD group (11%) (P=0.44). The incidence of acute rejection was not significantly different between the 2 groups (14% vs. 6%; P=0.33). Among patients who completed 4-week courses of prophylaxis, 32 of 58 patients (55%) in the HD group developed CMV infections vs. 18 of 30 patients (60%) in the LD group (P=0.66). CMV diseases occurred in 3 patients of the HD group (5%) and 4 of the LD group (13%) (P=0.22). Acute rejection incidence did not differ significantly between the 2 groups (17% vs. 7%; P=0.21). CONCLUSIONS: LD GCV for CMV prophylaxis may not be inferior to the HD regimen in seropositive HT recipients.

Electrical measurement of moisturizing effect on skin hydration and barrier function in psoriasis patients.

Transepidermal water loss (TEWL) in psoriatic skin lesions seems to be related to the severity of the psoriasis, and the electrical capacitance and conductance of the skin are indicators of the hydration level of the stratum corneum. We compared the characteristics of these electrical measurements, in assessing the persistent effect of a moisturizing cream on skin hydration and barrier function in psoriasis patients. Seventeen Korean psoriasis patients were recruited. Their right leg was treated with the moisturizer twice daily for 6 weeks, while their left leg was used as the control site. For each patient, one psoriatic plaque on each leg was selected as the involved psoriatic lesion. Uninvolved psoriatic skin was regarded as the apparently healthy looking skin 4-5 cm away from the periphery of the psoriatic lesion. The TEWL, electrical capacitance and conductance were measured, in order to evaluate the barrier function and hydration level of the stratum corneum. The clinical and biophysical data for each patient were recorded at the start of the study and after 2, 4 and 6 weeks. The degree of skin dryness at the applied area improved progressively. The electrical capacitance at the treated psoriatic lesion increased significantly after 2 weeks, and this improvement was maintained during the entire study period. However, no noticeable change was observed in the electrical conductance. The TEWL showed an inverse pattern to that of the skin capacitance, decreasing during the study period. The skin capacitance and TEWL exhibited good correlation with the visual assessment of skin dryness, but the skin conductance did not. Our data suggest that electrical capacitance and TEWL may be useful in the evaluation of the effect of a moisturizer on the hydration status and barrier function of psoriatic skin.

Quantitative assessment of narrow-band UVB induced tanning during phototherapy in Korea.

BACKGROUND/PURPOSE: Narrow-band (TL-01) UVB lamps are being increasingly used for phototherapy of psoriasis and other dermatoses, for their excellent effect compared with broad-band UVB sources. Many patients receiving phototherapy have complained about the tanning effect of ultraviolet radiation especially in dark-skinned ones. So we wished to know the degree of pigmentation induced by phototherapy during narrow-band UVB treatment. METHODS: A total of 20 psoriasis patients receiving narrow-band UVB phototherapy were included in this study. A Minolta spectrophotometer CM-2002 was used to measure pigmentation. All patients were evaluated for skin color every seventh day for 7 weeks. The L* value (luminance) gives information about the relative lightness ranging from total black to pure white. The a* value represents the balance between red and green, and the b* value between yellow and blue. RESULTS: The L* values which indicate luminance decreased continuously until the 5th week, when maximum tanning was obtained. Afterwards minimal change was observed until the 7th week. The change of a* and b* values also showed the pattern that was compatible with the above results. The mean individual typology angle of our subjects was 41.9 degrees, which indicated they fell into "light" group of constitutional skin color category. CONCLUSION: From this study, we found that pigmentation induced by narrow-band UVB phototherapy increased continuously until the 5th week and then did not progress. Our results provide standard data of skin pigmentation during narrow-band UVB phototherapy in Korean brown skin.

Epstein-Barr virus-associated peripheral T-cell lymphoma in adults with hydroa vacciniforme-like lesions.

We describe two Korean adult patients who had necrotizing papulovesicles mainly on their faces. Skin biopsy specimens showed perivascular and periadnexal infiltrate of atypical lymphoid cells with vasculitis in the dermis and subcutaneous tissue. In situ hybridization demonstrated a latent infection of Epstein-Barr virus in the majority of lymphoid cells in the dermis. These patients were diagnosed as having T-cell lymphoma. Interestingly, large granular lymphocytosis was found in the peripheral blood of Case 2.