Effects of NCSTN Mutation on Hair Follicle Components in Mice.

BACKGROUND AND OBJECTIVES: Hidradenitis suppurativa (HS)/acne inversa is an intractable skin disease that is characterized by destructive lesions - primarily on the flexural areas. Although its etiology is unknown, genetics is considered to be a factor of its pathology - mutations in γ-secretase genes have been identified in certain familial HS patients, and follicular occlusion is widely accepted as the primary cause of HS. But, no relationship between these mutations and the components of hair follicles has been reported. Thus, we examined changes in these components in mice with a mutation in NCSTN (a γ-secretase gene). METHODS: We generated C57BL/6 mice with an NCSTN mutation and examined their expression of hair cortex cytokeratin and trichohyalin by Western blot and immunohistochemistry, in addition to nicastrin, the product of NCSTN, and NICD compared with wild-type mice. The structure of hair follicles was analyzed by hematoxylin-eosin staining and transmission electron microscopy. RESULTS: In mice with an NCSTN mutation, HS-like skin lesions appeared after age 6 months, the pathological manifestations of which were consistent with the features of human HS. The structure of hair follicles was abnormal in mice with an NCSTN mutation versus wild-type mice, and hair cortex cytokeratin, trichohyalin, nicastrin, and NICD were downregulated in these mice. CONCLUSIONS: This NCSTN mutant mouse model could be an improved model to study early lesion development aspects of human HS pathogenesis and could perhaps be a better alternative for evaluating early-acting and preventive therapeutics for HS experimentally before clinical trials in HS patients. NCSTN mutations disrupt the development of hair follicles, leading to abnormal hair follicle structures, perhaps resulting in the onset of HS.

Comparison of intravitreal injection of conbercept and triamcinolone acetonide for macular edema secondary to branch retinal vein occlusion.

AIM: To compare the safety and efficacy of the intravitreal injection of conbercept (IVC) and triamcinolone acetonide (IVTA) for macular edema (ME) secondary to branch retinal vein occlusion (BRVO). METHODS: A prospective, randomized clinical study. Patients with ME secondary to BRVO were randomly assigned to either IVC group or IVTA group at a ratio of 2:1 and a 12-month follow-up was performed. The efficacy outcome measures included the mean changes and differences in best corrected visual acuity (BCVA) and the central retinal thickness (CRT). The safety profiles and the mean retreatment intervals were also compared. RESULTS: There was no statistically significant difference of baseline between the two groups (IVC group, n=36; IVTA group, n=17). At 12mo, the BCVA letters improved by 27.31±18.36 in the IVC group, and 13.53±11.37 in the IVTA group (P=0.0004). CRT reduction was 253.33±163.69 and 150.24±134.32 µm, respectively (P=0.0034). The mean BCVA in the IVC group was superior to that of the IVTA group for months 6-12 (P<0.01). The mean CRT at 9 and 12mo were thinner in the IVC group compared to the IVTA group (P<0.01). The mean retreatment interval in the IVC group was longer than that in the IVTA group (97.40±36.27d vs 68.71±36.38d, P=0.0030). One eye in the IVC group and seven eyes in the IVTA group developed elevated intraocular pressure (IOP; P=0.0012). The proportion of eyes with cataract new-onset or progression were 19.44% in the IVC group and 64.71% in the IVTA group (P=0.0012). CONCLUSION: IVC could maintain or improve BCVA and reduce CRT for a longer time and have longer retreatment interval than IVTA. In addition, patients treated with IVTA are more susceptible to IOP elevation and cataract progression.

A randomized controlled trial of combination treatment with ketoconazole 2% cream and adapalene 0.1% gel in pityriasis versicolor.

BACKGROUND: Ketoconazole cream and adapalene gel are effective drugs against pityriasis versicolor. However, there are no reports on combination treatment with both compounds in pityriasis versicolor. OBJECTIVE: To evaluate the efficacy and safety of combination therapy with adapalene 0.1% gel and ketoconazole 2% cream against pityriasis versicolor. METHODS: Participants with pityriasis versicolor were randomly assigned to two groups: the combination group was treated with adapalene 0.1% gel and ketoconazole 2% cream once daily, and the monotherapy group received ketoconazole 2% cream twice daily. The treatment lasted 2 weeks in both groups. Outcomes were assessed at baseline and 1, 2 and 4 weeks after the initiation of treatment. RESULTS: We noted clinically significant differences in total improvement rates between groups Weeks 1 and 2. A statistically significant difference was obtained Week 4. The treatment was well tolerated by all participants. CONCLUSIONS: The combination of adapalene 0.1% gel and ketoconazole 2% cream is effective and safe in the treatment of pityriasis versicolor. This therapeutic regimen was rapid, providing a valuable option for patients with pityriasis versicolor.

Combination treatment of oral terbinafine with topical terbinafine and 10% urea ointment in hyperkeratotic type tinea pedis.

Hyperkeratotic-type tinea pedis is chronic and recalcitrant to topical antifungal agents. Some topical antifungal agents are effective; however, long duration of therapy is required, which often reduce the treatment compliance of patients. To seek for short period therapy of hyperkeratotic type tinea pedis, in this study, we observed the efficacy and safety of treatment of topical terbinafine and 10% urea ointment combined oral terbinafine. Participants with hyperkeratotic type tinea pedis were randomly assigned to two groups. Patients in group I were treated with oral terbinafine for 2 weeks and topical terbinafine and 10% urea ointment for 4 weeks, whereas in group II, only the above topical agents were applied for 12 weeks. Clinical improvement rates and fungal eradication rates were compared between the two groups at 24 weeks after the initiation of treatment. The group I had stopped the topical therapy 8 weeks earlier than group II. There were no significant differences in mycological eradication rates and clinical improvement rates between the two groups, besides, no major side effects were noted in both groups. The short combination therapy with oral terbinafine was effective and safe; it should be a valuable option for patients with hyperkeratotic type tinea pedis.

Roles of adapalene in the treatment of pityriasis versicolor.

BACKGROUND: Ketoconazole is a typical treatment available for pityriasis versicolor; tretinoin cream is effective, too. Adapalene gel is a tretinoin derivative and has a lower incidence of irritation compared with other topical retinoid products. However, there are no reports on adapalene gel for the treatment of pityriasis versicolor. OBJECTIVE: To study the effect of adapalene gel comparing the treatment with adapalene gel and 2% ketoconazole cream in pityriasis versicolor. METHODS: Eighty patients suffering from pityriasis versicolor were randomly divided into two groups; one group were treated with 2% ketoconazole cream topically twice daily for 2 weeks, adapalene gel was used for the other group in a similar fashion. RESULTS: There were no significant differences in efficacy between the two groups. No major side effects were noted in any of the groups either. CONCLUSION: Adapalene was the favorable option in the treatment of pityriasis versicolor. The probable therapeutic mechanism of adapalene is also discussed.