Difamilast, a selective phosphodiesterase 4 inhibitor, ointment in paediatric patients with atopic dermatitis: a phase III randomized double-blind, vehicle-controlled trial.

BACKGROUND: In atopic dermatitis (AD), phosphodiesterase 4 (PDE4) inhibition reduces proinflammatory mediators and cytokines. Difamilast is a new selective PDE4 inhibitor. OBJECTIVES: To demonstrate the superiority of topical difamilast to vehicle in Japanese paediatric patients with AD. METHODS: This was a phase III randomized, double-blind, vehicle-controlled trial. Patients aged 2-14 years with an Investigator Global Assessment (IGA) score of 2 or 3 received difamilast 0·3% (n = 83), difamilast 1% (n = 85) or vehicle (n = 83) ointment twice daily for 4 weeks. RESULTS: The primary endpoint was the percentage of patients with an IGA score of 0 or 1 with improvement by at least two grades at week 4. The success rates in IGA score at week 4 were 44·6%, 47·1% and 18·1% in the difamilast 0·3%, difamilast 1% and vehicle groups, respectively. Both difamilast groups demonstrated significantly higher success rates in IGA score compared with vehicle at week 4 [difamilast 0·3% (P < 0·001); difamilast 1% (P < 0·001)]. Regarding secondary endpoints, improvements in Eczema Area and Severity Index (EASI; improvement of ≥ 50%, ≥ 75% and ≥ 90% in overall score) at week 4 were significantly higher in patients in the difamilast 0·3% and 1% groups than those in the vehicle group. EASI score in the difamilast 0·3% and 1% groups was significantly reduced compared with that of patients in the vehicle group at week 1. The significant difference between both the difamilast groups and the vehicle groups was maintained from week 1 through to week 4. Most treatment-emergent adverse events were mild or moderate, and no serious events or deaths were reported. CONCLUSIONS: Difamilast 0·3% and 1% ointments are superior to vehicle and well tolerated in Japanese paediatric patients with AD.

Liposomes incorporating essential oil of Brazilian cherry (Eugenia uniflora L.): characterization of aqueous dispersions and lyophilized formulations.

Multilamellar liposomes incorporating essential oil of Brazilian cherry (Eugenia uniflora L.) leaves were produced by dry film hydration. Gas chromatography demonstrated the compounds found in the essential oil were effectively incorporated in the aqueous dispersions of liposomes. Differential scanning calorimetry analyses revealed the incorporation of the essential oil did not cause phase separation in the membrane structure; the gel-liquid crystalline transition temperature (main transition) remained the same despite the higher heterogeneity indicated by the transition peak broadening. Different cryoprotectors (sucrose and trehalose) were added to the liposomal formulations to be tested in their ability to protect the liposomal structure during the lyophilization. The morphological aspect of the lyophilized powders analysed by scanning electron microscopy showed significant differences among the samples with and without cryoprotectors. Fourier-transform infrared spectroscopy indicated the cryoprotectors interacted effectively with the polar heads of phospholipids in the bilayer. In terms of water absorption, trehalose was identified as a much more effective protector agent against it than sucrose. The cryoprotectors showed different degrees of effectiveness of preservation of the liposomal structure when the rehydration assays of lyophilized liposomes were carried out, as particle size measurements indicated a moderate process of fusion when the formulations with sucrose were rehydrated.

[A study on cervical cerclage for a dilated cervix or bulging membranes without rupture of membranes].

During the period January 1, 1989 through December 31, 1991, one hundred thirty-six pregnant women with an effaced and widely dilated cervix or with bulging membranes were treated by emergent cervical cerclage. Suturing was carried out in 16 women before 20 weeks gestation, in 86 women between 20 and 28 weeks and in 34 women after 28 weeks. 16 patients in group A were those whose pregnancy was terminated with 3 days after operation and their tocolysis index was significantly higher than that of 69 patients in group D, whose pregnancy was prolonged move than two weeks. Clinical chorioamnionitis (WBC > 15,000/mm3 and CRP > 2mg/dl) was occurring in 43.7% of patients in group A, compared with 8.7% in group D at the time of operation. Vaginal delivery was accomplished in 38 patients at between 24 and 36 weeks gestation in our hospital, while 41 cesarean sections were performed. On the basis of these results, we conclude that the emergency cerclage operation may improve the outcome of pregnancy but we have to pay special attention to premature rupture of membranes and chorioamnionitis.

Laparoscopic treatment of ectopic pregnancies--reports of two cases.

Two cases with ectopic pregnancy were successfully treated by laparoscopic injection of methotrexate (MTX). Case 1: A 29 year-old housewife was laparoscopically treated with a 15 mg MTX injection to the left Fallopian tube. After the laparoscopy, the human chorionic gonadotropin (HCG) was reduced to the normal range. Case 2: A 34 year-old housewife was also laparoscopically treated with a 35 mg MTX injection to the right Fallopian tube. After the laparoscopy, the HCG was quickly reduced to the normal range. The endoscopic approach can be used as the surgical treatment of choice for ectopic pregnancies.

An experimental model for advanced ovarian cancer.

Intraperitoneally transplanted tumors implanted and began developing with ascites in about 62% of the female rats within 4 to 6 weeks after transplantation. The tumor used in this study was an adenocarcinoma and which originated from a primary ovarian cancer in rats of the same strain (Wistar). The morphology and biological behavior of the tumor were very similar to the tumor in humans. Moreover, the preliminary results with cisplatin therapy indicate that intraperitoneal cancer corresponding to stage III or IV in the FIGO classification is a promising model for experimental therapeutic studies of common epithelial carcinoma at an advanced stage.

[Effects of anticancer agents on 7, 12-dimethylbenz (a) anthracene induced rat ovarian cancer cell line (DMBA-OC-1) and human ovarian serous adenocarcinoma cell line (KOC-1S)].

The antitumor activities of five anticancer drugs, at IC50 dosages cisplatin (CDDP), adriamycin (ADM), etoposide (VP-16), mitomycin C (MMC) and carboplatin (CBDCA) were studies an 7,12-dimethylbenz (a) anthracene induced rat ovarian cancer cell line (DMBA-OC-1) and a human ovarian serous adenocarcinoma cell line (KOC-1S). The IC50 dosage of anticancer drugs for DMBA-OC-1 was: CDDP 0.2 microgram/ml. ADM 0.04 microgram/ml, VP-16 3.0 microgram/ml, MMC 0.1 microgram/ml and CBDCA 10.0 micrograms/ml. The results of our study except those for MMC were parallel with those published on in vivo studies. The IC50 dosages of DMBA-OC-1 did not have enough antitumor activity for KOC-1S, whereas the original KOC-1S tumor strongly resisted the combination chemotherapy (CDDP, ADM and cyclophosphamide). Therefore, our findings suggested the possibility of the separation of multiple drug resistant clones from KOC-1S. These two cell lines had quite different antitumor activity characteristics.