Antipruritic effect of the topical phosphodiesterase 4 inhibitor E6005 ameliorates skin lesions in a mouse atopic dermatitis model.

Phosphodiesterase (PDE) 4 inhibition is a well-known anti-inflammatory mechanism, but the development of PDE4 inhibitors has been hampered by side effects such as nausea and emesis. Local delivery of a PDE4 inhibitor to the site of inflammation may overcome these issues. The purpose of this study was to assess the therapeutic potential of E6005 (methyl 4-[({3-[6,7-dimethoxy-2-(methylamino)quinazolin-4-yl]phenyl}amino)carbonyl]benzoate), a novel PDE4 inhibitor developed as a topical agent for atopic dermatitis (AD). E6005 potently and selectively inhibited human PDE4 activity with an IC50 of 2.8 nM and suppressed the production of various cytokines from human lymphocytes and monocytes with IC50 values ranging from 0.49 to 3.1 nM. In mice models, the topical application of E6005 produced an immediate antipruritic effect as well as an anti-inflammatory effect with reduced expression of cytokines/adhesion molecules. On the basis of these observed effects, topical E6005 ameliorated the appearance of atopic dermatitis-like skin lesions in two types of AD models, hapten- and mite-elicited models, exhibiting inhibitory effects comparable to that of tacrolimus. The use of ¹4C-labeled E6005 showed rapid clearance from the blood and low distribution to the brain, contributing to the low emetic potential of this compound. These results suggest that E6005 may be a promising novel therapeutic agent with antipruritic activity for the treatment of AD.

Association of Psychological Readiness to Return to Sports With Subjective Level of Return at 12 Months After ACL Reconstruction.

Background: Return-to-sports (RTS) rates after anterior cruciate ligament (ACL) reconstruction (ACLR) differ according to the level at which patients return. It is unclear whether the level of RTS is affected by psychological readiness to return. Purpose: To examine the association between psychological readiness to RTS and subjective RTS level 12 months after ACLR. Study Design: Case-control study; Level of evidence, 3. Methods: A total of 47 patients who underwent unilateral primary ACLR surgery were enrolled. Assessments at 6 and 12 months postoperatively consisted of knee strength testing (isokinetic quadriceps and hamstring strength), the International Knee Documentation Committee Subjective Knee Evaluation Form (IKDC-SKF), and the Anterior Cruciate Ligament-Return to Sport after Injury (ACL-RSI) scale to measure psychological readiness to RTS. Patients were assigned to 1 of 3 subgroups based on their subjective assessment of RTS level at 12 months postoperatively: RTS at or above preinjury level (RTS≥Pre; n = 19), RTS below preinjury level (RTS

Psychological readiness at 9 months after anterior cruciate ligament reconstruction -which factors affect?

OBJECTIVE: To investigate the association of psychological readiness at 9 months after anterior cruciate ligament reconstruction (ACLR) with knee strength and range-of-motion (ROM) at 3 and 9 months postoperatively. DESIGN: Retrospective cohort study. SETTING: Private orthopedic hospital. PARTICIPANTS: Seventy-eight patients after ACLR. MAIN OUTCOMES MEASURES: The participants completed the anterior cruciate ligament-return to sport after injury (ACL-RSI) scale as an assessment of psychological readiness at 9 months after ACLR. Isometric and isokinetic quadriceps and hamstring strength were measured by a dynamometer at 3 and 9 months postoperatively. Knee extension and flexion ROM were measured in 5° increments with a standard goniometer at 3 and 9 months postoperatively. RESULTS: Univariate regression analysis showed that age, limb symmetry index (LSI) of quadriceps strength at 3 and 9 months, and knee extension ROM deficit (>5°) at 3 and 9 months were associated with ACL-RSI scores at 9 months (P < 0.05). Age and LSI of quadriceps strength at 3 months remained significant predictors of ACL-RSI scores at 9 months in multiple regression analysis (R2 = 0.20, P < 0.001). CONCLUSIONS: Early improvements in quadriceps strength after ACLR may have a positive impact on psychological readiness at 9 months postoperatively.

Enthalpy relaxation of freeze concentrated sucrose-water glass.

The enthalpy relaxation of freeze concentrated sucrose-water glass was investigated using 40% sucrose, differential scanning calorimetry (DSC) with isothermal ageing for 1-6 days at various temperatures (-70, -65, -60, and -55 degrees C). The enthalpy relaxation was observed as an endothermic peak superimposed on the endothermic step-wise change due to the glass transition around -47 degrees C. The enthalpy relaxation was found to increase with ageing time and temperature. An 80% sucrose glass was also investigated at ageing temperatures of -60 and -65 degrees C, and this material exhibited a similar glass transition and enthalpy relaxation to that observed with the frozen 40% sucrose solution. The calculated activation energy of the enthalpy relaxation of the sucrose-water glass was smaller than that reported for pure sucrose. These results suggest that the freeze concentrated sucrose-water glass could have a higher molecular mobility and less stability than pure sucrose glass.

Associative and segregative phase separations of gelatin/kappa-carrageenan aqueous mixtures.

The effects of ionic strength, temperature, and pH on the phase separation behavior of type B pigskin gelatin/sodium-type kappa-carrageenan aqueous mixtures were investigated. Depending on the different combinations of temperature and sodium chloride (NaCl) concentration, the mixtures showed compatible, associative, and segregative phase separation behaviors. Additionally, a coexistence of associative and segregative (associative-co-segregative) phase separations was expected at low temperature and low NaCl concentration. These different phase separation events were observed using confocal scanning laser microscopy. Moreover, it was found that the segregative phase separation when alone is induced by the ordering of kappa-carrageenan chains, while that in the coexistence region is induced by the ordering of gelatin chains. pH had a significant effect on the associative phase separation, resulting in morphologies changing from compatible solution to liquid coacervate and further to solid precipitate with decreasing pH. These were attributed to the dramatic changes of the charge density of amphoteric gelatin during the pH decrease.