Effective treatment for sensitive skin: 4-t-butylcyclohexanol and licochalcone A.

BACKGROUND: More than 50% of adults report to suffer from sensitive skin. This common condition is characterized by subjective sensations such as prickling, burning, skin tightness or pruritus, and is often accompanied by objective symptoms like inflammation and erythema. OBJECTIVE: The objective of this study was to develop an active ingredient concept for the treatment of sensitive skin. We tested compounds regarding their potential to (i) decrease the release of proinflammatory mediators, which among others induce erythema and (ii) counteract the hyperresponsiveness of nerve fibres and, thus, exert effects on cutaneous neurosensory dysfunction. METHODS: 4-t-butylcyclohexanol, licochalcone A and acetyl dipeptide-1 cetyl ester were analysed in vitro regarding their potential to (i) decrease the release of PGE2 and activation of NFκB and to (ii) inhibit TRPV1 activation or the release of neuronal CGRP. To assess subjective and objective symptoms of skin sensitivity in vivo, two controlled, single-blind, randomized studies were conducted with 4-t-butylcyclohexanol and the combination with licochalcone A. RESULTS: In vitro, 4-t-butylcyclohexanol significantly reduced TRPV1 activation, while acetyl dipeptide-1 cetyl ester had no effect on receptor activation. Licochalcone A significantly decreased NFκB signalling and PGE2 secretion, at lower concentrations than acetyl dipeptide-1 cetyl ester. A formulation containing 4-t-butylcyclohexanol showed a significant immediate anti-stinging/anti-burning effect in vivo, and a cream base containing a combination of 4-t-butylcyclohexanol and a licochalcone A-rich licorice extract reduced shaving-induced erythema. CONCLUSION: In vitro and in vivo data indicate that the combination of the TRPV1 antagonist 4-t-butylcyclohexanol and the potent anti-inflammatory licochalcone A provide an effective active ingredient concept for the treatment of sensitive skin, as the topical application resulted in an immediate relief from symptoms such as erythema and stinging.

Comparison of skin calming effects of cosmetic products containing 4-t-butylcyclohexanol or acetyl dipeptide-1 cetyl ester on capsaicin-induced facial stinging in volunteers with sensitive skin.

OBJECTIVE: To assess and compare the skin calming effect of cosmetic products containing 4-t-butylcyclohexanol (Eucerin(®) UltraSensitive Soothing Care Dry Skin) or acetyl dipeptide-1 cetyl ester (La Roche-Posay Toleriane(®) Ultra Intense Soothing Care) on subjective symptoms of skin sensitivity, a controlled, single-blind, randomized split-face capsaicin-induced stinging test was conducted. METHODS: Thirty-one female test subjects, ranging from 19 to 65 years of age, with self-perceived sensitive to very sensitive skin were enrolled. After a 3-day preconditioning period with no application of facial products and positive reaction to stimulation with a 40 ppm capsaicin cream, the test products were randomly applied to either the right or left nasolabial fold. Burning severity was assessed immediately after capsaicin application, and 1, 2, 5, 10 and 15 min after application of the test products. RESULTS: All 31 subjects reported a stinging/burning sensation on both nasolabial folds after application of capsaicin. Treatment with the 4-t-butylcyclohexanol containing product resulted in significant lower values for burning/stinging after one, and two minutes post-application in comparison to the values for the acetyl dipeptide-1 cetyl ester containing product. No significant difference was determined between the two test products for the point in time with most intense burning sensation, the severity of burning and the duration of burning after capsaicin application and subsequent application of the test products. CONCLUSION: Both products alleviated capsaicin-induced burning during the first 15 min after application. A faster and more pronounced soothing effect in vivo was demonstrated for the 4-t-butylcyclohexanol containing cosmetic product in comparison to the acetyl dipeptide-1 cetyl ester containing cosmetic formulation.

p34 is a novel regulator of the oncogenic behavior of NEDD4-1 and PTEN.

PTEN is one of the most frequently mutated or deleted tumor suppressors in human cancers. NEDD4-1 was recently identified as the E3 ubiquitin ligase for PTEN; however, a number of important questions remain regarding the role of ubiquitination in regulating PTEN function and the mechanisms by which PTEN ubiquitination is regulated. In the present study, we demonstrated that p34, which was identified as a binding partner of NEDD4-1, controls PTEN ubiquitination by regulating NEDD4-1 protein stability. p34 interacts with the WW1 domain of NEDD4-1, an interaction that enhances NEDD4-1 stability. Expression of p34 promotes PTEN poly-ubiquitination, leading to PTEN protein degradation, whereas p34 knockdown results in PTEN mono-ubiquitination. Notably, an inverse correlation between PTEN and p34/NEDD4-1 levels was confirmed in tumor samples from colon cancer patients. Thus, p34 acts as a key regulator of the oncogenic behavior of NEDD4-1 and PTEN.

Fungal peri-prosthetic joint infection after primary total knee replacement.

We retrospectively reviewed 30 two-stage revision procedures in 28 patients performed for fungal peri-prosthetic joint infection (PJI) after a primary total knee replacement. Patients were followed for at least two years or until the infection recurred. The mean follow-up for patients who remained free of infection was 4.3 years (2.3 to 6.1). Overall, 17 patients were assessed as American Society of Anesthesiologists grade 3 or 4. The surgical protocol included removal of the infected implant, vigorous debridement and insertion of an articulating cement spacer. This was followed by at least six weeks of antimicrobial treatment and delayed reimplantation in all patients. The mean interval between removal of the prosthesis and reimplantation was 9.5 weeks (6 to 24). After reimplantation, patients took antifungal agents orally for a maximum of six months. Two knees became reinfected at one and two months post-operatively, respectively: one of these subsequently required arthrodesis because of uncontrolled infection. Fungal PJIs can be treated successfully by removal of all infected material, appropriate antimicrobial treatment and delayed reimplantation.

Morphological changes of the lateral meniscus in end-stage lateral compartment osteoarthritis of the knee.

OBJECTIVE: The aim of this study was to evaluate the morphological changes of the lateral meniscus in end-stage lateral compartment osteoarthritis (OA) of the knee. METHODS: One hundred fifty-eight knee joints from 133 patients that subsequently underwent total knee joint arthroplasty from January 2008 to December 2009 were enrolled. There were 26 men and 107 women. Their ages ranged from 56 to 81 (mean 67.4 ± 6.5 years). All study participants had complete obliteration of the lateral joint space identified by weight-bearing radiography. Meniscal position was assessed by measuring meniscal subluxation and meniscal height. The meniscal morphology was assessed using a modification of the whole-organ magnetic resonance imaging score (WORMS). The frequency of different meniscal morphology and their respective positions was calculated. RESULTS: The predominant type (42.4%, 53.8% and 52.5% in the anterior horn, mid-body and posterior horn, respectively) of abnormal meniscal morphology was a complete maceration/destruction or complete resection. The anterior horn of non-macerated lateral meniscus was more subluxed than that of the non-macerated medial meniscus in patients with lateral OA. CONCLUSION: This study suggests that the lateral meniscus in persons with end-stage lateral OA are mostly macerated or destroyed. Also, unlike isolated end-staged medial compartment OA, the anterior horn of the lateral meniscus in isolated end-stage lateral OA is commonly affected.

The prevalence of cam-type femoroacetabular deformity in asymptomatic adults.

We performed a retrospective examination of the anteroposterior pelvic CT scout views of 419 randomly selected patients between April 2004 and August 2009 in order to determine the prevalence of cam-type femoroacetabular deformity in the asymptomatic population. The CT scans had all been undertaken for conditions unrelated to disorders of the hip. The frequency of cam-type femoroacetabular deformity was assessed by measuring the α-angle of each hip on the anteroposterior images. The α-angles were classified according to the Copenhagen Osteoarthritis Study. Among 215 male hips (108 patients) the mean α-angle was 59.12° (37.75° to 103.50°). Of these, a total of 30 hips (13.95%) were defined as pathological, 32 (14.88%) as borderline and 153 (71.16%) as normal. Among 540 female hips (272 patients) the mean α-angle was 45.47° (34.75° to 87.00°), with 30 hips (5.56%) defined as pathological, 33 (6.11%) as borderline and 477 (88.33%) as normal. It appears that the cam-type femoroacetabular deformity is not rare among the asymptomatic population. These anatomical abnormalities, as determined by an increased α-angle, appear to be twice as frequent in men as in women. Although an association between osteoarthritis and femoroacetabular impingement is believed to exist, a long-term epidemiological study is needed to determine the natural history of these anatomical abnormalities.

Serum cystatin C is an independent predictor of total homocysteine levels in stable Korean renal transplant recipients with normal serum creatinine.

OBJECTIVES: To examine the determinants of fasting plasma total homocysteine (tHcy) levels such as cystatin C, serum creatinine (SCr), estimated glomerular filtration rate (GFR) from Cockroft-Gault equation, albumin, plasma folate, vitamin B12, and pyridoxal-5'-phosphate (PLP) among Korean renal transplant recipients (RTR) with normal SCr levels (< or =1.4 mg/dL). DESIGN: Cross-sectional study. SETTING: Nephrology and Transplant Service, Catholic University Kangnam St. Mary's Hospital, Seoul, Korea. PARTICIPANTS: Fifty-one chronic stable Korean RTR with normal SCr levels (< or =1.4 mg/dL) 6 months or more following transplantation. MEASURES: Medical record review, anthropometric measurements, and overnight (10 to 14 hours) fasting blood samples for measurement of plasma tHcy, folate, vitamin B12, PLP, SCr, albumin, and cystatin C. RESULTS: General linear regression model including age, gender, vitamin status, and measurements of renal function showed that cystatin C and folate were independent predictors of tHcy levels. The partial regression coefficient for folate was -0.444 (P <.01) and for cystatin C, it was +0.334 (P <.05). SCr, estimated GFR, vitamin B12, PLP, age, and gender were not independent predictors of tHcy levels in this model. CONCLUSION: Both cystatin C and folate status were major independent determinants of fasting tHcy levels in the subgroup of Korean RTR with normal SCr.