The peroxisome proliferator-activated receptors (PPARs) impart diverse cellular effects in biological systems. Because stellate cell activation during liver injury is associated with declining PPARgamma expression, we hypothesized that its expression is critical in stellate cell-mediated fibrogenesis. We therefore modulated its expression during liver injury in vivo. PPARgamma was depleted in rat livers by using an adenovirus-Cre recombinase system. PPARgamma was overexpressed by using an additional adenoviral vector (AdPPARgamma). Bile duct ligation was utilized to induce stellate cell activation and liver fibrosis in vivo; phenotypic effects (collagen I, smooth muscle alpha-actin, hydroxyproline content, etc.) were measured. PPARgamma mRNA levels decreased fivefold and PPARgamma protein was undetectable in stellate cells after culture-induced activation. During activation in vivo, collagen accumulation, assessed histomorphometrically and by hydroxyproline content, was significantly increased after PPARgamma depletion compared with controls (1.28 +/- 0.14 vs. 1.89 +/- 0.21 mg/g liver tissue, P < 0.03). In isolated stellate cells, AdPPARgamma overexpression resulted in significantly increased adiponectin mRNA expression and decreased collagen I and smooth muscle alpha-actin mRNA expression compared with controls. During in vivo fibrogenesis, rat livers exposed to AdPPARgamma had significantly less fibrosis than controls. Collagen I and smooth muscle alpha-actin mRNA expression were significantly reduced in AdPPARgamma-infected rats compared with controls (P < 0.05, n = 10). PPARgamma-deficient mice exhibited enhanced fibrogenesis after liver injury, whereas PPARgamma receptor overexpression in vivo attenuated stellate cell activation and fibrosis. The data highlight a critical role for PPARgamma during in vivo fibrogenesis and emphasize the importance of the PPARgamma pathway in stellate cells during liver injury.

Chemotherapy-induced alopecia (CIA) is a highly distressing event for cancer patients, and hence, we here aimed to assess the efficacy of various interventions in the prevention of CIA. We searched PubMed, EMBASE and the Cochrane Library, from June 20, 2013 through August 31, 2013. Two of the authors independently reviewed and selected clinical trials that reported the efficacy of any intervention for prevention of CIA compared with that of controls. Two authors extracted data independently on dichotomized outcome in terms of CIA occurrence. Relative risks (RRs) and 95% confidential intervals (CIs) were calculated for efficacy of CIA prevention by using random-effect or fixed-effect models. Out of 691 articles retrieved, a total of eight randomized controlled trials and nine controlled clinical trials involving 1,098 participants (616 interventions and 482 controls), were included in the final analyses. Scalp cooling, scalp compression, a combination of cooling and compression, topical minoxidil and Panicum miliaceum were used as interventions. The participants were mainly breast cancer patients receiving doxorubicin-or epirubicin-containing chemotherapy. Scalp cooling, which is the most popular preventive method, significantly reduced the risk of CIA (RR 5 0.38, 95% CI 5 0.32-0.45), whereas topical 2% minoxidil and other interventions did not significantly reduce the risk of CIA. No serious adverse effects associated with scalp cooling were reported. Our results suggest that scalp cooling can prevent CIA in patients receiving chemotherapy. However, the long-term safety of scalp cooling should be confirmed in further studies.Chemotherapy-induced alopecia (CIA) is a common and stressful adverse effect associated with chemotherapy. 1 CIA generally starts at 1-3 weeks after the first cycle of chemotherapy, and is aggravated after subsequent cycles. 2 Fortunately CIA is spontaneously recovered after 3-6 months in usual cases. 3 However, not a few patients suffer from permanent CIA, and many patients experience changes in hair color, texture and growth rate even after regrowth of hairs. 4 The occurrence and severity of CIA is dependent on the chemotherapeutic dose, administration schedule and other protocols. 5 Various cytotoxic chemotherapeutics can cause CIA. The chemotherapeutics target all rapidly proliferating cells, and consequently damage not only tumor cells but also the hair follicles. At any given time, approximately 90% of the hair follicles in the human scalp are in the anagen stage, and these hair matrix cells proliferate fast. The apoptosis of these cells caused by cytotoxic chemotherapeutics results in hair shedding, which is called anagen effluvium. 6 Although CIA is generally reversible 3-6 months postchemotherapy, it commonly causes psychosocial stress to the patients, including negative changes in body image, sexuality, self-esteem and disturbances in social relationships. The fear of hair loss and the associated distress may even result in cancer patients refusing proper chemotherapy treatment. 7 ...

Background: Low 25-hydroxyvitamin D (25(OH)D) concentrations have been shown to predict risk of cardiovascular disease and all-cause mortality. Although the prevalence of 25(OH)D deficiency is high in patients with acute stroke, the prognostic value of 25(OH)D in stroke has not been clearly established. The purpose of this study was to determine whether the baseline serum 25(OH)D level was associated with the functional outcome in patients with acute ischemic stroke. Methods: From June 2011 to January 2014, consecutive patients with acute ischemic stroke within 7 days of symptom onset were enrolled in this study from a prospectively maintained stroke registry. Serum 25(OH)D level was measured at admission. Clinical and laboratory data including stroke severity using the National Institute of Health Stroke Scale (NIHSS) score were collected during admission, and the functional outcome at 3 months was assessed by modified Rankin scale (mRS). The association between the baseline 25(OH)D level and a good functional outcome (mRS 0-2) at 3 months was analyzed by multiple logistic regression models. Results: A total of 818 patients were enrolled in this study. Mean age was 66.2 (±12.9) years, and 40.5% were female. The mean 25(OH)D level was 47.2 ± 31.7 nmol/l, and the majority of patients met vitamin D deficient status (<50 nmol/l; 68.8%), while an optimal vitamin D level (≥75 nmol/l) was present in only 13.6% of the patients, and 436 (53.3%) patients showed good functional outcome at 3 months. Serum 25(OH)D levels in patients with good outcomes were significantly higher than those with poor outcome (50.2 ± 32.7 vs. 43.9 ± 30.0 nmol/l, p = 0.007). The 3-month functional outcome was significantly associated with month-specific 25(OH)D quartiles in multivariable logistic regression analysis. After adjustment for age and sex, the highest 25(OH)D quartile group had higher tendency for good functional outcome at 3 months (odds ratio (OR) = 1.68, 95% confidence interval (CI) = 1.13-2.51). After fully adjusting for other potential confounders, such as stroke severity and vascular risk factors, the association was further strengthened with an OR (95% CI) of 1.90 (1.14-3.16). Other factors associated with good functional outcome in multivariable analysis were younger age, lower initial NIHSS score and absence of diabetes. Conclusions: This study suggests that serum 25(OH)D level is an independent predictor of functional outcome in patients with acute ischemic stroke. Further studies are required to determine whether vitamin D supplementation could improve functional outcome in patients with ischemic stroke.

We should be aware of melanoma development from GCMN, and lifelong follow-up is required due to the risk of melanoma arising in GCMN.