Different effects of five depigmentary compounds,rhododendrol, raspberry ketone,monobenzone, rucinol and AP736 on melanogenesis and viability of human epidermal melanocytes

Numerous medications are used to treat hyperpigmentation. However, several reports have indicated that repeated application of some agents, such as rhododendrol (RD), raspberry ketone (RK) and monobenzone (MB), can be toxic to melanocytes. Although these agents had severe side effects in human trials, no current in vitro methods can predict the safety of such drugs. This study assessed the in vitro effects of five depigmentary compounds including leukoderma‐inducing agents. In particular, we determined the effects of different concentrations and exposure times of different depigmentary agents on cell viability and melanogenesis in the presence and absence of ultraviolet B (UVB) radiation. Concentrations of RD, RK and MB that inhibit melanogenesis are similar to concentrations that are cytotoxic; however, concentrations of rucinol (RC) and AP736 that inhibit melanogenesis are much lower than concentrations that are cytotoxic. Furthermore, the concentrations that cause toxic effects depend on exposure duration, and prolonged exposure to RD, RK and MB had more cytotoxic effects than prolonged exposure to RC and AP736. The cytotoxic effects of RD and RK appear to be mediated by apoptosis due to increased expression of caspase‐3 and caspase‐8; UVB radiation increased the cytotoxicity of these agents and also increased caspase activity. Our results indicate that different leukoderma‐inducing compounds have different effects on the viability of normal epidermal melanocytes and suggest that the in vitro assay used here can be used to predict whether an investigational compound that induces leukoderma may lead to adverse effects in human trials.     

Effects of Crede's method on urine voiding within the first 8 h after surgery among post‐haemorrhoidectomy patients: a comparison study

Urinary retention is a common complication among patients after haemorrhoidectomy. Although Crede's method is recommended for urinary retention in nursing practice textbooks, its effects require further examination. The purpose of this study was to investigate the rate of urine voiding within the first 8 h following haemorrhoidectomy and to examine the effects of Crede's method on this postoperative outcome. A two‐group comparison study was conducted. All participants were over 20 years of age, and each had undergone haemorrhoidectomy. Outcome measurements included patients' self‐reported urine voiding within 8 h of surgery, personal demographics and disease‐related data. Before the surgical procedure, participants were divided into Crede's group and non‐Crede's group, and written educational materials were given. Patients in the Crede's group were taught Crede's method for application in the event that they were unable to void urine after haemorrhoidectomy. The non‐Crede's group patients were taught traditional methods without Crede's method. We examined urine voiding within the first 8 h after haemorrhoidectomy. The mean rate of urine voiding within 8 h of surgery was 60·9% overall, with 91·3% (21/23) in the Crede's group and 30·4% (7/23) in the non‐Crede's group reporting successful voiding. After controlling for the two groups' personal characteristics and disease‐related variables, age, educational level and perioperative fluid administration were treated as covariates and included in the multinomial logistic regression model. The odds ratio of urine voiding within the first 8 h after surgery was 52·70‐fold higher in the Crede's group than in the non‐Crede's group (p < 0·01). This study shows that Crede's method is an effective strategy to aid in urine voiding within the first eight postsurgical hours among patients following haemorrhoidectomy. Clear and concise information about urinary retention and related management strategies should be given to patients before haemorrhoidectomy.     

Whiplash evokes descending muscle recruitment and sympathetic responses characteristic of startle

Whiplash injuries are the most common injuries following rear-end collisions. During a rear-end collision, the human muscle response consists of both a postural and a startle response that may exacerbate injury. However, most previous studies only assessed the presence of startle using data collected from the neck muscles and head/neck kinematics. The startle response also evokes a descending pattern of muscle recruitment and changes in autonomic activity. Here we examined the recruitment of axial and appendicular muscles along with autonomic responses to confirm whether these other features of a startle response were present during the first exposure to a whiplash perturbation. Ten subjects experienced a single whiplash perturbation while recording electromyography, electrocardiogram, and electrodermal responses. All subjects exhibited a descending pattern of muscle recruitment, and increasing heart rate and electrodermal responses following the collision. Our results provide further support that the startle response is a component of the response to whiplash collisions.     

Temporomandibular Joint Serial Sections Made with Mandible in Intercuspal Position

This article presents a method for preparing block sections of the human temporomandibular joint. The purpose of the study was to examine the relationship of the temporomandibular joint components without disturbing the anatomic arrangement of the parts. The mandibles of seven fresh cadavers were locked into a specific occlusal position (intercuspal) throughout all procedures. An acrylic embedding technique allowed serial sections in any plane without displacement or tearing of mineralized and soft tissues. Photographs were obtained using an Olympus transmitted light microscope with various magnifications from 1 × to 40 ×.     

Biomarker-based adaptive trials for patients with glioblastoma—lessons from I-SPY 2

The traditional clinical trials infrastructure may not be ideally suited to evaluate the numerous therapeutic hypotheses that result from the increasing number of available targeted agents combined with the various methodologies to molecularly subclassify patients with glioblastoma. Additionally, results from smaller screening studies are rarely translated to successful larger confirmatory studies, potentially related to a lack of efficient control arms or the use of unvalidated surrogate endpoints. Streamlining clinical trials and providing a flexible infrastructure for biomarker development is clearly needed for patients with glioblastoma. The experience developing and implementing the I-SPY studies in breast cancer may serve as a guide to developing such trials in neuro-oncology.     

Effect of Intra-Coronary Nicorandil Administration Prior to Reperfusion in Acute ST Segment Elevation Myocardial Infarction

Background Intravenous nicorandil infusion with percutaneous coronary intervention (PCI) has been reported to reduce reperfusion injury events and improve cardiac function in patients with acute myocardial infarction (MI). However, there is limited information on the use of intracoronary nicorandil. Methods and Results In the present study, 73 patients with acute ST segment elevation MI undergoing PCI were randomly assigned to the Nicorandil Group (n=37) or the Control Group (n=36). The composite endpoints were the incidences of ventricular arrhythmia, no-reflow and slow flow. A significant difference in the composite endpoint was observed in the Nicorandil Group when compared with the Control Group (p=0.037). The occurrence of post Thrombolysis In Myocardial Infarction (TIMI) grade 3 was significantly higher in the Nicorandil Group (p=0.019). Major adverse cardiac events during hospitalization and within 30 days of treatment were similar between the 2 groups. Conclusion Administration of intracoronary nicorandil reduced the occurrence of no-reflow, slow reflow, and reperfusion arrhythmia, and improved the myocardial perfusion grade, TIMI flow during PCI and improved clinical outcomes in patients with acute MI. (Circ J 2008; 72: 1425 - 1429).