Short peptide alpha helices induced by multiple metal clips

Alpha helices are key structural components of proteins and important recognition motifs in biology. New techniques for stabilizing short peptide helices could be valuable for studying protein folding, modeling proteins, creating artificial proteins, and may aid the design of inhibitors or mimics of protein function.

Differences in ethical attitudes between registered nurses and medical students

In this study we compared the ethical attitudes of a group of experienced, predominantly female, registered nurses (n = 67) with those of a group of final year, mixed sex, medical students (n = 125). The purpose was to determine the basis of differences in attitudes that could lead to ethical disagreements between these two groups when they came to work together. A questionnaire developed to explore ethical attitudes was administered and the responses of the two groups were compared using t-tests. Because of the preponderance of females among the nurses an analysis of variance of the gender-adjusted scores for each group was also carried out. On comparing the responses, the nurses differed significantly from the medical students in a number of ethical domains. A potential source of conflict between these two groups is that the nurses were inclined to adopt the perspective of patients but the medical students identified with their profession. When corrected for the effects of gender, the differences persisted, indicating that it was discipline that determined the differences. We recommend that students of nursing and medicine receive ethics education together, and that more open dialogue between doctors and nurses with respect to their different ethical viewpoints is needed in the work setting. This article will be of interest to educators of students of medicine and nursing, as well as to doctors and nurses who are eager to improve their professional relations and thereby improve patient care.

A phase I biological and pharmacologic study of the heparanase inhibitor PI-88 in patients with advanced solid tumors

Purpose: PI-88 is a mixture of highly sulfated oligosaccharides that inhibits heparanase, an extracellular matrix endoglycosidase, and the binding of angiogenic growth factors to heparan sulfate. This agent showed potent inhibition of placental blood vessel angiogenesis as well as growth inhibition in multiple xenograft models, thus forming the basis for this study. Experimental Design: This study evaluated the toxicity and pharmacokinetics of PI-88 (80-315 mg) when administered s.c. daily for 4 consecutive days bimonthly (part 1) or weekly (part 2). Results: Forty-two patients [median age, 53 years (range, 19-78 years); median performance status, 1] with a range of advanced solid tumors received a total of 232 courses. The maximum tolerated dose was 250 mg/d. Dose-limiting toxicity consisted of thrombocytopenia and pulmonary embolism. Other toxicity was generally mild and included prolongation of the activated partial thromboplastin time and injection site echymosis. The pharmacokinetics were linear with dose. Intrapatient variability was low and interpatient variability was moderate. Both AUC and C-max correlated with the percent increase in activated partial thromboplastin time, showing that this pharmacodynamic end point can be used as a surrogate for drug exposure, No association between PI-88 administration and vascular endothelial growth factor or basic fibroblast growth factor levels was observed. One patient with melanoma had a partial response, which was maintained for >50 months, and 9 patients had stable disease for >= 6 months. Conclusion: The recommended dose of PI-88 administered for 4 consecutive days bimonthly or weekly is 250 mg/d. PI-88 was generally well tolerated. Evidence of efficacy in melanoma supports further evaluation of PI-88 in phase II trials.