Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background There is an ongoing need for potent opioids with less adverse effects than commonly used opioids. R-dihydroetorphine is a full opioid receptor agonist with relatively high affinity at the μ-, δ- and κ-opioid receptors and low affinity at the nociception/orphanin FQ receptor. The authors quantified its antinociceptive and respiratory effects in healthy volunteers. The authors hypothesized that given its receptor profile, R-dihydroetorphine will exhibit an apparent plateau in respiratory depression, but not in antinociception. Methods The authors performed a population pharmacokinetic–pharmacodynamic study (Eudract registration No. 2009-010880-17). Four intravenous R-dihydroetorphine doses were studied: 12.5, 75, 125, and 150 ng/kg (infused more than 10 min) in 4 of 4, 6 of 6, 6 of 6, and 4 of 4 male subjects in pain and respiratory studies, respectively. The authors measured isohypercapnic ventilation, pain threshold, and tolerance responses to electrical noxious stimulation and arterial blood samples for pharmacokinetic analysis. Results R-dihydroetorphine displayed a dose-dependent increase in peak plasma concentrations at the end of the infusion. Concentration-effect relationships differed significantly between endpoints. R-dihydroetorphine produced respiratory depression best described by a sigmoid EMAX-model. A 50% reduction in ventilation in between baseline and minimum ventilation was observed at an R-dihydroetorphine concentration of 17 ± 4 pg/ml (median ± standard error of the estimate). The maximum reduction in ventilation observed was at 33% of baseline. In contrast, over the dose range studied, R-dihydroetorphine produced dose-dependent analgesia best described by a linear model. A 50% increase in stimulus intensity was observed at 34 ± 11 pg/ml. Conclusions Over the dose range studied, R-dihydroetorphine exhibited a plateau in respiratory depression, but not in analgesia. Whether these experimental advantages extrapolate to the clinical setting and whether analgesia has no plateau at higher concentrations than investigated requires further studies.

Serum zinc, copper, iron, and vitamin A levels were determined in patients with leprosy and healthy controls. Leprosy patients were classified according to the Ridley and Jopling classification and divided into two main groups as follows: tuberculoid, which consisted mainly of borderline tuberculoid patients and lepromatous, which consisted of borderline lepromatous and true lepromatous patients. The lepromatous group was found to have significantly lower serum levels of zinc and iron and elevated levels of copper. Vitamin A levels were also significantly lower in the lepromatous groups than in the tuberculoid group. Furthermore, the true lepromatous vitamin A determinations were significantly lower than those of the borderline lepromatous patients. The mechanism of these alterations in trace elements is probably due to a redistribution of these metals from the blood to various tissues; brought about by the release of leucocyte endogenous mediators by continuing phagocytosis of tissue macrophages in the lepromatous group of patients.

have some of the instability problems associated with the methods in which cerium (IV) or a cerium (IV) complex is the basis of the absorbance measurement.

Baboons were exposed to dust clouds of Ph3O4 of different size distribution but of the same total gravimetric concentration. Blood samples were taken immediately after each exposure of 4 hours and the total blood lead was determined. The exposure to the lead-bearing dust was stopped after four weeks, but the blood sampling continued for another six weeks. Graphs are presented comparing the patterns of lead absorption obtained with different sized lead particles. The coarser lead particles resulted in a higher blood lead concentration than the finer.