QUANTITATIVE IN VITRO STUDIES ON STIMULATION OF MURINE HAEMOPOIETIC CELLS BY COLONY STIMULATING FACTOR

A new standardization method for Colony Stimulating Factor (CSF) is described and criteria are introduced which enables stimulating activity to be assessed independent of absolute colony numbers. With this method CSF preparations from different sources are compared and evidence is presented that suggests an identical mechanism of action for these substances. Data are presented on the increase in colony numbers that is induced by the addition of erythrocyte lysates to the cultures. The relationship between colony forming cells that are stimulated by CSF alone and cells stimulated by the combined action of CSF and erythrocyte lysate is discussed.     

Weight Loss,HbA1c Reduction,and Tolerability of Cetilistat in a Randomized,Placebo‐controlled Phase 2 Trial in Obese Diabetics: Comparison With Orlistat (Xenical)

The objective of this multicenter, randomized, double‐blind study was to determine the efficacy and safety of cetilistat and orlistat relative to placebo in obese patients with type 2 diabetes, on metformin. Following a 2‐week run‐in, patients were randomized to placebo, cetilistat (40, 80, or 120 mg three times daily), or orlistat 120 mg t.i.d., for 12 weeks. The primary endpoint was absolute change in body weight from baseline. Secondary endpoints included other measures of obesity and glycemic control. Similar reductions in body weight were observed in patients receiving cetilistat 80 or 120 mg t.i.d. or 120 mg t.i.d. orlistat; these reductions were significant vs. placebo (3.85 kg, P = 0.01; 4.32 kg, P = 0.0002; 3.78 kg, P = 0.008). In the 40 mg t.i.d. and placebo groups, reductions were 2.94 kg, P = 0.958 and 2.86 kg, respectively. Statistically significant reductions in glycosylated hemoglobin (HbA_1c) were noted. Cetilistat was well tolerated, and showed fewer discontinuations due to adverse events (AEs) than in the placebo and orlistat groups. Discontinuation in the orlistat group was significantly worse than in the 120 mg cetilistat and placebo groups and was entirely due to gastrointestinal (GI) AEs. Treatment with cetilistat 80 or 120 mg t.i.d., or with orlistat 120 mg t.i.d., significantly reduced body weight and improved glycemic control relative to placebo in obese diabetic patients. Cetilistat was well tolerated with the number of discontinuations due to AEs being similar to placebo.     

Marginal hazard ratio estimates in joint frailty models for heart failure trials

This work is motivated by clinical trials in chronic heart failure disease, where treatment has effects both on morbidity (assessed as recurrent non‐fatal hospitalisations) and on mortality (assessed as cardiovascular death, CV death). Recently, a joint frailty proportional hazards model has been proposed for these kind of efficacy outcomes to account for a potential association between the risk rates for hospital admissions and CV death. However, more often clinical trial results are presented by treatment effect estimates that have been derived from marginal proportional hazards models, that is, a Cox model for mortality and an Andersen–Gill model for recurrent hospitalisations. We show how these marginal hazard ratios and their estimates depend on the association between the risk processes, when these are actually linked by shared or dependent frailty terms. First we derive the marginal hazard ratios as a function of time. Then, applying least false parameter theory, we show that the marginal hazard ratio estimate for the hospitalisation rate depends on study duration and on parameters of the underlying joint frailty model. In particular, we identify parameters, for example the treatment effect on mortality, that determine if the marginal hazard ratio estimate for hospitalisations is smaller, equal or larger than the conditional one. How this affects rejection probabilities is further investigated in simulation studies. Our findings can be used to interpret marginal hazard ratio estimates in heart failure trials and are illustrated by the results of the CHARM‐Preserved trial (where CHARM is the ‘Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity’ programme).     

Synthesis and characterization of the 1:1 adducts of copper(I) halides with bidentate N,N′-bis(benzophenone)-1,2-diiminoethane Schiff base: Crystal structures of [Cu(bz2en)2][CuX2] (X = Br, I) complexes

1:1 adducts of N,N′-bis(benzophenone)-1,2-diiminoethane (bz₂en) with copper(I) chloride, bromide and iodide, [Cu(bz₂en)₂][CuX₂] (X = Cl, Br, and I), have been synthesized and the structures of the solid bromide and iodide adducts were determined by X-ray crystallography from single-crystal data. The solid-state structure reveals ionic complexes containing a cation of copper(I) ion coordinated to four nitrogen atoms of two bz₂en molecules (distorted tetrahedron) and a linear dibromocuprate(I) and a di-μ-iodo-diiododicuprate(I) anion for the bromo and iodo adducts, respectively. The bromo adduct structure contains CH?Br intermolecular hydrogen bonds. The complexes are very stable towards atmospheric oxygen in the solid state. The spectral properties of the above complexes are also discussed.     

Die Alkoholkomponente des Bacteriochlorophyll a aus Rhodospirillum rubrum

Summary The esterifying alcohol of the bacteriochlorophyll a from Rhodospirillum rubrum was shown to be trans-trans-geranylgeraniol. Mass spectra of the corresponding bacteriopheophytins are used to determine the content and ratio of bacteriochlorophyll a_P and bacteriochlorophyll a_Gg in various strains of phototrophic bacteria.