Prognostic value of pharmacological stress echocardiography in patients with known or suspected coronary artery disease: a prospective, large-scale, multicenter, head-to-head comparison between dipyridamole and dobutamine test. Echo-Persantine International Cooperative (EPIC) and Echo-Dobutamine International Cooperative (EDIC) Study Groups

OBJECTIVES: The study compared the prognostic value of dipyridamole and dobutamine stress echocardiography in patients with known or suspected coronary artery disease. BACKGROUND: Extensive information is available on the relative diagnostic accuracy of the two tests assessed in a head-to-head fashion, whereas comparative data on their prognostic yield are largely preliminary to date. METHODS: Dipyridamole (up to 0.84 mg/kg over 10 min) atropine (up to 1 mg over 4 min) (DIP) and dobutamine (up to 40 microg/kg/min)-atropine (1 mg over 4 min) (DOB) stress tests were performed in 460 patients with known or suspected coronary artery disease. Patients were followed up for 38+/-21 months. RESULTS: The DIP was negative in 253 and positive in 207 patients. The DOB was negative in 242 and positive in 218 patients. During the follow-up, there were 80 cardiac events. For all cardiac events, the negative and positive predictive value were 83% and 17% for DOB, 84% and 19% for DIP, respectively (p = NS). Considering only cardiac death, by univariate analysis Wall-Motion Score Index (WMSI) at DIP peak dose (chi-square 13.80, p<0.0002) was the strongest predictor, followed by WMSI DOB (chi2 = 8.02, p<0.004) and WMSI at rest (chi2 = 6.85, p<0.008). By stepwise analysis, WMSI at DIP peak dose was the most important predictor (RR [relative risk] 7.4, p<0.0001). CONCLUSIONS: In patients at low-to-moderate risk of cardiac events, pharmacological stress echocardiography with either dobutamine or dipyridamole allows effective and grossly comparable, risk stratification on the basis of the presence, severity and extension of the induced ischemia.     

Anti-repulsive Guidance Molecule C (RGMc) Antibodies Increases Serum Iron in Rats and Cynomolgus Monkeys by Hepcidin Downregulation

High levels of hepcidin, the main regulator of systemic iron metabolism, lead to various diseases. Targeting hepcidin and lowering its concentration is a possible form of intervention in order to treat these diseases. High turnover rate of hepcidin is a major drawback of therapies directly targeting this peptide. We developed two monoclonal antibodies ABT-207 and h5F9-AM8 which inhibit hemojuvelin/repulsive guidance molecule C (RGMc) and downregulate hepcidin. We conducted single-application and dose response studies to understand the antibodies’ mechanism and subchronic toxicology studies to exclude safety-related concerns. Investigation was carried out at different biological levels through qPCR, Affymetrix, liquid chromatography coupled with mass spectrometry (LC-MS/MS), histopathology, serum iron, unsaturated iron binding capacity (UIBC), and drug concentration measurements. After a single application of these antibodies, hepcidin expression in liver and its serum protein levels were reduced. Serum iron increased for several weeks. The RGMc antibodies show a pronounced dose response relationship in rats with h5F9-AM8 having an IC₅₀ (UIBC) of approximately 80-fold higher than ABT-207. When hepcidin levels were downregulated, iron deposition in the liver was visible histologically 1 week post application. These antibody-mediated iron depositions were not associated with any adverse toxicologically relevant effect at the doses and time points evaluated. Iron depositions seen after 14 weekly treatments with ABT-207 were reversible in rats and in cynomolgus monkeys. Due to their long-lasting effects and excellent safety profile, both RGMc-blocking antibodies ABT-207 and h5F9-AM8 are favorable clinical candidates for diseases characterized by high serum hepcidin levels like anemia of chronic disease.

Electronic supplementary material

The online version of this article (doi:10.1208/s12248-015-9770-4) contains supplementary material, which is available to authorized users.KEY WORDS: ABT-207, h5F9-AM8, hepcidin, PK/PD analysis, safety assessment     

Amino acid ionic liquids as catalysts in a solvent-free Morita–Baylis–Hillman reaction

In the present work, we describe the preparation of ten amino acid ionic liquids (AAILs) formed from ammonium salts as cations, derivatives of glycerol, and natural amino acids as anions. All of them are viscous oils, colorless or pale yellow, and hygroscopic at room temperature. They have appreciable solubility in many protic and aprotic polar solvents. The AAILs were used as catalysts in a Morita–Baylis–Hillman (MBH) reaction. The ionic liquids derivative from l-proline and l-histidine demonstrated the ability to catalyze the reaction between methyl vinyl ketone and aromatic aldehydes differently substituted in the absence of an additional co-catalyst under organic solvent-free conditions. The AAIL derivatives from l-valine, l-leucine, and l-tyrosine catalyzed the MBH reaction only in the presence of imidazole. The MBH adducts were obtained in moderate to good yields. Although the catalytic site in the ILs was in its enantiomerically pure form, all the MBH adducts were obtained in their racemic form.

In this work, we describe the preparation of ten amino acid ionic liquids (AAILs). The AAILs were used as catalysts in a Morita–Baylis–Hillman (MBH) reaction. The MBH adducts were obtained from moderate to good yields and in their racemic form.     

A comparative study on the photocatalytic degradation of organic dyes using hybridized 1T/2H, 1T/3R and 2H MoS2 nano-sheets

MoS₂ is a very attractive material and has been well studied for potential applications in various areas. However, due to the wide variety of factors affecting the molecular and electronic structure of MoS₂, several contradictory reports about the adsorptive and photocatalytic properties of such materials have been published. In most of these reports, the effect of the actual phase of the materials on the properties was neglected. Here, different phases of MoS₂ nanosheets (1T/2H, 1T/3R and 2H) have been obtained using the hydrothermal method with different Mo : S molar ratios and different autoclave filling ratios. The obtained materials have been thoroughly characterized using Raman, UV-vis, powder XRD, SEM, TEM and XPS measurements in order to accurately identify the existing phases in each material. A comparative study of the photocatalytic organic dye degradation efficiency under white light irradiation has been conducted using methyl orange to correlate the different activity of each material to the respective phase composition. The results indicate a much higher performance of the 1T/2H phase compared to the 2H and 3R phases. Detailed computational studies of the different phases revealed the emergence of mid-gap states upon introducing 1T sites into the 2H lattice. This leads to the improvement of the photocatalytic activity of 1T/2H compared to the other prepared materials.

MoS₂ is a very attractive material and has been well studied for potential applications in various areas.     

Comparison of Porcine Epidemic Diarrhea Viruses from Germany and the United States, 2014

Since 2013, highly virulent porcine epidemic diarrhea virus has caused considerable economic losses in the United States. To determine the relation of US strains to those recently causing disease in Germany, we compared genomes and found that the strain from Germany is closely related to variants in the United States.     

Use of automated external defibrillators in a Brazilian airline. A 1-year experience

After the incorporation of automated external defibrillators by other airlines and the support of the Brazilian Society of Cardiology, Varig Airlines began the onboard defibrillation program with the initial purpose of equipping wide-body aircrafts frequently used in international flights and that airplanes use in the Rio - S?o Paulo route. With all flight attendants trained, the automated external defibrillation devices were incorporated to 34 airplanes of a total fleet of 80 aircrafts. The devices were installed in the baggage compartments secured with velcro straps and 2 pairs of electrodes, one or which pre-connected to the device to minimize application time. Later, a portable monitor was address to the resuscitation kit in the long flights. The expansion of the knowledge of the basic life support fundamentors and the corrected implantation of the survival chain and of the automated external defibrillators will increase the extense of recovery of cardiorespiratory arrest victims in aircrafts.