Hemodynamic response, arrhythmic risk, and overall safety of Regadenoson as a pharmacologic stress agent for myocardial perfusion imaging in chronic obstructive pulmonary disease and bronchial asthma patients

Regadenoson (REG) is a A2a receptor selective pharmacologic SPECT imaging agent. Its safety in unselected chronic obstructive pulmonary disease (COPD) or asthma (AM) undergoing SPECT imaging has not been well evaluated. We retrospectively identified 228 patients (COPD n = 126 and AM n = 102, Grp 1) undergoing REG SPECT from Jan to Nov 2009 and compared to 1,142 patients without COPD and AM (control, Grp 2). A standard 400 μg REG bolus was used and gated Tc-99 m tetrofosmin SPECT done. Patient demographics, REG SPECT data, side effects, arrhythmia occurrences, and any exacerbation of COPD or AM leading to treatment, hospitalization or death were evaluated. The side effect profile of Grp 1 was also compared to a historical cohort who underwent intravenous dipyridamole thallium-201 imaging and adenosine SPECT. Both groups were comparable with regards to baseline characteristics. There was 0% incidence of clinical exacerbation of COPD or AM after REG. COPD patients had more non-significant arrhythmias (58.3% vs. Grp 2, 43%, P = 0.004). There was 0% incidence of any atrio-ventricular block and only 2 instances of brief supraventricular tachycardia. When compared to the historical cohort of COPD who underwent IV dipyridamole thallium imaging, COPD in Grp 1, had more dyspnea and flushing and when compared to COPD/AM patients who underwent adenosine SPECT, Grp 1 pts had more of flushing and headache (24.9% vs. 2.8%, P = <0.001) but less of bronchospasm (1.3% vs. 6.9%, P = 0.022) and AV block (0% vs. 4.2%, P = 0.014). REG SPECT can be safely performed in COPD and AM population.     

Imaging of round pneumonia and mimics in children

Various diseases in the pediatric age group can present as an intrathoracic rounded opacity on a chest radiograph. The purpose of this pictorial essay is to emphasize the imaging appearance of round pneumonia, an entity that occurs especially in the pediatric population. Additional pathologies with similar chest radiographic appearances are also presented. The diagnosis of round pneumonia should be made in children who have the typical clinical presentation along with chest radiographs demonstrating the characteristic findings.     

A study of the molecular mechanism of binding kinetics and long residence times of human CCR5 receptor small molecule allosteric ligands

BACKGROUND AND PURPOSE

The human CCR5 receptor is a co-receptor for HIV-1 infection and a target for anti-viral therapy. A greater understanding of the binding kinetics of small molecule allosteric ligand interactions with CCR5 will lead to a better understanding of the binding process and may help discover new molecules that avoid resistance.

EXPERIMENTAL APPROACH

Using [³H] maraviroc as a radioligand, a number of different binding protocols were employed in conjunction with simulations to determine rate constants, kinetic mechanism and mutant kinetic fingerprints for wild-type and mutant human CCR5 with maraviroc, aplaviroc and vicriviroc.

KEY RESULTS

Kinetic characterization of maraviroc binding to the wild-type CCR5 was consistent with a two-step kinetic mechanism that involved an initial receptor–ligand complex (RA), which transitioned to a more stable complex, R''A, with at least a 13-fold increase in affinity. The dissociation rate from R''A, k₋₂, was 1.2 × 10⁻³ min⁻¹. The maraviroc time-dependent transition was influenced by F85L, W86A, Y108A, I198A and Y251A mutations of CCR5.

CONCLUSIONS AND IMPLICATIONS

The interaction between maraviroc and CCR5 proceeded according to a multi-step kinetic mechanism, whereby initial mass action binding and later reorganizations of the initial maraviroc–receptor complex lead to a complex with longer residence time. Site-directed mutagenesis identified a kinetic fingerprint of residues that affected the binding kinetics, leading to the conclusion that allosteric ligand binding to CCR5 involved the rearrangement of the binding site in a manner specific to each allosteric ligand.     

Bupropion for Interferon-Alpha-Induced Depression in Patients with Hepatitis C Viral Infection: An Open-Label Study

Interferon (IFN)-α therapy for chronic hepatitis C virus (HCV) infection is frequently associated with major depressive episodes. Bupropion, a commonly used antidepressant agent, has recently found to have strong anti-inflammatory effects in animal models. Despite of the theoretical relevancy, the antidepressant effect of bupropion in IFN-alpha-induced depression has never been studied. Ten HCV patients with IFN-α-induced depression were recruited to receive 8-week bupropion treatment and were assessed every 2 weeks for depressive symptoms by the Hamilton rating scale for depression (HAMD) and somatic symptoms by the Neurotoxicity Rating Scale (NRS). Four of the 10 patients met the criteria for remission (total HAMD scores≤7), and 5 patients met the criteria for response (at least 50% reduction in total HAMD scores). In addition, 5 patients had 50% decreases in NRS for neuropsychiatric symptoms. This preliminary open-label study suggests that bupropion is effective in treating IFN-alpha-induced depressive and somatic symptoms.     

Magnetically recyclable CoFe2O4/ZnO nanocatalysts for the efficient catalytic degradation of Acid Blue 113 under ambient conditions

CoFe₂O₄/ZnO magnetic nanocatalysts were synthesized using a low-frequency ultrasound-assisted technique to enhance the optical, morphological, magnetic and catalytic properties of ZnO. The as-synthesized nanocatalysts were characterized by XRD, Raman, TEM, DR-UV-Vis and VSM analyses in order to confirm the expected modifications of the resulting nanocatalysts. The Raman spectral analysis revealed substitutional Zn²⁺ in the CoFe₂O₄/ZnO nanocatalyst. The as-synthesized material was tested for its catalytic activity in the degradation of Acid Blue (AB113), a known textile pollutant. The CoFe₂O₄ and CoFe₂O₄/ZnO nanocatalysts revealed the efficient catalytic degradation of AB113 in ambient conditions. The nanocatalyst dosage and the initial concentration of AB113 were varied by fixing one parameter as constant in order to determine the maximum catalytic efficiency with the minimum catalyst loading for AB113 degradation. The CoFe₂O₄/ZnO nanocatalyst demonstrated 10-fold enhanced mineralization of AB113 compared to the individual bare nanocatalysts, which could be achieved within 3 hours of catalytic degradation of AB113. The magnetic CoFe₂O₄/ZnO nanocatalyst was found to be stable for six consecutive recycles of AB113 degradation, which indicates that the catalytic efficiency of the nanocatalyst was retained after various numbers of cycles.

CoFe₂O₄/ZnO magnetic nanocatalysts were synthesized using a low-frequency ultrasound-assisted technique to enhance the optical, morphological, magnetic and catalytic properties of ZnO.