Beliefs about hydroxyurea in youth with sickle cell disease

Background

Hydroxyurea reduces complications and improves health-related quality of life (HRQOL) in sickle cell disease (SCD) patients, however adherence remains suboptimal. Understanding patients’ views of hydroxyurea is critical to optimize adherence, particularly in adolescents and young adults (AYA). Study objectives were to assess beliefs about hydroxyurea using the Beliefs about Medicines Questionnaire (BMQ), and to examine the relationship of patients’ beliefs to their hydroxyurea adherence and HRQOL.

LC-ESI-MS/MS reveals the formation of reactive intermediates in brigatinib metabolism: elucidation of bioactivation pathways

Brigatinib (BGB) is a newly approved anaplastic lymphoma kinase (ALK) inhibitor. On April 28, 2017, BGB was approved by the U.S. FDA for the treatment of metastatic anaplastic lymphoma kinase-positive non-small cell lung cancer. The toxicity profile of BGB includes nausea, fatigue, diarrhea, elevated lipase, dyspnoea, hypertension, hypoxia, pneumonia, elevated amylase, pulmonary embolism, elevated ALT, hyponatraemia and hypophosphatemia. Using LC-MS/MS, we investigated the in vitro phase I metabolism of for BGB in rat liver microsomes (RLMs). In the in vitro metabolism of BGB, iminium reactive intermediates were trapped by potassium cyanide forming a stable complex that can be characterized by LC-MS/MS. Four BGB in vitro phase I metabolites were identified. In vitro phase I metabolic pathways were N-dealkylation, α hydroxylation and α oxidation. Additionally, three iminium reactive metabolites were found and the bioactivation mechanisms were proposed. A piperidine ring was found to be responsible for BGB bioactivation. The presence of these three reactive metabolites may be the main reason for BGB side effects. A literature review showed no previous article reported the in vitro phase I metabolism study of BGB or structural identification of the formed reactive metabolites.

Four phase I BGB metabolites and three cyano adducts for BGB were detected using LC-MS/MS. The piperidine ring was found to be responsible for BGB bioactivation and the bioactivation pathways are proposed.     

Capacitive performance of vertically aligned reduced titania nanotubes coated with Mn2O3 by reverse pulse electrodeposition

In this study, a composite material, manganese oxide/reduced titania nanotubes (Mn₂O₃/R-TNTs), was synthesized through incorporation of Mn₂O₃ onto R-TNTs via the reverse pulse electrodeposition technique. The influence of pulse reverse duty cycles on the morphological, structural and electrochemical performance of the surface was studied by varying the applied duty cycle from 10% to 90% for 5 min total on-time at an alternate potential of −0.90 V (E_on) and 0.00 V (E_off). FESEM analysis revealed the uniform deposition of Mn₂O₃ on the circumference of the nanotubes. The amount of Mn₂O₃ loaded onto the R-TNTs increased as a higher duty cycle was applied. Cyclic voltammetry and galvanostatic charge–discharge tests were employed to elucidate the electrochemical properties of all the synthesized samples in 1 M KCl. The specific capacitance per unit area was greatly enhanced upon the incorporation of Mn₂O₃ onto R-TNTs, but showed a decrease as a high duty cycle was applied. This proved that low amounts of Mn₂O₃ loading enhanced the facilitation of the active ions for charge storage purposes. The optimized sample, Mn₂O₃/R-TNTs synthesized at 10% duty cycle, exhibited high specific capacitance of 18.32 mF cm⁻² at a current density of 0.1 mA cm⁻² obtained from constant current charge–discharge measurements. This revealed that the specific capacitance possessed by Mn₂O₃/R-TNTs synthesized at 10% duty cycle was 6 times higher than bare R-TNTs.

Mn₂O₃ was coated onto reduced titania nanotubes by reverse pulse electrodeposition, showing smooth and homogenous deposits without covering the opening of the nanotubes.     

Evaluation of the use of direct oral anticoagulants for the management of heparin-induced thrombocytopenia

Journal of Thrombosis and Thrombolysis - Historically, treatment of heparin-induced thrombocytopenia (HIT) includes a non-heparin parenteral anticoagulant with bridging to warfarin once platelets...     

Rift Valley fever surveillance in mobile sheep flocks in the Nile Delta

Rift Valley fever (RVF) surveillance was carried out in the Nile Delta by monitoring mobile and stationary sheep flocks for antibodies to RVF virus. Sheep are known to be susceptible to RVF virus infection and experienced severe morbidity in 1977 and 1978 when RVF was epidemic in Egypt. Four hundred six sheep in 32 flocks were surveyed during 1984. Twenty-four sheep from 7 flocks had antibodies to RVF virus detected by hemagglutination inhibition and plaque reduction neutralization tests. Antibodies were found primarily in sheep greater than 3 years of age, although 1- and 2-year-old sheep were included in the sample. No seroconversion was observed among 177 seronegative sheep that were bled successively for a period of 10 months. These results indicate that epizootic RVF was probably not present in the Nile Delta during 1984.     

Soluble and membranous endothelial protein C receptor in systemic lupus erythematosus patients: Relation to nephritis

Aim of the work

To investigate the role of endothelial protein C receptor (EPCR) (membrane and soluble forms) as a biomarker of lupus nephritis (LN) in systemic lupus erythematosus (SLE) patients and to study its relation to the prognosis and response to treatment.