Biosimilar drug products must have a demonstrated similarity with respect to the reference product’s molecules in order to ensure both the effectiveness of the drug and the patients’ safety. In the paper the fusion framework of a highly sensitive NMR fingerprinting approach for conformational changes and mathematically-based biosimilarity metrics was introduced. The final goal was to translate the complex spectral information into biosimilarity scores, which were then used to estimate the degree of similarity between the biosimilar and the reference product. The proposed method was successfully applied to a small protein, i.e., filgrastim (neutropenia treatment), and a relatively large protein, i.e., monoclonal antibody rituximab (lymphoma treatment).
Extracellular vesicles (EVs) are membrane vesicles that are produced by cells to be released into their microenvironment. In this study, we present the EV concentration as a new factor for optimization of industrial bioprocess control. The release of EVs depends on many cell properties, including cell activation, stress status, and cell death. EV concentrations reflect the conditions in the bioreactor and provide new information regarding the state of the bioprocess. Therefore, we suggest EV concentration as a new and important parameter for the monitoring of industrial bioprocesses.
Incidence of drug-drug interactions (DDIs) increases with the complexity of the treatment regimens and presents burden to the health care system. Several of those can be prevented if timely recognized. This study evaluates the impact of pharmacist’s intervention on reduction of clinically relevant DDIs. Patients with chronic heart failure who met the inclusion criteria of presence of clinically relevant DDIs on admission were randomized into control or intervention group. 51 patients were included in the study, 26 in the intervention group. The number of clinically relevant DDIs at discharge was reduced to 31 in control group and to 14 in intervention group. Pharmacists’ intervention significantly reduces the incidence of clinically relevant DDIs and therefore improves the outcomes of patient management.
The shortcomings of clonazepam therapy include tolerance, withdrawal symptoms, and adverse effects such as drowsiness, dizziness, and confusion leading to increased risk of falls. Inter-individual variability in the incidence of adverse events in patients partly originates from the differences in clonazepam metabolism due to genetic and nongenetic factors. The association between the patients’ CYP3A status (genotype and expression) and NAT2 phenotype and clonazepam metabolism was evaluated in 98 psychiatric patients suffering from schizophrenia or bipolar disorders. Prospective assaying of CYP3A4 expression and NAT2 phenotype can better identify the patients with higher risk of adverse reactions and can facilitate the improvement of personalized clonazepam therapy and withdrawal regimen.
Cholesterol synthesis is among the oldest metabolic pathways, consisting of the Bloch and Kandutch-Russel branches. It is believed that, following lanosterol, sterols of both branches are dedicated mainly to cholesterol. We challenge this dogma by mathematical modeling and with experimental evidence. We provide evidence that four CYP enzymes can metabolize ten of the sterols from lanosterol to cholesterol in vitro, establishing novel branching points of cholesterol synthesis. Thus, sterols leaking from cholesterol synthesis can be oxidized further to metabolites that are not dedicated to cholesterol. Additionally, CYP7A1, CYP11A1, CYP27A1, and CYP46A1 can be considered as parts of a broader cholesterol synthesis network. This may affect future cholesterol controlling therapies.