Cytotoxic agents are classified according to the
severity of skin injury after extravasation. However, injuries caused by extravasation
of noncytotoxic agents have not been sufficiently investigated. In this study, the
authors focused on noncytotoxic electrolyte solutions and infusions and
evaluated skin injuries macroscopically and histopathologically using
extravasation model rats. As a result, the electrolyte solutions and infusions
were classified into three categories (vesicants, irritants, and
non-tissue-damaging agents) depending on the degree of skin injury. The
characteristic symptoms and severity of each drug extravasation revealed in
this study will provide basic information for preparation of guidelines for
treatment of extravasation.
MicroRNAs (miRNAs) are known “key regulator” of numerous gene expressions. In this study, authors determined the
effects of three miRNAs, miR-149-5p,
miR-362-5p, and miR-539-5p, on iron-ion transporter, SLC11A2 mRNA using the cultured
human colon carcinoma cell line. Authors found that they regulate SLC11A2 gene expression and iron-ion
transporting function in an in vitro
system. Authors believe that this study makes a significant contribution
to the literature because the use of these three miRNAs as surrogate biomarkers
could significantly advance the development of therapies for the treatments of
diseases caused by transporter disorders, such as anemia.
In antibody drugs, estimating the
viscosity at high concentrations is crucial in terms of designing drug
formulations since high viscosity could limit the choice of administration
routes. The authors hypothesized that the diffusion interaction coefficient may
be a key factor in estimating the viscosity and analyzed the relation between
them. Not only have the results showed the viscosity can be estimated by using
the diffusion interaction coefficient, but it has also succeeded in setting
criterions for the feasibility of high concentration formulations. Such
findings will deepen the understanding of the physicochemical properties,
leading to the promotion of future drug development.
An increase in
intracellular Ca2+ concentration activates Ca2+-sensitive
enzymes such as Ca2+/calmodulin-dependent kinases (CaMK) and induces
gene transcription in various types of cells through excitation-transcription
(E-T) coupling. In this study, the authors revealed that CaMK1α can be fully activated by both Ca2+ influx
through of L-type Ca2+ channels, Cav1.2, and phosphorylation by
CaMKK2 within caveolae in mouse vascular smooth muscle cells. This activated
(phosphorylated) CaMK1a can translocate
from the cytosol to the nucleus. These findings strongly suggest that CaMK1a can transduce Ca2+ signaling generated
within or very near caveolae to the nucleus and thus, promote E-T coupling.
Proton pump inhibitors (PPIs) or
potassium-competitive acid blocker (PCAB) are widely used in Japan. PPIs or
PCAB is known to have cardiovascular risk. Authors revealed the cardiovascular
risk in each PPI or PCAB components using a large claims data in 91,098
working-age workers. Finally, authors reveal that lansoprazole, a higher
CYP2C19 inhibition activity as compared other PPIs or PCAB, is a higher risk
for cardiovascular risk.