The authors evaluated the predictability of
various methods used to assess clinical CYP3A induction risk based on various
in vitro parameters, and demonstrated that correlation methods were better at
predicting clinical induction risk than direct methods recommended in guidance/guidelines.
Among correlation approaches, the Relative Factor (RF) and AUC/F2 methods showed
an especially good correlation with clinical induction, and can be used to
assess induction risk along with other correlation methods recommended in guidance/guidelines.
These findings may allow researchers to more confidently determine whether or
not a clinical induction study should be performed before clinical trials.
adipose tissue is characterized by increased immune cell infiltration.
Adipocyte-immune cell interaction overproduces inflammatory adipokine, which
contribute to the development of type 2 diabetes mellitus. The regulation of
immune cells infiltration and inflammation in adipose tissue may exert preventive
and therapeutic effects on obesity-related diseases. Flavonoids such as
hesperidin have anti-inflammatory properties, but their low bioavailability
limits their use as drugs and supplements. The authors report that glucosyl
hesperidin (GH), a water-soluble derivative of hesperidin, ameliorated glucose
intolerance and reduced macrophage infiltration into adipose tissue in high-fat
diet-fed mice. These results suggest the usefulness of GH against
transient receptor potential canonical (TRPC) subfamily members, TRPC3 and
TRPC6, reportedly participate in the development of fibrosis in cardiovascular
and renal systems. This study is to investigate whether
TRPC3 and TRPC6 channels also contribute to the formation of nonalcoholic
steatohepatitis (NASH) which includes liver fibrosis, using TRPC3 or TRPC6
systemic knockout mice fed with the choline-deficient, L-amino acid-defined,
high-fat diet. The authors found that systemic deletion of TRPC3 or
TRPC6 gene alone failed to attenuate liver dysfunction and fibrosis in NASH
Aripiprazole (ARP), an antipsychotic
drug, binds strongly to site II on human serum albumin (HSA). In this study, the
issue of how uremic toxins (indoxyl sulfate, indole acetic acid and p-cresyl
sulfate) affect the binding of ARP to HSA were investigated. Authors
demonstrated that these uremic toxins inhibit the binding of ARP to diazepam subsite
within site II, and these inhibitory effects were more significant, comparing
with those on the drug binding to arylpropionic acids subsite. These findings
provide important information for considering the pharmacokinetics of ARP and
the drugs that bind to site II during renal diseases.
combining whole-brain activation mapping of neurons activated in response to
dopamine D1 and D2 receptor antagonists with non-bias analysis, Niu et al.
provide the direct evidence that the orbital
cortex in addition to the striatum are important brain areas associated with DA
antagonists-induced movement abnormality.