Pharmacogenomic
(PGx) testing can predict therapeutic responses or adverse effects based on
genetic variants and is expected to be the preemptive precision medicine for patient
management. Tramadol is metabolized by CYP2D6 to an active
metabolite, which in turn acts as an analgesic. From the retrospective cohort
study in Japanese patients with postoperative pain after orthopedic
arthroscopic surgery, the authors demonstrated that the
analgesic effect in the early postoperative period was depended on CYP2D6 gene polymorphism.
These results suggested the clinical utility of preemptive treatment based on
the PGx test, which can consider dose adjustment or drug change in advance.
TRP ankyrin 1 (TRPA1) is present in the
afferent sensory neurons and is activated by food-derived ingredients, such as
Japanese horseradish, cinnamon, and garlic. The present study aimed to
investigate the expression of TRPA1 in taste buds, and determine its functional
roles in taste perception using TRPA1-deficient mice. TRPA1-immunoreactivities
are detectable in the taste nerve. TRPA1 deficiency significantly reduced sweet
sensitivity compared to that in WT mice as per the two-bottle preference tests.
Authors found that TRPA1 in the taste nerve contributes to the sense of sweet
taste in mice.
Allergic contact dermatitis is a common
dermatitis and is induced by contact with allergens. The authors found that
methionine suppressed this dermatitis in some strains of mice. They also found
that the strength of the effect depended on the suppression of liver betaine
homocysteine methyltransferase (Bhmt) expression by the dermatitis.
Although the mechanism has not been elucidated, the authors propose that while
dermatitis suppresses liver Bhmt expression in some strains of mice, the
fact that the metabolic state of the liver affects the suppression of
dermatitis suggests that there is at least a skin-liver interaction, especially
a dermatitis-liver interaction.
This study aimed to investigate the
mechanism underlying the skin pigmentation caused by anticancer drugs using
5-fluorouracil (5-FU), a widely used anticancer drug known to cause this
complication. Authors believe our study makes a significant contribution to the
literature because anticancer drug-induced skin pigmentation remarkably affects
the quality of life of cancer patients, has no established treatment, and has
an unknown mechanism. This result provides new insight into the role of the
ACTH/cAMP/tyrosinase pathway in 5-FU-mediated skin pigmentation and may help
manage this complication.
11β-Hydroxysteroid
dehydrogenase type 1 (11β-HSD1) is the only enzyme that converts inactive
glucocorticoids to active forms and plays an important role in regulating
glucocorticoid action in target tissues. Excess glucocorticoids cause insulin
resistance in the liver and adipose tissue. Several 11β-HSD1 inhibitors have
been reported, but all have been evaluated in obese diabetes models. In the
present study, the authors investigated the pharmacological properties of
JTT-654, a selective 11β-HSD1 inhibitor, in cortisone-treated rats and
non-obese Goto-Kakizaki rats with type 2 diabetes, because many Asians,
including Japanese, have non-obese type 2 diabetes. Information gained from
detailed analysis of the mechanism of action of JTT-654 may provide a new therapeutic
approach for the treatment of non-obese type 2 diabetic patients.