Toxicologic Pathology Forum: Current Status on the Use of Animal Models of Human Disease in the Pharmaceutical Industry in Japan in Nonclinical Safety Assessment-Opinion Paper.

In nonclinical safety studies for new drug development, healthy animals have been commonly used. However, in some cases, the use of animal models of human disease is considered to be more favorable in evaluating risks in patients. To elucidate the current status of the use of animal models for nonclinical safety assessment, an internal questionnaire from the Japan Pharmaceutical Manufacturers Association and surveys (questionnaire period: August 27 to September 30, 2015) of both common technical documents and review reports of approved drugs (approval period: May 1999 to May 2017) disclosed by the Pharmaceutical and Medical Devices Agency were conducted.

Social isolation stress induces hepatic hypertrophy in C57BL/6J mice.

We previously reported that social isolation stimulated a stress response leading to increasing plasma corticosterone level and disruption of the hepatic lipid metabolism-related pathway, without changing body and organ weights, in mice after 4 weeks of social isolation stress, compared with the grouped-housing control (5 mice/cage). In this study, we evaluated the effects of social isolation stress for an extended period on physiologic changes in male C57BL/6J mice. Plasma corticosterone was reduced after 13 weeks, indicating mice might adapt to social isolation stress.

Photo- and electro-chromic organometallics with dithienylethene (DTE) linker, L2CpM-DTE-MCpL2: dually stimuli-responsive molecular switch.

Photochromic dithienylethene (DTE) derivatives, M-DTE-M (M: M(η(5)-C(5)R(5))L(2); M = Fe, Ru; R = H, Me; L = CO, phosphine), with direct σ-bonded, redox-active organometallic attachments are prepared and their response to photo- and electro-chemical stimuli as well as wire-like and switching performance has been investigated. These properties turn out to be dependent on the metal and the auxiliary ligands. The DTE complexes with the MCp(CO)(2) and RuCp(CO)(PPh(3)) fragments undergo reversible photochemical ring-closing and -opening of the DTE moiety upon UV and visible-light irradiation, respectively, whereas the other FeCp(CO)(PPh(3)) and Fe(η(5)-C(5)R(5))(dppe) derivatives are virtually inert with respect to the photochemical ring closing process.

Quantitative risk assessment of Vibrio parahaemolyticus in finfish: a model of raw horse mackerel consumption in Japan.

The aim of this study was to evaluate the effects of implemented control measures to reduce illness induced by Vibrio parahaemolyticus (V. parahaemolyticus) in horse mackerel (Trachurus japonicus), seafood that is commonly consumed raw in Japan. On the basis of currently available experimental and survey data, we constructed a quantitative risk model of V.

Isolation stress for 30 days alters hepatic gene expression profiles, especially with reference to lipid metabolism in mice.

To elucidate the physiological responses to a social stressor, we exposed mice to an isolation stress and analyzed their hepatic gene expression profiles using a DNA microarray. Male BALB/c mice were exposed to isolation stress for 30 days, and then hepatic RNA was sampled and subjected to DNA microarray analysis. The isolation stress altered the expression of 420 genes (after considering the false discovery rate).

Remarkable switching behavior of bimodally stimuli-responsive photochromic dithienylethenes with redox-active organometallic attachments.

Organometallic dithienylethenes with the redox-active M(eta(5)-C(5)H(5))L(2)-type attachments (M = Fe, Ru; L = CO, PR(3)) exhibit bimodally stimuli-responsive, photo- and pseudo-electrochromic behavior with the remarkable switching factors [K(C)(closed)/K(C)(open)] up to 5.4 x 10(3).

Social stress increases biopyrrins, oxidative metabolites of bilirubin, in mouse urine.

We investigated whether or not three kinds of social stress (isolation, crowding, and confrontation) increase urinary excretion of biopyrrins, oxidative metabolites of bilirubin, in mice. Male BALB/c mice (4 weeks old) were housed 5 per cage for 10 days. After acclimatization, mice were exposed to the above mentioned three kinds of psychosocial stress.