Therapeutic and preventive effects of methotrexate on zymosan-induced arthritis in SKG mice.

The purpose of this study was to investigate the pathology of zymosan-induced arthritis in the SKG mouse model of rheumatoid arthritis in humans, and to validate this model as a reliable drug screening system. To achieve this purpose, methotrexate (1 or 10 mg/kg, once daily) or vehicle only was administered intraperitoneally to SKG mice with zymosan-induced arthritis. Histologically, this arthritis was characterized by the presence of granulation tissue rich in granulocytes. Methotrexate suppressed the development of arthritis in ankle and wrist joints in both clinical and histological studies. These results indicated that methotrexate has not only prophylactic, but also therapeutic effects on zymosan-induced arthritis developed in SKG mice and may thus be a promising control agent for drug research in the SKG mouse model of rheumatoid arthritis.

Diluted isoflurane as a suitable alternative for diethyl ether for rat anaesthesia in regular toxicology studies.

Despite its explosive properties and toxicity to both animals and humans, diethyl ether is an agent long used in Japan in the anaesthesia jar method of rat anaesthetises. However, in response to a recent report from the Science Council of Japan condemning diethyl ether as acceptable practice, we searched for an alternative rat anaesthesia method that provided data continuous with pre-existing regular toxicology studies already conducted under diethyl ether anaesthesia. For this, we examined two candidates; 30% isoflurane diluted with propylene glycol and pentobarbitone. Whereas isoflurane is considered to be one of the representatives of modern volatile anaesthetics, the method of propylene glycol-diluted 30% isoflurane used in this study was our modification of a recently reported method revealed to have several advantages as an inhalation anaesthesia. Intraperitoneal pentobarbitone has long been accepted as a humane method in laboratory animal anaesthesiology. These 2 modalities were scrutinized in terms of consistency of haematology and blood chemistry with previous results using ether. We found that pentobarbitone required a much longer induction time than diethyl ether, which is suspected to be the cause of fluctuations in several haematological and blood chemical results. Conversely, only calcium ion concentration showed a slight difference from traditional results in the case of 30% isoflurane. Additionally, serum prolactin and corticosterone levels indicated that 30% isoflurane induced less stress than ether, confirming that 30% isoflurane can both provide results consistent with diethyl ether, while at the same time remove its disadvantages. As such 30% isoflurane appears to be a strong alternative anaesthetic agent for future regular toxicology studies in Japan.

Tranilast suppresses the disease development of the adjuvant- and streptococcal cell wall-induced arthritis in rats.

This study explores the effects of the anti-allergic and anti-fibrotic agent tranilast on adjuvant- and streptococcal cell wall-induced arthritis in rats, animal models of rheumatoid arthritis in humans. Tranilast (150 or 300 mg/kg, twice daily) or vehicle only was administered orally to the two arthritis models, from 17 days before sensitization. As a comparative control, methotrexate (0.1 mg/kg, once daily) was given to another group. Tranilast suppressed the increase in foot volumes, paw thicknesses, clinical scores, and histopathological scores of the ankle joints in both models dose-dependently. In addition, the fibrosis indices of the ankles were dramatically decreased by tranilast in both of the models. Compared to the effects of methotrexate, tranilast seemed to work more effectively in the streptococcal cell wall-induced arthritis model than in the adjuvant-induced arthritis model. From these observations, it can be concluded that tranilast suppresses the development of arthritis in multiple models and is potentially a novel therapeutic agent for human rheumatoid arthritis.

Acceleration of wound healing by gelatin film dressings with epidermal growth factor.

We examined in vivo efficiency of a gelatin film sheet with epidermal growth factor (EGF) for a novel therapeutic device for cutaneous wound repair. NIH3T3 fibroblasts and PAM212 keratinocytes proliferated when the cells were incubated with the homogenate of EGF containing gelatin sheets, indicating that the gelatin sheet retained biologic activity of EGF in the process of sheet formation. To evaluate therapeutic effects, the EGF containing gelatin sheets or control sheets were applied onto partial-thickness skin wounds made on dorsa of hairless dogs. Wound closure in wounds treated with EGF containing gelatin sheets was accelerated when compared to that of wounds treated with control sheets, exhibiting earlier reepithelialization of the epidermis and highly regulated repair of extracellular matrix in the dermis. Therefore, we concluded that the gelatin film is a useful material to keep EGF stable and the EGF containing sheet has the ability to become an efficient therapeutic agent for superficial or deep partial-thickness wounds in the skin.