Consideration of Preventing Local Venous Pain by Dacarbazine.

Local venous pain caused by dacarbazine (DTIC) injection is due to its photodegradation product 5-diazoimidazole-4-carboxamide (Diazo-IC). The production of Diazo-IC can be decreased by protecting the drug from light. Furthermore, the production of Diazo-IC reportedly increases with time; however, there are no studies reporting the association between the injection preparation time and local venous pain caused by the DTIC injection. We evaluated the efficacy of the following: (1) method used to shorten the injection preparation time and (2) method used to change the diluting solution for DTIC. We found that shortening the injection preparation time tended to decrease the local venous pain expression due to DTIC, and Veen F decreased the production of Diazo-IC compared with the normal saline and 5% glucose solution. These results indicate that shortening the injection preparation time may be effective in preventing the local venous pain caused by the DTIC injection; moreover, using Veen F for DTIC may also reduce the pain.

The absence of urokinase-type plasminogen activator receptor plays a role in the insulin-independent glucose metabolism.

The urokinase-type plasminogen activator receptor (uPAR) is a glycosylphosphatidylinositol-anchored membrane protein with multiple functions. In the present study, we examined whether the uPAR plays any role in the regulation of glucose metabolism. The experiments were performed using male wild-type (uPAR) and uPAR knockout (uPAR) C57BL/6J mice. The blood glucose levels after the intraperitoneal injection of glucose were significantly decreased in uPAR mice compared with uPAR mice. On the other hand, there were no differences in the insulin secretion induced by glucose injection and the reactivity of insulin between uPAR and uPAR mice. The expression levels of glucose transporter 2 (GLUT2) in the liver and GLUT4 in the skeletal muscles from the uPAR mice were significantly increased compared with those of the uPAR mice. In addition, we found that the level of phosphorylation of AMP-activated protein kinase in skeletal muscles and myoblasts from the uPAR mice increased compared with those in uPAR mice. These data suggest that the increase in the GLUT2 and GLUT4 expression and the activation of AMP-activated protein kinase by uPAR deficiency enhances the glucose intake. These findings therefore provide new insights into the role of uPAR in the glucose metabolism.

The absence of uPAR is associated with the progression of dermal fibrosis.

The fibrinolytic system is considered to play an important role in the degradation of extracellular matrices (ECM). However, the detailed mechanism regarding how this system affects fibrosis remains unclear. Urokinase-type plasminogen activator receptor (uPAR) not only functions as a proteinase receptor but also plays a role in cellular adhesion, differentiation, proliferation, and migration through intracellular signaling. To investigate the effect of uPAR on dermal fibrosis, the skin of wild-type mice was compared with uPAR-deficient (uPAR(-/-)) mice. The results showed that the absence of uPAR increases dermal thickness. In addition, collagen synthesis as well as the number of myofibroblasts was greater in the skin of uPAR(-/-) mice than in the skin of uPAR(+/+) mice. Moreover, we showed that the absence of uPAR attenuates the activity of matrix metalloproteinases (MMP)-2, 9 in the skin. In conclusion, this study suggests that the absence of uPAR not only regulates fibrosis-related gene expression and MMP activity but also results in ECM deposition. Therefore, the absence of uPAR induces dermal fibrosis. These findings provide new insights into the role of uPAR on dermal fibrosis.

Acute heat stress induces jumping escape behavior in mice.

A new heat escape behavior was revealed in mice (ddY mice) under acute heat stress conditions. Mice in a fully covered cage were exposed to 24, 34, 37 and 38.5 degrees C for 60 min. Rectal temperature increased in conditions above 34 degrees C. Furthermore, serum osmolality and body weight loss also increased in conditions above 37 degrees C. At above 37 degrees C, a large number of mice attempted to escape from the partially covered cage, and so exhibited jumping behavior during a period of 60 min. However, mice exposed to 24 and 34 degrees C did not exhibit such behavior. These results indicated that acute heat stress above 37 degrees C induced evaporative water loss and jumping escape behavior in mice.

Differences in hypothalamic Fos expressions between two heat stress conditions in conscious mice.

Hyperthermia and dehydration were important physiological phenomena in heat stress. But, the degrees of these phenomena were changed by heat stress conditions, and the distinction between both phenomena is necessary for investigation of response for individual phenomenon. Heat stress at 34 degrees C for 60 min increased rectal temperature, and heat stress at 38.5 degrees C for 60 min further increased rectal temperature and increased osmolality in mice. We investigated the activated region in hypothalamus, which played a role in thermoregulation, fluid regulation and so on, using immunostaining for Fos protein under these conditions in conscious mice. At 34 degrees C, Fos-positive neurons increased in the median preoptic nucleus, lateral preoptic area and anterior hypothalamic area, which were known to be the thermoregulatory center, and the dorsomedial hypothalamic nucleus, which was known to control eating. At 38.5 degrees C, Fos-positive neurons further increased in the regions mentioned above and appeared in the lateral septal nucleus, medial preoptic area, lateral hypothalamic area and zona incerta, which were thought to be involved in thermoregulation and/or fluid regulation, and the paraventricular hypothalamic nucleus, supraoptic nucleus and supraoptic nucleus in the retrochiasmatic part, which were known to be involved in neuroendocrine effector systems. These results support that the activated regions in hypothalamus differed with heat stress conditions, which induced only hyperthermia and both hyperthermia and dehydration.

Dynamic responses to acute heat stress between 34 degrees C and 38.5 degrees C, and characteristics of heat stress response in mice.

We focused on dynamic responses to acute heat stress between 34 degrees C and 38.5 degrees C. Physiological and neuroendocrinological changes between 34 degrees C and 38.5 degrees C were studied in mice. The influence of humid conditions, 85% relative humidity (RH), on these changes was also investigated. Rectal temperatures increased above 34 degrees C and hematocrit levels increased at 38.5 degrees C 85% RH for 60 min. Food consumption and body weight gains decreased after a daily 60 min exposure to 34, 37 and 38.5 degrees C for 2 weeks. The corticosterone and vasopressin levels in the blood, and catecholamine and serotonin metabolite levels in the hypothalamus were not changed at 34 degrees C, but increased when above 37 degrees C for 60 min. Above 37 degrees C, these physiological and neuroendocrinological changes were accelerated by humid conditions. These results indicated that food consumption and body weight gains decreased above 34 degrees C, and the neuroendocrinological changes, which were accelerated by humid conditions, were induced above 37 degrees C. In comparison with restraint and water immersion stress, heat stress at 37 degrees C 85% RH showed a slower increase in serum corticosterone levels, smaller changes in plasma dopamine and dihydroxyphenylacetic acid levels, and, after repeated exposure, larger decreases in food consumption and body weight gains. This study clarified the relationships between temperature and humidity conditions and physiological and neuroendocrinological changes, along with the characteristics of responses in acute heat stress.