Proinflammatory cytokines are well-known to inhibit insulin signaling to result in insulin resistance. IL-1alpha is also one of the proinflammatory cytokines, but the mechanism of how IL-1alpha induces insulin resistance remains unclear. We have now examined the effects of IL-1alpha on insulin signaling in 3T3-L1 adipocytes. Prolonged IL-1alpha treatment for 12 to 24 hours partially decreased the protein levels as well as the insulin-stimulated tyrosine phosphorylation of IRS-1 and Akt phosphorylation. mRNA for SOCS3, an endogenous inhibitor of insulin signaling, was dramatically augmented 4 hours after IL-1alpha treatment. Concomitantly, the level of IL-6 in the medium and STAT3 phosphorylation were increased by the prolonged IL-1alpha treatment. Addition of anti-IL-6 neutralizing antibody to the medium or overexpression of dominant-negative STAT3 decreased the IL-1alpha-stimulated STAT3 activation and SOCS3 induction, and ameliorated insulin signaling. These results suggest that the IL-1alpha-mediated deterioration of insulin signaling is largely due to the IL-6 production and SOCS3 induction in 3T3-L1 adipocytes.

In recent years, the risk of heat disorder in daily life has increased dramatically because the thermal environment has been deteriorating. The main objective of this study was to examine regional differences in the relationship between heat disorder incidence rate and heat stress indices at Yamanashi Prefecture, Japan. Daily maximum air temperature and daily maximum WBGT were used as heat stress indices in each region. Nonlinear regression analysis was used to examine the regional difference in the relationship between the heat disorder incidence rate and heat stress indices in each region. The heat disorder incidence rate was correlated with both indices of heat stress in all regions. However, the more appropriate heat stress index for heat disorder prevention differed among regions. The distributions of heat stress indices, such as the slope of regression curve and the temperature threshold, differed in each region, irrespective of the index used. Therefore, the criteria for thermal conditions for heat disorder prevention need to be determined for each region, considering the regional characteristics of the relationship between the heat disorder incidence rate and heat stress indices.

Hyperthermia has been shown to induce an enhanced febrile response to the bacterial-derived endotoxin lipopolysaccharide (LPS). The aim of the present study was to test the hypothesis that the enhanced LPS-induced fever seen in heat stressed (HS) animals is caused by leakage of intestinal bacterial LPS into the circulation. Male rabbits were rendered transiently hyperthermic (a maximum rectal temperature of 43 degrees C) and divided into three groups. They were then allowed to recover in a room at 24 degrees C for 1, 2 or 3 days post-HS. One day after injection with LPS, the post-HS rabbits exhibited significantly higher fevers than the controls, though this was not seen in rabbits at either 2 or 3 days post-HS. The plasma levels of endogenous LPS were significantly increased during the HS as compared to those seen in normothermic rabbits prior to HS. LPS fevers were not induced in these animals. One day post-HS, rabbits that had been pretreated with oral antibiotics exhibited significantly attenuated LPS levels. When challenged with human recombinant interleukin-1beta instead of LPS, the 1-day post-HS rabbits did not respond with enhanced fevers. The plasma levels of TNFalpha increased similarly during LPS-induced fevers in both the control and 1-day post-HS rabbits, while the plasma levels of corticosterone and the osmolality of the 1-day post-HS rabbits showed no significant differences to those seen prior to the HS. These results suggest that the enhanced fever in the 1-day post-HS rabbits is LPS specific, and may be caused by increased leakage of intestinal endotoxin into blood circulation.

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A ground‐penetrating radar study of medieval kiln sites located near Suzu city, on the Noto peninsula, was conducted prior to excavation. Archaeological site plans estimated from time slices of the closely‐spaced parallel radar profiles are compared with excavations and a proton magnetometer survey. The results indicate that non‐destructive remote sensing with radar can help to determine effectively the presence and general structural features of intact kiln floors.