IL-1β Suppresses the Formation of Osteoclasts by Increasing OPG Production via an Autocrine Mechanism Involving Celecoxib-Related Prostaglandins in Chondrocytes

Elevated interleukin (IL)-1 concentrations in synovial fluid have been implicated in joint bone and cartilage destruction. Previously, we showed that IL-1β stimulated the expression of prostaglandin (PG) receptor EP4 via increased PGE2 production. However, the effect of IL-1β on osteoclast formation via chondrocytes is unclear. Therefore, we examined the effect of IL-1β and/or celecoxib on the expression of macrophage colony-stimulating factor (M-CSF), receptor activator of NF-κB ligand (RANKL), and osteoprotegerin (OPG) in human chondrocytes, and the indirect effect of IL-1β on osteoclast-like cell formation using RAW264.7 cells. OPG and RANKL expression increased with IL-1β; whereas M-CSF expression decreased. Celecoxib blocked the stimulatory effect of IL-1β. Conditioned medium from IL-1β-treated chondrocytes decreased TRAP staining in RAW264.7 cells. These results suggest that IL-1β suppresses the formation of osteoclast-like cells via increased OPG production and decreased M-CSF production in chondrocytes, and OPG production may increase through an autocrine mechanism involving celecoxib-related PGs

Effect of hypocapnia on the sensitivity of hyperthermic hyperventilation and the cerebrovascular response in resting heated humans

Elevating core temperature at rest causes increases in minute ventilation (V̇e), which lead to reductions in both arterial CO2 partial pressure (hypocapnia) and cerebral blood flow. We tested the hypothesis that in resting heated humans this hypocapnia diminishes the ventilatory sensitivity to rising core temperature but does not explain a large portion of the decrease in cerebral blood flow. Fourteen healthy men were passively heated using hot-water immersion (41°C) combined with a water-perfused suit, which caused esophageal temperature (Tes) to reach 39°C. During heating in two separate trials, end-tidal CO2 partial pressure decreased from the level before heating (39.4 ± 2.0 mmHg) to the end of heating (30.5 ± 6.3 mmHg) (P = 0.005) in the Control trial. This decrease was prevented by breathing CO2-enriched air throughout the heating such that end-tidal CO2 partial pressure did not differ between the beginning (39.8 ± 1.5 mmHg) and end (40.9 ± 2.7 mmHg) of heating (P = 1.00). The sensitivity to rising Tes (i.e., slope of the Tes − V̇E relation) did not differ between the Control and CO2-breathing trials (37.1 ± 43.1 vs. 16.5 ± 11.1 l·min−1·°C−1, P = 0.31). In both trials, middle cerebral artery blood velocity (MCAV) decreased early during heating (all P < 0.01), despite the absence of hyperventilation-induced hypocapnia. CO2 breathing increased MCAV relative to Control at the end of heating (P = 0.005) and explained 36.6% of the heat-induced reduction in MCAV. These results indicate that during passive heating at rest ventilatory sensitivity to rising core temperature is not suppressed by hypocapnia and that most of the decrease in cerebral blood flow occurs independently of hypocapnia

ポップアップアーカイバルタグおよび超音波発信器で調べたエチゼンクラゲの遊泳深度

The swimming depths of 12 individual Nemopilema nomurai with bell diameters of 0.8-1.6 m were investigated using pop-up archival transmitting tags and ultrasonic pingers, and the validity of the research method was evaluated. The N. nomurai studied frequently showed vertical movement, with the swimming depth ranging from 0 to 176 m, The mean swimming depths of most individuals were less than 40 m. The swimming depths of N. nomurai in the northern Japan Sea in the winter were mostly deeper than those of this species in the southern Japan Sea in the autumn. This result suggests that the range of the depths almost depends on the vertical structure of the ocean. Swimming depths during the nighttime were significantly deeper than those during the daytime. More specifically, during the daytime, the swimming depths in the afternoon tended to be shallower than those in the morning, while during the nighttime, the swimming depths after midnight were deeper than those before midnight.エチゼンクラゲ計12個体の遊泳深度をポップアップタグや超音波発信器により調べるとともに，調査手法の妥当性を確認した。エチゼンクラゲは活発な鉛直移動を繰り返していた。遊泳深度は0～176m の範囲で，ほとんどの個体の平均遊泳深度は40m より浅かった。遊泳深度は秋の日本海南部よりも冬の日本海北部の方が深くなる傾向があり，基本的に滞在深度範囲は海洋の鉛直構造に依存していると推測された。遊泳深度は日中よりも夜間の方が深かった。日中には午前より午後の方が浅く，夜間には前半夜よりも後半夜の方が深くなる日周性が確認された

Effects of CO2 on ventilatory and cerebrovascular responses during passive heating in humans

Effects of CO2 on ventilatory and cerebrovascular responses during passive heating in human

Neurotropin protects rotator cuff tendon cells from lidocaine-induced cell death

Background Local anesthetics often are used in rotator cuff tears as therapeutic tools, although some cases have reported that they have detrimental effects. Neurotropin (NTP) is used widely in Japan as a treatment for various chronic pain conditions and is shown to have protective effects on cartilage and nerve cells. In this study, we investigated the protective effect of NTP against lidocaine-induced cytotoxicity. Methods Tenocytes from rotator cuff tendons were incubated with lidocaine, NTP, lidocaine with NTP, and a control medium. Cell viability was evaluated using the WST-8 assay. Cell apoptosis was detected via annexin V staining using flow cytometry. The expression of BCL-2 and cytochrome c, which are involved in the intrinsic mitochondrial pathway of apoptosis, was evaluated via Western blotting and immunohistochemical staining. Results In the cell viability assay, lidocaine decreased cell viability in a dose-dependent manner, and NTP did not affect cell viability. Moreover, NTP significantly inhibited the cytotoxic effect of lidocaine. The flow cytometry analysis showed that lidocaine significantly induced apoptosis in tenocytes, and NTP considerably inhibited this lidocaine-induced apoptosis. Western blotting experiments showed that lidocaine decreased the protein expression of BCL-2, and that NTP conserved the expression of BCL-2, even when used with lidocaine. Immunohistochemical staining for cytochrome c showed that 0.1% lidocaine increased cytochrome c-positive cells, and NTP suppressed lidocaine-induced cytochrome c expression. Conclusions NTP suppresses lidocaine-induced apoptosis of tenocytes by inhibiting the mitochondrial apoptotic pathway. Intra-articular/ bursal injection of NTP with lidocaine could protect tenocytes in rotator cuff tendons against lidocaine-induced apoptosis