Norepinephrine, but not epinephrine, enhances platelet reactivity and coagulation after exercise in humans

The effects of exercise and catecholamineson platelet reactivity or coagulation and fibrinolysis appear to beinconsistent. This may be partly due to the methods employed inprevious studies. In the present study, we investigated the effects ofacute aerobic exercise and catecholamines on the thrombotic status by anovel in vitro method, shear-induced hemostatic plug formation(hemostatometry), using nonanticoagulated (native) blood. Aerobicexercise (60% maximal O₂consumption) was performed by healthy male volunteers for 20 min, andthe effect on platelet reactivity and coagulation was assessed byperforming hemostatometry before and immediately after exercise.Exercise significantly increased shear-induced platelet reactivity,coagulation, and catecholamine levels. The effect of catecholamines onplatelet reactivity and coagulation was assessed in vitro by addingcatecholamines to blood collected in the resting state. The mainfindings of the present study are that elevation of circulatingnorepinephrine at levels that are attained during exercise causesplatelet hyperreactivity and a platelet-mediated enhanced coagulation.This may be a mechanism of an association of aerobic exercise withthrombotic risk.

     

The contribution of a beneficial insectary plant <Emphasis Type="Italic">Scaevola aemula</Emphasis> to survival and long-term establishment of flightless <Emphasis Type="Italic">Harmonia axyridis</Emphasis> in greenhouses

The fairy fan flower, Scaevola aemula R. Br., is a primary candidate insectary plant for maintaining populations of generalist predators. We conducted release experiments in greenhouses of cultivated eggplants to evaluate the effects of intercropping S. aemula on the establishment of flightless Harmonia axyridis Pallas. Compared with a monoculture of eggplant, all release experiments showed that flightless H. axyridis remained in greater numbers in plots with S. aemula planted alongside eggplant. In the release experiment of flightless H. axyridis larvae, the incidence of aphids in the plot with transplanted S. aemula was suppressed compared with that in the release plot without transplanted S. aemula. In a laboratory experiment, the longevity of flightless H. axyridis adults on blossom stems of S. aemula was greater than when open flowers and buds were removed, suggesting that the insects fed on floral resources such as the pollen of S. aemula. Our findings showed that the floral resources of S. aemula can enhance aphid suppression by improving the establishment of flightless H. axyridis.     

IL-27 induces Th1 differentiation via p38 MAPK/T-bet- and intercellular adhesion molecule-1/LFA-1/ERK1/2-dependent pathways

IL-27, a novel member of the IL-6/IL-12 family, activates both STAT1 and STAT3 through its receptor, which consists of WSX-1 and gp130 subunits, resulting in positive and negative regulations of immune responses. We recently demonstrated that IL-27 induces Th1 differentiation through ICAM-1/LFA-1 interaction in a STAT1-dependent, but T-bet-independent mechanism. In this study, we further investigated the molecular mechanisms by focusing on p38 MAPK and ERK1/2. IL-27-induced Th1 differentiation was partially inhibited by lack of T-bet expression or by blocking ICAM-1/LFA-1 interaction with anti-ICAM-1 and/or anti-LFA-1, and further inhibited by both. Similarly, the p38 MAPK inhibitor, SB203580, or the inhibitor of ERK1/2 phosphorylation, PD98059, partially suppressed IL-27-induced Th1 differentiation and the combined treatment completely suppressed it. p38 MAPK was then revealed to be located upstream of T-bet, and SB203580, but not PD98059, inhibited T-bet-dependent Th1 differentiation. In contrast, ERK1/2 was shown to be located downstream of ICAM-1/LFA-1, and PD98059, but not SB203580, inhibited ICAM-1/LFA-1-dependent Th1 differentiation. Furthermore, it was demonstrated that STAT1 is important for IL-27-induced activation of ERK1/2, but not p38 MAPK, and that IL-27 directly induces mRNA expression of growth arrest and DNA damage-inducible 45gamma, which is known to mediate activation of p38 MAPK. Finally, IL-12Rbeta2 expression was shown to be up-regulated by IL-27 in both T-bet- and ICAM-1/LFA-1-dependent mechanisms. Taken together, these results suggest that IL-27 induces Th1 differentiation via two distinct pathways, p38 MAPK/T-bet- and ICAM-1/LFA-1/ERK1/2-dependent pathways. This is in contrast to IL-12, which induces it via only p38 MAPK/T-bet-dependent pathway.     

Force–velocity,force–power relationships of bilateral and unilateral leg multi-joint movements in young and elderly women

The present study investigated force–velocity and force–power relationships of bilateral and unilateral knee-hip extension movement in young and elderly women. Twelve healthy young (age, 19–31 yr) and 12 healthy elderly (age, 60–82 yr) women performed bilateral and unilateral knee-hip extension movements on the dynamometer against loads controlled by the servo system. Under the isotonic force condition, force–velocity relationships were measured. The maximum isometric force (F_max), unloaded velocity (V_max) and power output (P_max) of the movements were calculated from extrapolating force–velocity and force–power relationships. F_max and P_max of bilateral and unilateral knee-hip extension movements were 20–30% lower in elderly than in young women. On the other hand, there were no significant differences in V_max between young and elderly women and between bilateral and unilateral movements. Bilateral deficit was larger as the generation of force was larger in both young and elderly women. Also, bilateral deficit of F_max and P_max were not different between young and elderly women. The results were that lower maximum power output of bilateral and unilateral leg multi-joint movements in elderly women did not depend on the intrinsic shortening velocity of muscle action, but largely on reduction in force generating capacity. This suggests the importance of preventing a loss of force generating capacity of muscles during leg multi-joint movements in elderly women.     

The atomic structure of rice dwarf virus reveals the self-assembly mechanism of component proteins

Rice dwarf virus (RDV), the causal agent of rice dwarf disease, is a member of the genus Phytoreovirus in the family Reoviridae. RDV is a double-shelled virus with a molecular mass of approximately 70 million Dalton. This virus is widely prevalent and is one of the viruses that cause the most economic damage in many Asian countries. The atomic structure of RDV was determined at 3.5 A resolution by X-ray crystallography. The double-shelled structure consists of two different proteins, the core protein P3 and the outer shell protein P8. The atomic structure shows structural and electrostatic complementarities between both homologous (P3-P3 and P8-P8) and heterologous (P3-P8) interactions, as well as overall conformational changes found in P3-P3 dimer caused by the insertion of amino-terminal loop regions of one of the P3 protein into the other. These interactions suggest how the 900 protein components are built into a higher-ordered virus core structure.     

Vitamin K2 and geranylgeraniol, its side chain component, inhibited osteoclast formation in a different manner

We comparatively examined the mechanism by which vitamin K(2) (Menatetrenone, MK4) and its side chain component, geranylgeraniol (GGO), inhibited osteoclast formation in the co-culture system of stromal cells with spleen cells. Both MK4 and GGO inhibited osteoclast formation induced by 1alpha,25-dihydroxyvitamin D3 (1,25(OH)(2)D(3)). MK4, but not GGO, inhibited cyclooxygenase-2 (COX-2) expression and prostaglandin E(2) (PGE(2)) production in the co-culture system. To elucidate the precise mechanism of the inhibitory effect of GGO on osteoclast formation, the co-cultured cells were stimulated with PGE(2). GGO, but not MK4, inhibited osteoclast formation via suppression of the receptor activator of NF-kappaB ligand (RANKL) expression. Moreover, GGO abolished the disruption of osteoclastic actin rings induced by nitrogen-containing bisphosphonate (N-BP), whereas MK4 did not affect it at all. These data suggest that MK4 inhibited osteoclast formation independently of GGO, and that MK4, but not GGO, has no competitive action on the anti-osteoporotic effect of N-BP.     

Antiangiogenic and antitumor activities of IL-27

IL-27 is a novel IL-6/IL-12 family cytokine playing an important role in the early regulation of Th1 responses. We have recently demonstrated that IL-27 has potent antitumor activity, which is mainly mediated through CD8(+) T cells, against highly immunogenic murine colon carcinoma. In this study, we further evaluated the antitumor and antiangiogenic activities of IL-27, using poorly immunogenic murine melanoma B16F10 tumors, which were engineered to overexpress single-chain IL-27 (B16F10 + IL-27). B16F10 + IL-27 cells exerted antitumor activity against not only s.c. tumor but also experimental pulmonary metastasis. Similar antitumor and antimetastatic activities of IL-27 were also observed in IFN-gamma knockout mice. In NOD-SCID mice, these activities were decreased, but were still fairly well-retained, suggesting that different mechanisms other than the immune response are also involved in the exertion of these activities. Immunohistochemical analyses with Abs against vascular endothelial growth factor and CD31 revealed that B16F10 + IL-27 cells markedly suppressed tumor-induced neovascularization in lung metastases. Moreover, B16F10 + IL-27 cells clearly inhibited angiogenesis by dorsal air sac method, and IL-27 exhibited dose-dependent inhibition of angiogenesis on chick embryo chorioallantoic membrane. IL-27 was revealed to directly act on HUVECs and induce production of the antiangiogenic chemokines, IFN-gamma-inducible protein (IP-10) and monokine induced by IFN-gamma. Finally, augmented mRNA expression of IP-10 and monokine induced by IFN-gamma was detected at the s.c. B16F10 + IL-27 tumor site, and antitumor activity of IL-27 was partially inhibited by the administration of anti-IP-10. These results suggest that IL-27 possesses potent antiangiogenic activity, which plays an important role in its antitumor and antimetastatic activities.     

Hepatitis C Related Chronic Liver Cirrhosis: Feasibility of Texture Analysis of MR Images for Classification of Fibrosis Stage and Necroinflammatory Activity Grade

Purpose

To assess the feasibility of texture analysis for classifying fibrosis stage and necroinflammatory activity grade in patients with chronic hepatitis C on T2-weighted (T2W), T1-weighted (T1W) and Gd-EOB-DTPA-enhanced hepatocyte-phase (EOB-HP) imaging.

Materials and methods

From April 2008 to June 2012, MR images from 123 patients with pathologically proven chronic hepatitis C were retrospectively analyzed. Texture parameters derived from histogram, gradient, run-length matrix, co-occurrence matrix, autoregressive model and wavelet transform methods were estimated with imaging software. Fisher, probability of classification error and average correlation, and mutual information coefficients were used to extract subsets of optimized texture features. Linear discriminant analysis in combination with 1-nearest neighbor classifier (LDA/1-NN) was used for lesion classification. In compliance with the software requirement, classification was performed based on datasets from all patients, the patient group with necroinflammatory activity grade 1, and that with fibrosis stage 4, respectively.

Results

Based on all patient dataset, LDA/1-NN produced misclassification rates of 28.46%, 35.77% and 20.33% for fibrosis staging and 34.15%, 25.20% and 28.46% for necroinflammatory activity grading in T2W, T1W and EOB-HP images. In the patient group with necroinflammatory activity grade 1, LDA/1-NN yielded misclassification rates of 5.00%, 0% and 12.50% for fibrosis staging in T2W, T1W and EOB-HP images respectively. In the patient group with fibrosis stage 4, LDA/1-NN yielded misclassification rates of 5.88%, 12.94% and 11.76% for necroinflammatory activity grading in T2W, T1W and EOB-HP images respectively.

Conclusion

Texture quantitative parameters of MR images facilitate classification of the fibrosis stage as well as necroinflammatory activity grade in chronic hepatitis C, especially after categorizing the input dataset according to the activity or fibrosis degree in order to remove the interference between the fibrosis stage and necroinflammatory activity grade on texture features.