No abstract

Accelerated cardiovascular disease is a frequent complication of CKD. Monocyte-mediated inflammation and adhesion of monocytes to vascular endothelium are key events in atherogenesis. An oral adsorbent, AST-120, retards renal function deterioration by lowering IS, which is known to accumulate in CKD patients. However, the effect of AST-120 on CKD-related monocyte activation is unknown. We aimed to determine whether AST-120 improves monocyte-mediated inflammation through IS reduction. Flow cytometric analysis showed that Mac-1 expression and ROS production were significantly higher in peripheral blood monocytes of subtotal Nx CKD mice than in sham-operated mice. AST-120 treatment significantly decreased Mac-1 expression and ROS production in CKD model mice. Furthermore, administration of IS induced monocyte-mediated inflammation and ROS generation. In vitro studies indicated that IS dose-dependently increased THP-1 monocytic cell adhesion to IL-1β-activated HUVECs under physiological flow conditions. IS also induced monocyte-mediated inflammation and ROS production in THP-1 cells. Phosphorylation of p38 MAPK and membrane translocation of NAD(P)H oxidase subunit p47phox in THP-1 cells were induced by IS. Both SB203580 (p38 MAPK inhibitor) and apocynin [NAD(P)H oxidase inhibitor] reduced THP-1 cell adhesion to HUVECs. Apocynin also inhibited IS-induced ROS production in THP-1 cells. IS induced monocyte-driven inflammation through NAD(P)H oxidase- and p38 MAPK-dependent pathways in monocytes. The main finding of this study was that AST-120 inhibited monocyte activation by reducing IS in vivo. This provides new insights on how AST-120 attenuates the progression of atherosclerosis in CKD.

To delineate the determinants of right ventricular performance with acute right ventricular dysfunction, surgical electrical isolation of the right ventricular free wall was produced in 13 dogs. During atrioventricular (AV) pacing, hemodynamic and wall motion measurements were normal. When not paced, the right ventricular free wall became asystolic, resulting in a depressed and bifid right ventricular systolic pressure (33 +/- 5 to 18 +/- 4 mm Hg) and decreased left ventricular systolic pressure (100 +/- 18 to 80 +/- 18 mm Hg) and stroke volume (14 +/- 4 to 10.3 +/- 3.5 ml) (all p less than 0.05). Ultrasound demonstrated right ventricular free wall dyskinesia, increased right ventricular end-diastolic size (155 +/- 13% of control), but decreased left ventricular size (69 +/- 11% of control) (both p less than 0.05). Right atrial pressure increased (5.8 +/- 2.5 to 7.6 +/- 2.8 mm Hg, p less than 0.05) with an augmented A wave and blunted Y descent, indicating pandiastolic right ventricular dysfunction. The septum demonstrated reversed curvature in diastole and bulged paradoxically into the right ventricle during early systole, generating the initial peak of right ventricular pressure and reducing its volume. Later, posterior septal motion coincided with maximal left ventricular pressure and the second peak of the right ventricular waveform. Left ventricular pacing alone led to further decreases in right ventricular systolic pressure and size, left ventricular systolic pressure and stroke volume. The previously augmented A wave was replaced by a prominent V wave. Therefore, when contractility of its free wall is acutely depressed, right ventricular performance is dependent on left ventricular-septal contractile contributions transmitted by the septum.(ABSTRACT TRUNCATED AT 250 WORDS)

Tricholoma matsutake, a high-class edible mushroom in Japan, has been reported to have excellent biological activities, but difficulty in cultivating the fruit bodies and limited bulk availability have restricted detailed studies. We have developed a method of culturing in tanks, enabling the bulk supply of the mycelia. The preparation (CM6271) exerts modulative effects on the immune competence of mice and rats. In this study, a sodium hydroxide extract of CM6271 was defatted followed by fractionation with a combination of ion exchange chromatography and gel filtration in order to identify the components involved in the expression of the activity, and a single peak fraction (MPG-1) was obtained with reversed phase chromatography. MPG-1 was a glycoprotein (sugar:protein ratio, 94.3:5.7) with a relative molecular mass of 360 kDa, and the sugar moiety contained about 90% glucose. NMR spectra and methylation analysis revealed that the alpha-1,4-linkage was the predominant glucan linkage with alpha-1,6- and alpha-1,2-linkages in the minority. The amino acid composition in the protein moiety was rich in glutamine, alanine, asparagine, leucine, glycine, valine, serine, threonine, isoleucine, and proline. MPG-1 was resistant to degradation with amylase or protease. The oral administration of MPG-1 promoted, in a dose-dependent manner, the recovery of the mouse natural killer cell activity and serum IL-12 level that had been reduced by the loading of restraint stress. The dose of MPG-1 (25 mg/kg) required for the expression of the effect decreases to 1/12 of that of CM6271 (300 mg/kg). Furthermore, MPG-1 formed a complex with TGF-beta1 in vitro, modulating the biological activity of TGF-beta1 by binding to its active form. These results indicate that the mycelium of T. matsutake contains a novel alpha-glucan-protein complex with immunomodulatory activities.