High pressure conditions promote the proliferation of rat cultured mesangial cells in vitro

AbstractGlomerular capillary pressure is involved in the development of chronic renal failure and has at least two effects on mesangial cells: transmembrane hydrostatic pressure and stretch. To clarify whether pure hydrostatic pressure itself affects the proliferation of cultured rat mesangial cells, we compared the cell number under atmospheric pressure condition with high pressure condition. At 24 and 48h with 0.5% serum, cell number was significantly higher under high pressure condition than under atmospheric pressure condition. At 48h, cell number under high pressure condition was increased in a pressure-dependent manner. Furthermore, flow cytometric assay indicated that pressure-load could promote DNA synthesis rate at S phase and enhance G1/S progression induced by low concentration of serum (0.5%). These results suggest that pure hydrostatic pressure itself can promote the proliferation of cultured rat mesangial cells by advancing cell cycle progression in vitro

Beneficial effect of tetrahydrobiopterin on ischemia-reperfusion injury in isolated perfused rat hearts

AbstractObjective: It has recently been proposed that nitric oxide synthase, in the presence of suboptimal levels of tetrahydrobiopterin, an essential cofactor of this enzyme, might favor increased production of oxygen radicals. The aim of this study was to clarify whether supplement with tetrahydrobiopterin would exert a cardioprotective effect against ischemia-reperfusion injury. Methods: Isolated perfused rat hearts were subjected to 30 minutes of global ischemia and 30 minutes of reperfusion at 37°C. Hearts were treated with tetrahydrobiopterin or vehicle for 5 minutes just before ischemia and during the first 5 minutes of the reperfusion period. Effects of tetrahydrobiopterin on left ventricular function, myocardial contents of lipid peroxidation and high-energy phosphates, and levels of lactate dehydrogenase and nitrite plus nitrate in perfusate during ischemia and after reperfusion were estimated and further compared with those of superoxide dismutase plus catalase or l-ascorbic acid. Results: Tetrahydrobiopterin and superoxide dismutase plus catalase both improved contractile and metabolic abnormalities in reperfused hearts. On the other hand, l-ascorbic acid at a dose having an equipotent radical scavenging activity with tetrahydrobiopterin did not significantly affect the postischemic changes. Although tetrahydrobiopterin and superoxide dismutase plus catalase significantly alleviated ischemic contracture during ischemia, diminished perfusate levels of nitrite plus nitrate after reperfusion were restored only with tetrahydrobiopterin. Conclusion: Results demonstrated that tetrahydrobiopterin lessens ischemia-reperfusion injury in isolated perfused rat hearts, probably independent of its intrinsic radical scavenging action. The cardioprotective effect of tetrahydrobiopterin implies that tetrahydrobiopterin could be a novel and effective therapeutic option in the treatment of ischemia-reperfusion injury.J Thorac Cardiovasc Surg 2002;124:775-8

bFGF Regulates PI3-Kinase-Rac1-JNK Pathway and Promotes Fibroblast Migration in Wound Healing

Fibroblast proliferation and migration play important roles in wound healing. bFGF is known to promote both fibroblast proliferation and migration during the process of wound healing. However, the signal transduction of bFGF-induced fibroblast migration is still unclear, because bFGF can affect both proliferation and migration. Herein, we investigated the effect of bFGF on fibroblast migration regardless of its effect on fibroblast proliferation. We noticed involvement of the small GTPases of the Rho family, PI3-kinase, and JNK. bFGF activated RhoA, Rac1, PI3-kinase, and JNK in cultured fibroblasts. Inhibition of RhoA did not block bFGF-induced fibroblast migration, whereas inhibition of Rac1, PI3-kinase, or JNK blocked the fibroblast migration significantly. PI3-kinase-inhibited cells down-regulated the activities of Rac1 and JNK, and Rac1-inhibited cells down-regulated JNK activity, suggesting that PI3-kinase is upstream of Rac1 and that JNK is downstream of Rac1. Thus, we concluded that PI3-kinase, Rac1, and JNK were essential for bFGF-induced fibroblast migration, which is a novel pathway of bFGF-induced cell migration

Marylosides A-G, Norcycloartane Glycosides from Leaves of Cymbidium Great Flower ‘Marylaurencin’

Seven novel norcycloartane glycosides, maryloside A–G (1–7), were isolated from the leaves of Cymbidium Great Flower ‘Marylaurencin’, along with a known norcycloartane glycoside, cymbidoside (8). These structures were determined on the basis of mainly NMR experiments as well as chemical degradation and X-ray crystallographic analysis. The isolated compounds (1–6 and 8) were evaluated for the inhibitory activity on lipopolysaccharide (LPS) and interferon-γ (IFN-γ)-stimulated nitric oxide (NO) production in RAW 264.7 cells. Consequently, 1 and 3 exhibited moderate activity

Heparin-Eluting Tissue-Engineered Bioabsorbable Vascular Grafts

The creation of small-diameter tissue-engineered vascular grafts using biodegradable materials has the potential to change the quality of cardiovascular surgery in the future. The implantation of these tissue-engineered arterial grafts has yet to reach clinical application. One of the reasons for this is thrombus occlusion of the graft in the acute phase. In this paper, we first describe the causes of accelerated thrombus formation and discuss the drugs that are thought to inhibit thrombus formation. We then review the latest research on methods to locally bind the anticoagulant heparin to biodegradable materials and methods to extend the duration of sustained heparin release. We also discuss the results of studies using large animal models and the challenges that need to be overcome for future clinical applications

The Evolution of Tissue Engineered Vascular Graft Technologies: From Preclinical Trials to Advancing Patient Care

Currently available synthetic grafts have contributed to improved outcomes in cardiovascular surgery. However, the implementation of these graft materials at small diameters have demonstrated poor patency, inhibiting their use for coronary artery bypass surgery in adults. Additionally, when applied to a pediatric patient population, they are handicapped by their lack of growth ability. Tissue engineered alternatives could possibly address these limitations by producing biocompatible implants with the ability to repair, remodel, grow, and regenerate. A tissue engineered vascular graft (TEVG) generally consists of a scaffold, seeded cells, and the appropriate environmental cues (i.e., growth factors, physical stimulation) to induce tissue formation. This review critically appraises current state-of-the-art techniques for vascular graft production. We additionally examine current graft shortcomings and future prospects, as they relate to cardiovascular surgery, from two major clinical trials