Plasma endoglin as a marker to predict cardiovascular events in patients with chronic coronary artery diseases

Recent clinical studies have revealed that the expression of endoglin, an accessory protein for the TGF-β receptor, is increased in patients with atherosclerotic diseases. The plasma endoglin level is thought to represent endothelial activation, inflammation, and senescence. To clarify the significance of plasma endoglin in chronic coronary artery disease. Human umbilical vein endothelial cells (HUVECs) were cultured to examine changes in soluble endoglin (s-endoglin) levels caused by atherogenic stimulation in vitro. We studied 318 patients with stable coronary artery disease who underwent a successful percutaneous coronary intervention (PCI). Patients with acute coronary syndrome were excluded. Major adverse cardiovascular events (MACE) were congestive heart failure, acute myocardial infarction, stroke, and sudden cardiac death. All patients were followed-up to examine MACE after the procedure. We confirmed that the levels of s-endoglin was increased in the culture medium of HUVECs by senescence, tumor necrosis factor-α and hydrogen peroxide. In a clinical study, mean follow-up period was 1055?±?612?days (49–2136?days) with 27 incidents of MACE (8.5%). We divided patients into three groups according to the plasma s-endoglin levels. Kaplan–Meier curves revealed that the highest endoglin group had a significantly higher MACE rate than the lowest endoglin group (log-rank test, p?=?0.009). A Cox proportional hazards model showed that chronic kidney disease, left ventricular ejection fraction and s-endoglin level were significant factors to predict MACE. Plasma endoglin could be a marker to predict cardiovascular events in patients with chronic coronary artery disease after PCI.     

Possible utility of MRI using Gd-EOB-DTPA for estimating liver functional reserve

Background  

Preoperative estimation of the liver functional reserve is important in liver surgery. We evaluated the role of dynamic magnetic resonance (MR) imaging with gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA), i.e., EOB-MRI, for determining liver functional reserve.     

Efficacy of rosuvastatin for the treatment of non‐alcoholic steatohepatitis with dyslipidemia: An open‐label,pilot study

Aim: Statins, an inhibitor of 3‐hydroxy‐3‐methylglutaryl‐coenzyme A (HMG‐CoA) reductase, are reported to be useful for the treatment of non‐alcoholic steatohepatitis (NASH). Currently, there is no proven therapy for NASH. In this study, we assessed the efficacy of rosuvastatin in NASH patients with dyslipidemia. Methods: Nineteen patients with biopsy‐proven NASH with dyslipidemia who agreed to participate in this prospective study were enrolled. The patients were treated for 24 months with 2.5 mg/day rosuvastatin. Clinical and histological alterations were comparatively evaluated before and after treatment. Standard weight‐loss counseling was continued during the treatment period. Follow‐up liver biopsy was performed in nine patients. Results: Twenty‐six percent of patients had hyperlipoproteinemia type IIa and 74% had hyperlipoproteinemia type IIb at baseline. Body mass indices were not significantly changed during the treatment. The levels of transaminases were relatively low at the beginning, and were not significantly changed during the treatment. Lipid profiles were significantly improved by the treatment with rosuvastatin for 24 months. While non‐alcoholic fatty liver disease activity score and fibrotic stage did not change significantly in all patients, they were improved in 33.3% and 33.3% individual patients, and stayed stable in 33.3% and 55.6%, respectively. Conclusion: NASH‐related metabolic parameters improved with therapy including histology in some patients. However, one of nine patients had progression of fibrosis during the treatment. Our pilot study demonstrated the efficacy of rosuvastatin for the treatment of NASH with dyslipidemia, even if transaminases are not so elevated and controlled trials are needed in the future.     

Massive bone reconstruction with heat‐treated bone graft loaded autologous bone marrow‐derived stromal cells and β‐tricalcium phosphate composites in canine models

Bone marrow‐derived stromal cells (BMSCs) contain mesenchymal stem cells that are capable of forming various mesenchymal tissues. We hypothesized that BMSCs and β‐tricalcium phosphate (β‐TCP) composites would promote the remodeling of large‐sized autologous devitalized bone grafts; therefore, the aim of this study was to evaluate the effects of the composites on the remodeling of autologous devitalized bone grafts. Autologous BMSCs cultured in culture medium containing dexamethasone (10^?7 M) were loaded into porous β‐TCP granules under low‐pressure. Theses BMSC/TCP composites were put into the bone marrow cavity of autologous heat‐treated bone (femoral diaphysis, 65‐mm long, 100°C, 30 min) and put back to the harvest site. In the contralateral side, β‐TCP without BMSC were used in the same manner as the opposite side as the control. Treatment with the BMSC/TCP composites resulted in a significant increase in thickness, bone mineral density, and matured bone volume of the cortical bone at the center of the graft compared to the control. Histological analysis showed matured regenerated bone in the BMSC loaded group. These results indicate that BMSC/TCP composites facilitated bone regeneration and maturation at the graft site of large‐sized devitalized bone. This method could potentially be applied for clinical use in the reconstruction of large bone defects such as those associated with bone tumors. © 2013 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 31:1308–1316, 2013

     

Intravenous lidocaine and magnesium for management of intractable trigeminal neuralgia: a case series of nine patients

Most patients suffering from trigeminal neuralgia (TN) benefit from medical therapy, for example carbamazepin, gabapentin, and pregabalin, individually or in combination. Nonetheless, some patients experience severe and intractable pain despite such medication, or the medication eliminates their pain but they experience intolerable side effects sufficient to warrant discontinuation. Intravenous magnesium and lidocaine have been used for management of intractable neuropathic pain. We treated nine patients with TN by using an intravenous infusion of a combination of 1.2 g magnesium and 100 mg lidocaine for 1 hour, once a week for 3 weeks. All patients experienced sound pain relief after the combined intravenous infusion therapy. Two patients experienced short and mild dizziness after the therapy, but no severe side effects were reported.     

Different TRPV1‐mediated brain responses to intragastric infusion of capsaicin and capsiate

Capsaicin and capsiate, which is an analogue of capsaicin, are agonists of capsaicin‐binding transient potential vanilloid 1 (TRPV1) receptors. However, their physiological effects are different. Capsaicin induces thermogenesis and nociception, while the different kinetics of capsiate result in thermogenesis without nociception in the oral cavity. In the present study, using functional magnetic resonance imaging, we compared the brain activation after intragastric infusion of non‐nociceptive levels of capsaicin and capsiate in wild‐type and TRPV1‐knockout (KO) mice. Capsaicin activated several brain regions, such as the periaqueductal grey (PAG), thalamic nuclei and hypothalamus, including the medial preoptic area (mPOA) and ventromedial hypothalamus (VMH). Most of these areas were not activated in TRPV1‐KO mice. Capsiate activated several regions, including the thalamic nuclei, mPOA and VMH but not PAG in wild‐type mice. Most of the activated areas were not activated by intragastric capsiate infusion in TRPV1‐KO mice. These results demonstrate that TRPV1 is critical for the induction of activation in the hypothalamus by capsaicin and capsiate, and these distinct brain activations could help to explain the individual physiological reactions of capsaicin and capsiate.     

Correction to: Cost-effectiveness of mass screening for dipstick hematuria in Japan

Clinical and Experimental Nephrology -