Effect of preoperative statin therapy on myocardial protection and morbidity endpoints following off-pump coronary bypass surgery in patients with elevated C-reactive protein level

BACKGROUND: The aim of this study was to investigate the effects of preoperative statin therapy on myocardial protection and morbidity endpoints following off-pump coronary bypass graft surgery (OPCAB) in patients with elevated serum high-sensitivity C-reactive protein (hs-CRP) levels. METHODS: Of the 492 patients who underwent multivessel OPCAB from March 2007 to February 2009, the records of 144 patients whose baseline hs-CRP level > 2 mg/L were reviewed. According to the history of preoperative statin therapy for at least one week, patients were classified as either statin group or control group (72 subjects each). Preoperative and operative characteristics and postoperative data including troponin (Tn)-T level and major morbidity endpoints were obtained and compared. Major morbidity endpoints were defined as permanent stroke, renal dysfunction, hemostatic re-exploration, deep sternal wound infection, and the number of patients requiring prolonged ventilation. RESULTS: Preoperative and operative characteristics were similar between the two groups. There were no significant differences in the incidence of morbidity endpoints between the two groups, except for the number of patients requiring dialysis, which was significantly lower in the statin group (8 vs. 1, P = 0.033). Tn-T level at 24 h after surgery was also significantly lower in the statin group. CONCLUSIONS: In this study, we observed beneficial effects of preoperative statin therapy for at least one week in terms of less myocardial enzyme release and fewer patients requiring dialysis following OPCAB in patients whose preoperative hs-CRP was elevatedope

The ERK MAPK Pathway Is Essential for Skeletal Development and Homeostasis

Mitogen-activated protein kinases (MAPKs) are a family of protein kinases that function as key signal transducers of a wide spectrum of extracellular stimuli, including growth factors and pro-inflammatory cytokines. Dysregulation of the extracellular signal-regulated kinase (ERK) MAPK pathway is associated with human skeletal abnormalities including Noonan syndrome, neurofibromatosis type 1, and cardiofaciocutaneous syndrome. Here, we demonstrate that ERK activation in osteoprogenitors is required for bone formation during skeletal development and homeostasis. Deletion of Mek1 and Mek2, kinases upstream of ERK MAPK, in osteoprogenitors (Mek1(Osx)Mek2(-/-)), resulted in severe osteopenia and cleidocranial dysplasia (CCD), similar to that seen in humans and mice with impaired RUNX2 function. Additionally, tamoxifen-induced deletion of Mek1 and Mek2 in osteoprogenitors in adult mice (Mek1(Osx-ERT)Mek2(-/-)) significantly reduced bone mass. Mechanistically, this corresponded to decreased activation of osteoblast master regulators, including RUNX2, ATF4, and beta-catenin. Finally, we identified potential regulators of osteoblast differentiation in the ERK MAPK pathway using unbiased phospho-mass spectrometry. These observations demonstrate essential roles of ERK activation in osteogenesis and bone formation

The uncalibrated pulse contour cardiac output during off-pump coronary bypass surgery: performance in patients with a low cardiac output status and a reduced left ventricular function

BACKGROUND: We compared the continuous cardiac index measured by the FloTrac/Vigileo™ system (FCI) to that measured by a pulmonary artery catheter (CCI) with emphasis on the accuracy of the FCI in patients with a decreased left ventricular ejection fraction (LVEF) and a low cardiac output status during off-pump coronary bypass surgery (OPCAB). We also assessed the influence of several factors affecting the pulse contour, such as the mean arterial pressure (MAP), the systemic vascular resistance index (SVRI) and the use of norepinephrine. METHODS: Fifty patients who were undergoing OPCAB (30 patients with a LVEF ≥ 40%, 20 patients with a LVEF < 40%) were enrolled. The FCI and CCI were measured and we performed a Bland-Altman analysis. Subgroup analyses were done according to the LVEF (< 40%), the CCI (≤ 2.4 L/min/m), the MAP (60-80 mmHg), the SVRI (1,600-2,600 dyne/s/cm(5)/m(2)) and the use of norepinephrine. RESULTS: The FCI was reliable at all the time points of measurement with an overall bias and limit of agreement of -0.07 and 0.67 L/min/m(2), respectively, resulting in a percentage error of 26.9%. The percentage errors in the patients with a decreased LVEF and in a low cardiac output status were 28.2% and 22.3%, respectively. However, the percentage error in the 91 data pairs outside the normal range of the SVRI was 40.2%. CONCLUSIONS: The cardiac output measured by the FloTrac/Vigileo™ system was reliable even in patients with a decreased LVEF and in a low cardiac output status during OPCAB. Acceptable agreement was also noted during the period of heart displacement and grafting of the obtuse marginalis branch.ope

Antioxidant and Anti-Inflammatory Effects of Shungite against Ultraviolet B Irradiation-Induced Skin Damage in Hairless Mice

As fullerene-based compound applications have been rapidly increasing in the health industry, the need of biomedical research is urgently in demand. While shungite is regarded as a natural source of fullerene, it remains poorly documented. Here, we explored the in vivo effects of shungite against ultraviolet B- (UVB-) induced skin damage by investigating the physiological skin parameters, immune-redox profiling, and oxidative stress molecular signaling. Toward this, mice were UVB-irradiated with 0.75 mW/cm2 for two consecutive days. Consecutively, shungite was topically applied on the dorsal side of the mice for 7 days. First, we found significant improvements in the skin parameters of the shungite-treated groups revealed by the reduction in roughness, pigmentation, and wrinkle measurement. Second, the immunokine profiling in mouse serum and skin lysates showed a reduction in the proinflammatory response in the shungite-treated groups. Accordingly, the redox profile of shungite-treated groups showed counterbalance of ROS/RNS and superoxide levels in serum and skin lysates. Last, we have confirmed the involvement of Nrf2- and MAPK-mediated oxidative stress pathways in the antioxidant mechanism of shungite. Collectively, the results clearly show that shungite has an antioxidant and anti-inflammatory action against UVB-induced skin damage in hairless mice

Hemodynamic management during off-pump coronary artery bypass surgery: a narrative review of proper targets for safe execution and troubleshooting

Off-pump coronary surgery requires mechanical cardiac displacement, which results in bi-ventricular systolic and diastolic dysfunction. Although transient, subsequent hemodynamic deterioration can be associated with poor prognosis and, in extreme cases, emergency conversion to on-pump surgery, which is associated with high morbidity and mortality. Thus, appropriate decision-making regarding whether the surgery can be proceeded based on objective hemodynamic targets is essential before coronary arteriotomy. For adequate hemodynamic management, avoiding myocardial oxygen supply-demand imbalance, which includes maintaining mean arterial pressure above 70 mmHg and preventing an increase in oxygen demand beyond the patient’s coronary reserve, must be prioritized. Maintaining mixed venous oxygen saturation above 60%, which reflects the lower limit of adequate global oxygen supply-demand balance, is also essential. Above all, severe mechanical cardiac displacement incurring compressive syndromes, which cannot be overcome by adjusting major determinants of cardiac output, should be avoided. An uncompromising form of cardiac constraint can be ruled out as long as the central venous pressure is not equal to or greater than the pulmonary artery diastolic (or occlusion) pressure, as this would reflect tamponade physiology. In addition, transesophageal echocardiography should be conducted to rule out mechanical cardiac displacement-induced ventricular interdependence, dyskinesia, severe mitral regurgitation, and left ventricular outflow tract obstruction with or without systolic motion of the anterior leaflet of the mitral valve, which cannot be tolerated during grafting. Finally, the ascending aorta should be carefully inspected for gas bubbles to prevent hemodynamic collapse caused by a massive gas embolism obstructing the right coronary ostium

Cellular and Tissue Selectivity of AAV Serotypes for Gene Delivery to Chondrocytes and Cartilage

Background: Despite several studies on the effect of adeno-associated virus (AAV)-based therapeutics on osteoarthritis (OA), information on the transduction efficiency and applicable profiles of different AAV serotypes to chondrocytes in hard cartilage tissue is still limited. Moreover, the recent discovery of additional AAV serotypes makes it necessary to screen for more suitable AAV serotypes for specific tissues. Here, we compared the transduction efficiencies of 14 conventional AAV serotypes in human chondrocytes, mouse OA models, and human cartilage explants obtained from OA patients. Methods: To compare the transduction efficiency of individual AAV serotypes, green fluorescent protein (GFP) expression was detected by fluorescence microscopy or western blotting. Likewise, to compare the transduction efficiencies of individual AAV serotypes in cartilage tissues, GFP expression was determined using fluorescence microscopy or immunohistochemistry, and GFP-positive cells were counted. Results: Only AAV2, 5, 6, and 6.2 exhibited substantial transduction efficiencies in both normal and OA chondrocytes. All AAV serotypes except AAV6 and rh43 could effectively transduce human bone marrow mesenchymal stem cells. In human and mouse OA cartilage tissues, AAV2, AAV5, AAV6.2, AAV8, and AAV rh39 showed excellent tissue specificity based on transduction efficiency. These results indicate the differences in transduction efficiencies of AAV serotypes between cellular and tissue models. Conclusions: Our findings indicate that AAV2 and AAV6.2 may be the best choices for AAV-mediated gene delivery into intra-articular cartilage tissue. These AAV vectors hold the potential to be of use in clinical applications to prevent OA progression if appropriate therapeutic genes are inserted into the vector

Normal Ambulatory 24-Hour Esophageal pH Values in Koreans -A Multicenter Study-

Ambulatory 24-hr esophageal pH monitoring is considered the gold standard for diagnosing gastroesophageal reflux disease. The aim of this study was to establish normal values for gastroesophageal acid exposure in healthy Koreans. Fifty healthy volunteers (24 males and 26 females; mean age, 45 yr) without reflux symptoms and without reflux esophagitis or hiatal hernia on upper endoscopy underwent ambulatory 24-hr esophageal pH monitoring after esophageal manometry. The 95th percentiles for the reflux parameters were: the percent total time pH <4, 3.7%; the percent upright time pH <4, 5.7%; the percent supine time pH <4, 1.0%; the number of reflux episodes with pH <4, 76.5; the number of reflux episodes with pH <4 for >5 min, 1.5; the duration of the longest episode, 12.5 min; and the composite score, 14.2. Age and gender were not associated with any of the pH parameters. In conclusion, physiological gastroesophageal reflux occurs in healthy Koreans. These normal esophageal pH values will provide reference data for clinical and research studies in Korea