Development of in situ crosslinked hyaluronan as an adjunct to vitrectomy surgery.

Ophthalmologists have used hyaluronan (HA) products as adjuncts to ocular surgery since the 1970s. However, HA products are not always functional in surgeries of the posterior eye segment due to their lack of biomechanical strength. In this study, we developed an in situ crosslinked HA (XL-HA) and evaluated its potential as an adjunct to vitrectomy surgery in an in vitro model with a triamcinolone acetonide (TA) layer used as a pseudo residual vitreous cortex (RVC). Within a few minutes at concentrations over 0.9%, XL-HA, generated by the click chemistry of HA-dibenzocyclooctyne and HA-azidoethylamine, formed a hydrogel with the appropriate hardness for tweezers peeling. XL-HA (concentration, 0.76-1.73%) without dispersion successfully entered the TA layer and removed more than 45% of the total TA. Dynamic viscoelasticity helps to explain the rheological behavior of hydrogels, and the assessment results for XL-HA indicated that suitable concentrations were between 0.97% and 1.30%. For example, 1.30% XL-HA hydrogel reached sufficient hardness at 3 min for tweezers peeling, and the TA removal ability exceeded 70%. These results demonstrated that XL-HA was a potential adjunct to successful vitrectomy.

Association between coronary artery calcium score on non-contrast chest computed tomography and all-cause mortality among patients with congestive heart failure.

Coronary artery calcium (CAC) score is a robust prognostic tool to predict cardiac events. Although patients with congestive heart failure (CHF) occasionally undergo non-contrast computed tomography (NCCT), the prognostic utility of CAC by NCCT is not widely known. We aimed to determine if CAC measured on NCCT is associated with all-cause mortality (ACM) among patients with CHF. We identified 550 patients admitted due to CHF who underwent NCCT. Patients were categorized into three groups according to CAC scores 0, 1-999, and ≥ 1000. The multivariate Cox proportional hazards model was used to assess if CAC by NCCT was associated with ACM after adjusting for traditional coronary artery disease (CAD) risk factors, brain natriuretic peptide and left ventricular ejection fraction (LVEF). In a subset of 245 patients with invasive coronary angiography (ICA), the associations between CAC scores and ACM were assessed in the multivariate Cox proportional hazards model. Further, we assessed if CAC increased statin use at discharge. During a mean follow-up of 3.3 ± 3.1 years, ACM occurred in 168 patients (30.55%). Compared with patients with CAC 0, those with CAC ≥ 1000 (HR 1.564, 95% CI 0.969-2.524, P = 0.067) were more likely to experience ACM, while those with CAC score 1-999 (HR 0.971, 95% CI 0.673-1.399, P = 0.873) were not. Similarly, a trend toward significance was observed in patients with LVEF < 40% (HR 2.124, 95% CI 0.929-4.856, P = 0.074). In the sub-analysis, patients with CAC ≥ 1000 had increased ACM compared to those with CAC 0, only if ICA ≥ 50% (HR 3.668, 95% CI 1.141-11.797, P = 0.029). Multivariate logistic regression revealed that statin use at discharge was increased with ICA ≥ 50%, but not CAC. The CAC score measured by NCCT tended to be associated with ACM among CHF patients. Statin use was not increased by CAC on NCCT.

Substrate specificity of Chondroitinase ABC I based on analyses of biochemical reactions and crystal structures in complex with disaccharides.

Chondroitinase ABC I (cABC-I) is the enzyme which cleaves the ß-1,4 glycosidic linkage of chondroitin sulfate (CS) by ß-elimination. To elucidate more accurately the substrate specificity of cABC-I, we evaluated the kinetic parameters of cABC-I and its reactivity with CS isomers displaying less structural heterogeneity as substrates, e.g., approximately 90 percent of disaccharide units in Chondroitin sulfate A (CSA) or Chondroitin sulfate C (CSC) is D-glucuronic acid and 4-O-sulfated N-acetyl galactosamine (GalNAc) (A-unit) or D-glucuronic acid and 6-O-sulfated GalNAc (C-unit), respectively. cABC-I showed the highest reactivity to CSA and CSC among all CS isomers, and the kcat/Km of cABC-I was higher for CSA than for CSC. Next, we determined the crystal structures of cABC-I in complex with CS disaccharides, and analyzed the crystallographic data in combination with molecular docking data. Arg500 interacts with 4-O-sulfated and 6-O-sulfated GalNAc residues. The distance between Arg500 and the 4-O-sulfate group was 0.8 Å shorter than that between Arg500 and the 6-O-sulfated group. Moreover, it is likely that the 6-O-sulfated group is electrostatically repulsed by the nearby Asp490. Thus, we demonstrated that cABC-I has the highest affinity for the CSA richest in 4-O-sulfated GalNAc residues among all CS isomers. Recently, cABC-I was used to treat lumbar disc herniation. The results provide useful information to understand the mechanism of the pharmacological action of cABC-I.

Contemporary Management of Stable Coronary Artery Disease　- Implications of the ISCHEMIA Trial.

Coronary artery disease (CAD) remains a leading cause of mortality and morbidity in developed countries. Although urgent revascularization is the cornerstone of management of acute coronary syndrome (ACS), for patients with stable CAD recent large-scale clinical trials indicate that a mechanical 'fix' of a narrowed artery is not obviously beneficial; ACS and stable CAD are increasingly recognized as different clinical entities. We review the perspectives on (1) modifying the diagnostic pathway of stable CAD with the incorporation of modern estimates of pretest probability, (2) non-imaging evaluations based on their availability, (3) the optimal timing of invasive coronary angiography and revascularization, and (4) the implementation of medical therapy during the work-up.

Advances in Understanding the Mechanism of Ophthalmic Viscosurgical Device Retention in the Anterior Chamber or on the Corneal Surface during Ocular Surgery.

Retention durability, especially in the eye, is one of the most important properties of ophthalmic viscosurgical devices (OVDs) during ocular surgery. However, the information on the physical properties of OVDs is insufficient to explain their retention durability. The purpose of this study is to clarify the mechanism of OVD retention to improve understanding of the behavior of OVDs during ocular surgery. To elucidate the mechanism of OVD retention, we have developed a new test method for measuring repulsive force. As a result, the maximum repulsive force of OVDs was positively and well correlated with the retention durability of investigated OVDs. Consequently, we demonstrated that the repulsive force could be used as an index of retention durability on the ocular surface and in the eye. We directly compared the intraocular retention durability of three OVDs (Shellgan, Viscoat, and Opegan-Hi) in ex vivo porcine eyes. Opegan-Hi was immediately removed from the anterior chamber, but Shellgan and Viscoat remained largely in the anterior chamber as determined by fluorescence imaging. These results showed that the intraocular retention behavior of OVDs was similar to their ocular surface behavior in our previous report, suggesting that retention durability is dependent on the OVD itself. The retention durability of Shellgan seemed to be higher than that of Viscoat, and the maximum repulsive force of Shellgan was 1.35-fold higher than that of Viscoat. Therefore, the repulsive force might be a useful index for assessing the difference in the retention durability between OVDs such as Shellgan and Viscoat.

Heart Rate After Resuscitation From Out-of-Hospital Cardiac Arrest due to Acute Coronary Syndrome Is an Independent Predictor of Clinical Outcome.

BACKGROUND: Heart rate (HR) is a useful predictor of cardiovascular disease, especially in acute coronary syndrome (ACS). However, it is unclear whether there is an association between HR and clinical outcomes after resuscitation from out-of-hospital cardiac arrest (OHCA) due to ACS. The aim of this study was to investigate the impact of HR on clinical outcome in individuals resuscitated from OHCA due to ACS.Methods and Results:Data from 3,687 OHCA patients between October 2002 and October 2014 were retrospectively analyzed. We divided 154 patients diagnosed with ACS into 2 groups: those with tachycardia (HR >100 beats/min, n=71) and those without tachycardia (HR ≤100 beats/min, n=83) after resuscitation. The primary endpoint was 1-year mortality and the secondary endpoint was neurological injury at discharge according to cerebral performance category score. Overall, mean HR was 95.6 beats/min. There were several significant differences in patient characteristics, indicating poor general condition of patients with tachycardia. Mortality at 1-year was 41.6%, and neurological injury at discharge was observed in 44.1% of individuals. In the multivariate analysis, tachycardia after resuscitation was an independent predictor of both 1-year mortality (hazard ratio, 2.66; 95% CI: 1.20-5.85; P=0.03) and neurological injury at discharge (odds ratio, 2.65; 95% CI: 1.27-5.55; P=0.04). CONCLUSIONS: In patients who recovered from OHCA due to ACS, tachycardia after resuscitation predicted poor clinical outcome.

Frailty and coronary plaque characteristics on optical coherence tomography.

The relationship between frailty and plaque characteristics is unclear and was investigated by optical coherence tomography (OCT) in this study. One hundred and four patients undergoing OCT before percutaneous coronary intervention were evaluated. Frailty was defined as a clinical frailty scale score of ≧6. Frailty was found in 16% of the patients (17/104). Compared with the nonfrail patients, frail patients showed significantly lower body mass index (BMI; 20.8 ± 4.0 kg/m2 vs. 25.0 ± 3.9 kg/m2, P < 0.001), less dyslipidemia [47% (8/17) vs. 75% (65/87), P = 0.023], lower triglycerides levels (95 ± 42 mg/dL vs. 147 ± 81 mg/dL, P < 0.001), less use of statin [29% (5/17) vs. 60% (52/87), P = 0.021], more lipid-rich plaque [82% (14/17) vs. 46% (40/87), P = 0.006] on OCT, more thin-cap fibroatheromas [TCFAs; 71% (12/17) vs. 26% (23/87), P < 0.001], more plaque rupture [53% (9/17) vs. 25% (22/87), P = 0.023], and significantly higher adverse clinical outcomes (death, acute myocardial infarction, acute heart failure, acute coronary syndrome, or target lesion revascularization) [24% (4/17) vs. 6% (5/87), P = 0.007]. The multivariable analysis showed that frailty was one of the independent predictors of TCFAs (odds ratio 8.95, 95% CI 2.40-33.32, P = 0.001). In conclusion, frailty was associated with high plaque vulnerability due to more lipid-rich plaque, TCFAs and plaque rupture on OCT regardless of low BMI, less dyslipidemia and low triglycerides levels, and frail patients had higher adverse clinical outcomes.

Comparing the effects of milrinone and olprinone in patients with congestive heart failure.

Phosphodiesterase-3 (PDE3) inhibitors are widely used among patients with congestive heart failure (CHF). However, no studies have compared the cardiovascular outcomes between different PDE3 inhibitors in CHF management. In this report, we retrospectively compared the clinical benefits of two PDE3 inhibitors, milrinone and olprinone, to determine which better controls the progression of CHF. A total of 288 hospitalized patients who received PDE3 inhibitors [(milrinone; n = 77 and olprinone; n = 211, respectively)] for CHF were retrospectively enrolled. The primary endpoint was defined as having a major adverse cardiovascular and cerebrovascular event (MACCE) or cardiac death by day 60. Kaplan-Meier curves and multivariate Cox proportional models were used to compare the outcomes for patients treated with milrinone and olprinone. We found no significant differences in the baseline characteristics between the two groups. In patients treated with milrinone, a greater incidence of a MACCE or cardiac death was observed (log rank; P = 0.005 and P = 0.01, respectively). Milrinone-treated patients with ischemic heart disease and chronic kidney disease (CKD) at stage ≥ 4 presented with greater incidence of MACCE (log rank; P < 0.001 and P = 0.006, respectively). Similarly, these patients were significantly more likely to succumb to cardiac death (log rank; P < 0.001 and P = 0.02). Multivariate Cox proportional hazard models demonstrated that milrinone treatment was an independent predictor of MACCE [hazard ratio (HR) 3.17; 95% CI 1.64-6.10] and cardiac death (HR 2.64; 95% CI 1.42-4.91). Oral administration of a ß-blocker at discharge occurred more often in the olprinone-treated patients than in the milrinone-treated patients (63% vs. 29%, P = 0.004). We compared the outcomes of milrinone and olprinone treatment in patients with CHF. Those treated with milrinone were more likely to succumb to a MACCE or cardiac death within 60 days of treatment, which was especially true for patients with ischemic heart disease or CKD.

Plaque characteristics and slow flow during percutaneous coronary intervention of irregular protrusion by optical coherence tomography.

Irregular protrusion on optical coherence tomography (OCT) is associated with clinical events and target lesion revascularization. We investigated clinical and procedure characteristics, plaque characteristics, slow flow after stent implantation, and clinical outcomes with irregular protrusion using OCT. Eighty-four lesions in 76 patients undergoing OCT before percutaneous coronary intervention were evaluated. Irregular protrusion was defined as protrusion of material with an irregular surface into the lumen between stent struts with a maximum height of ≥100 µm. Lesions with irregular protrusion were found in 56% (47/84). Compared with lesions without irregular protrusion, those with irregular protrusion had significantly higher low-density lipoprotein cholesterol (LDL-C) levels (108 ± 31 mg/dl vs. 95 ± 25 mg/dl, P = 0.044); a tendency toward decreased use of statins [44% (19/43) vs. 67% (22/33), P = 0.065]; significantly larger reference vessel diameter (3.12 ± 0.53 mm vs. 2.74 ± 0.63 mm, P = 0.004); more frequent slow flow after stent implantation [38% (18/47) vs. 11% (4/37), P = 0.006]; higher incidence of thin-cap fibroatheromas [TCFAs; 49% (23/47) vs. 5% (2/37), P < 0.001]; plaque rupture [40% (19/47) vs. 16% (6/37), P = 0.018]; and a tendency higher incidence of 1-year adverse clinical outcomes (death, acute myocardial infarction, acute coronary syndrome, or target lesion revascularization) [12% (5/43) vs. 0% (0/33), P = 0.075]. In conclusion, irregular protrusion on OCT was associated with high plaque vulnerability, higher LDL-C, less frequent use of statin, larger vessel diameter, slow flow after stent implantation, and 1-year adverse clinical outcomes.

The relationship between serum indoxyl sulfate and the renal function after catheter ablation of atrial fibrillation in patients with mild renal dysfunction.

Indoxyl sulfate (IS), a protein-bound uremic toxin, induces renal disorders and atrial fibrillation (AF). It is well known that renal dysfunction is a risk factor for AF and radiofrequency catheter ablation (RFCA) improves the renal function. However, the improvement in the renal function after RFCA in patients with early stage chronic kidney disease (CKD) and the serial changes in the IS level have not been fully elucidated. This study aimed to investigate whether IS affects the improvement in the renal function. A total of 91 consecutive patients with mild kidney dysfunction (CKD stage I-II) who underwent RFCA and maintained sinus rhythm were prospectively enrolled. The plasma IS level and estimated glomerular filtration rate (eGFR) were determined before, 3 months, and 1 year after RFCA. The patients were divided according to the IS quartiles (Q1-4; < 0.4, 0.4-0.7, 0.7-1.2, and > 1.2 µg/ml). There was no significant difference in the eGFR among the IS quartiles. A significantly higher eGFR improvement rate was obtained for IS-Q4 than the other quartiles (p = 0.039). The IS-Q4 IS level significantly decreased at 1 year after RFCA (1.8 ± 0.8 to 1.2 ± 0.7 µg/ml, p < 0.01). The multivariable logistic model revealed that a high-IS level (IS-Q4) was an independent predictor of an eGFR improvement (OR 3.33; 95% CI 1.16-9.59; p = 0.026). A high-IS level reduction after RFCA improved the renal function in AF patients with mild kidney dysfunction.

Rheological and Adhesive Properties to Identify Cohesive and Dispersive Ophthalmic Viscosurgical Devices.

The purpose of this study is to evaluate the usefulness of the rheological properties and adhesive force of ophthalmic viscosurgical devices (OVDs) as parameters for understanding and identifying the surgical behavior of cohesive and dispersive OVDs. The apparent viscosity, and the storage and loss moduli (dynamic rheological parameters) of 50% chondroitin sulfate (CS), 3% sodium hyaluronate (HA), Shellgan (the combination of 3% HA and 4% CS), Opegan (1% HA with a low molecular mass) and Opegan-Hi (1% HA with a high molecular mass) were obtained with a rheometer. The adhesive force of each sample was measured by using a texture analyzer. Opegan-Hi showed a solid-like behavior, while 50% CS showed a fluid-like behavior from their apparent viscosity and dynamic rheological parameters. Shellgan, 3% HA, and Opegan exhibited similar rheological properties and intermediate characteristics between Opegan-Hi and 50% CS, although their respective values were slightly different. Among these OVD samples, the adhesive force was higher in the order of 50% CS > Shellgan, 3% HA > Opegan > Opegan-Hi. The adhesive force of dispersive OVDs tended to be higher than that of cohesive OVDs, which correlated well with the removal times of OVDs from the eye that have previously been reported. In conclusion, we demonstrated that cohesive OVDs and dispersive OVDs have particular rheological and adhesive properties that can be applied to identify both types. These parameters obtained in this study provide useful information for a greater understanding and prediction of the behavior of OVDs in the eye during surgery.

Prognostic Significance of Serum Indoxyl Sulfate and Albumin for Patients with Cardiovascular Disease.

The progression of renal dysfunction reduces serum albumin and deteriorates the binding capacity of protein-bound uremic toxins. We evaluated the prognostic implications of serum indoxyl sulfate (IS) and albumin levels in patients with cardiovascular disease.We prospectively enrolled 351 consecutive patients undergoing percutaneous revascularization for coronary artery disease or peripheral artery disease. The primary endpoint was all-cause mortality. Patients were assigned to four groups according to the median levels of serum IS (0.1 mg/dL) and albumin (3.9 g/dL).During the median follow-up time of 575 days, 16 patients died. The IS level was significantly higher in nonsurvivors (0.33 versus 0.85 mg/dL, P < 0.05). On the Kaplan-Meier curve, the high IS/low albumin group presented the highest mortality rate (log-rank test, P < 0.01). Cox proportional hazard analysis revealed that high IS/low albumin (hazard ratio (HR): 5.33; 95% confidence interval (CI): 1.71-16.5; P < 0.01), diastolic pressure (HR: 0.94; 95% CI: 0.91-0.98; P < 0.01), prior stroke (HR: 4.54; 95% CI: 1.33-15.4; P = 0.01), and left ventricular ejection fraction (LVEF) (HR: 0.92; 95% CI: 0.88-0.96; P < 0.001) were associated with increased mortality. Furthermore, the combination of IS and albumin levels significantly conferred an additive value to LVEF for predicting mortality (C-statistic: 0.69 versus 0.80; P < 0.001; net reclassification improvement: 0.83; P < 0.001; integrated discrimination improvement: 0.02; P = 0.02).A lower albumin level adds potentiating effects on IS as a prognostic factor for cardiovascular disease.

Combined assessment of left ventricular end-diastolic pressure and ejection fraction by left ventriculography predicts long-term outcomes of patients with ST-segment elevation myocardial infarction.

In patients with ST-segment elevation myocardial infarction (STEMI), it is unclear if combined assessment of left ventricular end-diastolic pressure (LVEDP) and left ventricular ejection fraction (LVEF) improves prediction of major adverse cardiac events (MACE). We analyzed data from 266 STEMI patients who underwent successful percutaneous coronary intervention and subsequent left ventriculography (LVG). Patients were divided into 4 groups, as follows: Group 1, LVEDP < 21 mmHg and LVEF ≥ 55%; Group 2, LVEDP < 21 mmHg and LVEF < 55%; Group 3, LVEDP ≥ 21 mmHg and LVEF ≥ 55%; and Group 4, LVEDP ≥ 21 mmHg and LVEF < 55%. Multivariate Cox proportional hazards analysis was used to determine if LVEDP and LVEF were associated with MACE (including cardiac death, non-fatal myocardial infarction, and heart failure requiring hospitalization). Change in LV parameters was assessed in the subset of 183 patients who underwent serial LVG (mean interval 6.3 ± 1.6 months). During a mean follow-up of 43 ± 31 months, 29 patients (10.9%) had a MACE. As compared to Group 1, MACE risk was significantly higher in Group 3 [hazard ratio (HR) 3.26; 95% confidence interval (CI) 1.05-10.0] and Group 4 (HR 3.99; 95% CI 1.44-11.0), but not in Group 2 (HR 0.46, 95% CI 0.54-3.96). In sub-analyses, LV end-systolic volume index after PCI was significantly higher in Group 4 than in the other groups and remained higher during follow-up. Combined LVEDP/LVEF assessment was useful in predicting MACE after successful PCI for STEMI patients and could facilitate risk stratification, as it predicts LV remodeling.

Pericoronary adipose tissue ratio is a stronger associated factor of plaque vulnerability than epicardial adipose tissue on coronary computed tomography angiography.

This study was designed to clarify the influence of pericoronary adipose tissue (PAT) on plaque vulnerability using coronary computed tomography angiography (CCTA). A total of 103 consecutive patients who underwent CCTA and subsequent percutaneous coronary intervention (PCI) using intravascular ultrasound (IVUS) for coronary artery disease were enrolled. The PAT ratio was calculated as the sum of the perpendicular thickness of the visceral layer between the coronary artery and the pericardium, or the coronary artery and the surface of the heart at the PCI site, divided by the PAT thickness without a plaque in the same vessel. PAT ratios were divided into low, mid and high tertile groups. Epicardial adipose tissue (EAT) thickness was measured at the eight points surrounding the heart. Multivariate logistic analysis was performed to determine whether the PAT ratio is predictive of vulnerable plaques (positive remodeling, low attenuation and/or spotty calcification) on CCTA or echo-attenuated plaque on IVUS. The Hounsfield unit of obstructive plaques >50% was lower in the high PAT group than in the mid and low PAT groups (47.5 ± 28.8 vs. 53.1 ± 29.7 vs. 64.7 ± 27.0, p = 0.04). In multivariate logistic analysis, a high PAT ratio was an independent, associated factor of vulnerable plaques on CCTA (OR: 3.55, 95% CI: 1.20-10.49), whereas mean EAT thickness was not (OR: 1.22, 95% CI: 0.82-1.83). We observed a similar result in predicting echo-attenuated plaque on IVUS. PAT ratio on CCTA was an associated factor of vulnerable plaques, while EAT was not. These results support the important concept of local effects of cardiac adipose tissue on plaque vulnerability.

Same or Different Drug-Eluting Stent Re-Implantation for Drug-Eluting Stent Restenosis: An Assessment Including Second-Generation Drug-Eluting Stents.

OBJECTIVES: We examined the long-term outcomes of implanting a different type of drug-eluting stent (DES), including second-generation DES, for treatment of DES-in stent restenosis (ISR). BACKGROUND: Treatment for DES-ISR has not been standardized. METHODS: The subjects were 80 patients with 89 lesions underwent DES implantation for DES-ISR. The patients were divided into the group of patients receiving the same DES for DES-ISR (Homo-stent: 24 patients, 25 lesions) and a different DES for DES-ISR (Hetero-stent: 56 patients, 64 lesions). The primary endpoint was survival free of major adverse cardiovascular events (MACE), including cardiac death, myocardial infarction, and target vessel revascularization (TVR). The secondary endpoint was late loss at 8-12 months follow-up. In the subgroup of patients who were treated with second-generation DES for DES-ISR, we also assessed the survival free of MACE. RESULTS: During a mean follow-up of 45.1 ± 21.2 months, 26 patients experienced MACE. There was no significant difference in the survival free of MACE (Log rank P = 0.17). In the sub-analysis of second generation DES, MACE was significantly higher in the Homo-stent group compared to the Hetero-stent group (Log rank P = 0.04). Late loss was significantly higher in the Homo-stent group than in the Hetero-stent group (0.86 ± 1.03 vs. 0.38 ± 0.74 mm, P = 0.03). This trend was prominent in the first-generation DES group. CONCLUSIONS: Although there was no significant difference in MACE between the Hetero-stent and the Homo-stent groups including both first and second-generation DES, the sub-analysis demonstrated different DES implantation for DES-ISR significantly improved the MACE rate among patients treated with second-generation DES. (J Interven Cardiol 2016;29:311-318).

Molecular Hydrogen Alleviates Cellular Senescence in Endothelial Cells.

BACKGROUND: Substantial evidence indicates that molecular hydrogen (H2) has beneficial vascular effects because of its antioxidant and/or anti-inflammatory effects. Thus, hydrogen-rich water may prove to be an effective anti-aging drink. This study examined the effects of H2on endothelial senescence and clarified the mechanisms involved. METHODS AND RESULTS: Hydrogen-rich medium was produced by a high-purity hydrogen gas generator. Human umbilical vein endothelial cells (HUVECs) were incubated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) for various time periods in normal or hydrogen-rich medium. The baseline H2concentration in hydrogen-rich medium was 0.55±0.07 mmol/L. This concentration gradually decreased, and H2was almost undetectable in medium after 12 h. At 24 h after TCDD exposure, HUVECs treated with TCDD exhibited increased 8OHdG and acetyl-p53 expression, decreased nicotinamide adenine dinucleotide (NAD(+))/NADH ratio, impaired Sirt1 activity, and enhanced senescence-associated ß-galactosidase. However, HUVECs incubated in hydrogen-rich medium did not exhibit these TCDD-induced changes accompanying Nrf2 activation, which was observed even after H2was undetectable in the medium. Chrysin, an inhibitor of Nrf2, abolished the protective effects of H2on HUVECs. CONCLUSIONS: H2has long-lasting antioxidant and anti-aging effects on vascular endothelial cells through the Nrf2 pathway, even after transient exposure to H2. Hydrogen-rich water may thus be a functional drink that increases longevity. (Circ J 2016; 80: 2037-2046).

Plaque Composition and No-Reflow Phenomenon During Percutaneous Coronary Intervention of Low-Echoic Structures in Grayscale Intravascular Ultrasound.

It has been reported that coronary vasa vasorum is associated with plaque vulnerability, and low-echoic structures in grayscale intravascular ultrasound (IVUS) are consistent pathologically with vasa vasorum. However, the association of low-echoic structures with plaque composition and no-reflow phenomenon during percutaneous coronary intervention (PCI) is unclear. We investigated plaque composition in virtual histology IVUS (VH-IVUS) and no-reflow phenomenon during PCI of low-echoic structures.A total of 106 lesions being treated by VH-IVUS before PCI were included in this study. Low-echoic structure was defined as a small tubular structure exterior to media without a connection to the vessel lumen in ≥ 3 consecutive crosssectional IVUS images. Lesions with low-echoic structures were found in 42% (45/106).Lesions with low-echoic structures were more prevalent in acute coronary syndrome (ACS) patients (53% [24/45] versus 20% [12/61], P < 0.001), had more positive remodeling (49% [22/45] versus 21% [13/61], P = 0.003), a larger number of VH-IVUS derived thin-cap fibroatheromas (VH-TCFAs) (0.64 ± 0.53 versus 0.05 ± 0.22, P < 0.001), more VH-TCFAs with a baseline plaque burden of 70% or more and minimal luminal area of 4.0 mm(2) or less (29% [13/45] versus 2% [1/61], P < 0.001), and more frequent no-reflow phenomenon after stent implantation and more final TIMI flow grade 0/1/2 (38% [17/45] versus 5% [3/61], P < 0.001; 9% [4/45] versus 0% [0/61], P = 0.03) than lesions without low-echo structures.Lesions with low-echoic structures in grayscale IVUS had high plaque vulnerability and were more prevalent in ACS patients, positive remolding, and VH-TCFAs, and they had more frequent no-reflow phenomenon during PCI than lesions without low-echoic structures.

Isolation and characterization of monoclonal antibodies specific for chondroitin sulfate E.

Chondroitin sulfate E (CSE) is a polysaccharide containing mainly disaccharide units of D-glucuronic acid (GlcA) and 4,6-O-disulfated N-acetyl-D-galactosamine (GalNAc) residues (E-unit) in the amount of ∼ 60%. CSE is involved in many biological and pathological processes. In this study, we established new monoclonal antibodies, termed E-12C and E-18H, by using CSE that contained more than 70% of E-units as an immunogen. These antibodies recognized CSE but not other CSs isomers or dermatan sulfate (DS). We evaluated the reactivities of the antibodies to 6-O-sulfated CSA (6S-CSA) and DS (6S-DS) that possessed ∼ 60% of GalNAc (4S, 6S) moieties in their structures. Neither of the antibodies reacted with 6S-DS. The antibodies strictly distinguished the structural difference of GlcA and L-iduronic acid in the polysaccharide. Binding affinities of the antibodies were determined by a surface plasmon resonance assay using CSE and 6S-CSA. The binding affinities were strongly associated with the molecular weight of CSE and the E-unit content of 6S-CSA. Moreover, we demonstrated that the antibodies are applicable to histochemical analysis. In conclusion, the new anti-CSE monoclonal antibodies specifically recognize the E-unit of CSE. The antibodies will become useful tools for the investigation of the biological and pathological significance of CSE.

[Efficacy of repeated subcostal transversus abdominis plane blocks with 0.2% lidocaine via 18-gauge intravenous catheters for patients undergoing abdominal aortic aneurism surgery].

BACKGROUND: There is an increasing number of patients scheduled for abdominal aortic aneurysm resection in whom epidural anesthesia cannot be performed because of concomitant antiplatelet/anticoagulant therapy. Instead of epidural anesthesia for postoperative analgesia in such patients it is possible to use repeated bilateral subcostal transversus abdominis plane (TAP) blocks. METHODS: Four patients receiving antiplatelet/anticoagulant therapy for abdominal aortic aneurysm resection under general anesthesia were studied. After the completion of surgery and before emergence from anesthesia 18-gauge intravenous catheters were inserted bilaterally into subcostal TAP and 100 ml (50 ml on each side) of 0.2% lidocaine with 1/500,000 epinephrine were injected via the catheters twice daily until the second postoperative day. Pain intensity was assessed using a 0-10 numerical rating scale at rest and during movement, before and after each block. RESULTS: Numerical pain ratings at rest and during movement decreased after each block, and good analgesia was obtained. No complications such as nausea, vomiting or infection were observed in the postoperative period. CONCLUSIONS: These findings suggest that repeated bilateral subcostal TAP blocks with 0.2% lidocaine performed via 18-gauge intravenous catheters provide good postoperative analgesia after abdominal aortic aneurysm resection.