Acorbine, a Corbicula japonica-derived tripeptide containing non-proteinogenic amino acids, suppresses ethanol-induced liver injury.

Since ancient times, Corbicula extract has been believed in Japan to have hepatoprotective effects, but it remains unclear whether these claims are true, and if so, which component is responsible for hepatoprotection. In this study, we showed that Corbicula extract exerted a protective effect against liver damage. Recent work identified acorbine (ß-alanyl-ornithyl-ornithine), a novel tripeptide containing non-proteinogenic amino acids, in the extract of Corbicula japonica. Synthesized acorbine cured alcohol-induced liver damage in mice. In addition, acorbine purified from Corbicula extract exerted a protective effect against alcohol-induced hepatotoxicity in a culture liver model derived from mouse ES/iPS cells. Thus, acorbine is one of the components of Corbicula extract that protects hepatocytes against ethanol-induced death.

[Reports of 12 Cases of Stanford Type A Acute Aortic Dissection Emergent Surgery for Jehovah's Witnesses patients].

The Jehovah's Witnesses (JW) is well known for declining blood transfusions. Especially, cardiovascular surgery on JW poses unique challenges. We herein report 12 JW emergent cases of Stanford type A acute aortic dissection which underwent graft replacement between 2003 and 2019. Graft replacement of ascending aorta was performed in all cases. Operative time and anesthetic time were 344±100 and 396±109 minutes respectively. The mean intraoperative hemoglobin nadir was 4.9±1.2 g/dl. The postoperative hemoglobin nadir was 6.3 ±2.4 g/dl. There were 2 deaths within 24 hours after surgery. We did not transfuse any packed red blood cells, fresh frozen plasma or platelets for JW patients of Stanford type A acute aortic dissection surgery.

Total synthesis of pectenotoxin-2.

Pectenotoxin-2 (PTX2) is a shellfish toxin and has a non-anomeric spiroacetal, which is not stabilized by an anomeric effect. The selective construction of the non-anomeric spiroacetal has been a major problem in the synthesis of PTX2. Described herein is the stereoselective total synthesis of PTX2 via the isomerization of anomeric spiroacetal pectenotoxin-2b (PTX2b). The synthesis of PTX2b was achieved by a simple process including sulfone-mediated assembly of spirocyclic and bicyclic acetals and subsequent macrocyclization by ring-closing olefin metathesis. Finally, the selective construction of PTX2 was accomplished by the early termination of a dynamic transition process to equilibrium in the acid-catalyzed isomerization of anomeric PTX2b. [6,6]-Spiroacetal pectenotoxin-2c (PTX2c) was also synthesized from PTX2b. The cytotoxicity assay of the synthetic compounds against HepG2 and Caco2 cancer cells showed a potency of the order: PTX2≫PTX2b>PTX2c.

Surgical repair of an aortoesophageal fistula after salvage thoracic endovascular aortic repair: a case report.

BACKGROUND: An aortoesophageal fistula can prove to be fatal. Salvage thoracic endovascular aortic repair as a bridging therapy and radical surgery with thoracotomy should be considered while treating aortoesophageal fistula without spontaneous closure. Moreover, it is essential to select a technique that reduces the risk of reinfection. Here we report a rare case of a ruptured thoracic aortic aneurysm related to esophageal perforation by a fish bone that led to massive hematemesis and shock, and the surgical treatment of an aortoesophageal fistula that developed after salvage thoracic endovascular aortic repair. CASE PRESENTATION: A 70-year-old Japanese female patient was admitted with hematemesis, thoracic pain, and shock related to esophageal perforation of a ruptured descending aortic aneurysm caused by fish bone aspiration and esophageal perforation 1 month previously. An emergency thoracic endovascular aortic repair was performed. Postoperatively, an aortoesophageal fistula that remained open and a food intake-related increase in the inflammatory response was noted. Radical blood-vessel prosthesis implantation and fistula closure were performed. The patient's postoperative course was favorable and the patient was discharged 22 days after the blood vessel prosthesis implantation. CONCLUSION: Such a case of rupture of a descending aortic aneurysm related to perforation by a fish bone and an aortoesophageal fistula is considerably rare. Thus, we report the therapeutic strategy of this particular case and review the relevant literature.

Restrictive mitral annuloplasty with or without surgical ventricular restoration in ischemic dilated cardiomyopathy with severe mitral regurgitation.

BACKGROUND: We assessed changes in left ventricular (LV) volume and function and in regional myocardial wall stress in noninfarcted segments after restrictive mitral annuloplasty (RMA) with or without surgical ventricular restoration (SVR). METHODS AND RESULTS: Thirty-nine patients with ischemic cardiomyopathy (ejection fraction ≤ 0.35) and severe mitral regurgitation (≥ 3) were studied before and 2.8 months after surgery with cine-angiographic multidetector computed tomography (cine-MDCT). Eighteen underwent RMA alone (RMA group) and 21 underwent RMA and SVR (RMA+SVR group). In addition to measuring conventional parameters (LV end-diastolic volume index [LVEDVI], LV end-systolic volume index [LVESVI], and LV ejection fraction), we evaluated the regional circumferential end-systolic wall stress and mean circumferential fiber shortening in both the basal and mid-LV regions using 3-dimensional cine-MDCT images. LV end-diastolic and end-systolic volume indexes were significantly greater in the RMA+SVR group than in the RMA group preoperatively, but these values did not differ significantly postoperatively. LV end-diastolic and end-systolic volume indexes decreased significantly, by 21% and 27% after RMA and by 35% and 42% after RMA and SVR, and the percent reductions in LV end-diastolic and end-systolic volume indexes were significantly larger in the RMA+SVR group. Regional end-systolic wall stress decreased and circumferential fiber shortening increased significantly in the noninfarcted regions after RMA with or without SVR. CONCLUSIONS: RMA plus SVR showed a potentially greater reduction of LV end-diastolic and end-systolic volume indexes than RMA alone. In selected patients with more advanced LV remodeling, concomitant SVR may favorably affect the LV reverse-remodeling process induced by RMA.

Total synthesis of thelephantin O, vialinin A/terrestrin A, and terrestrins B-D.

The first total synthesis of natural, unsymmetrical 2',3'-diacyloxy-p-terphenyls, thelephantin O (1) and terrestrins C and D (2 and 3, respectively), was achieved via a practical route which was also applicable to the synthesis of the symmetrical diesters vialinin A/terrestrin A (4) and terrestrin B (5). Compounds 1-5 exhibited cytotoxicity against cancer cells (HepG2 and Caco2) with IC(50) values of 13.6-26.7 µmol/L.

Mechanism of beneficial effects of restrictive mitral annuloplasty in patients with dilated cardiomyopathy and functional mitral regurgitation.

BACKGROUND: Restrictive mitral annuloplasty (RMA) often leads to reverse left ventricular (LV) remodeling in patients with advanced cardiomyopathy and functional mitral regurgitation. However, the mechanism responsible for its favorable effects on LV ejection performance has been poorly understood. We evaluated systolic wall stress using cineangiographic multidetector computed tomography (MDCT) and our developed software system to assess stress-shortening relations before and after RMA. METHODS AND RESULTS: Twenty-four patients with dilated cardiomyopathy underwent 64-row MDCT before and 2 months after RMA. All patients underwent stringent downsizing annuloplasty with a semirigid complete ring. Reconstructed images were used to calculate LV end-diastolic index (EDVI) and end-systolic volume index (ESVI), LV ejection fraction, and regional and global end-systolic wall stress (ESS). After RMA, LVEDVI and LVESVI decreased from 151±52 to 131±53 mL/m(2) (P=0.0001) and from 114±48 to 92±50 mL/m(2) (P=0.0001), respectively. Global ESS decreased from 157±43 to 139±50 kdyne/cm(2) (P=0.01), and LV ejection fraction improved from 27±8.0 to 33±13% (P=0.0007). There were significant correlations between change in LVEDVI and LVESVI (r=0.88, P<0.0001) and change in LVESVI and global ESS (r=0.68, P=0.0002). Moreover, the magnitude of increase in LV ejection fraction significantly correlated with the degree of reduction in global ESS (r=-0.61, P=0.002). Patients without significant reverse LV remodeling had significantly higher preoperative and postoperative global ESS than those with it. CONCLUSIONS: Our study suggests that decrease in afterload after reduction in volume overload was responsible for postoperative reverse LV remodeling process after RMA.

Redo arch aneurysm repair for new-onset aortic arch dissection following ascending aortic surgery: long elephant trunk technique combined with trifurcate-branched graft.

Reoperative surgical intervention for a new-onset aortic arch dissection following a Bentall procedure or graft replacement for the ascending aorta is often difficult, especially in elderly patients. Herein, we report a re-do arch replacement method using a trifurcate-branched graft and long elephant trunk anastomosis at the composite root graft on the ascending aorta. The present technique is feasible as an alternative for new-onset or residual aortic arch aneurysm, as well as dissection following an operation for the ascending aorta.

A simplified echocardiographic measurements of direct effects of restrictive annuloplasty on mitral valve geometry.

OBJECTIVE: The purpose of this study was to evaluate the direct effects of restrictive mitral annuloplasty on mitral valve geometry. METHODS: We studied 23 patients (mean age: 63 ± 5 years) with functional mitral regurgitation (moderate to severe) and advanced cardiomyopathy (ejection fraction: 25 ± 8%) with ischemic (n = 15) or nonischemic (n = 8) conditions, who underwent restrictive annuloplasty. We determined annular septal-lateral diameter, tenting height, tenting area, vertical length of coaptation of the mitral leaflets (coaptation length), and ratio of coaptation length to septal-lateral diameter (coaptation length index) at end-systole, before and after surgery, using transthoracic echocardiography. RESULTS: Annular septal-lateral diameter, tenting height, and tenting area were significantly decreased (34 ± 7 to 20 ± 5 mm, P < 0.05; 9 ± 4 to 5 ± 2 mm, P < 0.05; 210 ± 120 to 80 ± 50 mm(2) , P < 0.05, respectively), whereas coaptation length and coaptation length index were significantly increased (3.4 ± 1.3 to 6.5 ± 2.9 mm, P < 0.05; 0.11 ± 0.06 to 0.33 ± 0.15, P < 0.05, respectively). Spearman's rank correlation analysis revealed that these five variables had a statistically significant correlation with the degree of mitral regurgitation. Furthermore, stepwise regression analysis showed that coaptation length index, in contrast to coaptation length, was the most important correlate with the degree of mitral regurgitation. CONCLUSION: Our simplified parameters were useful for quantitative and geometrical descriptions of mitral valve geometry, and may also provide important information for developing a surgical strategy for functional mitral regurgitation.

Beneficial effects of restrictive annuloplasty on subvalvular geometry in patients with functional mitral regurgitation and advanced cardiomyopathy.

OBJECTIVES: The effects of restrictive mitral annuloplasty (RMA) on subvalvular geometry remains unknown. We evaluated changes in left ventricular (LV) function, severity of mitral regurgitation (MR), and leaflet tethering parameters after RMA and clarified their associations. METHODS: In 44 patients with clinically relevant functional MR who underwent RMA, distances between papillary muscle (PM) tips and anterior mitral annulus (PM tethering distance), leaflet angles relative to lines connecting annuli, and interpapillary muscle distance (IPMD) were serially quantified. RESULTS: One month after surgery, LV function and MR severity improved with decreased anterior (34 ± 5 to 30 ± 4 mm) and posterior PM tethering distance (37 ± 4 to 32 ± 4 mm), anterior leaflet angle (32 ± 8° to 22 ± 7°), and IPMD (31 ± 6 to 25 ± 5 mm), whereas these variables remained abnormal and posterior leaflet angle increased (34 ± 8° to 48 ± 14°; P < .01 for all). During follow-up (66 ± 37 months), these effects were maintained in 33 patients without MR recurrence, whereas 11 with it showed worsened tethering with less LV function recovery. Multiple linear regression analyses identified that change in MR severity from baseline to 12-month examination independently associated with corresponding change in IPMD (parameter estimate of 0.100 with standard error of 0.039; P = .019) and that in posterior PM tethering distance (parameter estimate of -0.104 with standard error of 0.045; P = .035), whereas not with change in posterior-leaflet angle. The IPMD change was independently associated with change in LV end-systolic dimension (parameter estimate of 0.299 with standard error of 0.110; P = .013). CONCLUSIONS: The RMA procedure partially relieved leaflet tethering, evidenced by decreased tethering distances and IPMD; the latter was the main determinant of MR. These beneficial effects might be mainly attributed to post-RMA reverse LV remodeling, potentially offsetting the negative effect of augmented posterior leaflet angle in selected patients.

Left ventricular mass: impact on left ventricular contractile function and its reversibility in patients undergoing aortic valve replacement.

BACKGROUND: We examined the relationships of left ventricular (LV) contractile state with LV geometry and hypertrophy in patients with aortic valve disease, and investigated the reversibility of LV hypertrophy and contractility following aortic valve replacement. METHODS: Preoperative data from quantitative cineangiography and pressure measurements in 132 patients with chronic aortic valve disease, of whom 82 aortic regurgitation (AR), 41 aortic stenosis (AS), and 9 had mixed stenosis and regurgitation (AS-AR), were reviewed. Late after surgery, 59 of the patients (39 with AR, 20 with AS) were studied to elucidate the postoperative reversibility of LV performance and regression of LV hypertrophy. RESULTS: Preoperatively, multiple comparison tests found significant changes in the variables of LV volumes and dimensions in relation to LV contractile state. In stepwise regression analysis, the LV mass index was initially incorporated into a multivariate regression model as an important correlate of LV contractile state. LV geometric variables showed either no or a poor correlation with contractile state. Following aortic valve replacement, improvement of LV contractile dysfunction and regression of LV hypertrophy were limited in many of the patients who had severe preoperative hypertrophy (LV mass index 200% of normal or greater). Further, a close association between LV hypertrophy and LV contractility persisted postoperatively. CONCLUSION: Our results suggest that the development of LV hypertrophy in terms of an increase in LV mass index, in contrast to changes in geometric patterns, is significantly associated with deterioration in contractile function. LV hypertrophy may become irreversible and pathological at equivalent degrees of hypertrophy (LV mass index >/=200% of normal), regardless of the type of aortic valve lesion.

[Stentless bioprosthesis for aortic valve replacement].

The stentless aortic bioprosthesis was reported to reduce left ventricular mass (LVM) in the early period after implantation and have better hemodynamic performance and a larger effective orifice area (EOA) than stented valves. However, its clinical advantage over the stented valve is still unclear. We have implanted stentless bioprostheses in 61 patients and had a low operative mortality rate (1.6%). LVM index, left ventricular end-diastolic volume (LVEDV) index, left ventricular end-systolic volume (LVESV) index, and peak pressure gradient (PG) were rapidly reduced after implantation. Ten-year-freedom from cardiac-related death, thromboemolism, and structural valve deterioration rates were 91.0%, 100%, and 95.0%, respectively. Furthermore, using MRI analysis, blood velocity through stentless valves was similar to that through native aortic valves in comparison with stented valves. In conclusion, the stentless valve enables more physiologic blood flow through the valve, and thus it may be useful in patients with small annuli or those who require better hemodynamic performance to enable physical activity.

Alpha-glucosidase inhibitory and antihyperglycemic effects of polyphenols in the fruit of Viburnum dilatatum Thunb.

Small crimson fruit of Viburnum dilatatum Thunb. (gamazumi), a wild deciduous low tree belonging to a family of Caprifoliaceae, has strong antioxidant activity, and cyanidin 3-sambubioside (C3S) and 5-caffeoyl quinic acid (5-CQA) are identified as active compounds. The freeze-dried powder of V. dilatatum fruit juice (CEV) was orally administered to streptozotocin-induced diabetic rats for 4 weeks repeatedly. Consequently, the elevation of plasma glucose level after oral administration of 2 g/kg glucose was suppressed by the repeated administration of CEV. The action was dependent on the dose of CEV, and plasma glucose level in rats administered 500 mg/kg of CEV was decreased significantly from that in rats without CEV. Increase of insulin secretion was not found in rats with or without administration of CEV. It was expected that CEV had some effects on glucose uptake. In five compounds identified from V. dilatatum fruit, C3S and 5-CQA showed inhibitory activity on sucrase and maltase. Inhibitory activity of cyanidin 3-glucoside and cyanidin aglycon (Cy) was not found markedly, and so it was thought that the activity was a characteristic property in Cy diglycosides. Moreover, 5-CQA and C3S were main polyphenol in the fruit of V. dilatatum. These results suggest that V. dilatatum fruit has the alpha-glucosidase inhibitory activities and the antihyperglycemic action.

Granulin-like peptide in the mid-gut gland of the bivalve mollusk, Patinopecten yessoensis.

A cysteine-rich polypeptide, termed CRP1, with a molecular mass of 5829 Da was found to occur in the mid-gut gland of the scallop Patinopecten yessoensis. CRP1 was purified by reverse phase and cation-exchange chromatographies. The amino acid sequence of CRP1 was deduced from its N-terminal amino acid sequence, amino acid composition and the sequence of a partial cDNA, indicating that CRP1 is a 57-amino-acid polypeptide containing 12 cysteine residues with a calculated molecular mass of 5841 Da (5829 Da when oxidized to form six disulfide bridges). A homology search of databases revealed that the deduced amino acid sequence of CRP1 displays significant similarity to those of granulin/epithelins, a family of growth-modulating factors; all cysteine residues in CRP1 are located at the same positions as those conserved characteristically in other known granulin/epithelins. Purified CRP1 inhibited the proliferation of mouse embryo cells. The results suggest that CRP1 functions as a growth-modulating factor in the scallop, and that granulin/epithelin family polypeptides and their precursors play physiologically important roles in invertebrates.

Mid-term results of freestyle aortic stentless bioprosthetic valve: clinical impact of quantitative analysis of in-vivo three-dimensional flow velocity profile by magnetic resonance imaging.

BACKGROUND AND AIM OF THE STUDY: The study aim was to investigate the in-vivo flow profiles of a stentless aortic bioprosthetic valve by MRI flow quantification, and to identify the clinical implication of prosthesis size and implantation method. METHODS: Twenty-six patients with a Freestyle stentless aortic bioprosthetic valve were studied using three-dimensional flow velocity profile by MRI, and compared with four patients with a stented aortic bioprosthetic valve and four healthy volunteers. Flow velocity profiles were analyzed quantitatively by the hydromechanics parameter, mean to peak velocity ratio at peak systole and compared with parameters monitored echocardiographically. RESULTS: In larger-sized valves or full root implantation, flow profiles showed an optimal pattern with low gradients, a high mean to peak velocity ratio, and minimum disturbance which approximated that of a normal valve. By contrast, a subset of patients, notably with 21 mm valves and subcoronary implantation, showed suboptimal flow pattern with high gradient and low mean to peak velocity ratio which approximated that of stented valves. The mean to peak velocity ratio was more strongly related to peak velocity than to the indexed effective orifice area. CONCLUSION: Although stentless aortic bioprostheses have excellent hemodynamic performance, some patients show suboptimal results. This seems to occur more often when the subcoronary technique is used, and especially with 21-mm valves. Care must be taken when using the subcoronary technique with a 21-mm valve in patients with a small body surface area.

Dilated left atrium as a predictor of late outcome after pulmonary vein isolation concomitant with aortic valve replacement and/or coronary artery bypass grafting†.

OBJECTIVES: Left atrial (LA) dimension can predict atrial fibrillation (AF) recurrence after catheter-based or surgical ablation. Pulmonary vein isolation (PVI) may be a surgical option during aortic valve replacement (AVR) and/or coronary artery bypass grafting (CABG), though consensus regarding patient selection and late outcome is lacking. METHODS: We studied 160 patients (mean age 70 ± 9 years) with paroxysmal AF who underwent radiofrequency-based PVI during AVR and/or CABG, and were followed up postoperatively for at least 6 months. Mean preoperative LA dimension was 44 ± 7 mm. Serial echocardiography was performed to evaluate left ventricular (LV) and LA dimensions, E/e', estimated systolic pulmonary artery (PA) pressure and degree of valvular regurgitation. Follow-up was completed with a mean duration of 47 ± 25 months. RESULTS: At the latest follow-up, 133 patients (83%) remained in sinus rhythm. Preoperative LA dimension was independently associated with increased risk of AF recurrence at 6 months after surgery [adjusted odds ratio 1.3 per 1-mm increase in LA dimension, 95% confidence interval (CI) 1.1-1.6, P < 0.001]. Receiver-operating characteristic curve analysis demonstrated an optimal cut-off value for preoperative LA dimension of 45 mm to predict sinus rhythm restoration (98% for <45 mm vs 55% for ≥45 mm, P < 0.001). Patients with LA dimension ≥45 mm had a significantly lower 5-year survival rate (62 ± 7 vs 82 ± 7%, P = 0.025) and freedom from adverse events defined as cerebral infarction/haemorrhage, admission for heart failure, catheter ablation and permanent pacemaker implantation (58 ± 7 vs 91 ± 4%, P < 0.001). Multivariate analysis showed that preoperative LA dimension ≥45 mm was independently associated with adverse events (adjusted hazards ratio 2.4, 95% CI 1.2-5.1, P = 0.019). Serial echocardiography demonstrated improvement in LV systolic function irrespective of LA dimension, whereas patients with LA dimension ≥45 mm showed less improvement in LA dimension and systolic PA pressure (interaction effect P < 0.001) and persistent higher E/e' (group effect P < 0.001), along with aggravated tricuspid regurgitation. CONCLUSIONS: In patients with paroxysmal AF related to aortic valve disease and/or coronary artery disease, a dilated left atrium (≥45 mm) was associated with inferior AF- and event-free survival after PVI, accompanied by persistent abnormalities in cardiac and haemodynamic function. These findings may assist patient selection for PVI during AVR and/or CABG.

Fluorescent labeling of pectic oligosaccharides with 2-aminobenzamide and enzyme assay for pectin.

Oligogalacturonides [oligomers composed of (1-->4)-linked alpha-D-galactosyluronic acid residues] with degrees of polymerization (DP) from 1 to 10, and a tri-, penta-, and heptasaccharide generated from the backbone of rhamnogalacturonan I (RG-I) were labeled at their reducing ends using aqueous 2-aminobenzamide (2AB) in the presence of sodium cyanoborohydride in over 90% yield. These derivatives were analyzed by high-performance anion-exchange chromatography (HPAEC) and structurally characterized by electrospray-ionization mass spectrometry (ESIMS) and by 1H and 13C NMR spectroscopy. The 2AB-labeled oligogalacturonides and RG-I oligomers are fragmented by endo- and exo-polygalacturonase and by Driselase, respectively. 2AB-labeled oligogalacturonide is an exogenous acceptor for galacturonosyltransferase of transferring galacturonic acid from UDP-GalA. Thus, the 2AB-labeled oligogalacturonides and RG-I oligomers are useful for studying enzymes involved in pectin degradation and biosynthesis and may be of value in determining the biological functions of pectic fragments in plants.

Inhibitory effects of viburnum dilatatum Thunb. (gamazumi) on oxidation and hyperglycemia in rats with streptozotocin-induced diabetes.

The fruit of Viburnum dilatatum Thunb. (gamazumi) was found in a previous study to have strong radical scavenging activity. The present study investigated the antioxidative functions of gamazumi crude extract (GCE) in rats having diabetes induced by the administration of streptozotocin. In rats given water (H(2)O group), plasma levels of glucose, total cholesterol, and lipid peroxide (TBARS) and erythrocyte levels of TBARS increased with time over the experimental period of 10 weeks. These increases were inhibited in rats given GCE (GCE group). After 10 weeks, hepatic, renal, and pancreatic TBARS in the GCE group were significantly lower than those in the H(2)O group. GCE contains a high concentration of polyphenols, and it is expected that they are the active components. These results demonstrate that GCE has an inhibitory effect on the oxidative stress induced by diabetes and suggest that GCE may be useful for the prevention of diabetic complications. Furthermore, as the increase of plasma glucose and total cholesterol was inhibited in the GCE group, GCE may also have anti-hyperglycemic activity in diabetes.