A tissue-silicone integrated simulator for right ventricular pulsatile circulation with severe functional tricuspid regurgitation.

There is a great demand for development of a functional tricuspid regurgitation (FTR) model for accelerating development and preclinical study of tricuspid interventional repair devices. This study aimed to develop a severe FTR model by creating a tissue-silicone integrated right ventricular pulsatile circulatory simulator. The simulator incorporates the porcine tricuspid annulus, valve leaflets, chordae tendineae, papillary muscles, and right ventricular wall as one continuous piece of tissue, thereby preserving essential anatomical relationships of the tricuspid valve (TV) complex. We dilated the TV annulus with collagenolytic enzymes under applying stepwise dilation, and successfully achieved a severe FTR model with a regurgitant volume of 45 ± 9 mL/beat and a flow jet area of 15.8 ± 2.3 cm2 (n = 6). Compared to a normal model, the severe FTR model exhibited a larger annular circumference (133.1 ± 8.2 mm vs. 115.7 ± 5.5 mm; p = 0.009) and lower coaptation height (6.6 ± 1.0 mm vs. 17.7 ± 1.3 mm; p = 0.003). Following the De-Vega annular augmentation procedure to the severe FTR model, a significant reduction in regurgitant volume and flow jet area were observed. This severe FTR model may open new avenues for the development and evaluation of transcatheter TV devices.

POFUT1 and PLAGL2 are characteristic markers of mucinous colorectal cancer associated with MUC2 expression.

Colorectal mucinous adenocarcinoma (MAC) is one of the most lethal histological types of colorectal cancer, and its mechanism of development is not well understood. In this study, we aimed to clarify the molecular characteristics of MAC via in silico analysis using The Cancer Genome Atlas database. The expression of genes on chromosome 20q (Chr20q) was negatively associated with the expression of MUC2, which is a key molecule that can be used to distinguish between MAC and nonmucinous adenocarcinoma (NMAC). This was consistent with a significant difference in copy number alteration of Chr20q between the two histological types. We further identified 475 differentially expressed genes (DEGs) between MAC and NMAC, and some of the Chr20q genes among the DEGs are considered to be pivotal genes used to define MAC. Both in vitro and in vivo analysis showed that simultaneous knockdown of POFUT1 and PLAGL2, both of which are located on Chr20q, promoted MUC2 expression. Moreover, these genes were highly expressed in NMAC but not in MAC according to the results of immunohistological studies using human samples. In conclusion, POFUT1 and PLAGL2 are considered to be important for defining MAC, and these genes are associated with MUC2 expression.

Angiopoietin-like 4 promotes glucose metabolism by regulating glucose transporter expression in colorectal cancer.

PURPOSE: Angiopoietin-like 4 (ANGPTL4) was recently shown to be associated with cancer progression but little is known about its contribution to cancer metabolism. The purpose of this study was to elucidate the role of ANGPTL4 in glucose metabolism in colorectal cancer (CRC). METHODS: Immunohistochemical staining of CRC specimens classified 84 patients into two groups according to ANGPTL4 expression. Clinicopathological characteristics, gene mutation status obtained by next-generation sequencing, and fluorodeoxyglucose (FDG) uptake measured by positron emission tomography/computed tomography (PET/CT) were compared between the two groups. Furthermore, the impact of ANGPTL4 expression on cancer metabolism was investigated by a subcutaneous xenograft mouse model using the ANGPTL4 knockout CRC cell line, and glucose transporter (GLUT) expression was evaluated. RESULTS: There were significantly more cases of T3/4 tumours (94.3% vs. 57.1%, P < 0.001) and perineural invasion (42.9% vs. 22.4%, P = 0.046) in the ANGPTL4-high group than in the low group. Genetic exploration revealed a higher frequency of KRAS mutation (54.3% vs. 22.4%, P = 0.003) in the ANGPTL4-high tumours. All the FDG uptake parameters were significantly higher in ANGPTL4-high tumours. In vivo analysis showed a significant reduction in tumour size due to ANGPTL4 knockout with lower expression of GLUT1 and GLUT3, and suppression of AKT phosphorylation. CONCLUSION: ANGPTL4 regulates the expression of GLUTs by activating the PI3K-AKT pathway and thereby promoting glucose metabolism in CRC. These findings establish a new functional role of ANGPTL4 in cancer progression and lay the foundation for developing a novel therapeutic target.

An adolescent with Behçet's aortitis mimicking infective endocarditis: a case report.

BACKGROUND: Aortic valve involvement is rare in patients with Behçet' s disease (BD); however, recurrent prosthetic valve detachment after valve surgery has frequently been reported. We report a rare case of Behçet's aortitis involving the aortic valve, mimicking active infective endocarditis (IE) with perivalvular abscess. CASE SUMMARY: A 16-year-old boy, with an unknown case of BD, presented with pyrexia of unknown origin, severe aortic valve regurgitation, vegetation, and perivalvular abscess in the aortic valve. All cultures tested negative for microorganisms. As we suspected IE, aortic valve replacement was performed. After the initial surgery, recurrent prosthetic valve detachment and pseudoaneurysm formation occurred, which resulted in the diagnosis of BD. The patient underwent a modified Bentall procedure, in which the valve conduit was proximally sutured to the left ventricular outflow tract instead of the aortic annulus. Immunosuppressive therapy was initiated on the 10th postoperative day. His condition became stable, and additional surgery was not required. DISCUSSION: The echocardiographic findings of Behçet's aortitis involving the aortic valve resemble those of aortic valve IE. Modified Bentall procedure, combined with effective immunosuppressive therapy, may be useful in preventing prosthetic valve detachment.

Bicuspid aortic valve morphology and aortic valvular outflow jets: an experimental analysis using an MRI-compatible pulsatile flow circulation system.

The characteristics of aortic valvular outflow jet affect aortopathy in the bicuspid aortic valve (BAV). This study aimed to elucidate the effects of BAV morphology on the aortic valvular outflow jets. Morphotype-specific valve-devising apparatuses were developed to create aortic valve models. A magnetic resonance imaging-compatible pulsatile flow circulation system was developed to quantify the outflow jet. The eccentricity and circulation values of the peak systolic jet were compared among tricuspid aortic valve (TAV), three asymmetric BAVs, and two symmetric BAVs. The results showed mean aortic flow and leakage did not differ among the five BAVs (six samples, each). Asymmetric BAVs demonstrated the eccentric outflow jets directed to the aortic wall facing the smaller leaflets. In the asymmetric BAV with the smaller leaflet facing the right-anterior, left-posterior, and left-anterior quadrants of the aorta, the outflow jets exclusively impinged on the outer curvature of the ascending aorta, proximal arch, and the supra-valvular aortic wall, respectively. Symmetric BAVs demonstrated mildly eccentric outflow jets that did not impinge on the aortic wall. The circulation values at peak systole increased in asymmetric BAVs. The bicuspid symmetry and the position of smaller leaflet were determinant factors of the characteristics of aortic valvular outflow jet.

Surgical embolectomy for paradoxical cerebral embolism with massive pulmonary embolism.

The patient was a 68-year-old woman with a history of multiple cerebral emboli. The patient presented with dysarthria, dysphagia, and left facial paralysis. Emergent MRI demonstrated multiple emboli in the brain stem and left occipital lobe. Echocardiography and chest CT demonstrated floating emboli entrapped in the foramen ovale and pulmonary emboli in both main pulmonary arteries. Emergent pulmonary embolectomy and extraction of the emboli on the foramen ovale were successfully performed without neurological exacerbation.

Rate of Stenotic Bicuspid Aortic Valve Aortic Dilatation After Aortic Valve Replacement, Calculated Using a 3-Dimensional Reconstruction Tool.

BACKGROUND: Progression of asymmetric dilated aorta associated with bicuspid aortic valve (BAV) is difficult to evaluate conventionally. The aim of the study was to calculate the rate of progression of the dilated BAV aorta after aortic valve replacement (AVR) using a 3-dimensional (3-D) reconstruction tool.Methods and Results:Fourteen stenotic BAV and 14 stenotic tricuspid aortic valve (TAV) patients with mildly dilated ascending aorta were reviewed. A patient-specific 3-D aortic model was reconstructed from preoperative and postoperative computed tomography data (BAV, 2.5±1.9 years after AVR; TAV, 2.2±1.8 years after AVR). Aortic diameter, including the longest and shortest, was measured on the maximum perpendicular cross-section tangential to the 3-D centerline of the reconstructed model. The longest diameter was defined as that passing through the distal point of the greater curvature of the aorta. The shortest diameter was defined as perpendicular to the longest. The progression rates were compared between the BAV and TAV groups. The progression rate of ascending aortic diameter was greater for BAV (longest diameter, 1.02±1.03 vs. -0.075±0.78 mm/year, P<0.001; shortest diameter, 0.41±0.62 vs. -0.016±0.59 mm/year, P=0.003). The longest diameter of the proximal arch also grew more rapidly in the BAV group (P<0.001). CONCLUSIONS: Ascending aortic dilatation with stenotic BAV progresses after AVR at a maximum rate of 1.02±1.03 mm/year. Expansion toward the greater curvature frequently progresses to the proximal arch.

Posteromedial papillary muscle rupture due to squeezing of the left anterior descending coronary artery.

An unusual case of posteromedial papillary muscle (PPM) rupture due to isolated left anterior descending (LAD) artery ischaemia, associated with severe myocardial bridge contraction, is presented. The unusual blood supply to the PPM was associated with its apical origin and apex-forming LAD.

Management of Pulmonary Thromboembolism Based on Severity and Vulnerability to Thrombolysis.

Background: The incidence of pulmonary thromboembolism has been considered rare in Japan. However, its occurrence has been increasing because of westernized lifestyle and diet, increased diagnostic technique, and recognition of this disease. Method: Between January 2003 and September 2014, 179 patients were treated for pulmonary thromboembolism. We classified these patients into 3 groups; Massive (n=35), Sub-massive (n=29) and Nonmassive (n=115) and retrospectively reviewed the treatment options and the outcome. Results: Percutaneous cardiopulmonary support (PCPS) was applied for patients with hemodynamic instability and IVC filter was inserted if there was proximal DVT. In non-massive group (n=115), 95.7% of the patient underwent anticoagulant therapy and 47.0% of the patients received IVC filter. In submassive group (n=29), 48.3% of the patient received thrombolytic therapy and 93.1% of the patient underwent IVC filter insertion. Surgical pulmonary embolectomy was performed in 3 patients who had high risk of thrombolytic therapy in submassive group. There was no death in this group. In massive group, 4 patients who had cardiogenic shock died in acute phase. PCPS was applied in 5 patients, pulmonary embolectomy was performed in 13 patients, thrombolytic therapy was performed in 4 patients and 13 patients underwent anticoagulant therapy alone. There were 7 deaths (20.0%) in this group. Conclusions: In submassive group, treatment should be decided depending on the bleeding risk. In massive group, pulmonary embolectomy was effective. (This is a translation of Jpn J Phlebol 2016; 27: 53-59.).

A novel surgical procedure for scimitar syndrome: scimitar vein with right atrium and inferior vena cava wall flap.

We describe a new surgical procedure for the scimitar syndrome using the walls of the right atrium and inferior vena cava as a flap to prevent kinking and stenosis of the scimitar vein-left atrium anastomosis.

Electrochemiluminescence of Tris(2,2'-bipyridyl)ruthenium(II) with Ascorbic Acid and Dehydroascorbic Acid in Aqueous and Non-aqueous Solutions.

The electrochemiluminescence (ECL) of tris(2,2'-bipyridyl)ruthenium(II) (Ru(bpy)3(2+)) is studied in non-aqueous media using dehydroascorbic acid (DHA) as coreactant to validate the evidence for the mechanism of the ascorbic acid (H2A)/Ru(bpy)3(2+) ECL system in an aqueous media. DHA is electrochemically reduced around -1.2 V vs. Ag/Ag(+) in pure acetonitrile to generate the ascorbyl radical anion (A(•-)), which is confirmed by in-situ UV-visible absorption measurements using a thin-layer spectroelectrochemical cell. The ECL of the DHA/Ru(bpy)3(2+) system in non-aqueous media is not observed in the potential range from 0 to +1.4 V in anodic potential sweep mode; however, distinct ECL is detected using double potential step electrolysis from -1.2 to +1.4 V vs. Ag/Ag(+). The ECL may be generated by a homogeneous charge-transfer process between A(•-) produced during the first pulse potential step (-1.2 V) and Ru(bpy)3(3+) generated during the second pulse potential step (+1.4 V). The calculated standard enthalpy (-ΔH°) for the charge-transfer reaction between A(•-) and Ru(bpy)3(3+) is 2.29 eV, which is larger than the lowest excited singlet state energy of Ru(bpy)3(2+) (*Ru(bpy)3(2+); 2.03 eV, 610 nm). It is determined that the generated intermediate A(•-) is crucial in the Ru(bpy)3(2+) ECL reaction.

[Surgery for Infective Endocarditis Involving Valve Annulus].

Surgical treatment for isolated infective endocarditis( IE) has been improving over the last 2 decades. However, surgery for complicated IE such as disruption of paravalvular structure remains a challenge. The aim of this retrospective study is to evaluate our surgical results for IE with paravalvular structural disruption. From January 2002 to March 2015, we performed cardiac surgery for 68 patients who suffered from IE. Thirteen patients had paravalvular abscess and fistula. Valve disruptions were seen in aortic valve in 10 patients [2 fistulas from right coronary cuspid to right atrium or ventricle, 3 abscess formation from right coronary cuspid to interventricular septum, 1 abscess formation from left coronary cuspid to anterior mitral leaflet, 1 left ventricle to right atrium communication from non-coronary cuspid (NCC), 2 abscess formation under NCC and 1 circular annulas infection]. Mitral valve involvement was found in 2 patients [1 posterior mitral leaflet (PML) infection and submitral abscess infiltrating to annula calcification and 1 PML infection with submitral abscess]. One patient who had tricuspid valve involvement had giant vegetation from tricuspid to pulmonary valve through right ventricular outflow tract. Radical debridement of infected tissue and reconstruction using allograft, artificial valve and conduit were performed in all cases.

Novel Method of Assessing Ascending Aorta with a Stenotic Bicuspid Aortic Valve.

BACKGROUND AND AIM OF THE STUDY: Patients with bicuspid aortic valve (BAV) have an increased risk of serious aortic complications such as aortic dissection, rupture and dilatation of the ascending aorta. Previous findings have suggested that ascending aortic dilatation with a BAV has a typical asymmetric configuration at the right-anterior aspect of the aorta. The study aim was to quantify asymmetric configurations of the aorta using a three-dimensional (3D) reconstruction tool. METHODS: A retrospective review was conducted of 52 patients (27 males, 25 females; mean age 69 ? 9 years) with aortic stenosis who presented with ascending aortic dilatation defined as an aortic diameter >35 mm. Of these patients, 24 (46%) had a BAV and 28 (54%) had a tricuspid aortic valve (TAV). A patient-specific 3D thoracic aortic model was reconstructed from computed tomography (CT) data. Three-dimensional centerlines were automatically calculated. The size of the ascending aorta was determined by calculating the cross-sectional area (in mm2) of the vertical section against the centerline. The symmetry of the dilated aorta was evaluated as the ellipticity of the maximum vertical section of the ascending aorta. The size and symmetry of the ascending aorta, and background factors including pressure gradient, aortic valve area, degree of regurgitation, ejection fraction and cardiovascular risk factors, were compared between the BAV and TAV groups. RESULTS: Only age differed significantly between the groups (p = 0.003). The size and ellipticity of the ascending aorta and the maximum cross-sectional area of the aortic arch were significantly greater in the BAV group (p = 0 .001 and p = 0.004, respectively). CONCLUSION: The ascending aorta assessed using Mimics 3D reconstruction software was frequently asymmetrically dilated in stenotic BAV, and the expansion progressed to the aortic arch. It is believed that calculating the ellipticity of the vertical section against the centerline offers an innovative means of quantifying aortic symmetry in three dimensions.

Maternal-to-fetal transfer and concentration profiles of PCB congeners for Steller sea lions (Eumetopias jubatus) from Hokkaido, Japan.

The concentrations of PCB congeners in the blubber and liver of mother Steller sea lions (Eumetopias jubatus; SSLs) and their fetuses from the coast of Hokkaido, Japan in 2008, 2010 and 2012 were analyzed by HRGC-HRMS, in order to elucidate PCB congener profiles and maternal-to-fetal transfer of PCBs in SSLs. ΣPCBs in the fetuses were 1400 ± 660 (the mean ± SD) ng/g-fat in the blubber and 570 ± 320 ng/g-fat in the liver, respectively. There was a concern that SSLs had been contaminated by PCBs during the fetal period. The concentrations of the major congeners in the blubber and liver were a correlation between the fetus and mother (blubber: r=0.9934, liver: r=0.9160; P ≦ 0.05). The results indicated that PCBs in the fetuses came from the mothers. #177 and #199 showed no correlations between the fetus and the mother in the blubber and liver. This indicated a selective capture by some natural protector such as the placenta.

Concentration profiles of PCB congeners in the blubber and liver of Steller sea lions (Eumetopias jubatus) from the coast of Hokkaido, Japan.

The concentrations of PCB congeners in the blubber and liver of male and female Steller sea lions (Eumetopias jubatus; SSLs) collected from the Shakotan Peninsula and the Nemuro Strait, Hokkaido, Japan in 2008 and 2010 were measured by HRGC-HRMS, in order to express the concentration profiles in SSLs at these regions. #153 predominated in both organs, followed by #138, #99 and #118. In males, #28 and #31 were concentrated particularly in the blubber, while #177 and #199 were accumulated specifically in the liver. The differences in these concentration profiles might be expressed by the differences in the organs and their functions. The concentrations of #99, #118, #138, #153, and #180 in the blubber appeared to correspond significantly with the differences between genders. The details of the surveys on PCB congeners in SSLs could clarify the differences in the residue levels of individual congeners for organs and genders.

Age-related change and allometry of skull and canine of sea otters, Enhydra lutris.

Skulls and canines of 460 sea otters from Lopatka Cape, Kamchatka, were examined to assess development patterns, individual variation and sexual differences. An allometric formula was applied to morphometrical data, and the relative growth of each character to total length of skull was analyzed. In both sexes, most morphometrical characters ceased growth at about 2 years of age. Canine root length increased rapidly during the first year of life, while crown length decreased due to remarkable wear. There was large individual variation in the feeding and breathing/sniffing apparatus, while there was little variation in braincase size. There were sexual differences in most characteristics, although males and females showed similar growth patterns. The coronoid process of the mandible showed positive allometry in both sexes, and we attributed this finding to feeding habits. The fact that only male mastoids showed positive allometry may be due to the need for male otters to maintain a passing territory.

Augmentation of NO-mediated vasodilation in metabolic acidosis.

Reduction of perivascular pH in acidemia produces hyporesponsiveness of vascular bed to vasoconstrictors. In the present study, we examined the effects of modest acidification on dilatory responses of isolated rat thoracic aorta. Acetylcholine produced endothelium-dependent relaxation in phenylephrine-precontracted aorta, which was markedly enhanced by acidification of Krebs-Henseleit solution from pH 7.4 to 7.0. A similar augmentation was observed in the relaxing responses to NO donors (SNP, SIN-1, SNAP), 8-Br-cGMP and NS-1619 (a putative K(Ca) channel opener and/or Ca channel inhibitor) in endothelium-denuded, phenylephrine-contracted aorta. However, papaverine-induced relaxation was not affected by the change in pH. At pH 7.4, the relaxing responses to acetylcholine and SNP were partially inhibited by charybdotoxin (K(Ca) channel inhibitor) but not glibenclamide (K(ATP) channel inhibitor), while at pH 7.0 the relaxation induced by either drug was not affected by K(+) channel inhibitors. Relaxation induced by 8-Br-cGMP or NS-1619 was not inhibited by charybdotoxin or glibenclamide. Acidification to pH 7.0 increased the cGMP production in response to acetylcholine in endothelium-intact aorta and to SNP in endothelium-denuded aorta. These results show that modest acidification augments NO-mediated relaxation in rat aorta, probably due to an enhancement of cGMP-dependent but K(+) channel-unrelated relaxation mechanisms.

Effects of chronic administration of sarpogrelate on systolic blood pressure of spontaneously hypertensive rats: comparison with quinapril.

Effects of long-term sarpogrelate (5-HT(2) antagonist) administration on the systolic blood pressure of Wistar-Kyoto normotensive rats (WKYs) and spontaneously hypertensive rats (SHRs) were studied and compared with those of quinapril (ACE-I). Sarpogrelate and quinapril were administered orally for 12 weeks and body and heart weights, systolic blood pressure and the relationships between heart weight and systolic blood pressure were determined. Although both drug treatments caused decreases in the body weight of WKYs and SHRs, only quinapril induced a decrease in the heart weight of SHRs. In addition, quinapril induced a dose-dependent decrease in systolic blood pressure in WKYs and SHRs while sarpogrelate had no effect on systolic blood pressure. Thus, quinapril showed hemodynamic effects on WKYs and SHRs, but the 5-HT(2) antagonists sarpogrelate did not shown such effects, suggesting that 5-HT(2) receptor antagonists may not be important for controlling systolic blood pressure.