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Defatted soybean and soybean germ were fermented by Aspergillus sp. by a method based on traditional. Japanese fermentation technology. From this process we developed AglyMax, a product rich in isoflavone aglycones, and ImmuSoy, a fermentation culture made by a propriety kojic mold fermentation. Both products have an immunopotentiation activity in the intestinal tract. Their biological effect on bone marrow stem cells had not been elucidated and thus was examined in this study. Six-week-old male and female ICR/JCL mice purchased from Charles River Japan were used. For female mice, groups a and b were fed a normal diet and group c was fed a 1% ImmuSoy diet. For male mice, groups a and b were fed a normal diet; groups c and d were fed AglyMax at 30 mg/kg body weight and 100 mg/kg body weight, respectively; and group h was fed a 10% miso diet. After 3 wk all groups except group a were whole-body irradiated by 8 Gy of gamma-irradiation and isologous bone marrow nucleated cells (0.5 x 106 cells/0.5 mL) were injected intravenously into all experimental groups. One week later, the mice were killed, the macroscopic nodules on the surface of spleen were numerated under a microscope, and some nodules were studied histopathologically. Cells were stained with hematoxylin and eosin, iron staining was done with potassium ferrocyanide, and immuno-histochemical staining was done for monoclonal anti-CD34 and CD45 antibodies. For female mice, average spleen weight (relative to a 10-g body weight) was 53.0 mg in group a, 8.5 mg in group b, and 16.4 mg in group c, with significant differences between groups b and c. Similarly, average numbers of spleen colonies were 0 in group a, 1.6 in group b, and 18.6 in group c, with a significant increase in group c. For male mice, average spleen colony numbers were significantly increased in groups d and h compared with group b. Although prominent spleen colony foci were composed of lymphoblasts, none of the CD34 nor CD45 antibodies reacted to those colony foci. This evidence indicates that fermented soybean may contain factors that will potentiate bone marrow stem cell proliferation in spleen.

The main purpose of our study was to assess the effects of fermented soybean extraction (FSE) containing 30% isofiavone aglycones on the production of nitric oxide and on systolic blood pressure in SHR-SP rats. After the administration of FSE, significant decreases in systolic blood pressure were confirmed in the FSE group compared with the control group. Nitric oxide levels in urine and serum were also significantly higher in the FSE group than in the control group. Brain and ventricular weights were significantly lower in the FSE group than in the control group. Significantly higher levels of eNOS mRNA were also confirmed in the FSE group than in the control group. In conclusion, isoflavone aglycones could decrease systolic blood pressure significantly through an increase in the formation of nitric oxide, and the promotion effects of FSE on the formation of eNOS mRNA were confirmed in SHR-SP rats. If clinically applied without any detrimental effect, isoflavone aglycones are expected to contribute to preventive cardiology.

Objective: Despite key differences in pathological processes, both Intramural Hematomas and Aortic Dissections are Acute Aortic Syndromes repaired with similar surgical technique. The objective of this study was to determine differences in surgical outcomes between patients with Intramural Hematoma versus Type A Aortic Dissection undergoing Ascending Aortic Arch repair., Methods: This retrospective review of prospectively collected data included all patients with acute Intramural Hematoma or Type A Aortic Dissection who underwent emergent Ascending- or Arch Repair from January 2018 to May 2023 at a single academic institution. Primary outcomes included intraoperative mortality, 30-Day mortality, and postoperative stay. Secondary outcomes included postoperative complications. Outcomes were analyzed using Chi-squared, Fisher's Exact, and t-tests, with significance set at p < 0.05., Results: A total of 107 patients were included, 27 of whom (25%) had Intramural Hematoma and 80 (75%) had Type A Aortic Dissection. There were no differences in preoperative characteristics such as age, gender, and comorbidities, and no differences in perioperative characteristics such as case length, cardiopulmonary bypass, aortic cross-clamp, and circulatory arrest times. When comparing postoperative outcomes, there was a higher rate of postoperative pericardial effusions requiring pericardial window in the Intramural Hematoma cohort compared to the Aortic Dissection cohort (15% [n = 4] vs. 3% [n = 2]; p = 0.02). There were no differences in other primary outcomes such as intraoperative mortality, 30-Day mortality, and postoperative length of stay. There were also no differences in the rates of postoperative complications such as bleeding requiring reoperation, cerebrovascular accident, atrial fibrillation, pleural effusion requiring thoracentesis, and surgery-related Emergency Department visits., Conclusions: Our analysis demonstrates similar outcomes for patients undergoing Ascending Aortic Arch repair between patients with Intramural Hematoma and Type A Aortic Dissection. Despite the higher rate of required postoperative pericardial windows in the Intramural Hematoma cohort, the overall primary outcomes remained comparable. These findings better elucidate the standard of care for patients with acute Intramural Hematoma undergoing Ascending Aortic Arch repair., (© 2024. The Author(s).)

We describe a rare complication of intraprocedural spontaneous thrombus formation on a transcatheter edge-to-edge repair (MitraClip; Abbott Laboratories) device in a hypercoagulable yet adequately anticoagulated patient. We also outline the novel use of a vacuum (Penumbra) aspiration system, which resulted in rapid and effective thrombus elimination., Competing Interests: The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Dishcook is a new cooking system that allows individual cooking using a dedicated induction heater. This study investigated whether Dishcook use affects the nutritional value of individuals with intellectual disabilities. This study was conducted on users receiving support from a continuous-employment office in Obama City, Fukui Prefecture, in 2022. Of these participants, 18 (seven women and 11 men) who requested the use of the Dishcook were included in the analysis. The study period was from January to August 2023. The mean age was 48.72±16.24 y. A significant increase in the overall phase angles of the limbs was observed. Triglyceride, LDL cholesterol, HbA1c, and serum zinc levels improved in patients who used the Dishcook. The phase angle obtained using Bioelectrical Impedance Analysis also improved, indicating the usefulness of the Dishcook in treating metabolic diseases and the possibility of individualized nutritional management.

Objective: To investigate the effect of minimally invasive cardiac surgery (MICS) on resource utilization, cost, and postoperative outcomes in patients undergoing left-heart valve operations., Methods: Data were retrospectively reviewed for patients undergoing single-valve surgery (eg, aortic valve replacement, mitral valve replacement, or mitral valve repair) at a single center from 2018 to 2021, stratified by surgical approach: MICS vs full sternotomy (FS). Baseline characteristics and postoperative outcomes were compared. Primary outcome was high resource utilization, defined as direct procedure cost higher than the third quartile or either postoperative LOS ≥7 days or 30-day readmission. Secondary outcomes were direct cost, length of stay, 30-day readmission, in-hospital and 30-day mortality, and major morbidity. Multiple regression analysis was conducted, controlling for baseline characteristics, operative approach, valve operation, and lead surgeon to assess high resource utilization., Results: MICS was correlated with a significantly lower rate of high resource utilization (MICS, 31.25% [n = 115] vs FS 61.29% [n = 76]; P  < .001). Median postoperative length of stay (MICS, 4 days [range, 3-6 days] vs FS, 6 days [range, 4 to 9 days]; P  < .001) and direct cost (MICS, $22,900 [$19,500-$28,600] vs FS, $31,900 [$25,900-$50,000]; P  < .001) were lower in the MICS group. FS patients were more likely to experience postoperative atrial fibrillation ( P  = .040) and renal failure ( P  = .027). Other outcomes did not differ between groups. Controlling for stratified Society of Thoracic Surgeons predicted risk of mortality, cardiac valve operation, and lead surgeon, FS demonstrated increased likelihood of high resource utilization ( P  < .001)., Conclusions: MICS for left-heart valve pathology demonstrated improved postoperative outcomes and resource utilization., (© 2023 The Author(s).)

Background: Establishing cardiopulmonary bypass remains critical to the successful repair of an acute type A aortic dissection. A recent trend away from femoral arterial cannulation has occurred in part due to concerns of stroke risk from retrograde perfusion to the brain. The purpose of this study was to determine if arterial cannulation site for aortic dissection repair impacts surgical outcomes., Methods: A retrospective chart review was performed at Rutgers Robert Wood Johnson Medical School from January 1st, 2011 to March 8th, 2021. Of the 135 patients included, 98 (73%) underwent femoral arterial cannulation, 21 (16%) axillary artery cannulation, and 16 (12%) direct aorta cannulation. The study variables included demographic data, cannulation site, and complications., Results: The mean age was 63.6±14 years, with no difference between the femoral, axillary, and direct cannulation groups. Eighty-four patients (62%) were male, with similar percentages amongst each group. The rates of bleeding, stroke, and mortality specifically due to the arterial cannulation did not significantly differ based on cannulation site. None of the patients had strokes that were attributable to cannulation type. No patients died as a direct complication of arterial access. The overall in-hospital mortality was 22%, similar between groups., Conclusions: This study found no statistically significant different in rates of stroke or other complications based on cannulation site. Femoral arterial cannulation thus remains a safe and efficient choice for arterial cannulation in the repair of acute type A aortic dissection., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-22-576/coif). The authors have no conflicts of interest to declare., (2023 Journal of Thoracic Disease. All rights reserved.)

Objective: Over the last two decades there has been an increase in the number of cardiac implantable electronic devices and consequently, there has also been an increased need for lead extractions. Fibrotic attachments develop between the lead and the venous and cardiac structures that may require the use of a laser to mobilize the lead. Cardiothoracic surgeons (CTS) have traditionally provided backup for surgical emergencies for these extractions. This study evaluates the surgical outcomes of patients undergoing transvenous laser lead extractions (TLE) and determines if CTS are still needed for backup., Methods: A retrospective review of consecutive patients undergoing laser lead extractions at a single academic center. Lead extractions using only laser sheaths were analyzed. The clinical characteristics, complications, and mortality of the patients were evaluated., Results: One hundred and twenty-one patients underwent TLEs from January 1st, 2014 to December 31st, 2018. The majority were male (N = 80, 66.1%), and the average age was 66.48 ± 14 years. The indication for removal was either laser lead malfunction or infection. A total of 30 patients (24.8%) had complications postoperatively including wound hematomas, superficial infections, and arrhythmias. The average length of stay was 9 ± 12 for all the patients in the study. 2 patients (1.6%) had injuries that required emergency surgical repair with injuries to the posterior superior vena cava and right ventricle. Both patients survived the initial injury with one patient was discharged home on day 4 and the other succumbing to his injuries on postoperative day 20., Conclusion: Although the incidence of surgical emergencies is rare the morbidity and mortality for TLE require that surgical backup be available., (© 2022. The Author(s).)

Foreign bodies in the heart are a rare condition and an exact mechanism for this occurrence has not been well described. These objects can reach the heart by direct penetration due to local trauma or through intravenous migration or may remain in the heart after medical procedures. The most common foreign bodies that reach the heart are bullets and shrapnel. The purpose of this study is to review a case where a patient injected himself with recreational drugs. The needle subsequently dislodged from the syringe and migrated into the heart., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Lemaire et al.)

Delayed presentation of penetrating cardiac injuries is exceedingly rare due to the observed near 100% pre-hospital mortality. We describe a case of a patient who presented for evaluation nearly 24 h after sustaining a self-inflicted pneumatic nail gun injury to the right ventricular outflow tract. Remarkably, the patient had no evidence of hemodynamic compromise. This case highlights the importance of maintaining a high index of suspicion for cardiac injury with penetrating trauma to the cardiac box regardless of presenting signs and symptoms, and the value of adhering to advanced trauma life support principles., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. No funding was received to assist with this publication., (© 2021 The Authors.)

A 73-year-old male with a history of severe coronary artery disease and prior coronary artery bypass grafting (CABG) presented with chest pain and elevated troponins. His workup revealed an ejection fraction of 15%, severe native coronary disease, as well as stenosis of his bypass grafts. He underwent a high-risk redo CABG with an Impella 5.5® (Abiomed, Danvers, MA) placement. The device was removed on postoperative day eight, at which time he went into cardiogenic shock from aortic valve leaflet injury. Given that he had no calcium deposits around the aortic valve annulus and severe aortic insufficiency, a multidisciplinary heart team decided he would be best served by a surgical aortic valve replacement. He was taken back to the operating room for a surgical aortic valve and intra-aortic balloon pump. His postoperative course was complicated by pneumonia, sepsis, and renal failure requiring continuous renal replacement therapy. He was discharged to a rehabilitation facility after 42 days. The following case encompasses the high morbidity risk of acute aortic valve insufficiency after Impella placement, never before documented in an Impella 5.5., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Ghannam et al.)

Photoactivated adenylyl cyclase (PAC) is a unique protein that, upon blue light exposure, catalyzes cAMP production. The crystal structures of two PACs, from Oscillatoria acuminata (OaPAC) and Beggiatoa sp. (bPAC), have been solved, and they show a high degree of similarity. However, the photoactivity of OaPAC is much lower than that of bPAC, and the regulatory mechanism of PAC photoactivity, which induces the difference in activity between OaPAC and bPAC, has not yet been clarified. Here, we investigated the role of the C-terminal region in OaPAC, the length of which is the only notable difference from bPAC. We found that the photoactivity of OaPAC was inversely proportional to the C-terminal length. However, the deletion of more than nine amino acids did not further increase the activity, indicating that the nine amino acids at the C-terminal critically affect the photoactivity. Besides, absorption spectral features of light-sensing domains (BLUF domains) of the C-terminal deletion mutants showed similar light-dependent spectral shifts as in WT, indicating that the C-terminal region influences the activity without interacting with the BLUF domain. The study characterizes new PAC mutants with modified photoactivities, which could be useful as optogenetics tools.

Objectives: Patients with patent internal thoracic artery (ITA) grafts after prior coronary artery bypass grafting surgery who require aortic valve replacement (AVR) pose unique technical challenges for safe and optimal myocardial protection. The purpose of this study is to review our short- and long-term outcomes with redo minimally invasive AVR in patients with patent in situ ITA grafts., Methods: From 2008 to 2016, 48 patients with at least 1 patent in situ mammary artery graft underwent minimally invasive AVR. Preoperative computed tomography was performed in all patients to evaluate the relationship of patent grafts to the sternum. Retrograde coronary sinus and pulmonary vent catheters were placed via the right internal jugular vein. The in situ ITA grafts were not clamped during AVR. Transverse aortotomy, taking care to avoid the grafts arising from the aorta, was performed to expose the aortic valve., Results: The median age of the patients was 78 years [Quartile 1 (Q1)-Quartile 3 (Q3): 71-81]. Thirty-nine (81%) patients were men, and 46 (96%) patients had aortic stenosis. The median cardiopulmonary bypass and cross-clamp times were 124 (Q1-Q3: 108-164) and 92 (Q1-Q3: 83-116) min, respectively. Moderate hypothermia at 28-30°C was used in all patients. Most patients received cold blood cardioplegia with antegrade induction and continuous retrograde delivery. Four patients received only retrograde delivery due to some degree of aortic insufficiency. Thirty-day mortality was 4% (2 of 48 patients). There was no conversion to full sternotomy, and no reoperations were performed for postoperative bleeding or sternal wound infection. Excluding the 2 patients who died in the hospital, the median postoperative length of stay was 7 days (Q1-Q3: 5-8). Overall survival at 1, 5 and 10 years was 94%, 87% and 44%, respectively., Conclusions: Percutaneous retrograde cardioplegia combined with antegrade cardioplegia and moderate hypothermia, without interruption of ITA flow, is a safe and reliable strategy in patients with patent ITA grafts undergoing aortic valve replacement. This strategy combined with a minimally invasive approach may reduce surgical trauma, and is a safe and effective technique in these challenging patients., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Degenerative mitral valve disease is associated with variable and complex defects in valve morphology. Three-dimensional echocardiography (3DE) has shown promise in aiding preoperative planning for patients with this disease but to date has not been as transformative as initially predicted. The clinical usefulness of 3DE has been limited by the laborious methods currently required to extract quantitative data from the images., Methods: To maximize the utility of 3DE for preoperative valve evaluation, this work describes an automated 3DE image analysis method for generating models of the mitral valve that are well suited for both qualitative and quantitative assessment. The method is unique in that it captures detailed alterations in mitral leaflet and annular morphology and produces image-derived models with locally varying leaflet thickness. The method is evaluated on midsystolic transesophageal 3DE images acquired from 22 subjects with myxomatous degeneration and from 22 subjects with normal mitral valve morphology., Results: Relative to manual image analysis, the automated method accurately represents both normal and complex leaflet geometries with a mean boundary displacement error on the order of one image voxel. A detailed quantitative analysis of the valves is presented and reveals statistically significant differences between normal and myxomatous valves with respect to numerous aspects of annular and leaflet geometry., Conclusions: This work demonstrates a successful methodology for the relatively rapid quantitative description of the complex mitral valve distortions associated with myxomatous degeneration. The methodology has the potential to significantly improve surgical planning for patients with complex mitral valve disease., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Cyclic-AMP is one of the most important second messengers, regulating many crucial cellular events in both prokaryotes and eukaryotes, and precise spatial and temporal control of cAMP levels by light shows great promise as a simple means of manipulating and studying numerous cell pathways and processes. The photoactivated adenylate cyclase (PAC) from the photosynthetic cyanobacterium Oscillatoria acuminata (OaPAC) is a small homodimer eminently suitable for this task, requiring only a simple flavin chromophore within a blue light using flavin (BLUF) domain. These domains, one of the most studied types of biological photoreceptor, respond to blue light and either regulate the activity of an attached enzyme domain or change its affinity for a repressor protein. BLUF domains were discovered through studies of photo-induced movements of Euglena gracilis, a unicellular flagellate, and gene expression in the purple bacterium Rhodobacter sphaeroides, but the precise details of light activation remain unknown. Here, we describe crystal structures and the light regulation mechanism of the previously undescribed OaPAC, showing a central coiled coil transmits changes from the light-sensing domains to the active sites with minimal structural rearrangement. Site-directed mutants show residues essential for signal transduction over 45 Å across the protein. The use of the protein in living human cells is demonstrated with cAMP-dependent luciferase, showing a rapid and stable response to light over many hours and activation cycles. The structures determined in this study will assist future efforts to create artificial light-regulated control modules as part of a general optogenetic toolkit.

Background: There is continued need for therapies which reverse or abate the remodeling process after myocardial infarction (MI). In this study, we evaluate the longitudinal effects of calcium hydroxyapatite microsphere gel on regional strain, global ventricular function, and mitral regurgitation (MR) in a porcine MI model., Methods: Twenty-five Yorkshire swine were enrolled. Five were dedicated weight-matched controls. Twenty underwent posterolateral infarction by direct ligation of the circumflex artery and its branches. Infarcted animals were randomly divided into the following 4 groups: 1-week treatment; 1-week control; 4-week treatment; and 4-week control. After infarction, animals received either twenty 150 μL calcium hydroxyapatite gel or saline injections within the infarct. At their respective time points, echocardiograms, cardiac magnetic resonance imaging, and tissue were collected for evaluation of MR, regional and global left ventricular function, wall thickness, and collagen content., Results: Global and regional left ventricular functions were depressed in all infarcted subjects at 1 week compared with healthy controls. By 4-weeks post-infarction, global function had significantly improved in the calcium hydroxyapatite group compared with infarcted controls (ejection fraction 0.485 ± 0.019 vs 0.38 ± 0.017, p < 0.01). Similarly, regional borderzone radial contractile strain (16.3% ± 1.5% vs 11.2% ± 1.5%, p = 0.04), MR grade (0.4 ± 0.2 vs 1.2 ± 0.2, p = 0.04), and infarct thickness (7.8 ± 0.5 mm vs 4.5 ± 0.2 mm, p < 0.01) were improved at this time point in the treatment group compared with infarct controls., Conclusions: Calcium hydroxyapatite injection after MI progressively improves global left ventricular function, borderzone function, and mitral regurgitation. Using novel biomaterials to augment infarct material properties is a viable alternative in the current management of heart failure., (Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

A 74-year-old woman underwent replacement of the ascending aorta for acute type A aortic dissection. The patient suffered from bacteremia postoperatively and repeated computed tomography showed an increasing diameter of pseudoaneurysms at the site of the proximal anastomosis due to graft infection. Re-mechanical Bentall operation and arch replacement were therefore performed using a composite graft of a rifampicin-bonded gelatin-sealed 24-mm woven Dacron graft and a mechanical valve. The postoperative course was uneventful. We report the successful in situ reconstruction using the above-mentioned Dacron graft and describe the preparation of the rifampicin solution using a surfactant.

Cardiac hemangiomas are extremely rare benign tumors. These tumors are usually asymptomatic but they can present symptoms such as palpitations, shortness of breath, and arrythmia. We report the case of a 73-year-old man who presented with an abnormal shadow on chest computed tomography during follow-up for lung metastatic tumor after resection of his rectal cancer. A cardiac tumor was detected, and surgical resection and right ventricular plasty were successfully performed with the patient under cardiopulmonary bypass. Histopathologic examination revealed a benign cardiac hemangioma, which was categorized as a hemangioma of the mixed cavernous and capillary type., (Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Purpose: Transcatheter mitral valve replacement would represent a major advance in heart valve therapy. Such a device requires a specialized anchoring and sealing technology. This study was designed to test the feasibility of a novel mitral valve replacement device (the sutureless mitral valve [SMV]) designed to anchor and seal in the mitral position without need for sutures., Description: The SMV is a self-expanding device consisting of a custom-designed nitinol framework and a pericardial leaflet valve mechanism., Evaluation: Ten sheep underwent successful surgical SMV device implantation. All animals underwent cardiac catheterization 6 hours postoperatively. Hemodynamic, angiographic, echocardiographic and necroscopic data were recorded. The mean aortic cross-clamp time was 9.5 ± 3.1 minutes. Echocardiography and angiography revealed excellent left ventricular systolic function, no significant perivalvular leak, no mitral valve stenosis, no left ventricular outflow tract obstruction, and no aortic valve insufficiency. Necropsy demonstrated that the SMV devices were anchored securely., Conclusions: This study demonstrates the feasibility and short-term success of sutureless mitral valve replacement using a novel SMV device., (Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Heart failure after myocardial infarction (MI) is a result of increased myocardial workload, adverse left ventricular (LV) geometric remodeling, and less efficient LV fluid movement. In this study we utilize cardiac magnetic resonance imaging to evaluate ventricular function and flow after placement of a novel directed epicardial assist device., Methods: Five swine underwent posterolateral MI and were allowed to remodel for 12 weeks. An inflatable bladder was positioned centrally within the infarct and secured with mesh. The device was connected to an external gas exchange pump, which inflated and deflated in synchrony with the cardiac cycle. Animals then underwent cardiac magnetic resonance imaging during active epicardial assistance and with no assistance., Results: Active epicardial assistance of the infarct showed immediate improvement in LV function and intraventricular flow. Ejection fraction significantly improved from 26.0% ± 4.9% to 37.3% ± 4.5% (p < 0.01). End-systolic volume (85.5 ± 12.7 mL versus 70.1 ± 11.9 mL, p < 0.01) and stroke volume (28.5 ± 4.4 mL versus 39.9 ± 3.1 mL, p = 0.03) were also improved with assistance. End-diastolic volume and regurgitant fraction did not change with treatment. Regional LV flow improved both qualitatively and quantitatively during assistance. Unassisted infarct regional flow showed highly discoordinate blood movement with very slow egress from the posterolateral wall. Large areas of stagnant flow were also identified. With assistance, posterolateral wall blood velocities improved significantly during both systole (26.4% ± 3.2% versus 12.6% ± 1.2% maximum velocity; p < 0.001) and diastole (54.3% ± 9.3% versus 24.2% ± 2.5% maximum velocity; p < 0.01)., Conclusions: Directed epicardial assistance can improve LV function and flow in ischemic cardiomyopathy. This novel device may provide a valuable alternative to currently available heart failure therapies., (Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Olprinone, a specific phosphodiesterase III inhibitor, and corforsin daropate, a direct adenylate cyclase activator, are now being used in critical conditions. We investigated whether their therapeutic use provides protection against septic acute lung injury (ALI) and mortality. Polymicrobial sepsis was induced by cecal ligation and puncture (CLP) in BALB/c mice. Olprinone or colforsin daropate was continuously given through an osmotic pump that was implanted into the peritoneal cavity immediately following CLP. These treatments prevented the ALI development in CLP mice, as indicated by the findings that severe hypoxemia, increased pulmonary vascular permeability, and histological lung damage were strikingly remedied. Furthermore, continued administration of olprinone or colforsin daropate suppressed apoptosis induction in septic lungs and improved the survival of CLP mice. Olprinone and corforsin daropate enhanced Akt phosphorylation in septic lungs. Wortmannin, which inhibits the Akt upstream regulator phosphatidylinositol 3-kinase, abrogated the protective effects of olprinone and corforsin daropate on sepsis-associated lung inflammation and apoptosis. In vivo transfection of cyclic AMP response element binding protein (CREB) decoy oligodeoxynucleotide failed to negate the abilities of these agents to increase Akt phosphorylation and to inhibit IκBα degradation in septic lungs. These results demonstrate for the first time that CREB-independent Akt-mediated signaling is a critical mechanism contributing to the therapeutic effects of olprinone and corforsin daropate on septic ALI. Moreover, our data also suggest that these cyclic AMP-related agents, by blocking both nuclear factor-κB activation and apoptosis induction, may represent an effective therapeutic approach to the treatment of the septic syndrome.

Background: The recurrence of regurgitation after surgical mitral valve (MV) repair remains a significant clinical problem. Mitral annuloplasty rings are commonly used in MV repair procedures. The purpose of this study was to demonstrate the feasibility of transvenous valve-in-ring (VIR) implantation using the Melody valve (Medtronic, Minneapolis, MN), which is a valved-stent designed for percutaneous pulmonary valve replacement, and 4 distinct types of annuloplasty ring (AR) in an ovine model., Methods: Ten sheep underwent surgical MV annuloplasty ring placement (n=10): CE-Physio, Edwards Lifesciences, Irvine, CA [n=5]; partial ring [n=3]; flexible ring [n=1]; and saddle ring [n=1]). All animals underwent cardiac catheterization, hemodynamic assessment, and Melody VIR implantation through a transfemoral venous, transatrial septal approach 1 week after surgery. Follow-up hemodynamic, angiographic, and echocardiographic data were recorded., Results: Melody VIR implantation was technically successful in all but 1 animal. In this animal a 26-mm partial AR proved too large for secure anchoring of the Melody valve. In the remaining 9 animals, fluoroscopy showed the Melody devices securely positioned within the annuloplasty rings. Echocardiography revealed no perivalvular leak, and angiography revealed no left ventricular outflow tract obstruction, vigorous left ventricular function, and no aortic valve insufficiency. The median procedure time was 55.5 (range, 45 to 78) minutes., Conclusions: This study demonstrates the feasibility of a purely percutaneous approach to MV replacement in patients with preexisting annuloplasty rings, regardless of ring type. This approach may be of particular benefit to patients with failed repair of ischemic mitral regurgitation., (Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

The nitrogen (N) status of a plant determines the composition of its major components (amino acids, proteins, carbohydrates and organic acids) and, directly or indirectly, affects the quality of agricultural products in terms of their calorific value and taste. Although these effects are guided by changes in metabolic pathways, no overall metabolic analysis has previously been conducted to demonstrate such effects. Here, metabolite profiling using gas chromatography-mass spectrometry (GC-MS) was used to evaluate the effect of N levels on spinach tissue, comparing two cultivars that differed in their ability to use N. Wide variation in N content was observed without any distinct inhibition of growth in either cultivar. Principal component analysis (PCA) and self-organizing mapping (SOM) were undertaken to describe changes in the metabolites of mature spinach leaves. In PCA, the first component accounted for 44.5% of the total variance, the scores of which was positively correlated with the plant's N content, and a close relationship between metabolite profiles and N status was observed. Both PCA and SOM revealed that metabolites could be broadly divided into two types, correlating either positively or negatively with plant N content. The simple and co-coordinated metabolic stream, containing both general and spinach-specific aspects of plant N content, will be useful in future research on such topics as the detection of environmental effects on spinach through comprehensive metabolic profiling.

We previously reported that continuous intravenous (IV) administration of nicorandil (NIC) inhibits QT dispersion (QTd). However, no prior study has evaluated the efficacy of NIC when administered orally to acute myocardial infarction (AMI) patients following continuous IV administration. Thirty patients with anteroseptal infarction in whom revascularization was performed successfully within 6 hours of AMI onset were included in the study and assigned to one of 3 groups: group A (continuous IV administration of NIC), group B (continuous IV and oral administration of NIC), and group C (no treatment with NIC). After 24 hours, QTd in groups A and B was significantly decreased compared to QTd in group C (P < 0.01) (group A, 58.1; group B, 58.2; and group C, 81.3). The QTd obtained 3 months later was significantly shorter in group B subjects who were orally administered NIC, and QTd before percutaneous coronary intervention (PCI) was restored in group A, in which no NIC had been administered orally [group A, 66.7; group B, 54.1; and group C, 73.9; P < 0.05 (group A versus group B) and P < 0.01 (group B versus group C)]. The effects were evaluated by comparing different routes of administration. Continuous IV and subsequent oral administration of NIC inhibited prolongation of QTd, suggesting that these effects may prevent the occurrence of cardiac events during both the acute and chronic phases of AMI.

Levels of cytokinins and abscisic acid (ABA) and the expression of senescence-related genes were investigated in two maize (Zea mays L.) cultivars of different senescence type, cv. P3845 (stay-green) and cv. Hokkou 55 (earlier senescent), in a field study. The delay in leaf senescence in P3845 was correlated with increased levels of chlorophyll and nitrogen and a higher photon-saturated photosynthetic rate (P(sat)). Compared with the earlier senescent Hokkou 55, P3845 showed enhanced contents of cytokinins (trans-zeatin riboside, t-ZR; dihydrozeatin riboside, DHZR; isopentenyladenosine, iPA) and reduced levels of ABA in its leaves. In roots, P3845 had increased levels of t-ZR, DHZR, and ABA, but decreased concentrations of iPA. It was concluded that a higher rate of cytokinin transport from roots to leaves contributes to the delay of senescence in P3845. By contrast, the translocation of ABA from roots to shoots may be blocked in the stay-green cultivar, which also results in retarded leaf senescence. P3845 ear leaves contained more malondialdehyde (MDA) and higher catalase (CAT) and superoxide dismutase (SOD) activities than Hokkou 55. Since the accumulation of the mRNAs for Rubisco small subunit (rbcS), phosphoenolpyruvate carboxylase (PEPC), and SOD peaked after Chl content and P(sat) had reached their maxima, it is speculated that when leaf senescence is initiated, Chl contents decrease first, followed by the degradation of the photosynthetic apparatus and of photosynthesis-related enzymes. See1 and See2 encode senescence-related cysteine proteases; their mRNAs were most abundant in yellowing leaves, suggesting that these proteins are involved in the process of senescence rather than its initiation. mRNAs of both genes were more abundant in Hokkou 55 than in P3845, which suggests a regulation of leaf senescence at the transcriptional level.

Recent studies have reported that estrogen replacement therapy (ERT) reduces the risk of cardiovascular diseases in postmenopausal women. However, mechanisms responsible for this effect are not yet completely understood, and ERT is associated with carcinogenic side effects in women and feminizing effects in men. Because soybean isoflavones, a group of natural phytoestrogens, have only weak estrogenic activity and are not known to have side effects such as carcinogenesis and feminization, we evaluated the effects of genistein, daidzein and glycitein on the growth and DNA synthesis of aortic smooth muscle cells (SMC) from stroke-prone spontaneously hypertensive rats (SHRSP). SMC were cultured in dishes and proliferated on 10% dextran-coated charcoal/fetal bovine serum, and then treated with 0.1-30 micromol/L of genistein, daidzein or glycitein to investigate cell proliferation (cell number) and DNA synthesis (cell proliferation ELISA system), respectively. We also studied their effects on platelet-derived growth factor (PDGF)-BB (20 microg/L)-induced SMC proliferation. Soybean isoflavones inhibited proliferation and DNA synthesis of SMC from SHRSP in a concentration-dependent manner. Inhibition was significant at 3 micromol/L of genistein and 10 micromol/L of both daidzein and glycitein. For significant inhibition of PDGF-BB-induced SMC proliferation, concentrations as low as 0.1 micromol/L of each isoflavone were effective. These isoflavones, with their inhibitory effects on natural and PDGF-BB-induced SMC proliferation, may be useful in attenuatating such proliferation, a basic mechanism involved in atherosclerotic vascular change, thereby preventing atherosclerotic cardiovascular diseases.

The truncated Aalpha-chain of fibrinogen Marburg is partly linked with albumin by a disulfide bond. Based on the recovery of the first six amino acid residues assigned to the subunit polypeptides of fibrinogen (the Aalpha-and gamma-chains) and albumin, 0.33 mol of albumin was estimated to be linked to 1 mol of the Marburg fibrinogen. When the Marburg fibrinogen was clotted with thrombin-factor XIIIa-Ca2+, various alpham gamman heteromultimers were produced, and part of the albumin was cross-linked to the gamma-chain. Acid-solubilized Marburg fibrin monomer failed to form large aggregates that could be detected by monitoring turbidity at A350, but it was able to enhance tissue-type plasminogen-activator-catalyzed plasmin generation, though not as avidly as the normal control, indicating that the double-stranded protofibrils had, to some extent, been constructed. This idea seems to be supported by normal factor XIIIa-catalyzed cross-linking of the fibrin gamma-chains. However, the cross-linked Marburg fibrin, being apparently fragile and translucent, was highly resistant against plasmin, and its subunit components were considerably retained for 48 hours as noted by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Although the exact mechanisms are still unclear, the albumin-incorporated factor XIIIa-cross-linked Marburg fibrin seems to have undergone a critical structural alteration(s) to acquire resistance against plasmin. This aquisition of plasmin resistance may be contributed to the postoperative pelvic vein thrombosis and recurrent pulmonary embolisms in the patient after caesarian section for her first delivery at the age of 20 years.

A number of fine bands which occur in positions between the beta- and pre-beta-lipoproteins in polyacrylamide gell electrophresis are called mid-bands (MB). In this study, the relationship between the occurrence of these MB and metabolic abnormalities or vascular complications was evaluated in 181 patients with non-insulin-dependent diabetes mellitus (NIDDM). The incidence of MB in diabetic patients was significantly higher than that in 149 healthy control subjects (35 vs. 20%, p < 0.01). Analysis according to the type of MB revealed that the incidence of the central type in diabetic patients was significantly higher than that in healthy control subject (11 vs. 5%, p < 0.05). When the values of HbAlc were elevated, the incidence of MB and its central type slightly increased. The occurrence of the lower type of MB showed no relationship with the levels of HbAlc. The incidence of MB and its central type were significantly higher in patients with type IIb hyperlipidemia (86 and 41%, respectively) and with type IV hyperlipidemia (63 and 25%) than in those with normolipidemia (21 and 5%) (p < 0.01 of all). The incidence of the lower type of MB was significantly higher in patients with type IIa hyperlipidemia (25%) and with type IIb hyperlipidemia (36%) than in those with normolipidemia (11%) (p < 0.05, p < 0.01, respectively). There was no significant difference in the occurrences of MB and of the central and lower types of MB between the normolipidemic patients and healthy control subjects. The incidence of MB and its central type were significantly higher in patients with nephropathy (54 and 23%, respectively) than in those without nephropathy (32 and 9%) (p < 0.05 of all). There was no significant difference in the incidence of lower type of MB between patients with and without nephropathy. These results indicate that the incidence of central type of MB may be high in NIDDM, and that the occurrence of central type may be associated with abnormal metabolism of glucose or lipid and with diabetic nephropathy.