Search

To study the origins of biologically active substances in marine sponges, a carotenoid produced by a marine bacterium, Pseudomonas sp. strain number KK10206C, which was associated with a marine sponge, Halichondra okadai, was investigated. A visible absorption spectrum-guided isolation procedure led to the isolation of a novel C-carotenoid, okadaxanthin. Its structure, 2,2′-bis(4-hydroxy-2-methyl-2-butenyl)-ε,ε-carotene, was elucidated mainly by spectroscopic methods. Okadaxanthin turned out to be a potent singlet oxygen quencher, approximately 10 times as strong as α-tocopherol. [ABSTRACT FROM AUTHOR]

Objective: The optimal surgical strategy for atrial functional mitral regurgitation remains uncertain. Preoperative mitral-septal angle ≤ 70° has been reported as a risk factor for an abnormal vortex pattern in mitral valve repair. This study aimed to elucidate the change in the mitral-septal angle after surgery for atrial functional mitral regurgitation and its effect on the mid-term outcomes., Methods: Forty patients underwent mitral valve repair for atrial functional mitral regurgitation. The mitral-septal angle was defined as the angle between the mitral annulus and the anteroseptal wall of the left ventricular mid-portion in the parasternal long-axis view on transthoracic echocardiography. All patients underwent mitral ring annuloplasty. Left atrial plication was performed in nine patients. The mean clinical follow-up period was 42 ± 24 months., Results: The ratio of left atrial volume to left ventricular end-systolic volume was negatively correlated with the preoperative mitral-septal angle. The postoperative mitral-septal angles were significantly smaller than the preoperative ones. The mitral-septal angle decreased with a decrease in the mitral annuloplasty ring size. Patients who underwent left atrial plication tended to show an increase in the mitral-septal angle postoperatively. There were no significant differences in mid-term morbidities, including heart failure, requiring re-hospitalization and mortalities between patients with postoperative MSA > 70° and those with postoperative MSA ≤ 70°., Conclusions: Mitral ring annuloplasty negatively changed the mitral-septal angle, while left atrial plication may induce a positive change to the mitral-septal angle. An association between the mitral-septal angle and mid-term outcomes was not revealed in this study.

Background: Annular dilation by left atrial remodeling is considered the main cause of atrial function mitral regurgitation. Although acceptable outcomes have been obtained using mitral ring annuloplasty alone for atrial functional mitral regurgitation, data assessing outcomes of this procedure are limited. Therefore, we aimed to assess midterm outcomes of mitral valve repair in patients with atrial functional mitral regurgitation., Methods: We retrospectively studied 40 patients (mean age: 69 ± 9 years) who had atrial fibrillation that persisted for > 1 year, preserved left ventricular ejection fraction of > 40%, and mitral valve repair for atrial functional mitral regurgitation. The mean clinical follow-up duration was 42 ± 24 months., Results: Mitral ring annuloplasty was performed for all patients. Additional repair including anterior mitral leaflet neochordoplasty was performed for 22 patients. Concomitant procedures included maze procedure in 20 patients and tricuspid ring annuloplasty in 31 patients. Follow-up echocardiography showed significant decreases in left atrial dimensions and left ventricular end-diastolic dimensions. Recurrent mitral regurgitation due to ring detachment or leaflet tethering was observed in five patients and was seen more frequently among those with preoperative left ventricular dilatation. Three patients without tricuspid ring annuloplasty or sinus rhythm recovery by maze procedure developed significant tricuspid regurgitation. Five patients who underwent the maze procedure showed sinus rhythm recovery. Rates of freedom from re-admission for heart failure at 1 and 5 years after surgery were 95 and 86%, respectively., Conclusions: Mitral valve repair is not sufficient to prevent recurrent atrial functional mitral regurgitation in patients with preoperative left ventricular dilatation. Tricuspid ring annuloplasty may be required for long-term prevention of significant tricuspid regurgitation.

Objectives: Although the patency of internal artery grafts in coronary artery bypass grafting (CABG) is superior to that of saphenous vein grafts (SVGs), good long-term patency rates have been reported with SVGs harvested using the no-touch technique. Here, we report the early results of CABG with no-touch SVGs (NT-SVGs) along with the precautions required while handling these grafts., Methods: This retrospective study included 41 patients who underwent CABG with NT-SVGs between May 2016 and March 2018. NT-SVGs were harvested with minimal electric scalpel use, and post-harvesting vascular overdilation with a syringe was not performed. Blood with heparinized saline was used to prevent vascular endothelial damage. A drain was inserted into the SVG harvest site, which was closed with a single interrupted suture, and elasticated bandage and compression stockings were used to prevent fluid retention and avoid delayed wound healing., Results: There was no case of postoperative thoracotomy due to bleeding or myocardial infarction, and postoperative graft assessment confirmed graft patency in all patients, with a little mismatch between the diameters of SVG and the anastomotic vessel. Delayed wound healing at the graft harvest site seemed to improve after introducing the above procedures., Conclusions: Early results of CABG with NT-SVGs were good. Some precautions must be taken during harvesting and anastomosis. Taking precautions described in this study may help reduce the risk of perioperative complications and make the no-touch technique the standard procedure for harvesting SVGs for CABG.

Background: The Trifecta valve (Abbott, St Paul, MN) has excellent hemodynamic performance with acceptable rates of freedom from structural valve degeneration. However, some recent studies have reported early Trifecta valve failure. Here, we report a case series of seven Trifecta valve failures with a review of the literature., Methods: Of 107 implantations of Trifecta bioprostheses between 2012 and 2014, we encountered seven Trifecta valve failures (6.5%). Failure of a 19-mm Trifecta valve occurred in 1 patient, failure of a 21-mm Trifecta valve occurred in 5 patients, and failure of a 23-mm Trifecta valve occurred in 1 patient. The mean duration of valve durability was 51 ± 16 months. The mean effective orifice area index on the first echocardiogram after Trifecta valve implantation was 0.96 ± 0.26. The mode of presentation was prosthetic valve stenosis in 3 patients and severe aortic regurgitation in 4 patients., Results: Six patients underwent redo surgical aortic valve replacement. The common pathologic findings were circumferential pannus formation with noncoronary cusp tear and leaflet calcification. The rates of preoperative end-renal stage disease and postoperative prosthesis-patient mismatch were higher in patients with Trifecta valve failure. The incidence of early Trifecta valve failure was 3.1% at 48 months and 13.1% at 72 months., Conclusions: In our experience, early Trifecta valve failure was caused by cusp tears or leaflet calcification. Patients with end-renal stage disease and prosthesis-patient mismatch should be closely followed. Some patients with cusp tears may require urgent surgery., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Good mid-term durability of mitral valve repair of bileaflet lesions has been reported; however, patients may develop failure during follow-up. This study assessed late outcomes and mechanisms of failure associated with mitral valve repair of bileaflet lesions., Methods: Fifty-six patients (mean age 67 ± 12 years) underwent mitral valve repair of bileaflet lesions due to degenerative disease in 2011-2018. Mitral annuloplasty was added to all procedures except for 1 patient with annular calcification. Mitral valve lesions were identified by surgical inspection. Mean clinical and echocardiography follow-up occurred at 2.7 ± 2.1 and 2.5 ± 1.9 years, respectively., Results: Additional mitral valve repair techniques involved triangular resection (n = 15 patients), quadrangular resection with sliding plasty (n = 12), neochordoplasty (n = 52), and commissural plication (n = 26). Prolapse of ≥2 anterior and posterior leaflet scallops occurred in 22 (39%) and 30 (54%) patients, respectively. During follow-up, 10 (17.8%) patients developed moderate or severe mitral regurgitation. Whereas prolapse or tethering was observed early after neochordoplasty or quadrangular resection, recurrent regurgitation occurred late after commissural repair. Five-year freedom from recurrent moderate or severe mitral regurgitation rates was 71.1 ± 11.0%., Conclusions: Seventeen percent of patients developed recurrent mitral regurgitation during follow-up. Repair failure in the early phase occurred owing to aggressive resection of the posterior mitral leaflet or maladjustment of the artificial neochordae. Recurrent mitral regurgitation might occur in the late phase even after acceptable commissural repair. A sequential approach may be useful to improve the quality of mitral valve repair in bileaflet lesions.

A 19-year-old Asian woman presented to the emergency department with ventricular fibrillation. Emergent coronary angiography revealed a 99% ostial stenosis of the left main coronary trunk, and percutaneous coronary intervention was performed. Takayasu arteritis was suspected, but fluorodeoxyglucose positron emission tomography scanning showed no active inflammation. Cardiac function was affected by ischemic cardiomyopathy, and an extracorporeal left ventricular assisted device was implanted under INTERMACS profile 1 status. Histopathology of the ascending aortic wall at the outflow anastomosis site showed no significant sign of Takayasu arteritis. The absence of systemic inflammation led to the replacement of the extracorporeal left ventricular assisted device with a Jervik 2000 as a bridge to transplant. An orthotropic heart transplant took place after a 39-month wait. Histopathology of the explanted heart revealed intimal and adventitial thickening with destruction of the elastic lamina localized at the sinus of Valsalva. Our final pathologic diagnosis was localized Takayasu arteritis. To counter the increased risk of stenosis or pseudoaneurysm formation at the vascular anastomosis site, anti-inflammatory therapy was essential in Takayasu arteritis. The post-heart transplant immunosuppression regime was considered stronger than that for Takayasu arteritis, and we therefore administered prednisolone, mycophenolate mofetil, and tacrolimus as standard protocol. There have been no signs of either relapse or rejection of transplantation for over 1 year. Further closed observation is required to clarify the long-term outcome of this rare condition with regard to heart transplantation., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: We investigated current mechanisms causing low graft flow (LGF) following coronary artery bypass grafting, particularly for the right coronary artery (RCA)., Methods: We retrospectively assessed 230 individual bypass grafts as the sole bypass graft for the RCA using preoperative and postoperative quantitative angiography. Overall, 155 in-situ gastroepiploic arteries (GEAs) and 75 saphenous vein grafts (SVGs) were included. The size and status of the revascularised area were examined to determine whether these factors were associated with LGF (defined as ≤ 20 mL/min with intraoperative flowmetry). A distal lesion was defined as stenosis at segment #4, whereas a proximal lesion was stenosis at #1, #2 and #3., Results: Graft flow in the SVG and the GEA for distal lesion was significantly less compared with that for proximal lesion (34 ± 26 vs. 60 ± 46, p < 0.0001 and 22 ± 12 vs. 43 ± 28, p = 0.0004, respectively). For proximal lesion, LGF was significantly more frequent when the minimal luminal diameter was over 1.27 compared with when it was less than 1.27 (p = 0.02). Prior myocardial infarction significantly correlated with LGF in the GEA (p = 0.007) and the SVG (p = 0.03). In 55 bypass grafts with LGF, the causes were competitive flow in 20.0%, small revascularised area in 38.1% and prior myocardial infarction in 32.7%., Conclusions: Along with the current strategy based on the severity of native coronary stenosis, the incidence of competitive flow decreased remarkably. This resulted in flow demand, myocardial status and collateral vessels more influential on graft patency.

Here we describe the case of a 33-year-old woman who was diagnosed with interrupted aortic arch (IAA) type A and who underwent radical surgery in her infancy. She developed a 42-mm anastomotic pseudoaneurysm in the distal aortic arch. We decided to perform thoracic endovascular aortic repair because of the patient's special request to avoid open surgery. We selected a reversed taper-type leg stent graft for the iliac artery and successfully implanted it without problems. However, the long-term outcomes of the stent graft in young people remain unclear, and careful regular follow-up for a long period is mandatory.

Background: The aim of this study was to delineate impacts of percutaneous coronary intervention (PCI), flow demand, and status of myocardium on graft flow., Methods: We retrospectively assessed 736 individual coronary artery bypass grafts that had been created as the sole bypass graft for a vascular region in 405 patients. The grafts comprised 334 internal thoracic artery (ITA) to left anterior descending (LAD), 129 ITA and 65 saphenous vein grafts (SVG) to left circumflex (LCX), and 142 gastroepiploic artery (GEA) and 66 SVG to right coronary artery (RCA). Minimal luminal diameter, size of revascularized area, history of myocardial infarction, and PCI in the relevant area were examined to determine whether these factors are associated with flow insufficiency (FI), which was defined as ≤ 20 mL/min., Results: FI developed in 123/736 grafts (16.7%) and correlated significantly with stenosis in the distal portion (23.0% vs. 12.8%, p = 0.0003). Prior myocardial infarction significantly correlated with FI in GEA-RCA (p = 0.002) and ITA-LCX grafts (p = 0.04). There was a history of PCI to the LAD (PCI group) in 54 ITA to LAD bypass grafts (16.2%), whereas the remaining 280 had no history of PCI to the LAD (no-PCI group). Graft flow was significantly greater in the no-PCI than in the PCI group (53 ± 29 vs. 42 ± 27; p = 0.006). The incidences of FI and graft failure were significantly higher in the PCI than the no-PCI group (22.2%, vs. 8.2%; p = 0.003; 9.2% vs. 1.8%; p = 0.003, respectively)., Conclusions: Prior PCI has a negative impact on graft flow. The influences of small revascularized area, myocardial infarction, and PCI are greater, necessitating consideration of factors associated with flow demand or microvasculature when planning revascularization.

Autoimmune hypophysitis (AH) is thought to be an autoimmune disease characterized by lymphocytic infiltration of the pituitary gland. Among AH pathologies, lymphocytic infundibulo-neurohypophysitis (LINH) involves infiltration of the neurohypophysis and/or the hypothalamic infundibulum, causing central diabetes insipidus resulting from insufficiency of arginine vasopressin secretion. The pathophysiological and pathogenetic mechanisms underlying LINH are largely unknown. Clinically, differentiating LINH from other pituitary diseases accompanied by mass lesions, including tumours, has often been difficult, because of similar clinical manifestations. We recently reported that rabphilin-3A is an autoantigen and that anti-rabphilin-3A antibodies constitute a possible diagnostic marker for LINH. However, the involvement of rabphilin-3A in the pathogenesis of LINH remains to be elucidated. This study was undertaken to explore the role of rabphilin-3A in lymphocytic neurohypophysitis and to investigate the mechanism. We found that immunization of mice with rabphilin-3A led to neurohypophysitis. Lymphocytic infiltration was observed in the neurohypophysis and supraoptic nucleus 1 month after the first immunization. Mice immunized with rabphilin-3A showed an increase in the volume of urine that was hypotonic as compared with control mice. Administration of a cocktail of monoclonal anti-rabphilin-3A antibodies did not induce neurohypophysitis. However, abatacept, which is a chimeric protein that suppresses T-cell activation, decreased the number of T cells specific for rabphilin-3A in peripheral blood mononuclear cells (PBMCs). It ameliorated lymphocytic infiltration of CD3 + T cells in the neurohypophysis of mice that had been immunized with rabphilin-3A. Additionally, there was a linear association between the number of T cells specific for rabphilin-3A in PBMCs and the number of CD3 + T cells infiltrating the neurohypophysis. In conclusion, we suggest that rabphilin-3A is a pathogenic antigen, and that T cells specific for rabphilin-3A are involved in the pathogenesis of neurohypophysitis in mice. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd., (Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)

Selective apoptosis of granule cells in the hippocampal dentate gyrus (DG) of rats with bilateral adrenalectomy (ADX) and in patients who died of adrenal insufficiency has been reported. Although adrenal insufficiency is a common disease and is usually associated with hyponatremia, its effect on the central nervous system and in apoptosis in the hippocampus remain to be elucidated. Using rat models to represent clinical hyponatremia accompanying adrenal insufficiency, we show that reduced serum [Na + ] was associated with selective apoptosis in the DG. Nine days after ADX, apoptotic cells were observed in the DG of rats whose serum [Na + ] was <125mEq/L (moderate hyponatremia), but rarely in those whose serum [Na + ] was ≥125mEq/L or in normonatremic rats. Although all hyponatremic ADX rats survived following treatment with corticosterone and saline started 7days after ADX when apoptosis had not yet occurred, selective apoptosis on day 9 was not prevented in moderately hyponatremic rats. Interestingly, treatment with memantine, a noncompetitive NMDAR antagonist, prevented the selective apoptosis in the DG in moderately hyponatremic, ADX rats, and improved electrophysiological dysfunction, including impaired basal synaptic transmission and long-term potentiation at the entorhinal cortex-DG synapses. These results demonstrated that in adrenal insufficient rats, hyponatremia was associated with apoptosis in the DG, and that memantine prevented the apoptosis and improved cell function. Our data imply the importance of assessing the possibility of neurological impairments after treatment with CORT in patients with moderate or severe hyponatremia accompanying adrenal insufficiency and that memantine may represent a beneficial therapeutic strategy to prevent neurological impairments in such patients., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Arginine vasopressin (AVP) is secreted via exocytosis; however, the precise molecular mechanism underlying the exocytosis of AVP remains to be elucidated. To better understand the mechanisms of AVP secretion, in our study we have identified proteins that bind with a 25 kDa synaptosomal-associated protein (SNAP25). SNAP25 plays a crucial role in exocytosis, in the posterior pituitary. Embryonic stem (ES) cell-derived AVP neurons were established to investigate the functions of the identified proteins. Using glutathione S-transferase (GST)-pulldown assays and proteomic analyses, we identified tomosyn-1 (syntaxin-binding protein 5) as a SNAP25-binding protein in the posterior pituitary. Coimmunoprecipitation assays indicated that tomosyn formed N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complexes with SNAP25 and syntaxin1. Immunohistochemistry showed that tomosyn localized to the posterior pituitary. Mouse ES cells self-differentiated into AVP neurons (mES-AVP) that expressed tomosyn and two transmembrane SNARE proteins, including SNAP25 and syntaxin1. KCl increased AVP secretion in mES-AVP, and overexpression of tomosyn-1 reduced KCl-stimulated AVP secretion. Downregulation of tomosyn-1 with siRNA increased KCl-stimulated AVP secretion. These results suggested that tomosyn-1 negatively regulated AVP secretion in mES-AVP and further suggest the possibility of using mES-AVP culture systems to evaluate the role of synaptic proteins from AVP neurons., Competing Interests: The authors have declared that no competing interests exist.

Hyponatremia is the most common clinical electrolyte disorder. Once thought to be asymptomatic in response to adaptation by the brain, recent evidence suggests that chronic hyponatremia may be linked to attention deficits, gait disturbances, risk of falls, and cognitive impairments. Such neurologic defects are associated with a reduction in quality of life and may be a significant cause of mortality. However, because underlying diseases such as adrenal insufficiency, heart failure, liver cirrhosis, and cancer may also affect brain function, the contribution of hyponatremia alone to neurologic manifestations and the underlying mechanisms remain unclear. Using a syndrome of inappropriate secretion of antidiuretic hormone rat model, we show here that sustained reduction of serum sodium ion concentration induced gait disturbances; facilitated the extinction of a contextual fear memory; caused cognitive impairment in a novel object recognition test; and impaired long-term potentiation at hippocampal CA3-CA1 synapses. In vivo microdialysis revealed an elevated extracellular glutamate concentration in the hippocampus of chronically hyponatremic rats. A sustained low extracellular sodium ion concentration also decreased glutamate uptake by primary astrocyte cultures, suggesting an underlying mechanism of impaired long-term potentiation. Furthermore, gait and memory performances of corrected hyponatremic rats were equivalent to those of control rats. Thus, these results suggest chronic hyponatremia in humans may cause gait disturbance and cognitive impairment, but these abnormalities are reversible and careful correction of this condition may improve quality of life and reduce mortality., (Copyright © 2016 by the American Society of Nephrology.)

Context: Central diabetes insipidus (CDI) can be caused by several diseases, but in about half of the patients the etiological diagnosis remains unknown. Lymphocytic infundibulo-neurohypophysitis (LINH) is an increasingly recognized entity among cases of idiopathic CDI; however, the differential diagnosis from other pituitary diseases including tumors can be difficult because of similar clinical and radiological manifestations. The definite diagnosis of LINH requires invasive pituitary biopsy., Objective: The study was designed to identify the autoantigen(s) in LINH and thus develop a diagnostic test based on serum autoantibodies., Design: Rat posterior pituitary lysate was immunoprecipitated with IgGs purified from the sera of patients with LINH or control subjects. The immunoprecipitates were subjected to liquid chromatography-tandem mass spectrometry to screen for pituitary autoantigens of LINH. Subsequently, we made recombinant proteins of candidate autoantigens and analyzed autoantibodies in serum by Western blotting., Results: Rabphilin-3A proved to be the most diagnostically useful autoantigen. Anti-rabphilin-3A antibodies were detected in 22 of the 29 (76%) patients (including 4 of the 4 biopsy-proven samples) with LINH and 2 of 18 (11.1%) patients with biopsy-proven lymphocytic adeno-hypophysitis. In contrast, these antibodies were absent in patients with biopsy-proven sellar/suprasellar masses without lymphocytic hypophysitis (n = 34), including 18 patients with CDI. Rabphilin-3A was expressed in posterior pituitary and hypothalamic vasopressin neurons but not anterior pituitary., Conclusions: These results suggest that rabphilin-3A is a major autoantigen in LINH. Autoantibodies to rabphilin-3A may serve as a biomarker for the diagnosis of LINH and be useful for the differential diagnosis in patients with CDI.

Introduction: It has been well documented that labral tear is frequently associated with femoroacetabular impingement and dysplasia of the hip; however, there have been few reported cases of labral tear associated with idiopathic osteonecrosis of the hip. Here we report the case of a patient with labral tear associated with idiopathic osteonecrosis of the femoral head who was treated by hip arthroscopy, with a favorable short-term outcome., Case Presentation: Under the diagnosis of systemic lupus erythematosus, a 28-year-old Japanese woman was treated with the oral administration of steroid in 2007. A year after the treatment, she developed right hip joint pain and was diagnosed with idiopathic osteonecrosis of the femoral head at our institution. In November of 2011, she revisited our hospital when her right hip joint pain exacerbated and she became unable to walk. On the visit, the anterior impingement sign and Patrick test were positive. Radiography and magnetic resonance imaging in 2011 demonstrated neither spreading of the osteonecrosis area nor collapse of the femoral head in the right joint; however, magnetic resonance imaging showed a high-intensity area in the articular labrum in a T2-weighted image, leading to a diagnosis of labral tear. She underwent labral repair with hip arthroscopy in August of 2012. Now, 1 year after surgery, she does not feel any pain during walking and her modified Harris hip score has improved from 20 prior to surgery to 85., Conclusion: The case indicated that it is important to be aware of the possibility of labral tear in patients with idiopathic osteonecrosis of the femoral head, when spreading of the osteonecrosis area or collapse of the femoral head has not been seen on magnetic resonance imaging.

Overly rapid correction of chronic hyponatremia can cause osmotic demyelination syndrome (ODS). Minocycline protects ODS associated with overly rapid correction of chronic hyponatremia with hypertonic saline infusion in rats. In clinical practice, inadvertent rapid correction frequently occurs due to water diuresis, when vasopressin action suddenly ceases. In addition, vasopressin receptor antagonists have been applied to treat hyponatremia. Here the susceptibility to and pathology of ODS were evaluated using rat models developed to represent rapid correction of chronic hyponatremia in the clinical setting. The protective effect of minocycline against ODS was assessed. Chronic hyponatremia was rapidly corrected by 1 (T1) or 10 mg/kg (T10) of tolvaptan, removal of desmopressin infusion pumps (RP), or administration of hypertonic saline. The severity of neurological impairment in the T1 group was significantly milder than in other groups and brain hemorrhage was found only in the T10 and desmopressin infusion removal groups. Minocycline inhibited demyelination in the T1 group. Further, immunohistochemistry showed loss of aquaporin-4 (AQP4) in astrocytes before demyelination developed. Interestingly, serum AQP4 levels were associated with neurological impairments. Thus, minocycline can prevent ODS caused by overly rapid correction of hyponatremia due to water diuresis associated with vasopressin action suppression. Increased serum AQP4 levels may be a predictive marker for ODS.

Acute respiratory distress syndrome (ARDS) is a noncardiogenic pulmonary edema resulting from increased capillary permeability. Numerous pharmacologic therapies have been studied for prevention and treatment of ARDS. Although several pharmacological therapies could improve patient's respiratory function, there have been no controlled studies which clearly demonstrated the clinical benefit for ARDS-related mortality. The role of corticosteroids in ARDS remains controversial. Available evidence is against early administration of high-dose corticosteroids (methylprednisolon 120 mg x kg-1 x day - 1). In contrast, low-dose corticosteroid therapy (methylprednisolon 0.5-2.5mgg kg-1 xday-1)remains controversial. With regard to sivelestat sodium, a specific inhibitor of neutrophil elastase, although the effectiveness in decreasing mortality was not clarified, increases in lung oxygenation and ventilator-free days have consistently been revealed. Other probable pharmacologic therapies for ARDS include continuous infusion of cisatracurium. In conclusion, there are not established drugs for ARDS, and further studies are necessary to reveal the clinical effectiveness of the above mentioned and novel pharmacologic therapies.

Thraustochytrium aureum ATCC 34304 was grown in the presence and absence of polyoxyethylene sorbitan monooleate (Tween 80). The aim of this work was to obtain basic knowledge about the effect of Tween 80 on growth, lipid accumulation and fatty acid composition in T. aureum. The addition of Tween 80 to a culture medium significantly enhanced the growth of T. aureum, and the biomass increased with an increase of Tween 80 content. Total lipid content and total fatty acid content were significantly higher in 1.0% Tween 80 in comparison with the control (absence of Tween 80). The fatty acid profile showed that the content of C18:1n-9 (oleic acid) significantly increased as a result of the addition of Tween 80. These results indicated that part of the Tween 80 added to the medium was utilized as a carbon source or that the oleate included in Tween 80 was directly incorporated into T. aureum cells as a fatty acid. Neither the DHA content nor the percentage of DHA did not change in spite of the addition of Tween 80. However, the DHA yield significantly increased because the biomass increased due to the addition of Tween 80., (Copyright © 2010 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.)

To examine the effect of cold shock treatment on the fatty acid composition of Aurantiochytrium limacinum strain mh0186, a marine thraustochytrid, we cultivated this strain at 28°C for 72 h with shaking and stored the obtained biomass at 10°C for 72 h. A growth experiment was carried out for comparison, wherein strain mh0186 was grown at 10 and 15°C for 72 h with shaking, and it was found that the unsaturation of fatty acids was accelerated relative to that at 28°C. In the cold shock experiment, the total lipid content significantly increased during storage at 10°C for 72 h. Overall, the percentage of unsaturated fatty acids such as docosahexaenoic acid was almost stable while that of n-6 docosapentaenoic acid decreased slightly, but significantly, relative to that in the growth experiment.

The inhibitory effect of amphotericin B (AMPH) on the growth of fungi during the isolation of thraustochytrids was examined. The growth of fungi was significantly inhibited by addition of AMPH, and therefore colonies of thraustochytrids were not overlaid with fungal mycelia, which resulted in increased efficiency of thraustochytrids isolation., (Copyright © 2010 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.)

The growth, lipid content, and fatty acid composition of Aurantiochytrium sp. strain mh0186 at different temperatures were investigated. Strain mh0186 grew well at 15-30 degrees C, but weakly at 10 degrees C. The biomass at 15-30 degrees C was significantly higher than at 10 and 35 degrees C, and the total lipid at 15-35 degrees C was significantly higher than that at 10 degrees C. The amount of DHA in the total fatty acid was highest at 10 degrees C and decreased in response to temperature increase. The content of DHA (mg/g-dry cell weight) at 15-30 degrees C were significantly higher than those at 35 degrees C and those at 15-25 degrees C were significantly higher than those at 10 and 35 degrees C. The DHA yield at 15-35 degrees C was significantly higher than those at 10 and 35 degrees C. Unsaturation of fatty acid was regulated by temperature and was enhanced in response to temperature decrease. The ratio of DHA to DPA varied at different temperatures.

Extracellular enzymes produced by six strains of thraustochytrids, Thraustochytrium, Schizochytrium, and Aurantiochytrium, were investigated. These strains produced 5 to 8 kinds of the extracellular enzymes, depending on the species. Only the genus Thraustochytrium produced amylase. When insoluble cellulose was used as substrate, cellulase was not detected in the six strains of thraustochytrids. This study indicates that marine eukaryotes, thraustochytrids, produced a wide variety of extracellular enzymes.

Tween 80, KH(2)PO(4) and tomato juice were added to basal medium for the isolation of thraustochytrids. By the addition of Tween 80 and KH(2)PO(4), the number of thraustochytrids isolated from seawater increased. KH(2)PO(4) and Tween 80 were considered to be useful for isolating thraustochytrids.

Photo-crosslinked polymer beads were introduced into a laboratory activated-sludge unit containing municipal sewage sludge and the effect on nitrifying capacity was examined. The ammonia load started at a nitrogen-loading rate of 0.02 kg m(-3) day(-1) and was increased stepwise. It was found that the bead-containing unit could almost completely oxidize ammonia (over 95%) up to a nitrogen-loading rate of 0.216 kg m(-3) day(-1), whereas the maximum loading rate of the control unit (without polymer beads) was 0.096 kg m(-3) day(-1). The nitrifying potential of suspended and bead-associated organisms in the bead-containing unit was measured under different loading conditions. It was found that the bead-associated organisms exhibited high specific activities under high loading conditions and that the contribution of the bead-associated organisms to nitrification was greater than that of the suspended solids under these conditions. The bacterial population dynamics in the suspended solids and bead-associated organisms were analysed by denaturing gradient gel electrophoresis (DGGE) of PCR-amplified 16S rRNA gene fragments and by fluorescence in situ hybridization with group-specific probes. Among the known nitrifying organisms, ammonia-oxidizing beta-proteobacteria and Nitrospira-related organisms were detected by these approaches. A comparison of the activity dynamics and population dynamics, however, suggested a possibility that other organisms may also have been involved in the nitrification process under high loading conditions.

A new xanthine oxidase inhibitor named hydroxyakalone was isolated from the culture broth of a marine bacterium Agrobacterium aurantiacum N-81106. Structure of hydroxyakalone was determined to be 4-amino-1H-pyrazolo[3,4-d]pyrimidine-3-one-6-ol by the spectral studies of hydroxyakalone and its permethyl derivative. The concentration to induce 50% inhibition (IC50) was 4.6 microM against xanthine oxidase.

A new chitinase inhibitor, CI-4, was isolated from the culture broth of a marine bacterium Pseudomonas sp. IZ208. The structure of CI-4 was determined to be cyclo(L-Arg-D-Pro) by spectral studies and comparison with a synthetic sample. CI-4 showed inhibitory activity against chitinase.

Polar orange pigments were extracted from the cultured cells of marine bacterium strain SD-212 and purified by chromatographic methods. The structures of two new trihydroxy-keto-carotenoids, (2R,3S,3'S)-2-hydroxyastaxanthin (1) and (2R,3S,3'R)-2-hydroxyadonixanthin (2) were determined by means of spectral methods. Known carotenoids (3S,2'R,3'R)-erythroxanthin (3), (2R,3S',2' R,3'S)-2,3,2',3'-tetrahydroxy-β,β-carotene-4,4'-dione (4), (2R,3S,2'R,3'R)-2,3,2',3'-tetrahydroxy-β,β-caroten-4-one (5), (3S,3'S)-astaxanthin (6), and (3S,3'R)-adonixanthin (7) were also isolated.