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A study published in Acta Physiologica examined the effects of postmenopausal hormone replacement therapy (HRT) on skeletal muscle mitochondrial function. The researchers found that postmenopausal women who received a combination of estradiol and progestin had higher mitochondrial respiratory capacity in their skeletal muscles compared to non-treated postmenopausal women. Menopause is associated with skeletal muscle dysfunction, and HRT may help prevent this impairment. While previous studies have shown the effects of estrogen on skeletal muscle mitochondria in animal models, this study is the first to demonstrate the association in humans. Further research is needed to fully understand the effects of HRT on skeletal muscle mitochondrial function. [Extracted from the article]

Oxidative stress plays a role in the progression of chronic heart failure (CHF). We investigated whether systemic oxidative stress is linked to exercise intolerance and skeletal muscle abnormalities in patients with CHF. We recruited 30 males: 17 CHF patients, 13 healthy controls. All participants underwent blood testing, cardiopulmonary exercise testing, and magnetic resonance spectroscopy (MRS). The serum thiobarbituric acid reactive substances (TBARS; lipid peroxides) were significantly higher (5.1 ± 1.1 vs. 3.4 ± 0.7 μmol/L, p < 0.01) and the serum activities of superoxide dismutase (SOD), an antioxidant, were significantly lower (9.2 ± 7.1 vs. 29.4 ± 9.7 units/L, p < 0.01) in the CHF cohort versus the controls. The oxygen uptake (VO2) at both peak exercise and anaerobic threshold was significantly depressed in the CHF patients; the parameters of aerobic capacity were inversely correlated with serum TBARS and positively correlated with serum SOD activity. The phosphocreatine loss during plantar-flexion exercise and intramyocellular lipid content in the participants' leg muscle measured by 31phosphorus- and 1proton-MRS, respectively, were significantly elevated in the CHF patients, indicating abnormal intramuscular energy metabolism. Notably, the skeletal muscle abnormalities were related to the enhanced systemic oxidative stress. Our analyses revealed that systemic oxidative stress is related to lowered whole-body aerobic capacity and skeletal muscle dysfunction in CHF patients. [ABSTRACT FROM AUTHOR]

Epicardial adipose tissue (EAT) is an active endocrine organ that is closely associated with occurrence of atrial fibrillation (AF). However, the role of EAT in the development of postoperative AF (POAF) remains unclear. We aimed to investigate the association between EAT profile and POAF occurrence in patients who underwent cardiovascular surgery. We obtained EAT samples from 53 patients to evaluate gene expression, histological changes, mitochondrial oxidative phosphorylation (OXPHOS) capacity in the EAT, and protein secretion in EAT‐conditioned medium. EAT volume was measured using computed tomography scan. Eighteen patients (34%) experienced POAF within 7 days after surgery. Although no significant difference was observed in EAT profile between patients with and without POAF, logistic regression analysis identified that the mRNA expression levels of tumor necrosis factor‐alpha (TNF‐α) were positively correlated and adipocyte size in the EAT was inversely correlated with onset of POAF, respectively. Mitochondrial OXPHOS capacity in the EAT was not associated with POAF occurrence; however, it showed an inverse correlation with adipocyte size and a positive correlation with adiponectin secretion. In conclusion, changes in the secretory profile and adipocyte morphology of the EAT, which represent qualitative aspects of the adipose tissue, were present before the onset of AF. [ABSTRACT FROM AUTHOR]

Aims/Introduction Low aerobic capacity is a strong and independent predictor of all-cause mortality in patients with metabolic syndrome (MetS). Here, we investigated the effects of pioglitazone treatment on whole-body aerobic capacity and skeletal muscle energy metabolism in MetS patients. Materials and Methods A total of 14 male patients with MetS received oral pioglitazone 15 mg/day for 4 months. To assess whole-body aerobic capacity, exercise testing with a bicycle ergometer was carried out before and after pioglitazone treatment. To assess skeletal muscle energy metabolism, intramyocellular lipid in the resting leg and high-energy phosphates in the calf muscle during plantar-flexion exercise were measured using 1proton- and 31phosphorus magnetic resonance spectroscopy, respectively. Results Pioglitazone significantly increased peak oxygen uptake (25.1 ± 4.9 mL/kg/min pretreatment vs 27.2 ± 3.9 mL/kg/min post- treatment, P < 0.05) and anaerobic threshold (12.7 ± 1.9 mL/kg/min pretreatment vs 13.6 ± 1.6 mL/kg/min post-treatment, P < 0.05), although daily physical activity was comparable before and after the treatment. Intramyocellular lipid content was significantly reduced after pioglitazone treatment by 26%, indicating improved skeletal muscle fatty acid metabolism. Pioglitazone also significantly decreased the muscle phosphocreatine loss during exercise by 13%, indicating improved skeletal muscle high-energy phosphate metabolism. Notably, the increase in anaerobic threshold; that is, submaximal aerobic capacity, closely correlated with the decrease in intramyocellular lipid content after pioglitazone treatment. Conclusions Pioglitazone significantly improved the MetS patients' whole-body aerobic capacity and skeletal muscle energy metabolism. The beneficial effect of pioglitazone on whole-body aerobic capacity might be at least in part through improved fatty acid metabolism in the skeletal muscle. [ABSTRACT FROM AUTHOR]

Key points Pre-ischaemic administration of aminooxiacetate (AOA), an inhibitor of the malate-aspartate shuttle (MAS), provides cardioprotection against ischaemia-reperfusion injury. The underlying mechanism remains unknown., We examined whether transient inhibition of the MAS during ischaemia and early reperfusion by AOA treatment could prevent mitochondrial damage at later reperfusion., The AOA treatment preserved mitochondrial respiratory capacity with reduced mitochondrial oxidative stress during late reperfusion to the same extent as ischaemic preconditioning (IPC)., However, AOA treatment, but not IPC, reduced the myocardial interstitial concentration of tricarboxylic acid cycle intermediates at the onset of reperfusion., The results obtained in the present study demonstrate that metabolic regulation by inhibition of the MAS at the onset of reperfusion may be beneficial for the preservation of mitochondrial function during late reperfusion in an IR-injured heart., Abstract Mitochondrial dysfunction plays a central role in ischaemia-reperfusion (IR) injury. Pre-ischaemic administration of aminooxyacetate (AOA), an inhibitor of the malate-aspartate shuttle (MAS), provides cardioprotection against IR injury, although the underlying mechanism remains unknown. We hypothesized that a transient inhibition of the MAS during ischaemia and early reperfusion could preserve mitochondrial function at later phase of reperfusion in the IR-injured heart to the same extent as ischaemic preconditioning (IPC), which is a well-validated cardioprotective strategy against IR injury. In the present study, we show that pre-ischaemic administration of AOA preserved mitochondrial complex I-linked state 3 respiration and fatty acid oxidation during late reperfusion in IR-injured isolated rat hearts. AOA treatment also attenuated the excessive emission of mitochondrial reactive oxygen species during state 3 with complex I-linked substrates during late reperfusion, which was consistent with reduced oxidative damage in the IR-injured heart. As a result, AOA treatment reduced infarct size after reperfusion. These protective effects of MAS inhibition on the mitochondria were similar to those of IPC. Intriguingly, the protection of mitochondrial function by AOA treatment appears to be different from that of IPC because AOA treatment, but not IPC, downregulated myocardial tricarboxilic acid (TCA)-cycle intermediates at the onset of reperfusion. MAS inhibition thus preserved mitochondrial respiratory capacity and decreased mitochondrial oxidative stress during late reperfusion in the IR-injured heart, at least in part, via metabolic regulation of TCA cycle intermediates in the mitochondria at the onset of reperfusion. [ABSTRACT FROM AUTHOR]

Fucoidan, a sulfated polysaccharide extracted from brown seaweeds, possesses many biological activities including anti-inflammatory and antioxidant activities. We aimed to investigate the protective effects of fucoidan on dyslipidemia and atherosclerosis in apolipoprotein E-deficient mice (ApoE(shl) mice) and to elucidate its molecular targets in the liver by using a transcriptomic approach. For 12weeks, ApoE(shl) mice were fed a high-fat diet (HFD) supplemented with either 1% or 5% fucoidan. Fucoidan supplementation significantly reduced tissue weight (liver and white adipose tissue), blood lipid, total cholesterol (TC), triglyceride (TG), non-high-density lipoprotein cholesterol (non-HDL-C) and glucose levels in HFD-fed ApoE(shl) mice but increased plasma lipoprotein lipase (LPL) activity and HDL-C levels. Fucoidan also reduced hepatic steatosis levels (liver size, TC and TG levels, and lipid peroxidation) and increased white adipose tissue LPL activity. DNA microarray analysis and quantitative reverse transcription-polymerase chain reaction demonstrated differential expression of genes encoding proteins involved in lipid metabolism, energy homeostasis and insulin sensitivity, by activating Ppara and inactivating Srebf1. Fucoidan supplementation markedly reduced the thickness of the lipid-rich plaque, lipid peroxidation and foaming macrophage accumulation in the aorta in HFD-fed ApoE(shl) mice. Thus, fucoidan supplementation appears to have anti-dyslipidemic and anti-atherosclerotic effects by inducing LPL activity and inhibiting the effects of inflammation and oxidative stress in HFD-fed ApoE(shl) mice. [ABSTRACT FROM AUTHOR]

The effects of starvation at the first feeding stage on the survival and growth of walleye pollock Gadus chalcogrammus larvae were examined in rearing experiments performed in the laboratory. Newly hatched larvae grown at 2 °C, 5 °C, and 8 °C that commenced feeding at 3, 2, and 1 days post-hatching (dph) exhibited yolk exhaustion at 8, 8, and 5 dph and reached the point-of-no-return (PNR) at 15, 14, and 10 dph, respectively. Larvae kept at 5 °C were starved for 2-16 dph and then reared to examine the effect of delayed initial feeding on growth and survival. The larvae that were fed earlier grew better and showed higher survival rates. The time thresholds after which delayed feeding would prevent the larvae from growing and surviving were 2-3 and 0-1 days, respectively, before the PNR. Walleye pollock larvae have a long mixed endogenous and exogenous feeding period and relatively high starvation tolerance, as is typically observed in cold water fishes. Delayed initial feeding affects their survival and growth, even during the mixed feeding period. The availability of prey at the first feeding stage would have a critical effect on the stock size of this species. [ABSTRACT FROM AUTHOR]

Background Oxidative and nitrative processes have an important role in the pathogenesis of glaucomatous neurodegeneration. Oxidative stress occurs when cellular production of reactive oxygen species outweighs the protective capacity of antioxidant defences. Reactive oxygen species are generated as by-products of cellular metabolism, primarily in the mitochondria. Herein, we present a novel investigation of the effects of molecular hydrogen ( H2) on retinal cells exposed to oxidative stress. Methods We cultured adult rat retinal tissues in an organotypic culture system with a nitric oxide donor, S-nitroso- N-acetylpenicillamine, in the presence or absence of H2. Loss of mitochondrial membrane potential and apoptosis of retinal cells were analysed using a MitoTMRE detection kit and TdT-mediated dUTP nick end labeling ( TUNEL) assay, respectively. Tyrosine nitration levels and oxidative stress damage in the retina were evaluated using immunohistochemical staining. Retinal damage was quantified by measuring the numbers of cells in the ganglion cell and inner nuclear layers and the thickness of the retina. Results H2 suppressed loss of mitochondrial membrane potential and apoptosis in retinal cells. Moreover, H2 decreased the tyrosine nitration level and suppressed oxidative stress damage in retinal cells. S-nitroso- N-acetylpenicillamine treatment decreased the cell numbers in the ganglion cell layer and inner nuclear layer, but the presence of H2 inhibited this reduction. These findings suggest that H2 has a neuroprotective effect against retinal cell oxidative damage, presumably by scavenging peroxynitrite. Conclusions H2 reduces cellular peroxynitrite, a highly toxic reactive nitrogen species. Thus, H2 may be an effective and novel clinical tool for treating glaucoma and other oxidative stress-related diseases. [ABSTRACT FROM AUTHOR]

Keywords: androgen receptor; BDNF; Kennedy's disease; muscles; spinal bulbar muscular atrophy EN androgen receptor BDNF Kennedy's disease muscles spinal bulbar muscular atrophy 2543 2544 2 07/03/20 20200701 NES 200701 Kennedy's disease (KD), also known as a spinal and bulbar muscular atrophy (SBMA), is a rare, X-linked neuromuscular disease characterized by slowly progressive weakness and atrophy of the bulbar and extremity muscles. The phenotype of this mouse model is similar to that of human KD, as male AR-97Q mice exhibit progressive muscle weakness and atrophy with neuropathological changes that are commonly observed in KD patients. Androgen receptor, BDNF, Kennedy's disease, muscles, spinal bulbar muscular atrophy. [Extracted from the article]

Objective: Systemic oxidative stress is associated with insulin resistance and obesity. We tested the hypothesis that systemic oxidative stress is linked to lower aerobic capacity and skeletal muscle dysfunction in metabolic syndrome (MetS).Research Design and Methods: The incremental exercise testing with cycle ergometer was performed in 14 male patients with MetS and 13 age-, sex-, and activity-matched healthy subjects. Systemic lipid peroxidation was assessed by serum thiobarbituric acid reactive substances (TBARS), and systemic antioxidant defense capacity was assessed by serum total thiols and enzymatic activity of superoxide dismutase (SOD). To assess skeletal muscle energy metabolism, we measured high-energy phosphates in the calf muscle during plantar flexion exercise and intramyocellular lipid (IMCL) in the resting leg muscle, using (31)P- and (1)proton-magnetic resonance spectroscopy, respectively.Results: Serum TBARS were elevated (12.4 ± 7.1 vs. 3.7 ± 1.1 μmol/L; P < 0.01), and serum total thiols and SOD activity were decreased (290.8 ± 51.2 vs. 398.7 ± 105.2 μmol/L, P < 0.01; and 22.2 ± 8.4 vs. 31.5 ± 8.5 units/L, P < 0.05, respectively) in patients with MetS compared with healthy subjects. Peak VO2 and anaerobic threshold normalized to body weight were significantly lower in MetS patients by 25 and 31%, respectively, and inversely correlated with serum TBARS (r = -0.49 and r = -0.50, respectively). Moreover, muscle phosphocreatine loss during exercise was 1.4-fold greater in patients with MetS (P < 0.05), and IMCL content was 2.9-fold higher in patients with MetS (P < 0.01), indicating impaired skeletal muscle energy metabolism, and these indices positively correlated with serum TBARS (r = 0.45 and r = 0.63, respectively).Conclusions: Systemic oxidative stress was associated with lower aerobic capacity and impaired skeletal muscle energy metabolism in patients with MetS. [ABSTRACT FROM AUTHOR]

OBJECTIVE--Systemic oxidative stress is associated with insulin resistance and obesity. We tested the hypothesis that systemic oxidative stress is linked to lower aerobic capacity and skeletal muscle dysfunction in metabolic syndrome (MetS). RESEARCH DESIGN AND METHODS--The incremental exercise testing with cycle ergometer was performed in 14 male patients with MetS and 13 age-, sex-, and activity-matched healthy subjects. Systemic lipid peroxidation was assessed by serum thiobarbituric acid reactive substances (TBARS), and systemic antioxidant defense capacity was assessed by serum total thiols and enzymatic activity of superoxide dismutase (SOD). To assess skeletal muscle energy metabolism, we measured high-energy phosphates in the calf muscle during plantar exion exercise and intramyocellular lipid (IMCL) in the resting leg muscle, using 31P- and proton-magnetic resonance spectroscopy, respectively. RESULTS--Serum TBARS were elevated (12.4 ± 7.1 vs. 3.7 ± 1.1 υmol/L; P < 0.01), and serum total thiols and SOD activity were decreased (290.8 ± 51.2 vs. 398.7 ± 105.2 υmol/L, P < 0.01; and 22.2 ± 8.4 vs. 31.5 ± 8.5 units/L, P < 0.05, respectively) in patients with MetS compared with healthy subjects. Peak VO2 and anaerobic threshold normalized to body weight were significantly lower in MetS patients by 25 and 31%, respectively, and inversely correlated with serum TBARS (r = 20.49 and r = 20.50, respectively). Moreover, muscle phosphocreatine loss during exercise was 1.4-fold greater in patients with MetS (P < 0.05), and IMCL content was 2.9-fold higher in patients with MetS (P < 0.01), indicating impaired skeletal muscle energy metabolism, and these indices positively correlated with serum TBARS (r = 0.45and r = 0.63, respectively). CONCLUSIONS--Systemic oxidative stress was associated with lower aerobic capacity and d impaired skeletal muscle energy metabolism in patients with MetS. [ABSTRACT FROM AUTHOR]

Abstract: The anti-predatory performance of hatchery-reared red tilefish (Branchiostegus japonicus) using tube-shaped burrows was studied together with the behavioral characteristics of potential predators, the white spotted conger (Conger myriaster) and the marbled rockfish (Sebastiscus marmoratus). White spotted conger were released in Maizuru Bay (Kyoto, Japan) and tracked using acoustic telemetry; they were also observed in a tank using video recording. White spotted conger tended to remain inside shelters, but occasionally swam outside briefly at night. Attacking behavior of predators and predation avoidance behavior of red tilefish were also recorded in a tank. Red tilefish construct tube-shaped burrows into which they retreat to avoid attack. White spotted conger wandered around the tank, often invading the burrows to prey on red tilefish. Predation by white spotted conger occurred at night. Inside the burrows, red tilefish were not easily caught and were able to escape through the other entrance of the tube-shaped burrow. Marbled rockfish, on the other hand, pounced on red tilefish immediately after prey recognition, ambushing their prey near the burrow entrance. Predation by marbled rockfish was frequently observed around dusk and dawn, but some red tilefish that remained inside burrows survived. White spotted conger is nocturnal and probably an olfactory predator, whilst marbled rockfish is crepuscular and an ambush predator. For stock enhancement of red tilefish, the construction of tube-shaped burrows and their diurnal behavior around the burrows are desirable characteristics in reducing predation by both white spotted conger and marbled rockfish. [Copyright &y& Elsevier]

Enalapril is effective in the suppression of left ventricular remodeling after acute myocardial infarction (AMI), but the effect of telmisartan is unclear. The consecutive 163 AMI patients underwent primary percutaneous coronary intervention and were randomized to telmisartan ( n = 82) or enalapril ( n = 81). Left ventriculography was performed in the acute and chronic (6 months) phases. Matrix metalloproteinase (MMP)-2 and MMP-9 activities were measured by zymography in the acute (days 1, 7, and 14) and chronic (6 months) phases. Plasma pentraxin3 (PTX3), a marker of vascular inflammation, was also measured. There were no adverse effects in the telmisartan group. The analysis of the left ventriculograms in the acute and chronic phases revealed no difference between the two groups. MMP-9 activities at days 7 and 14 and in the chronic phase were decreased compared to that at day 1 in both groups. MMP-2 activity was also decreased in the acute phase, but increased in the chronic phase in both groups. There was no difference in the plasma PTX3 level in the acute phase, but in the chronic phase, PTX3 was significantly lower in telmisartan than in enalapril group (2.6 ± 1.4 vs. 3.2 ± 1.6 ng/ml, p = 0.04). Telmisartan is well tolerated, shows similar effects on the markers of left ventricular remodeling to those of enalapril, and suppresses vascular inflammation more effectively than enalapril in AMI patients. Telmisartan can be an alternative to angiotensin converting enzyme inhibitor in patients with AMI. [ABSTRACT FROM AUTHOR]

Insulin resistance or diabetes is associated with limited exercise capacity, which can be caused by the abnormal energy metabolism in skeletal muscle. Oxidative stress is involved in mitochondrial dysfunction in diabetes. We hypothesized that increased oxidative stress could cause mitochondrial dysfunction in skeletal muscle and make contribution to exercise intolerance in diabetes. C57/BL6J mice were fed on normal diet or high fat diet (HFD) for 8 wk to induce obesity with insulin resistance and diabetes. Treadmill tests with expired gas analysis were performed to determine the exercise capacity and whole body oxygen uptake (Vo2). The work (vertical distance X body weight) to exhaustion was reduced in the HFD mice by 36%, accompanied by a 16% decrease of peak Vo2. Mitochondrial ADP-stimulated respiration, electron transport chain complex I and Ill activities, and mitochondrial content in skeletal muscle were decreased in the HFD mice. Furthermore, superoxide production and NAD(P)H oxidase activity in skeletal muscle were significantly increased in the HFD mice. Intriguingly, the treatment of HFD-fed mice with apocynin [10 mmol/l; an inhibitor of NAD(P)H oxidase activation] improved exercise intolerance and mitochondrial dysfunction in skeletal muscle without affecting glucose metabolism itself. The exercise capacity and mitochondrial function in skeletal muscle were impaired in type 2 diabetes, which might be due to enhanced oxidative stress. Therapies designed to regulate oxidative stress and maintain mitochondrial function could be beneficial to improve the exercise capacity in type 2 diabetes. [ABSTRACT FROM AUTHOR]

Abstract: Aims: Fucoidan, a sulfated polysaccharide extracted from brown seaweed (F. vesiculosus) is recognized as an effective anticoagulant but its anti-lipidemic potency has not been well defined. We investigated the effect of fucoidan on lipoprotein lipase (LPL) secretion by human adipocytes. Main methods: LPL mRNA and protein expressions were measured using semi-quantitative RT-PCR, ELISA and immunohistochemistry in cultured adipocytes with or without fucoidan treatment. LPL enzyme activity was determined by a fluorometric assay. Key findings: In cultured adipocytes, fucoidan induced LPL secretion in a dose- and time-dependent manner. An initial increase in LPL was maintained at a significant level but much slower than that in heparin-treated cells. Fucoidan also dose-dependently induced a cofactor of LPL, the apolipoprotein C-II (ApoC-II) secretion. In fucoidan-treated cells, LPL mRNA was time-dependently increased and LPL protein expression was also inceased. Treatment with both heparin and fucoidan showed no further increase in media LPL activity compared to heparin alone. In the conditioned medium from fucoidan-treated cells followed for 4 h, LPL activity decayed exponentially with half-life of about 180 min. In addition, the extracellular LPL mass in cycloheximide (a protein synthesis inhibitor) and fucoidan-treated cells did not change markedly, but LPL shifted significantly from active to inactive form. Significance: These results suggest that fucoidan acts like heparin by releasing LPL in addition to increasing the intracellular transport and decreasing the degradation of LPL in the medium. Furthermore, LPL and ApoC-II secretion induced by fucoidan may be involved in regulating plasma triglyceride lowering clearance. [Copyright &y& Elsevier]

X-chromosome inactivation (XCI) depends on the noncoding Xist gene. Xist transcription is negatively regulated by its antisense partner Tsix, whose disruption results in nonrandom XCI in females. However, males can maintain Xist in a repressed state without Tsix, indicating participation of additional factor(s) in the protection of the single male X from inactivation. Here, we provide evidence that the histone methyltransferase Eed is also involved in the process. Male embryonic stem cells with Eed-null and Tsix mutations (XΔY Eed−/−) showed Xist hyperactivation upon differentiation, whereas cells with either mutation alone did not. Impaired X-linked gene expression was observed in the XΔY Eed−/− ES cells at the onset of differentiation. The Xist promoter in the XΔY Eed−/− cells showed elevated histone H3-dimethyl lysine 4 modifications and lowered CpG methylation, which are characteristics of open chromatin. Hence, we identified Eed as an additional major player in the regulation of Xist expression. The synergy of Polycomb group proteins and antisense Tsix transcription in Xist gene regulation explains why males can repress Xist without Tsix. [ABSTRACT FROM AUTHOR]

To determine characteristics which may reflect the behavioral quality of red tilefish Branchiostegus japonicus after release, five wild and four hatchery-reared fish were observed in a laboratory and in the sea. The diel activity of the fish was recorded on video tape for 2 days in a tank, where the light condition was regulated to vary periodically over 24 h. The individuals were then released in Maizuru Bay and tracked using acoustic telemetry. Four wild individuals became most active at dawn during a day in the tank, and settled near the release area to stay for 28–104 days after release in Maizuru Bay. In contrast, one wild and four hatchery-reared individuals were not active at dawn, and then did not settle in Maizuru Bay after release. Among the four settled wild individuals, the more active a fish had been in the tank, the more distant the individual moved from the release point until its settlement. The diel activity pattern should be a factor deciding whether red tilefish would settle nearby after release, and the relative amount of activity during rearing is probably related to the degree of dispersion within the release area. [ABSTRACT FROM AUTHOR]

The behavior of wild and hatchery-reared red tilefish Branchiostegus japonicus was analyzed using two different methods: video observation and acoustic telemetry tracking. In the laboratory, digging and swimming activity of seven wild and five hatchery-reared fish were recorded for 2–4 days in an experimental aquarium and related to changes in light intensity. The activity of wild individuals increased with light intensity, while hatchery-reared individuals were active during both day and night. In the field, 18 wild and 9 hatchery-reared fish were released and tracked using an acoustic telemetry system during the winter and the summer in Maizuru Bay, Kyoto (Japan). Seven wild and three hatchery-reared fish settled within 2 km of the release point for 21–200 days whilst 11 wild and 6 hatchery-reared fish were detected in the central part of the bay within 13 days. The settled fish demonstrated a diel pattern of behavior; most of them probably stayed outside their burrows in the daytime but inside their burrows during the nighttime. During the winter wild fish tended to stay near the release site for longer periods than the hatchery-reared fish. However, in summer the hatchery-reared fish tended to remain close to the release site for longer than the wild fish. Based on these two experiments, we suggest that the activity of wild red tilefish respond to changes in low levels of light intensity (0–0.1 μmol m−2 s−1) at dawn and display a diel behavior. Hatchery-reared fish may differ from wild fish with regard to their behavior, response to water temperature and light conditions. [ABSTRACT FROM AUTHOR]

Abstract: It is well known that mouse embryonic stem (ES) cells can be maintained by the presence of leukemia inhibitory factor (LIF). Recent studies have revealed that Wnt also exhibits activity similar to LIF. The molecular mechanism behind the maintenance of ES cells by these factors, however, is not fully understood. In this study, we found that LIF enhances level of nuclear β-catenin, a component of the Wnt signaling pathway. Expression of an activated mutant of β-catenin led to the long-term proliferation of ES cells, even in the absence of LIF. Furthermore, it was found that β-catenin up-regulates Nanog in an Oct-3/4-dependent manner and that β-catenin physically associates with Oct-3/4. These results suggest that up-regulating Nanog through interaction with Oct-3/4 involves β-catenin in the LIF- and Wnt-mediated maintenance of ES cell self-renewal. [Copyright &y& Elsevier]

In order to establish techniques for the stock enhancement of red tilefish Branchiostegus japonicus, it is important to understand the behavioral characteristic of both hatchery-reared and wild fish. Four hatchery-reared and six wild fish were released and tracked using acoustic biotelemetry in Maizuru Bay, Kyoto, Japan, from August 2003 to February 2004. Data for the four wild fish released and tracked from January 2003 to May 2003 were also referred to for analysis. The released fish moved around in relatively large areas within about 10 days after the release, and then three hatchery-reared and two wild fish settled and stayed within limited areas. Fish of both origins showed strong site fidelity and diel activity patterns, i.e. they were detectable in the day but not at night, probably due to hiding behavior in their burrows at night. However, some discrepancies between fish of both origins were detected by comparing their track terms and activity patterns in detail. These discrepancies are probably attributable to the differences in environmental conditions that the fish had experienced before release. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM), the most malignant class of glial neoplasm (grade IV in WHO criteria), carries the worst clinical prognosis among primary brain tumors in adults. To identify a set of genes involved in the tumorigenesis of GBM, we evaluated expression profiles of GBM tissues from 11 patients using a cDNA microarray representing 25,344 human genes. By comparing the profiles with those of normal brain tissue, we identified a number of differentially expressed genes: 54 with increased expression and 45 with reduced expression in GBMs. Semi-quantitative RT-PCR experiments with 6 of those genes confirmed higher expression of DNCH2, ARHGEF6, NPM1 and SRI and lower expression of NRGN and TM4SF2 in GBM tumors. Immunohistochemical staining for 3 of the respective gene products, dynein (product of DNCH2), α-PIX (product of ARHGEF6), and sorcin (product of SRI) indicated that this technique might be useful for histological grading of glial tumors. To establish criteria for this diagnostic approach, we scored glial tumor tissues of different histological grades according to the staining results; the scores were significantly higher in anaplastic astrocytomas and GBMs than in diffuse astrocytomas or normal brain tissues. These findings indicated that levels of these three proteins might serve as histological markers for malignant glioma classification. [ABSTRACT FROM AUTHOR]

Phlegmonous gastritis is a rare inflammatory lesion in which bacterial infection occurs in the gastric wall. A case of phlegmonous gastritis producing an intramural filling defect in the stomach is presented. Endoscopy showed edematous and reddened gastric mucosa with a mass lesion in the gastric body and antrum. An abdominal CT scan showed diffuse and irregular thickening of the gastric wall. At emergency operation, a total gastrectomy with splenectomy was performed. The most important differential diagnosis is carcinoma, especially scirrhous-type gastric cancer. Radiographic findings of phlegmonous gastritis resemble those of scirrhous gastric cancer. More frequent recognition of this disease, early diagnosis and prompt institution of treatment is essential. [ABSTRACT FROM AUTHOR]

We report a case of liver abscesses associated with sigmoid colon cancer in an 81-year-old woman. The patient was referred to our hospital because of a tumorous lesion of the sigmoid colon. Five days before the scheduled operation, she presented abdominal pain, fever and chill. Imaging scans revealed multiple liver abscesses in both lobes, which were successfully treated with intravenously administered antibiotics. Two weeks later, the patient underwent laparoscopic-assisted sigmoidectomy. Nineteen cases of liver abscess associated with colonic cancer have been reported during the past ten years in Japan, and we report the clinical features of these cases in this paper. An aggressive search for the underlying cause of pyogenic liver abscess should be an integral part of the definitive treatment of this disease. [ABSTRACT FROM AUTHOR]

Familial ependymal tumors are a very rare disease, the pathogenesis of which is unknown. Previous studies indicate an involvement of tumor suppressor genes localized within chromosomal region 22q, whereas details are still unclear. Here we report a non-neurofibromatosis type-2 (non-NF2) Japanese family in which two of the four members are affected with cervical spinal cord ependymoma, and one of the four is affected with schwannoma. Loss of heterozygosity (LOH) studies were carried out searching for common allelic loss at chromosomal region 22q11.2-qtel in two of the affected patients. Our findings support a prediction for existence of a tumor suppressor gene on chromosome 22 especially related to the tumorigenesis of familial ependymal tumors. [ABSTRACT FROM AUTHOR]

Surgical practice for gastric cancer in Japan is based on the Gastric Cancer Treatment Guidelines issued in 2001 by the Japanese Gastric Cancer Association. These recommendations list options for treatment of each stage of cancer, with clear distinctions between interventions recommended for routine use and those that should be confined to trial settings until further evidence for their curative potential becomes available. In this review, we discuss standard surgery, local resection, segmental resection, and pylorus-preserving gastrectomy (PPG) as examples of limited resection and describe in detail the indications for limited lymph-node dissection in cases of early-stage gastric cancer. At present, evidence does not support the conclusion that limited surgery is effective for local resection or for improving quality of life. Thus, use of limited surgery should be considered an experimental approach both in Japan and the West. We conclude that surgeons who are familiar with the criteria for selecting surgical procedures should decide on a case-by-case basis which technique is most appropriate. Choices should be made with consideration of the stage of the cancer, invasiveness of the surgical procedure, and the patient''s history. For all procedures, the patient must give informed consent and the surgeons must accurately assess the success of the operation after surgery. [Copyright &y& Elsevier]

Purpose: Although many studies have focused on clinical risk factors for prognosis of patients with surgically treated gastric cancer, little information is available regarding the timing of recurrent malignant disease. The purpose of this study was to determine the factors that are predictive of early and late recurrences after gastrectomy. Patients and Methods: We reviewed the hospital records of patients with histological proof of gastric cancer who were admitted to Sendal National Hospital during the period from 1985 to 1995. A total of 923 records were examined, and 251 patients with recurrent disease were identified. The patients were divided into an "early recurrence group" consisting of 195 patients (died within one year after surgery) and a "late recurrence group" of 56 patients (died two years or more after surgery). Clinicopathological characteristics were examined, and independent risk factors influencing the timing of recurrence were determined by a multiple logistic regression analysis. Results: The mean tumor size of early recurrence cases was larger than that of late recurrence cases (p=0.0294). Tumors penetrating the serosa with direct invasion to continuous structures were found more frequently in the early recurrence group than in the late recurrence group. The patients with early recurrence showed a higher tendency to have nodal involvement, lymphatic invasion and vascular invasion. The relative risks of early and late recurrences associated with different variables were estimated by a multiple logistic regression method. The following variables were found to be significant risk factors for early recurrence: male gender (p=0.0382), lymph node metastasis (p=0.0016), and vascular invasion (p=0.0006). Conclusion: Male patients who have node-positive gastric cancer with vascular invasion have a high risk of early recurrence. [ABSTRACT FROM AUTHOR]

Background Advanced gastric cancer is classified into four Borrmann types, types 1 to 4. Type 4 is a relatively undifferentiated carcinoma with little or no gland-forming capability. Despite recent advances in the diagnosis and surgical management of gastric cancer, most tumors of Borrmann type 4 are not detected at an early stage and the prognosis remains poor; the five-year survival rate after gastric resection ranges from 10 to 20 percent. We evaluated the affects of several clinicopathologic variables on the 5-year survival rate after resection of Borrmann type 4 gastric cancer. Methods Data on clinical characteristics were obtained from the records of patients who underwent gastric resection between 1985 and 1995 at the Department of Surgery, Sendai National Hospital, and follow-up data were obtained tram our tumor registry. Pathologic characteristics were determined from a detailed review of all available histopathologic slides. The relationship between clinicopathologic variables and 5-year survival rate was estimated by the KaplanMeier survival curve and the logrank test. Multivariate Cox's proportional hazards regression analysis was then performed to determine which variables were independent prognostic factors. Results Eighty-seven patients with Borrmann type 4 gastric cancer underwent a resection during the study period at our hospital. The overall 5-year survival rate was 14.8%. The relationship between clinicopathologic variables and 5-year survival rate was determined by constructing a Kaplan-Meier survival curve. Tumor location (upper, middle and distal vs whole stomach, p=0.0214), lymph nude metastasis, capillary microinvasion, and peritonitis carcinomatosa (absent vs present, p<0.05) significantly influenced survival. When multivariate analysts using Cox's proportional hazards regression of 5-year survival was performed, capillary microinvasion, peritonitis carcinomatosa (absent vs present) and tumor location (distal vs whole stomach) emerged... [ABSTRACT FROM AUTHOR]

Discusses the usefulness of activated carbon particles (CH40) as a vital staining dye for visualizing lymphatic vessels and lymph nodes in breast cancer. Study conducted at the Sendai National Hospital in Japan; Identification of as many lymph nodes as possible in the axillary fat; Technical advantages of the use of the CH40 technique.

Determines whether there is a specific pattern of clinicopathological features that could distinguish Borrmann's type IV gastric cancer from other types of gastric cancer. Study design and setting; Medical profile of patients involved in the study; Main outcome measures.

Evaluates the clinicopathological study on early gastric cancer. Review of cases of early gastric carcinoma in patients under 50 years old from 1985 to 1995; Incidence of gastric cancer in male and female groups; Prevalence of depressed lesions in younger patients.

We aimed to determine the mechanism by which the sodium glucose co-transporter 2 inhibitor, luseogliflozin, preserves pancreatic beta-cell mass and function in db/db mice. Six-week-old db/db mice were fed to standard chow or standard chow containing 0.01% luseogliflozin. After 4 weeks, DNA microarray analysis, real-time PCR analysis, and measurement of mitochondrial respiratory capacity and reactive oxygen species (ROS) generation were performed using isolated islets. Immunohistochemistry and electron microscopic analysis were performed using pancreatic tissues. Metabolites extracted from the islets were measured by capillary electrophoresis mass spectrometry. The expression of genes involved in the tricarboxylic acid (TCA) cycle and electron transport chain was upregulated by luseogliflozin. Luseogliflozin improved the mitochondrial complex II-linked oxidative phosphorylation capacity and reduced ROS generation. Mitochondrial morphology was normally maintained by luseogliflozin. Luseogliflozin increased NK6 homeobox 1 (NKX6.1) expression and TCA cycle metabolites. Relief of glucotoxicity by luseogliflozin may involve lower mitochondrial ROS generation and an improvement in complex II-linked mitochondrial respiration. Reducing ROS generation through preventing complex II damage likely increases NKX6.1 expression and ameliorate glucose metabolism in the TCA cycle, contributing to the protection of pancreatic beta-cells. Protection of complex II in pancreatic beta-cells represents a novel therapeutic target for type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background: Although type 2 diabetes mellitus (T2DM) is one of the most frequent comorbidities in patients with chronic heart failure (CHF), the effects of T2DM on the exercise capacity of CHF patients are fully unknown. Here, we tested the hypothesis that the coexistence of T2DM lowers CHF patients' peak aerobic capacity. Methods: We retrospectively analyzed the cases of 275 Japanese CHF patients with non-reduced ejection fraction (left ventricular ejection fraction [LVEF] ≥ 40%) or reduced EF (LVEF < 40%) who underwent cardiopulmonary exercise testing. We divided them into diabetic and nondiabetic groups in each CHF cohort. Results: The mean peak oxygen uptake (VO2) value was 16.87 mL/kg/min in the non-reduced LVEF cohort and 15.52 mL/kg/min in the reduced LVEF cohort. The peak VO2 was lower in the diabetics versus the nondiabetics in the non-reduced LVEF cohort with the mean difference (95% confidence interval [95% CI]) of − 0.93 (− 1.82 to − 0.04) mL/kg/min and in the reduced LVEF cohort with the mean difference of − 1.05 (− 1.96 to − 0.15) mL/kg/min, after adjustment for age-squared, gender, anemia, renal function, LVEF, and log B-type natriuretic peptide (BNP). The adjusted VO2 at anaerobic threshold (AT), a submaximal aerobic capacity, was also decreased in the diabetic patients with both non-reduced and reduced LVEFs. Intriguingly, the diabetic patients had a lower adjusted peak O2 pulse than the nondiabetic patients in the reduced LVEF cohort, but not in the non-reduced LVEF cohort. A multivariate analysis showed that the presence of T2DM was an independent predictor of lowered peak VO2 in CHF patients with non-reduced LVEF and those with reduced LVEF. Conclusions: T2DM was associated with lowered peak VO2 in CHF patients with non-reduced or reduced LVEF. The presence of T2DM has a negative impact on CHF patients' exercise capacity, and the degree of impact is partly dependent on their LV systolic function. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented reporting on two cases of diffuse peritonitis caused by perforation of ileal lymphoma in Japan.

Systemic oxidative stress plays a key role in the development of chronic heart failure (CHF). We tested the hypothesis that mitochondrial reactive oxygen species (ROS) generation in circulating peripheral blood mononuclear cells (PBMCs) contributes to CHF progression. A total of 31 patients who had a history of hospital admission due to worsening HF were enrolled and grouped as having either mild CHF defined as New York Heart Association (NYHA) functional class I-II or moderate-to-severe CHF defined as NYHA functional class III. ROS levels in PBMC mitochondria were significantly increased in CHF patients with NYHA functional class III compared to those with NYHA functional class I-II, accompanied by impaired mitochondrial respiratory capacity in PBMCs. ROS generation in PBMC mitochondria was positively correlated with urinary 8-hydroxydeoxyguanosine, a systemic oxidative stress marker, in CHF patients. Importantly, mitochondrial ROS generation in PBMCs was directly correlated with plasma levels of B-type natriuretic peptide, a biomarker for severity of HF, and inversely correlated with peak oxygen uptake, a parameter of exercise capacity, in CHF patients. The study showed that ROS generation in PBMC mitochondria was higher in patients with advanced CHF, and it was associated with disease severity and exercise intolerance in CHF patients. [ABSTRACT FROM AUTHOR]

Presents a case report on epithelioid leiomyosarcoma of the stomach. Patient characteristics; Symptoms; Diagnosis; Treatment.

Aim: We compared muscular metabolic stress during exercise performed at multiple intensities, from very low to moderate, with blood flow restriction (BFR) adjusted by the same work volume. Methods: Twenty‐five healthy young adults performed unilateral plantar flexion at 1 repetition/2 s in a magnetic resonance system. The BFR exercise protocols were as follows: (A) exercise with 10% of one repetition maximum (1‐RM) for 360 s, (B) 15% 1‐RM for 240 s, (C) 20% 1‐RM for 180 s, (D) 30% 1‐RM for 120 s, and (E) 40% 1‐RM for 90 s. All protocols had the same total work volume (load × repetitions = 1800). A high‐intensity protocol at 65% 1‐RM without BFR (60 s) was also performed for comparison. We used 31P‐magnetic resonance spectroscopy to evaluate the muscular metabolic stress in the subjects' calf muscle, defined as decreases in phosphocreatine and intramuscular pH. Results: The phosphocreatine depletion (A: 15.6 ± 0.7, B: 14.8 ± 0.8, C: 15.2 ± 0.6, D: 14.3 ± 0.6, E: 10.9 ± 0.5 mM; no significant difference [ns]) and the intramuscular pH decrease (A: 6.82 ± 0.02, B: 6.84 ± 0.01, C: 6.83 ± 0.02, D: 6.83 ± 0.02, E: 6.77 ± 0.02; ns) at the end of each exercise were similar and greater than those produced by the 65% 1‐RM without BFR. Conclusion: If the total work volumes are equal, the metabolic stress in exercising muscle may reach similar levels at the end of exercise with BFR and could provide similar successful training effects. [ABSTRACT FROM AUTHOR]

Nintedanib is a unique tyrosine kinase inhibitor used to suppress fibrosis in patients with idiopathic pulmonary fibrosis (IPF). Nintedanib has been shown to suppress multiple processes of fibrosis, thereby reducing the rate of lung function decline in patients with IPF. Since vascular endothelial growth factor is one of this agent's targets, nephrotoxicity, including renal thrombotic microangiopathy (TMA), is a possible major adverse effect. However, only 2 previous cases of nintedanib-induced renal TMA have been published. Our patient was an 83-year-old man with IPF. As adverse effects including liver enzyme level elevation, diarrhoea, anorexia, and nephrotoxicity developed, the nintedanib dosage was reduced after 9 months. The digestive symptoms resolved promptly, but the proteinuria and reduced kidney function remained. Although the kidney injury had improved to some extent, we performed a percutaneous renal biopsy. The biopsy revealed typical TMA findings such as microaneurysms filled with pale material, segmental double contours of glomerular basement membranes, and intracapillary foam cells. After discontinuation of nintedanib, the patient's nephrotoxicity improved. Nintedanib-induced renal TMA is reversible and is possibly dose-dependent. Here, we report the clinical course of our case and review the characteristics of nintedanib-induced renal TMA. [ABSTRACT FROM AUTHOR]

Background: Low aerobic capacity is a strong and independent predictor of all-cause mortality for both diabetic patients and chronic heart failure (CHF) patients. We tested the hypothesis that coexistence of type 2 diabetes lowers peak aerobic capacity in patients with CHF. Methods: We retrospectively studied 276 CHF patients with or without type 2 diabetes who underwent cardiopulmonary exercise testing (CPET). All CHF patients had a history of hospital admission due to worsening HF with either non-reduced left ventricular ejection fraction (LVEF; ≥40%) or reduced LVEF (<40%). Results: Peak oxygen uptake (VO2) was significantly decreased in diabetic group compared to nondiabetic group not only in total CHF population (median 13.8 [interquartile range 11.8-16.4] vs. 16.4 [13.2-20.2] mL/kg/min) but also in CHF patients with LVEF ≥40% (14.1 [12.4-16.6] vs. 17.4 [13.9-20.7] mL/kg/min) and in CHF patients with LVEF <40% (13.4 [10.3-16.3] vs. 16.0 [12.5-20.0] mL/kg/min). There was an inverse correlation between peak VO2 and glycosylated hemoglobin in total CHF population (r=-0.16, P=0.017). Multivariate analysis showed that the presence of type 2 diabetes was an independent predictor of the lowered peak VO2 in CHF patients with LVEF ≥40% and <40%, respectively, after adjustment for age, gender, anemia, renal function, LVEF, and B-type natriuretic peptide. Conclusions: Type 2 diabetes is an independent predictor of the lowered peak VO2 in CHF patients. The presence of type 2 diabetes has a negative impact on peak aerobic capacity in CHF patients with both reduced and non-reduced LVEF. Disclosure: T. Abe: None. T. Yokota: None. [ABSTRACT FROM AUTHOR]

Epicardial adipose tissue (EAT), a source of adipokines, is metabolically active, but the role of EAT mitochondria in coronary artery disease (CAD) has not been established. We investigated the association between EAT mitochondrial respiratory capacity, adiponectin concentration in the EAT, and coronary atherosclerosis. EAT samples were obtained from 25 patients who underwent elective cardiac surgery. Based on the coronary angiographycal findings, the patients were divided into two groups; coronary artery disease (CAD; n = 14) and non-CAD (n = 11) groups. The mitochondrial respiratory capacities including oxidative phosphorylation (OXPHOS) capacity with non-fatty acid (complex I and complex I + II-linked) substrates and fatty acids in the EAT were significantly lowered in CAD patients. The EAT mitochondrial OXPHOS capacities had a close and inverse correlation with the severity of coronary artery stenosis evaluated by the Gensini score. Intriguingly, the protein level of adiponectin, an anti-atherogenic adipokine, in the EAT was significantly reduced in CAD patients, and it was positively correlated with the mitochondrial OXPHOS capacities in the EAT and inversely correlated with the Gensini score. Our study showed that impaired mitochondrial OXPHOS capacity in the EAT was closely linked to decreased concentration of adiponectin in the EAT and severity of coronary atherosclerosis. [ABSTRACT FROM AUTHOR]

Introduction: Mitochondrial dysfunction and oxidative stress play a crucial role in the development of heart failure. However, the role of reactive oxygen species (ROS) originating from peripheral blood mononuclear cell (PBMC) mitochondria in chronic heart failure (HF) is unknown. Hypothesis: Mitochondrial ROS emission from PBMCs is increased in symptomatic HF patients, which is linked to systemic oxidative stress, HF severity, and exercise intolerance. Methods: We enrolled 36 patients with chronic HF (62 ± 13 years, New York Heart Association [NYHA] functional class I-III) and the patients were divided into two groups; NYHA I-II group (n=17) and NYHA III group (n=19). To assess exercise capacity, we performed cardiopulmonary exercise testing with bicycle ergometer. We measured mitochondrial respiratory capacity and mitochondrial ROS emission in permeabilized PBMCs with the use of high-resolution respirometry and spectrofluorometry. We also measured urine 8-OHdG as a marker of systemic oxidative stress. Results: Plasma levels of B-type natriuretic peptide (BNP), a biomarker for severity of HF, were significantly higher in NYHA III group than in NYHA I-II group (286.0±251.0 vs. 93.4±101.2 pg/mL, P <0.01). HF patients with NYHA III had a lowered peak oxygen uptake (VO2) compared to HF patients with NYHA I-II (14.4±4.1 vs. 19.7±4.5 mL/kg/min, P <0.01). Mitochondrial oxidative phosphorylation capacities with complex I, complex II, or complex I+II-linked substrates in PBMCs were comparable between groups, however, maximal capacity of mitochondrial electron transfer system with complex II-linked substrates in PBMCs was significantly reduced in NYHA III group in association with the lowered peak VO2. Notably, HF patients with NYHA III had a significantly higher mitochondrial ROS emission from PBMCs, and this was closely correlated with the elevated urine 8-OHdG levels, the increased plasma levels of BNP, and the lowered peak VO2, respectively. Conclusions: Increased mitochondrial ROS emission in circulating PBMCs is associated with systemic oxidative stress, HF severity, and exercise intolerance in patients with chronic HF. [ABSTRACT FROM AUTHOR]