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1.
Angew Chem Int Ed Engl ; 63(30): e202405950, 2024 Jul 22.
Article in English | MEDLINE | ID: mdl-38735848

ABSTRACT

Vapor-phase propylene (C3H6) epoxidation kinetics with hydrogen peroxide (H2O2) strongly reflects the physical properties of Ti-incorporated zeolite catalysts and the presence of spectating molecules ("solvent") near active sites even without a bulk liquid phase. Steady-state turnover rates of C3H6 epoxidation and product selectivities vary by orders of magnitudes, depending on the zeolite silanol ((SiOH)x) density, pore topology (MFI, *BEA, FAU), and the quantity of condensed acetonitrile (CH3CN) molecules nearby active sites, under identical reaction mechanisms sharing activated H2O2 intermediates on Ti surfaces. Individual kinetic analyses for propylene oxide (PO) ring-opening, homogeneous diol oxidative cleavage, and homogeneous aldehyde oxidation reveal that secondary reaction kinetics following C3H6 epoxidation responds more sensitively to the changes in zeolite physical properties and pore condensation with CH3CN. Thus, higher PO selectivities achieved in hydrophilic Ti-MFI at steady-state reflect the preferential stabilization of transition states for C3H6 epoxidation (a primary reaction) relative to PO ring-opening and oxidative cleavage (secondary reactions) that solvation effects that reflect interactions among condensed CH3CN within pores and the extended pore structure.

2.
J Clin Med ; 13(8)2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38673563

ABSTRACT

Background/Aims: Well-known risk factors for gallbladder polyps include metabolic syndrome, age, and dyslipidemia. Jeju Island is approximately 80 km from the Korean peninsula and is divided into two administrative regions (Jeju City and Seogwipo City), with Mount Halla intervening in the center. Jeju City has higher employment and birth rates than Seogwipo City. Age and alcohol consumption differ between the two regions, and these factors may affect the prevalence of gallbladder polyps (GBPs). Therefore, we investigated the prevalence of GBPs and compared various factors, including alcohol consumption habits and age, associated with GBPs among residents in the two regions. Methods: This study included 21,734 residents who visited the Health Screening and Promotion Center of Jeju National University Hospital between January 2009 and December 2019. We investigated the prevalence and associated factors of GBPs among residents of Jeju City and Seogwipo City. Results: The prevalence of GBPs in Jeju City and Seogwipo City was 9.8% and 8.9% (p = 0.043), respectively. The mean age and rate of high-risk alcohol intake were higher in Seogwipo City. The mean body mass index and levels of fasting blood glucose, total cholesterol, low-density lipoprotein cholesterol, aspartate aminotransferase, gamma-glutamyl transferase, and alkaline phosphatase were lower in Jeju City. Conclusions: This study demonstrated a significant difference in GBP prevalence between the two regions of Jeju Island. Age and alcohol consumption might contribute to this difference; however, further prospective cohort studies are warranted to confirm our findings.

3.
Chem Sci ; 14(12): 3160-3181, 2023 Mar 22.
Article in English | MEDLINE | ID: mdl-36970093

ABSTRACT

Solvent molecules alter the free energies of liquid phase species and adsorbed intermediates during catalytic reactions, thereby impacting rates and selectivities. Here, we examine these effects through the epoxidation of 1-hexene (C6H12) with hydrogen peroxide (H2O2) over hydrophilic and hydrophobic Ti-BEA zeolites immersed in aqueous solvent mixtures (acetonitrile, methanol, and γ-butyrolactone). Greater H2O mole fractions provide greater epoxidation rates, lower H2O2 decomposition rates, and hence improved H2O2 selectivities to the desired epoxide product in each combination of solvent and zeolite. The mechanisms for epoxidation and H2O2 decomposition remain constant across solvent compositions; however, H2O2 activates reversibly in protic solutions. Differences in rates and selectivities reflect the disproportionate stabilization of transition states within zeolite pores with respect to surface intermediates and fluid phase reactants, as evinced by turnover rates normalized by the activity coefficients of C6H12 and H2O2. Opposing trends in activation barriers suggest that the hydrophobic epoxidation transition state disrupts hydrogen bonds with solvent molecules, while the hydrophilic decomposition transition state forms hydrogen bonds with surrounding solvent molecules. Solvent compositions and adsorption volumes within pores, from 1H NMR spectroscopy and vapor adsorption, depend on the composition of the bulk solution and the density of silanol defects within pores. Strong correlations between epoxidation activation enthalpies and epoxide adsorption enthalpies from isothermal titration calorimetry indicate that the reorganization of solvent molecules (and associated entropy gains) required to accommodate transition states provides the most significant contribution to the stability of transition states that determine rates and selectivities. These results demonstrate that replacing a portion of organic solvents with H2O offers opportunities to increase rates and selectivities for zeolite-catalyzed reactions while reducing usage of organic solvents for chemical manufacturing.

4.
Adv Mater ; 35(10): e2207076, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36583605

ABSTRACT

During solid-state calcination, with increasing temperature, materials undergo complex phase transitions with heterogeneous solid-state reactions and mass transport. Precise control of the calcination chemistry is therefore crucial for synthesizing state-of-the-art Ni-rich layered oxides (LiNi1-x-y Cox Mny O2 , NRNCM) as cathode materials for lithium-ion batteries. Although the battery performance depends on the chemical heterogeneity during NRNCM calcination, it has not yet been elucidated. Herein, through synchrotron-based X-ray, mass spectrometry microscopy, and structural analyses, it is revealed that the temperature-dependent reaction kinetics, the diffusivity of solid-state lithium sources, and the ambient oxygen control the local chemical compositions of the reaction intermediates within a calcined particle. Additionally, it is found that the variations in the reducing power of the transition metals (i.e., Ni, Co, and Mn) determine the local structures at the nanoscale. The investigation of the reaction mechanism via imaging analysis provides valuable information for tuning the calcination chemistry and developing high-energy/power density lithium-ion batteries.

5.
Medicine (Baltimore) ; 100(35): e27115, 2021 Sep 03.
Article in English | MEDLINE | ID: mdl-34477153

ABSTRACT

ABSTRACT: Gallbladder polyps (GBPs), especially GBPs ≥5 mm in diameter, are clinically important because they can progress to gallbladder cancer. The known modifiable risk factors for GBP are obesity, metabolic syndrome, and dyslipidemia; however, there is limited evidence regarding specific modifiable risk factors for GBPs ≥5 mm in diameter. Therefore, this study is aimed to investigate the existence of modifiable risk factors affecting the prevalence of GBPs and GBPs ≥5 mm in diameter in a Korean population.A total of 10,119 subjects who visited a single health-screening center at Jeju National University Hospital between January 2009 and December 2019 was included in this study. Binary logistic analyses were performed to identify risk factors affecting the prevalence of GBPs and GBPs ≥5 mm in diameter.The overall prevalence of GBPs and GBPs ≥5 mm in diameter were 9.0% and 4.1%, respectively. Multivariable analysis identified male gender as an independent risk factor affecting the prevalence of GBPs. Moreover, multivariable analysis revealed age and high-density lipoprotein cholesterol levels as independent risk factors for GBPs ≥5 mm in diameter.This study showed that gender was a risk factor affecting the prevalence of GBPs and that age and high-density lipoprotein-cholesterol levels were risk factors for the presence of GBPs ≥5 mm in diameter. High-density lipoprotein cholesterol levels could be a modifiable risk factor affecting the prevalence of large-diameter GBPs.


Subject(s)
Gallbladder Diseases/epidemiology , Polyps/epidemiology , Adult , Age Factors , Aged , Cross-Sectional Studies , Female , Gallbladder/pathology , Gallbladder Diseases/pathology , Humans , Male , Middle Aged , Polyps/pathology , Prevalence , Republic of Korea/epidemiology , Retrospective Studies , Risk Factors , Sex Factors
6.
Am J Physiol Endocrinol Metab ; 321(1): E80-E89, 2021 07 01.
Article in English | MEDLINE | ID: mdl-34121449

ABSTRACT

Because patients with chronic obstructive pulmonary disease (COPD) are often physically inactive, it is still unclear whether the lower respiratory capacity in the locomotor muscles of these patients is due to cigarette smoking per se or is secondary to physical deconditioning. Accordingly, the purpose of this study was to examine mitochondrial alterations in the quadriceps muscle of 10 mice exposed to 8 mo of cigarette smoke, a sedentary mouse model of emphysema, and 9 control mice, using immunoblotting, spectrophotometry, and high-resolution respirometry in permeabilized muscle fibers. Mice exposed to smoke displayed a twofold increase in the oxidative stress marker, 4-HNE, (P < 0.05) compared with control mice. This was accompanied by significant decrease in protein expression of UCP3 (65%), ANT (58%), and mitochondrial complexes II-V (∼60%-75%). In contrast, maximal ADP-stimulated respiration with complex I and II substrates (CON: 23.6 ± 6.6 and SMO: 19.2 ± 8.2 ρM·mg-1·s-1) or octanoylcarnitine (CON: 21.8 ± 9.0 and SMO: 16.5 ± 6.6 ρM·mg-1·s-1) measured in permeabilized muscle fibers, as well as citrate synthase activity, were not significantly different between groups. Collectively, our findings revealed that sedentary mice exposed to cigarette smoke for 8 mo, which is typically associated with pulmonary inflammation and emphysema, exhibited a preserved mitochondrial respiratory capacity for various substrates, including fatty acid, in the skeletal muscle. However, the mitochondrial adaptations induced by cigarette smoke favored the development of chronic oxidative stress, which can indirectly contribute to augment the susceptibility to muscle fatigue and exercise intolerance.NEW & NOTEWORTHY It is unclear whether the exercise intolerance and skeletal muscle mitochondrial dysfunction observed in patients with COPD is due to cigarette smoke exposure, per se, or if they are secondary consequences to inactivity. Herein, while long-term exposure to cigarette smoke induces oxidative stress and an altered skeletal muscle phenotype, cigarette smoke does not directly contribute to mitochondrial dysfunction. With this evidence, we demonstrate the critical role of physical inactivity in cigarette smoke-related skeletal muscle dysfunction.


Subject(s)
Adaptation, Physiological/drug effects , Mitochondria, Muscle/metabolism , Muscle, Skeletal/ultrastructure , Nicotiana , Smoke/adverse effects , Animals , Citrate (si)-Synthase/metabolism , Disease Models, Animal , Emphysema/pathology , Female , Gene Expression , Male , Mice , Mice, Inbred C57BL , Muscle Proteins/genetics , Oxidative Stress , Oxygen Consumption , Quadriceps Muscle/ultrastructure , Sedentary Behavior
7.
Medicine (Baltimore) ; 99(26): e20763, 2020 Jun 26.
Article in English | MEDLINE | ID: mdl-32590752

ABSTRACT

Several previous studies have reported that physical activity (PA) levels can independently affect the prevalence of gallstone disease (GD) in Western countries. However, this association has not been reported in Eastern countries. Therefore, this study aimed to determine whether PA is an independent determinant of GD prevalence in a Korean population, according to the World Health Organizations Global Recommendations on PA for Health.A total of 8908 subjects who completed a questionnaire underwent medical examination and ultrasound scanning at the Health Promotion Center of the Jeju National University Hospital between January 2009 and December 2018. GD and fatty liver disease were diagnosed by abdominal ultrasound. Biochemical parameters and body mass index were determined, and metabolic syndrome status, age, and PA levels were extracted from medical records. Univariate and multivariate analyses were performed to identify independent factors affecting GD.The estimated rates of PA and GD among male subjects were 23.7% and 4.6%, whereas the rates among females were 18.4% and 4.2%, respectively. Multivariate analysis suggested that no PA, old age, and higher aspartate aminotransferase level in males and nonalcoholic fatty liver disease status in females were independent factors affecting GD.In our study, PA was associated with a reduction in GD among males but not females.


Subject(s)
Exercise/physiology , Gallstones , Non-alcoholic Fatty Liver Disease , Sex Factors , Age Factors , Body Mass Index , Female , Gallstones/blood , Gallstones/diagnostic imaging , Gallstones/epidemiology , Humans , Male , Middle Aged , Non-alcoholic Fatty Liver Disease/diagnosis , Non-alcoholic Fatty Liver Disease/epidemiology , Prevalence , Protective Factors , Republic of Korea/epidemiology , Risk Factors , Ultrasonography/methods
8.
Medicine (Baltimore) ; 98(27): e16018, 2019 Jul.
Article in English | MEDLINE | ID: mdl-31277096

ABSTRACT

There have been reports linking nonalcoholic fatty liver disease (NAFLD) with gallstone disease (GD) owing to shared risk factors. However, there are no reported associations between the different NAFLD grades and GD. This study aimed to determine whether NAFLD grade is an independent risk factor for GD in a Korean population.This study enrolled 7886 participants who completed a questionnaire and underwent medical examination and ultrasound scanning at the Health Promotion Center of Jeju National University Hospital in Korea, from January 2009 to December 2017. Fatty liver grading and presence of gallstones were investigated using abdominal ultrasound. Body mass index and biochemical parameters were measured, and age, sex, and metabolic syndrome status were collected from medical records. Univariate and multivariate analyses were performed to identify risk factors for GD.The estimated prevalences of NAFLD and GD were 40.6% and 4.5%, respectively. In the univariate analysis, factors associated with GD were age; NAFLD; presence of metabolic syndrome; and levels of fasting blood glucose, high-density lipoproteins, aspartate aminotransferase, and alanine aminotransferase. Multivariate logistic regression analysis revealed older age and higher NAFLD grade as independent risk factors for GD.Older age and higher grade of NAFLD were independent risk factors for GD in our cohort. There was a strong correlation between grade of NAFLD on abdominal ultrasonography and GD.


Subject(s)
Cholelithiasis/epidemiology , Non-alcoholic Fatty Liver Disease/epidemiology , Severity of Illness Index , Adult , Age Factors , Aged , Case-Control Studies , Cholelithiasis/diagnostic imaging , Humans , Logistic Models , Middle Aged , Non-alcoholic Fatty Liver Disease/classification , Non-alcoholic Fatty Liver Disease/diagnostic imaging , Odds Ratio , Republic of Korea/epidemiology , Risk Factors , Surveys and Questionnaires , Young Adult
9.
Neural Netw ; 111: 1-10, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30616099

ABSTRACT

Nonlinear hysteretic systems are common in many engineering problems. The maximum response estimation of a nonlinear hysteretic system under stochastic excitations is an important task for designing and maintaining such systems. Although a nonlinear time history analysis is the most rigorous method to accurately estimate the responses in many situations, high computational costs and modelingtime hamper adoption of the approach in a routine engineering practice. Thus, various simplified regression equations are often introduced to replace a nonlinear time history analysis in engineering practices, but the accuracy of the estimated responses is limited. This paper proposes a deep neural network trained by the results of the nonlinear time history analyses as an alternative of such simplified regression equations. To this end, a convolutional neural network (CNN) which is usually applied to abstract features from visual imagery is introduced to analyze the information of the hysteretic behavior of the system, then, merged with neural networks representing the stochastic random excitation to predict the responses of a nonlinear hysteretic system. For verification, the proposed deep neural network is applied to the earthquake engineering area to predict the structural responses under earthquake excitations. The results confirm that the proposed deep neural network provides a superior performance compared to the simplified regression equations which are developed based on a limited dataset. Moreover, to give an insight of the proposed deep neural network, the extracted features from the deep neural network are investigated with various numerical examples. The method is expected to enable engineers to effectively predict the response of the hysteretic system without performing nonlinear time history analyses, and provide a new prospect in the relevant engineering fields. The supporting source code and data are available for download at https://github.com/TyongKim/ERD2.


Subject(s)
Neural Networks, Computer , Nonlinear Dynamics , Forecasting , Humans
10.
Korean J Fam Med ; 39(3): 147-154, 2018 May.
Article in English | MEDLINE | ID: mdl-29788702

ABSTRACT

BACKGROUND: The eating habits of Jeju Island natives are quite different from those of the mainland people because of geographic isolation. Diet is a main factor affecting gallstone disease. We investigated the prevalence of gallstone disease in both Jeju Island natives and migrants and studied the risk factors affecting gallstone disease in the Jeju Island people. METHODS: A total of 20,763 subjects who underwent medical checkups at the Health Promotion Center of Jeju National University Hospital in Korea from January 2003 to December 2015 were enrolled in the study. Ultrasonography was used to determine the presence of gallbladder stones. Body mass index and biochemical parameters, including liver function test results, lipid profiles, and fasting blood glucose levels, were verified, and data on age, birthplace, and sex were collected from medical records. Univariate and multivariate analyses were performed to identify risk factors affecting gallstone disease. RESULTS: The prevalence of gallstone disease in the Jeju Island people was 4.0%: Jeju Island natives, 3.8% and migrants, 4.4% (P=0.047). After multivariate logistic regression analysis, the independent risk factors were older age, Jeju migrants, higher fasting blood glucose and alanine aminotransferase levels, and lower high-density lipoprotein cholesterol levels. CONCLUSION: The prevalence of gallstone disease was significantly lower in natives than in migrants from Jeju Island. Older age, Jeju migrants, higher fasting blood glucose and alanine aminotransferase levels, and lower highdensity lipoprotein cholesterol levels contributed to gallstone disease prevalence in the Jeju Island people.

11.
J Appl Physiol (1985) ; 124(4): 1045-1053, 2018 04 01.
Article in English | MEDLINE | ID: mdl-29357496

ABSTRACT

Patients with chronic obstructive pulmonary disease (COPD) exhibit an altered skeletal muscle mitochondrial phenotype, which often includes reduced mitochondrial density, altered respiratory function, and elevated oxidative stress. As this phenotype may be explained by the sedentary lifestyle that commonly accompanies this disease, the aim of this study was to determine whether such alterations are still evident when patients with COPD are compared to control subjects matched for objectively measured physical activity (PA; accelerometry). Indexes of mitochondrial density [citrate synthase (CS) activity], respiratory function (respirometry in permeabilized fibers), and muscle oxidative stress [4-hydroxynonenal (4-HNE) content] were assessed in muscle fibers biopsied from the vastus lateralis of nine patients with COPD and nine PA-matched control subjects (CON). Despite performing similar levels of PA (CON: 18 ± 3, COPD: 20 ± 7 daily minutes moderate-to-vigorous PA; CON: 4,596 ± 683, COPD: 4,219 ± 763 steps per day, P > 0.70), patients with COPD still exhibited several alterations in their mitochondrial phenotype, including attenuated skeletal muscle mitochondrial density (CS activity; CON 70.6 ± 3.8, COPD 52.7 ± 6.5 U/mg, P < 0.05), altered mitochondrial respiration [e.g., ratio of complex I-driven state 3 to complex II-driven state 3 (CI/CII); CON: 1.20 ± 0.11, COPD: 0.90 ± 0.05, P < 0.05), and oxidative stress (4-HNE; CON: 1.35 ± 0.19, COPD: 2.26 ± 0.25 relative to ß-actin, P < 0.05). Furthermore, CS activity ( r = 0.55), CI/CII ( r = 0.60), and 4-HNE ( r = 0.49) were all correlated with pulmonary function, assessed as forced expiratory volume in 1 s ( P < 0.05), but not PA ( P > 0.05). In conclusion, the altered mitochondrial phenotype in COPD is present even in the absence of differing levels of PA and appears to be related to the disease itself. NEW & NOTEWORTHY Chronic obstructive pulmonary disease (COPD) is associated with debilitating alterations in the function of skeletal muscle mitochondria. By comparing the mitochondrial phenotype of patients with COPD to that of healthy control subjects who perform the same amount of physical activity each day, this study provides evidence that many aspects of the dysfunctional mitochondrial phenotype observed in COPD are not merely due to reduced physical activity but are likely related to the disease itself.


Subject(s)
Mitochondria, Muscle/metabolism , Pulmonary Disease, Chronic Obstructive/metabolism , Aged , Case-Control Studies , Cell Respiration , Exercise , Female , Humans , Male , Middle Aged , Oxidative Stress
12.
Am J Physiol Endocrinol Metab ; 313(1): E94-E104, 2017 07 01.
Article in English | MEDLINE | ID: mdl-28292763

ABSTRACT

Patients with chronic obstructive pulmonary disease (COPD) experience a delayed recovery from skeletal muscle fatigue following exhaustive exercise that likely contributes to their progressive loss of mobility. As this phenomenon is not well understood, this study sought to examine postexercise peripheral oxygen (O2) transport and muscle metabolism dynamics in patients with COPD, two important determinants of muscle recovery. Twenty-four subjects, 12 nonhypoxemic patients with COPD and 12 healthy subjects with a sedentary lifestyle, performed dynamic plantar flexion exercise at 40% of the maximal work rate (WRmax) with phosphorus magnetic resonance spectroscopy (31P-MRS), near-infrared spectroscopy (NIRS), and vascular Doppler ultrasound assessments. The mean response time of limb blood flow at the offset of exercise was significantly prolonged in patients with COPD (controls: 56 ± 27 s; COPD: 120 ± 87 s; P < 0.05). In contrast, the postexercise time constant for capillary blood flow was not significantly different between groups (controls: 49 ± 23 s; COPD: 51 ± 21 s; P > 0.05). The initial postexercise convective O2 delivery (controls: 0.15 ± 0.06 l/min; COPD: 0.15 ± 0.06 l/min) and the corresponding oxidative adenosine triphosphate (ATP) demand (controls: 14 ± 6 mM/min; COPD: 14 ± 6 mM/min) in the calf were not significantly different between controls and patients with COPD (P > 0.05). The phosphocreatine resynthesis time constant (controls: 46 ± 20 s; COPD: 49 ± 21 s), peak mitochondrial phosphorylation rate, and initial proton efflux were also not significantly different between groups (P > 0.05). Therefore, despite perturbed peripheral hemodynamics, intracellular O2 availability, proton efflux, and aerobic metabolism recovery in the skeletal muscle of nonhypoxemic patients with COPD are preserved following plantar flexion exercise and thus are unlikely to contribute to the delayed recovery from exercise in this population.


Subject(s)
Exercise Tolerance , Exercise , Muscle, Skeletal/physiopathology , Oxygen Consumption , Pulmonary Disease, Chronic Obstructive/physiopathology , Recovery of Function/physiology , Aged , Energy Metabolism , Exercise Therapy/methods , Female , Humans , Male , Muscle Fatigue , Muscle Strength
13.
Asian J Androl ; 18(6): 937-941, 2016.
Article in English | MEDLINE | ID: mdl-26470836

ABSTRACT

The aim of this study was to determine whether the neutrophil-to-lymphocyte ratio (NLR), a measure of the systemic inflammatory response is associated with the overall prostate cancer detection rate in men who underwent contemporary multi (≥12)-core transrectal ultrasound (TRUS) biopsy. We reviewed the records of 3913 patients with initial prostate-specific antigen (PSA) levels ranging from 4 to 10 ng ml-1 who underwent TRUS-guided prostate biopsy between April 2006 and May 2014. NLR was calculated by prebiopsy neutrophil and lymphocyte counts. We excluded patients who had evidence of acute prostatitis, a history of prostate surgery, and any systemic inflammatory disease. A multivariate logistic regression model was used to analyze prostate cancer detection. After adjusting for confounding factors, predictive values were determined according to the receiver operating characteristic-derived area under the curve, both including and excluding the NLR variable. In univariate analyses, NLR was a significant predictor of prostate cancer detection (P < 0.001). In multivariate analyses, a higher NLR was significantly associated with prostate cancer detection after adjusting for other factors (OR = 1.372, P= 0.038). The addition of NLR increased the accuracy from 0.712 to 0.725 (P = 0.005) in the multivariate model for prostate cancer detection. NLR may be a potentially useful clinical marker in the detection of prostate cancer among men with a PSA level in the 4-10 ng ml-1 range. These findings are derived from a retrospective analysis and should be validated in larger populations through prospective studies.


Subject(s)
Lymphocytes/pathology , Neutrophils/pathology , Prostate-Specific Antigen/blood , Prostate/pathology , Prostatic Neoplasms/diagnosis , Aged , Biopsy, Large-Core Needle , Humans , Male , Middle Aged , Neoplasm Grading , Predictive Value of Tests , Prostatic Neoplasms/blood , Prostatic Neoplasms/pathology , Sensitivity and Specificity
14.
J Physiol ; 593(8): 2017-36, 2015 Apr 15.
Article in English | MEDLINE | ID: mdl-25643692

ABSTRACT

Although doxorubicin (DOX) is a highly effective anti-tumour agent used to treat a variety of cancers, DOX administration is associated with significant side effects, including myopathy of both cardiac and skeletal muscles. The mechanisms responsible for DOX-mediated myopathy remain a topic of debate. We tested the hypothesis that both increased mitochondrial reactive oxygen species (ROS) emission and activation of the cysteine protease calpain are required for DOX-induced myopathy in rat cardiac and skeletal muscle. Cause and effect was determined by administering a novel mitochondrial-targeted anti-oxidant to prevent DOX-induced increases in mitochondrial ROS emission, whereas a highly-selective pharmacological inhibitor was exploited to inhibit calpain activity. Our findings reveal that mitochondria are a major site of DOX-mediated ROS production in both cardiac and skeletal muscle fibres and the prevention of DOX-induced increases in mitochondrial ROS emission protects against fibre atrophy and contractile dysfunction in both cardiac and skeletal muscles. Furthermore, our results indicate that DOX-induced increases in mitochondrial ROS emission are required to activate calpain in heart and skeletal muscles and, importantly, calpain activation is a major contributor to DOX-induced myopathy. Taken together, these findings show that increased mitochondrial ROS production and calpain activation are significant contributors to the development of DOX-induced myopathy in both cardiac and skeletal muscle fibres.


Subject(s)
Calpain/metabolism , Doxorubicin/pharmacology , Mitochondria/metabolism , Muscle, Skeletal/metabolism , Muscular Diseases/metabolism , Myocardium/metabolism , Reactive Oxygen Species/metabolism , Animals , Female , Heart/drug effects , Mitochondria/drug effects , Mitochondria/pathology , Muscle, Skeletal/drug effects , Muscle, Skeletal/pathology , Muscular Diseases/chemically induced , Muscular Diseases/pathology , Myocardium/pathology , Oxidative Stress/drug effects , Rats , Rats, Sprague-Dawley
15.
J Exerc Rehabil ; 11(6): 289-95, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26730378

ABSTRACT

Whole body vibration training (WBVT) has been used as a supplement to conventional exercise training such as resistance exercise training to improve skeletal muscle strength, specifically, in rehabilitation field. Recently, this exercise modality has been utilized by cardiovascular studies to examine whether WBVT can be a useful exercise modality to improve cardiovascular health. These studies reported that WBVT has not only beneficial effects on muscular strength but also cardiovascular health in elderly and disease population. However, its mechanism underlying the beneficial effects of WBVT in cardiovascular health has not been well documented. Therefore, this review highlighted the impacts of WBVT on cardiovascular health, and its mechanisms in conjunction with the improved muscular strength and body composition in various populations.

16.
J Surg Res ; 188(2): 510-6, 2014 May 15.
Article in English | MEDLINE | ID: mdl-24630519

ABSTRACT

BACKGROUND: Mechanical ventilation (MV) is a method of maintaining appropriate gas exchange in patients who are unable to sustain adequate alveolar ventilation. While lifesaving in the short-term, prolonged MV leads to altered cardiovascular responses and enhanced lung injury, but the exact mechanism is unknown. Therefore, we investigated the involvement of the sympathoadrenergic and renin-angiotensin system in MV-induced altered cardiovascular responses. METHODS: Sprague-Dawley rats were divided into six groups: (1) spontaneous breathing (SB); (2) SB + enalapril (100 µg/kg intravenous infusion); (3) SB + losartan (100 µg/kg infusion); (4) 12 h of MV; (5) MV + enalapril; and (6) MV + losartan. After the animals were sacrificed, blood and tissue samples were collected. Tyrosine hydroxylase, dopamine beta hydroxylase, and neuropeptide Y were measured in adrenal medulla and hypothalamus, whereas AT1 was measured in lung tissues by Western blot. Norepinephrine enzyme-linked immunosorbent assay and total antioxidant capacity were assayed in plasma. RESULTS: Our findings indicated that MV increases the sympathetic activation markers in adrenal medulla and hypothalamus. Moreover, oxidative stress was increased in lung and brain tissues. Treatment with enalapril or losartan reduced the lipid peroxidation in lung and brain tissues, while preserving the tissue glutathione content and plasma antioxidant capacity. CONCLUSIONS: These data demonstrate that the inhibition of the renin-angiotensin system by enalapril or losartan may reduce the MV-induced increase in sympathetic activity markers and oxidative stress, and thus, may have a beneficial effect as adjuvant therapy.


Subject(s)
Adrenal Medulla/metabolism , Enalapril/pharmacology , Hypothalamus/metabolism , Oxidative Stress/drug effects , Respiration, Artificial/adverse effects , Adrenal Medulla/drug effects , Angiotensin II Type 1 Receptor Blockers/pharmacology , Angiotensin II Type 1 Receptor Blockers/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Animals , Enalapril/therapeutic use , Female , Hypothalamus/drug effects , Losartan/pharmacology , Losartan/therapeutic use , Lung Diseases/prevention & control , Rats , Rats, Sprague-Dawley , Sympathetic Nervous System/drug effects
17.
FASEB J ; 28(7): 2790-803, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24671708

ABSTRACT

Controlled mechanical ventilation (CMV) is associated with the development of diaphragm atrophy and contractile dysfunction, and respiratory muscle weakness is thought to contribute significantly to delayed weaning of patients. Therefore, therapeutic strategies for preventing these processes may have clinical benefit. The aim of the current study was to investigate the role of the Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) signaling pathway in CMV-mediated diaphragm wasting and weakness in rats. CMV-induced diaphragm atrophy and contractile dysfunction coincided with marked increases in STAT3 phosphorylation on both tyrosine 705 (Tyr705) and serine 727 (Ser727). STAT3 activation was accompanied by its translocation into mitochondria within diaphragm muscle and mitochondrial dysfunction. Inhibition of JAK signaling during CMV prevented phosphorylation of both target sites on STAT3, eliminated the accumulation of phosphorylated STAT3 within the mitochondria, and reversed the pathologic alterations in mitochondrial function, reduced oxidative stress in the diaphragm, and maintained normal diaphragm contractility. In addition, JAK inhibition during CMV blunted the activation of key proteolytic pathways in the diaphragm, as well as diaphragm atrophy. These findings implicate JAK/STAT3 signaling in the development of diaphragm muscle atrophy and dysfunction during CMV and suggest that the delayed extubation times associated with CMV can be prevented by inhibition of Janus kinase signaling.-Smith, I. J., Godinez, G. L., Singh, B. K., McCaughey, K. M., Alcantara, R. R., Gururaja, T., Ho, M. S., Nguyen, H. N., Friera, A. M., White, K. A., McLaughlin, J. R., Hansen, D., Romero, J. M., Baltgalvis, K. A., Claypool, M. D., Li, W., Lang, W., Yam, G. C., Gelman, M. S., Ding, R., Yung, S. L., Creger, D. P., Chen, Y., Singh, R., Smuder, A. J., Wiggs, M. P., Kwon, O.-S., Sollanek, K. J., Powers, S. K., Masuda, E. S., Taylor, V. C., Payan, D. G., Kinoshita, T., Kinsella, T. M. Inhibition of Janus kinase signaling during controlled mechanical ventilation prevents ventilation-induced diaphragm dysfunction.


Subject(s)
Diaphragm/metabolism , Janus Kinases/metabolism , Respiration, Artificial/adverse effects , Signal Transduction/physiology , Animals , Interleukin-6/metabolism , Male , Mitochondria/metabolism , Muscle Weakness/metabolism , Muscular Atrophy/metabolism , Oxidative Stress/physiology , Phosphorylation/physiology , Proteolysis , Rats , Rats, Sprague-Dawley , STAT3 Transcription Factor/metabolism , Serine/metabolism , Tyrosine/metabolism
18.
J Phys Ther Sci ; 25(5): 587-90, 2013 May.
Article in English | MEDLINE | ID: mdl-24259808

ABSTRACT

[Purpose] This study was conducted in order to investigate the effect of repetitive passive movement and repetitive active movement on proprioception in forearm supination. [Subjects] This study had a cross-sectional design. Twenty-three right-handed healthy subjects were recruited. All subjects randomly received both repetitive passive movement and repetitive active movement (repetitive passive/active movement at 120°/s with 60 repetitions over a 0-80° range). Active and passive joint repositioning of all subjects was measured using the error score for position sense, both before and after repositioning intervention. [Results] In the repetitive passive movement test, there was a statistically significant decrease in the pre- versus post-repositioning error scores in the active and passive angle examinations. In the repetitive active movement test, there was a statistically significant increase in pre- versus post-repositioning error scores in the active and passive angle examinations. In the comparison of position sense, there was a statistically significant decrease in both active and passive angle repositioning error scores in repetitive passive movement versus repetitive active movement. [Conclusion] Repetitive passive movement improved the proprioception results for forearm supination, compared to repetitive active movement. Results of this study indicate that repetitive passive movement can be recommended to clinicians for rehabilitation therapy as it provides greater proprioception benefits.

19.
J Phys Ther Sci ; 25(7): 765-7, 2013 Jul.
Article in English | MEDLINE | ID: mdl-24259848

ABSTRACT

This study aimed to identify what impact the thickness differences between the leftside and rightside transversus abdominis (TrA), internal obliquus (IO) and external obliquus (EO) have on balance ability in the abdominal drawing-in maneuver (ADIM) and resting postures. [Subjects and Methods] In this study, 41 young adults were asked to adopt a resting posture and to perform ADIM. The thicknesses of the abdominal muscles (TrA, IO, EO) were measured using ultrasound imaging, Then balance ability was measured, so that a comparative analysis could be carried out. [Results] According to the results, the thicknesses of TrA and IO very significantly increased when ADIM was performed. The changes in thickness of the muscles on the left and right sides showed no significant correlations with balance ability. [Conclusion] According to the study results, the difference in thickness between the left and right side muscles in a normal person is small (symmetric), and the differences in the thickness of TrA and IO on the left and right side reduced when the ADIM, which is a re-education method for abdominal muscles was performed. Therefore, we consider that the ADIM should be used in future clinical trials to induce symmetric contraction of the abdominal muscles. Also, the correlation results of muscle balance and body balance can be used as empirical data.

20.
J Phys Ther Sci ; 25(7): 817-9, 2013 Jul.
Article in English | MEDLINE | ID: mdl-24259861

ABSTRACT

[Purpose] This study was conducted in order to investigate the importance of trunk muscle strength in stroke patients. By comparing the thicknesses of the abdominal wall muscles through ultrasonography, relative to the duration of illness, the results of the objective data were applied. [Methods] Thirty stroke patients were divided into three groups including an acute phase group participating in the study within 1 month after the onset of a stroke (n=10), a subacute phase group participating less than 6 months (n=10) after a stroke, and a chronic phase group participating more than 6 months (n=10) after suffering a stroke. The thicknesses of the transversus abdominis muscles (TrA), internal oblique muscle (IO), and the external oblique muscle (EO) were measured at rest and during abdominal draw-in maneuver (ADIM) in a supine hook-lying position, and their differences were compared. [Results] The results showed that, in comparison of the thicknesses of the paretic and nonparetic sides, the TrA of the subacute phase and chronic phase groups showed significant differences. In addition, the IO of the subacute phase group and the EO of the chronic phase groups also showed significant differences. [Conclusion] According to the duration of illness in stroke patients, the abdominal wall muscles become noticeably infirm and asymmetric. By improving their symmetry, the functions of the trunk muscles can be recovered.

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