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3.
Life Sci ; 137: 20-7, 2015 Sep 15.
Article in English | MEDLINE | ID: mdl-26141987

ABSTRACT

AIMS: Heart failure (HF) is associated with changes in energy metabolism of the heart, as well as in extra-cardiac organs such as the skeletal muscles. Cardiac cachexia is a common complication and is associated with poor prognosis. Branched-chain amino acids (BCAAs) reportedly improve sarcopenia and cancer cachexia. We tested the hypothesis that BCAA ameliorates HF with cardiac cachexia. MAIN METHODS: We used Dahl salt-sensitive (DS) rats fed a high-salt diet as a model of HF. DS rats fed a low-salt diet were used as a control. BCAA were administered in drinking water from 11weeks of age, when cardiac hypertrophy was established but the cardiac function was preserved. Survival and the cardiac function were monitored, and animals were sacrificed at 21weeks of age and analyzed. KEY FINDINGS: In HF rats, BCAA treatment decreased the heart rate, preserved the cardiac function, and prolonged survival. BCAA also prevented body weight loss, associated with preservation of the skeletal muscle weight. Moreover, gene expression related to mitochondrial biogenesis and function was increased with BCAA in skeletal muscles. SIGNIFICANCE: BCAA preserved the body weight and cardiac function and prolonged survival in HF rats. The expression of genes involved in mitochondrial biogenesis and function in skeletal muscles was increased by BCAA.


Subject(s)
Amino Acids, Branched-Chain/pharmacology , Amino Acids, Branched-Chain/therapeutic use , Cachexia/complications , Cachexia/drug therapy , Heart Failure/complications , Heart Failure/drug therapy , Muscle, Skeletal/drug effects , Animals , Cachexia/metabolism , Energy Metabolism/drug effects , Gene Expression/drug effects , Heart/drug effects , Heart/physiopathology , Heart Failure/metabolism , Heart Failure/physiopathology , Hemodynamics/drug effects , Male , Muscle Proteins/biosynthesis , Muscle, Skeletal/metabolism , Myocardium/metabolism , Myocardium/pathology , Organ Size/drug effects , Rats , Rats, Inbred Dahl , SKP Cullin F-Box Protein Ligases/biosynthesis , Signal Transduction/drug effects , TOR Serine-Threonine Kinases/metabolism , Tripartite Motif Proteins , Ubiquitin-Protein Ligases/biosynthesis
5.
PLoS One ; 10(1): e0117091, 2015.
Article in English | MEDLINE | ID: mdl-25594546

ABSTRACT

BACKGROUND: Many methods have been used to assess mitochondrial function. Technetium-99m sestamibi ((99m)Tc-MIBI), a lipophilic cation, is rapidly incorporated into myocardial cells by diffusion and mainly localizes to the mitochondria. The purpose of this study was to investigate whether measurement of (99m)Tc-MIBI signals in animal models could be used as a tool to quantify mitochondrial membrane potential at the organ level. METHODS AND RESULTS: We analyzed (99m)Tc-MIBI signals in Sprague-Dawley (SD) rat hearts perfused with carbonyl cyanide m-chlorophenylhydrazone (CCCP), a mitochondrial uncoupler known to reduce the mitochondrial membrane potential. (99m)Tc-MIBI signals could be used to detect changes in the mitochondrial membrane potential with sensitivity comparable to that obtained by two-photon laser microscopy with the cationic probe tetramethylrhodamine ethyl ester (TMRE). We also measured (99m)Tc-MIBI signals in the hearts of SD rats administered CCCP (4 mg/kg intraperitoneally) or vehicle. (99m)Tc-MIBI signals decreased in rat hearts administered CCCP, and the ATP content, as measured by (31)P magnetic resonance spectroscopy, decreased simultaneously. Next, we administered (99m)Tc-MIBI to Dahl salt-sensitive rats fed a high-salt diet, which leads to hypertension and heart failure. The (99m)Tc-MIBI signal per heart tissue weight was inversely correlated with heart weight, cardiac function, and the expression of atrial natriuretic factor, a marker of heart failure, and positively correlated with the accumulation of labeled fatty acid analog. The (99m)Tc-MIBI signal per liver tissue weight was lower than that per heart tissue weight. CONCLUSION: Measurement of (99m)Tc-MIBI signals can be an effective tool for semiquantitative investigation of cardiac mitochondrial membrane potential in the SD rat model by using a chemical to decrease the mitochondrial membrane potential. The (99m)Tc-MIBI signal per heart tissue weight was inversely correlated with the severity of heart failure in the Dahl rat model.


Subject(s)
Heart Failure/diagnosis , Technetium Tc 99m Sestamibi , Animals , Carbonyl Cyanide m-Chlorophenyl Hydrazone/pharmacology , Disease Models, Animal , Male , Membrane Potential, Mitochondrial/drug effects , Mitochondria, Heart/metabolism , Proton Ionophores/pharmacology , Rats , Rats, Sprague-Dawley
6.
Biomed Eng Online ; 13: 166, 2014 Dec 15.
Article in English | MEDLINE | ID: mdl-25511926

ABSTRACT

BACKGROUND: Intraoperative morphological and functional monitoring is essential for safe neurosurgery. Functional monitoring is based on electroencephalography (EEG), which uses silver electrodes. However, these electrodes generate metal artifacts as silver blocks X-rays, creating white radial lines on computed tomography (CT) images during surgery. Thick electrodes interfere with surgical procedures. Thus, thinner and lighter electrodes are ideal for intraoperative use. METHODS: The authors developed thin brain electrodes using carbon nanotubes that were formed into thin sheets and connected to electrical wires. RESULTS: The nanotube sheets were soft and fitted the curve of the head very well. When attached to the head using paste, the impedance of the newly developed electrodes was 5 kΩ or lower, which was similar to that of conventional metal electrodes. These electrodes can be used in combination with intraoperative CT, magnetic resonance imaging (MRI), or cerebral angiography. Somatosensory-evoked potentials, auditory brainstem responses, and visually evoked potentials were clearly identified in ten volunteers. The electrodes, without any artifacts that distort images, did not interfere with X-rays, CT, or MR images. They also did not cause skin damage. CONCLUSIONS: Carbon nanotube electrodes may be ideal for neurosurgery.


Subject(s)
Electroencephalography/methods , Nanotechnology/methods , Nanotubes, Carbon/chemistry , Neurosurgery/methods , Artifacts , Carbon/chemistry , Cost-Benefit Analysis , Electrodes , Electrophysiology , Equipment Design , Evoked Potentials , Humans , Magnetic Resonance Imaging/methods , Materials Testing , Metals/chemistry , Silver/chemistry , Skin/pathology , Tomography, X-Ray Computed/methods , X-Rays
7.
PLoS One ; 8(8): e72173, 2013.
Article in English | MEDLINE | ID: mdl-23951293

ABSTRACT

BACKGROUND: Heart failure is associated with changes in cardiac energy metabolism. Glucose metabolism in particular is thought to be important in the pathogenesis of heart failure. We examined the effects of persistent overexpression of phosphoglycerate mutase 2 (Pgam2), a glycolytic enzyme, on cardiac energy metabolism and function. METHODS AND RESULTS: Transgenic mice constitutively overexpressing Pgam2 in a heart-specific manner were generated, and cardiac energy metabolism and function were analyzed. Cardiac function at rest was normal. The uptake of analogs of glucose or fatty acids and the phosphocreatine/ßATP ratio at rest were normal. A comprehensive metabolomic analysis revealed an increase in the levels of a few metabolites immediately upstream and downstream of Pgam2 in the glycolytic pathway, whereas the levels of metabolites in the initial few steps of glycolysis and lactate remained unchanged. The levels of metabolites in the tricarboxylic acid (TCA) cycle were altered. The capacity for respiration by isolated mitochondria in vitro was decreased, and that for the generation of reactive oxygen species (ROS) in vitro was increased. Impaired cardiac function was observed in response to dobutamine. Mice developed systolic dysfunction upon pressure overload. CONCLUSIONS: Constitutive overexpression of Pgam2 modified energy metabolism and reduced stress resistance of heart in mice.


Subject(s)
Energy Metabolism/genetics , Gene Expression , Myocardium/metabolism , Phosphoglycerate Mutase/genetics , Stress, Physiological/genetics , Animals , Cardiotonic Agents/pharmacology , Dobutamine/pharmacology , Echocardiography , Enzyme Activation , Fibrosis , Glucose/metabolism , Glycolysis/genetics , Heart/diagnostic imaging , Heart/drug effects , Heart/physiopathology , Magnetic Resonance Spectroscopy , Male , Metabolome , Metabolomics/methods , Mice , Mice, Transgenic , Mitochondria/genetics , Mitochondria/metabolism , Myocardium/pathology , Organ Specificity/genetics , Phosphoglycerate Mutase/metabolism , Radionuclide Imaging , Reactive Oxygen Species/metabolism
8.
Int J Cardiol ; 161(3): 130-6, 2012 Nov 29.
Article in English | MEDLINE | ID: mdl-21839528

ABSTRACT

BACKGROUND: Cachexia, namely body wasting, is a common complication in cases of congestive heart failure (CHF). Although, neurohumoral and immune abnormalities are associated with the condition, precisely how the imbalance of catabolism and anabolism is responsible for the wasting process is not known. METHODS: We analyzed markers of cachexia in Dahl salt-sensitive rats which show marked hypertension with preserved systolic function at 11 weeks and CHF at 17-19 weeks of age. We also analyzed the change in hepatic metabolism associated with CHF since liver plays a central role in the systemic regulation of catabolism and anabolism. RESULTS: In CHF rats, a failure to grow was observed and blood hepatic protein levels were decreased associated with increased blood proinflammatory cytokine levels, indicating that Dahl rats serve as a model of cardiac cachexia. Food intake was reduced, and blood sugar and insulin levels were decreased. Despite the apparent fasting condition, blood fatty acid levels were decreased and triglycerides levels were increased. In CHF rats, liver incorporated more glucose, the gene expression related to gluconeogenesis was decreased, the gene expression related to lipogenesis was increased, and the triglyceride content of the liver was increased. The paradoxical production of triglycerides synthesis in fasting rats was associated with a proinflammatory response in liver. CONCLUSIONS: The Dahl salt-sensitive rat can be used as a model of cardiac cachexia. The cachexia was associated with abnormal hepatic metabolism that might work as a maladaptive response during the progression of CHF.


Subject(s)
Disease Models, Animal , Heart Failure/metabolism , Liver/metabolism , Animals , Blood Glucose/metabolism , Body Weight/physiology , Eating/physiology , Heart Failure/physiopathology , Male , Rats , Rats, Inbred Dahl , Triglycerides/blood
9.
J Mol Cell Cardiol ; 51(6): 1026-36, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21964378

ABSTRACT

Heart failure is associated with a change in cardiac energy metabolism. SIRT1 is a NAD(+)-dependent protein deacetylase, and important in the regulation of cellular energy metabolism. To examine the role of SIRT1 in cardiac energy metabolism, we created transgenic mice overexpressing SIRT1 in a cardiac-specific manner, and investigated cardiac functional reserve, energy reserve, substrate uptake, and markers of mitochondrial function. High overexpression of SIRT1 caused dilated cardiomyopathy. Moderate overexpression of SIRT1 impaired cardiac diastolic function, but did not cause heart failure. Fatty acid uptake was decreased and the number of degenerated mitochondria was increased dependent on SIRT1 gene dosage. Markers of reactive oxygen species were decreased. Changes in morphology and reactive oxygen species were associated with the reduced expression of genes related to mitochondrial function and autophagy. In addition, the respiration of isolated mitochondria was decreased. Cardiac function was normal in transgenic mice expressing a low level of SIRT1 at baseline, but the mice developed cardiac dysfunction upon pressure overload. In summary, the constitutive overexpression of SIRT1 reduced cardiac function associated with impaired mitochondria in mice.


Subject(s)
Mitochondria, Heart/metabolism , Myocardium/metabolism , Sirtuin 1/genetics , Sirtuin 1/metabolism , Animals , Autophagy/genetics , Blood Glucose/metabolism , Electron Transport Chain Complex Proteins/metabolism , Energy Metabolism/genetics , Fatty Acids/metabolism , Gene Dosage , Gene Expression , Gene Expression Regulation , Heart Failure, Diastolic/genetics , Heart Failure, Diastolic/metabolism , Heart Failure, Diastolic/mortality , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Mitochondria, Heart/genetics , Mitochondria, Heart/ultrastructure , NAD/metabolism , Nicotinamide Phosphoribosyltransferase/genetics , Reactive Oxygen Species/metabolism
10.
Opt Express ; 16(14): 10762-8, 2008 Jul 07.
Article in English | MEDLINE | ID: mdl-18607492

ABSTRACT

We produced a high power radially-polarized output directly from a diode-pumped Nd:YVO(4) bounce amplifier, using an autocloned photonic crystal mirror as an output coupler, with a simple cavity configuration. The radially-polarized output power of approximately 6 W was achieved, and a corresponding slope efficiency was estimated to be approximately 17 %. The output was characterized to be an ideal radially-polarized beam from its polarization distribution profiles. The output mode was not an eigenmode in the resonator. We discussed and clarified intra-cavity mode dynamics in terms of polarization distribution in the wavefront.

11.
J Interv Cardiol ; 17(5): 295-300, 2004 Oct.
Article in English | MEDLINE | ID: mdl-15491332

ABSTRACT

Stenting of small coronary arteries has been limited by high rates of restenosis, and restenosis after stenting has chiefly been attributed to inflammatory reactions resulting in cell proliferation and intimal hyperplasia. In order to suppress this inflammatory process, we examined the effects of hydrocortisone, an antiinflammatory agent, on restenosis after stenting in a nonrandomized retrospective registry. The study population consisted of 193 patients treated at two hospitals, who underwent stent implantations in coronary arteries of reference diameter <3 mm between February 1999 and September 2001. Target lesions included complex, restenotic, diabetic, or chronic total lesions and types of implanted stents were Multi-Link, S-series, and gfx stents. Effect of intravenous administration of hydrocortisone (200 mg) before stenting was compared to control patients who did not receive this treatment. There was no significant difference of early outcomes between the hydrocortisone group and the control group. On angiographic follow-up at 6 months after stenting, the rate of restenosis was significantly lower in patients treated with hydrocortisone as compared with control group (22.8% vs 37%, respectively; P < 0.05). The revascularization rate of target lesion at 6 months was also significantly lower in the treated group (16.5% vs 29%, respectively; P < 0.05). These results suggest that preprocedural intravenous administration of hydrocortisone reduces restenosis after stenting of small coronary arteries. Prospectively controlled trials will be necessary to confirm this preventive effect of hydrocortisone on coronary in-stent restenosis.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Coronary Artery Disease/therapy , Coronary Restenosis/prevention & control , Coronary Vessels/surgery , Hydrocortisone/therapeutic use , Stents , Aged , Anti-Inflammatory Agents/administration & dosage , Case-Control Studies , Coronary Angiography , Female , Follow-Up Studies , Humans , Hydrocortisone/administration & dosage , Injections, Intravenous , Male , Middle Aged , Retrospective Studies , Treatment Outcome
12.
Intern Med ; 42(11): 1084-9, 2003 Nov.
Article in English | MEDLINE | ID: mdl-14686746

ABSTRACT

OBJECTIVE: Stenting of small coronary arteries has always been limited by high rates of restenosis, and restenosis has mainly been attributed to inflammatory reactions resulting in cell proliferation and intimal hyperplasia. Based on our experience for several years, we retrospectively investigated the effect of hydrocortisone on reducing in-stent restenosis. PATIENTS AND METHODS: Study population consisted of consecutive 166 patients, 221 lesions, who electively underwent stent implantations stent diameter less than 3 mm into coronary arteries between February 1999 and October 2002. We intravenously administered hydrocortisone before the procedure to 40 patients for preventing allergic reactions due to contrast material, and the effect of hydrocortisone on reducing restenosis was retrospectively compared with 126 patients who did not receive this treatment. RESULTS: There was no significant difference in the prevalence of diabetes mellitus, hyperlipidemia, or hypertension between the two groups. There was no significant difference in the type of lesion, length of stent, balloon/artery ratio, or initial success rate between the two groups, but stent diameter was significantly smaller in the hydrocortisone group compared with the control group. On six-month angiographic follow-up, the restenosis rate was significantly lower in the hydrocortisone group compared with the control group (16.2% vs 34.0%, respectively), and the target lesion revascularization rate was also significantly lower in the hydrocortisone group compared with the control group (13.2% vs 27.5%, respectively). CONCLUSION: These results suggest that intravenous administration of hydrocortisone reduces in-stent restenosis of small coronary arteries. Prospectively controlled trials will be necessary to confirm this preventive effect of hydrocortisone.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Coronary Restenosis/drug therapy , Hydrocortisone/pharmacology , Stents , Aged , Angioplasty, Balloon, Coronary , Anti-Inflammatory Agents/administration & dosage , Coronary Restenosis/diagnostic imaging , Female , Humans , Hydrocortisone/administration & dosage , Injections, Intravenous , Male , Middle Aged , Radiography , Regression Analysis , Retrospective Studies
13.
J Allergy Clin Immunol ; 112(3): 525-30, 2003 Sep.
Article in English | MEDLINE | ID: mdl-13679811

ABSTRACT

BACKGROUND: Complement component C3a, an anaphylatoxin, provokes acute inflammatory responses, including smooth muscle contraction, mucus hypersecretion, increase in vascular permeability, and recruitment of inflammatory cells. Thus C3a may be related to airway inflammation and bronchoconstriction in acute asthma exacerbation. OBJECTIVE: We sought to determine whether plasma C3a is elevated in patients presenting for emergency treatment of acute asthma exacerbations and to correlate C3a concentrations with response to therapy. METHODS: Plasma C3a and serum eosinophil cationic protein were measured in 52 patients with acute asthma with peak expiratory flow of < or =50% the predicted value. Control subjects were 42 patients with stable chronic asthma. Patients with severe acute asthma were classified into 2 groups (admitted and discharged), according to how effective inhaled bronchodilators and systemic corticosteroids were in the first 2 hours of treatment. RESULTS: Concentrations of C3a in plasma from subjects in the admitted group (median, 256 ng/mL; range, 94 to 454) were significantly higher than those in the discharged group (197 ng/mL; 72 to 300) or those in patients with stable chronic asthma (166 ng/mL; 89 to 254; P <.0001). Elevated plasma C3a concentrations in admitted asthmatic patients decreased significantly by 7 days after admission (P =.0005). No significant difference was evident in serum eosinophil cationic protein concentration between the admitted group (33.1 microg/L; 6.3 to 143) and the discharged group (32.7 microg/L; 14.6 to 160; P =.99). CONCLUSIONS: Concentrations of C3a, which can induce airway inflammation and bronchoconstriction, were associated with differences in response to emergency treatment of severe asthma exacerbation.


Subject(s)
Asthma/drug therapy , Asthma/immunology , Complement C3a/metabolism , Ribonucleases , Acute Disease , Adolescent , Adrenal Cortex Hormones/therapeutic use , Adult , Aged , Asthma/physiopathology , Blood Proteins/metabolism , Bronchodilator Agents/therapeutic use , Case-Control Studies , Emergencies , Eosinophil Granule Proteins , Female , Humans , Inflammation Mediators/blood , Male , Middle Aged , Peak Expiratory Flow Rate
14.
Ann Allergy Asthma Immunol ; 90(3): 331-7, 2003 Mar.
Article in English | MEDLINE | ID: mdl-12669897

ABSTRACT

BACKGROUND: International guidelines recommend multiple doses of inhaled beta2-agonists and anticholinergics plus early administration of systemic corticosteroids for acute, severe asthma. This study examined the efficacy of this protocol in adults and analyzed those factors associated with unresponsiveness to the protocol therapy. OBJECTIVE: Ninety-three consecutive patients 18 to 55 years old presenting for treatment of acute asthma with a peak expiratory flow rate (PEFR) < or = 50% of the predicted value were analyzed. METHODS: All subjects received 400 microg of salbutamol every 20 minutes for three doses and 400 microg of oxitropium bromide with each of the three salbutamol doses by means of a metered-dose inhaler with a spacer device, plus intravenously 8 mg betamethasone. PEFR was measured at baseline and at 20, 40, 60, and 120 minutes. RESULTS: Sixty-nine percent of subjects improved sufficiently to be discharged. In 31% of subjects, the protocol therapy failed. There were no significant differences in age, sex, smoking status, or beta-agonist use within 6 hours between the two groups. Logistic regression analysis demonstrated that a PEFR < 35% of the predicted value at presentation (odds ratio [OR]; 16.3, 95% confidence interval [CI] 4.5 to 59.9), viral respiratory tract infection symptoms > or = 2 days (OR, 4.8, 95% CI 1.3 to 17.1), and asthma hospitalization in the past year (OR, 4.6, 95% CI 1.1 to 19.9) were significantly associated with unresponsiveness to the protocol. CONCLUSIONS: Unresponsiveness to protocol therapy occurs in nearly one-third of individuals presenting with acute, severe asthma. Our findings underscore the need to explore more effective strategies for improving lung function and reducing hospital admission rates.


Subject(s)
Anti-Asthmatic Agents/therapeutic use , Asthma/drug therapy , Acute Disease , Adolescent , Adrenergic beta-Agonists/administration & dosage , Adrenergic beta-Agonists/therapeutic use , Adult , Albuterol/administration & dosage , Albuterol/therapeutic use , Anti-Asthmatic Agents/administration & dosage , Asthma/diagnosis , Betamethasone/administration & dosage , Betamethasone/therapeutic use , Cholinergic Antagonists/administration & dosage , Cholinergic Antagonists/therapeutic use , Clinical Protocols , Consensus , Female , Humans , Male , Middle Aged , Peak Expiratory Flow Rate , Scopolamine Derivatives/administration & dosage , Scopolamine Derivatives/therapeutic use , Treatment Failure
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