Virology & Mycology Infectious Diseases
 
   Publications A-Z
A
»Accounting & Marketing
» Addiction Research & Therapy
» Advanced Chemical Engineering
»Advances in Automobile Engineering
»Advances in Crop Science and Technology
»Advances in Dairy Research
»Advancements in Genetic Engineering
»Advances in Pharmacoepidemiology & Drug Safety
»Advances in Robotics & Automation
»Advanced Techniques in Biology & Medicine
»Advance Research in Meteorological Sciences
»Aeronautics & Aerospace Engineering
»Aging Science
»Agrotechnology
»AIDS & Clinical Research
»Alcoholism and Drug Dependence
»Allergy & Therapy
»Alternative & Integrative Medicine
»Air & Water borne Diseases
»Alzheimers Disease & Parkinsonism
»Analytical & Bioanalytical Techniques
»Anaplastology
»Anatomy & Physiology
»Ancient Diseases & Preventive Remedies
»Andrology-Open Access
»Anesthesia & Clinical Research
»Angiology: Open Access
»Antivirals & Antiretrovirals
»Anthropology
»Applied & Computational Mathematics
»Applied Mechanical Engineering
»Aquaculture Research & Development
» Arabian Journal Business and Management Review
»Architectural Engineering Technology
»Arthritis
»Arts and Social Sciences Journal
» Astrobiology & Outreach
»Astrophysics & Aerospace technology
»Autacoids
»Automatic Control of Physiological State and Function
»Autism-Open Access
  
B
»Bacteriology & Parasitology
»Bioanalysis & Biomedicine
»Bioceramics Development and Applications
»Biochemistry and Analytical Biochemistry
»Biochemistry & Pharmacology: Open Access
»Biochips & Tissue Chips
»Biodiversity & Endangered Species
»Bioenergetics: Open Access
»Bioengineering & Biomedical Science
»Bioequivalence & Bioavailability
»Biosafety & Health Education
»Biofertilizers & Biopesticides
»Biometrics & Biostatistics
»Biomimetics Biomaterials and Tissue Engineering
»Biomolecular Research & Therapeutics
» Biomusical Engineering
»Biochemistry & Physiology: Open Access
»Biological Systems- Open Access
»Biology and Medicine
»Bioprocessing & Biotechniques
»Bioremediation & Biodegradation
»Biosafety
»Biosensors & Bioelectronics
» Biosensors Journal
»Biotechnology & Biomaterials
»Bioterrorism & Biodefense
»Blood Disorders & Transfusion
»Blood & Lymph
»Bone Marrow Research
»Brain Disorders & Therapy
»Business and Economics Journal
»Business and Financial Affairs
  
C
»Cancer Science & Therapy
»Climatology & Weather forecasting
»Carcinogenesis & Mutagenesis
»Cardiovascular Diseases & Diagnosis
»Cardiovascular Pharmacology: Open Access
»Cell & Developmental Biology
»Cell Science & Therapy
»Chemical Engineering & Process Technology
»Chemical Sciences Journal
»Chemotherapy: Open Access
»Child and Adolescent Behavior
»Chromatography & Separation Techniques
»Civil & Environmental Engineering
»Civil & Legal Sciences
»Clinical & Cellular Immunology
»Clinical Case Reports
»Clinical & Experimental Cardiology
»Clinical & Experimental Dermatology Research
»Clinical & Experimental Ophthalmology
»Clinical & Experimental Pathology
»Clinical & Experimental Pharmacology
»Clinical Microbiology: Open Access
»Clinical Pharmacology & Biopharmaceutics
»Clinical Research & Bioethics
»Clinical Research on Foot & Ankle
»Clinical Toxicology
»Clinical Trials
»Clinics in Mother and Child Health
»Cloning & Transgenesis
»Community Medicine & Health Education
»Communication Disorders, Deaf Studies & Hearing Aids
»Computer Science & Systems Biology
» Current Synthetic & Systems Biology
»Cytology & Histology
D
»Data Mining in Genomics & Proteomics
»Defense Management
»Dentistry
»Depression and Anxiety
»Developing Drugs
»Diabetes & Metabolism
»Drug Designing
»Drug Metabolism & Toxicology
  
E
»Earth Science & Climatic Change
»Ecosystem & Ecography
»Endocrinology & Metabolic Syndrome
»Entomology, Ornithology & Herpetology
»Environmental & Analytical Toxicology
»Epidemiology: Open Access
»Emergency Medicine
»Ergonomics
»Electrical & Electronics
»Enzyme Engineering
»Entrepreneurship & Organization Management
  
F
»Family Medicine & Medical Science Research
»Fermentation Technology
»Fertilization: In Vitro - IVF-Worldwide
»Fisheries and Aquaculture Journal
»Fisheries & Livestock Production
»Food Processing & Technology
»Forensic Biomechanics
»Forensic Research
»Forest Research: Open Access
»Fundamentals of Renewable Energy and Applications
»Fungal Genomics & Biology
  
G
»Gastrointestinal & Digestive System
»Genetic Syndromes & Gene Therapy
»Gene Technology
»Generalized Lie Theory and Applications
»Glycobiology
»Glycomics & Lipidomics
»Gynecology& Obstetrics
»General Medicine
»General Practice
»Geography & Natural Disasters
»Geology & Geosciences
»Geophysics & Remote Sensing
»Gerontology & Geriatric Research
»Global Economics
»Global Journal of Technology and Optimization
  
H
»Hair : Therapy & Transplantation
»Hematology & Thromboembolic Diseases
»Health Care : Current Reviews
»Health & Medical Informatics
»Hereditary Genetics
»Homeopathy & Ayurvedic Medicine
»Horticulture
»Hotel & Business Management
»Human Genetics & Embryology
»Hydrology: Current Research
»Hypertension- Open Access
  
I
»Industrial Engineering & Management
»Irrigation and Drainage Systems Engineering
»Infectious Diseases and Therapy
»Information Technology & Software Engineering
»Intellectual Property Rights: Open Access
»Integrative Oncology
»Internal Medicine
»International Journal of Accounting Research
»International Journal of Advanced Innovations, Thoughts & Ideas
»International Journal of Biomedical Data Mining
»International Journal of Economics and Management Science
»International Journal of Sensor Networks and Data Communications
»International Journal of Swarm Intelligence and Evolutionary Computation
»International Journal of waste resources
»International Journal of Genomic Medicine
»International Journal of Physical Medicine & Rehabilitation
»Innovative Energy Policies
»Immunome Research
  
J
»JBR Journal of Interdisciplinary Medicine and Dental Science
»JBR Journal of Clinical Diagnosis and Research
»JBR Journal of Young Scientist
  
L
»Liver
» Leukemia
» Lovotics
  
M
»Marine Science: Research & Development
»Malaria Chemotherapy, Control & Elimination
»Mass Communication & Journalism
»Material Sciences & Engineering
»Medicinal Chemistry
»Medicinal & Aromatic Plants
»Medical Diagnostic Methods
»Medical Microbiology & Diagnosis
»Medical & Surgical Urology
»Membrane Science & Technology
»Metabolic Syndrome
»Metabolomics:Open Access
»Microbial & Biochemical Technology
»Modern Chemistry & Applications
»Molecular Biology
»Molecular Biomarkers & Diagnosis
»Molecular and Genetic Medicine
»Molecular Imaging & Dynamics
»Molecular Pharmaceutics & Organic Process Research
»Mycobacterial Diseases
N
»Natural Products Chemistry & Research
»Nanomedicine & Biotherapeutic Discovery
»Nanomedicine & Nanotechnology
»Neonatal Biology
»Nephrology & Therapeutics
»Neurology & Neurophysiology
»Neuroinfectious Diseases
»Neurological Disorders
»Novel Physiotherapies
»Nuclear Medicine & Radiation Therapy
»Nutrition & Food Sciences
»Nutritional Disorders & Therapy
»Nursing & Care
  
O
»Obesity & Weight Loss Therapy
»Oceanography-Open Access
»Occupational Medicine & Health Affairs
»OMICS Journal of Radiology
»Osteoporosis and Physical Activity
»Oral Health and Dental Management
»Oral Hygiene & Health
»Organic Chemistry: Current Research
»Orthopedic & Muscular System: Current Research
»Otolaryngology
  
P
»Pain & Relief
»Palliative Care & Medicine
»Pancreatic Disorders & Therapy
»Pediatrics & Therapeutics
»Petroleum & Environmental Biotechnology
»Pharmaceutica Analytica Acta
»Pharmaceutical Regulatory Affairs: Open Access
»Pharmacogenomics & Pharmacoproteomics
»Pharmacovigilance
»Physical Chemistry & Biophysics
»Physical Mathematics
»Plant Pathology & Microbiology
»Plant Biochemistry & Physiology
»Pollution Effects & Control
»political Sciences & public affairs
»Poultry, Fisheries & Wildlife Sciences
»Powder Metallurgy & Mining
»Primatology
»Primary Health Care: Open Access
»Probiotics & Health
» Phylogenetics & Evolutionary Biology
»Proteomics & Bioinformatics
»Phylogenetics & Evolutionary Biology
»Psychology & Psychotherapy
»Psychological Abnormalities in Children
»Pulmonary & Respiratory Medicine
  
R
»Reproductive System & Sexual Disorders
»Research and Development
»Review of Public Adminstration and Management
»Rheumatology: Current Research
»Rice Research: Open Access
  
S
» Single Cell Biology
»Sleep Disorders & Therapy
»Socialomics
»Sociology and Criminology-Open Access
»Sports Medicine & Doping Studies
»Spine
»Stem Cell Research & Therapy
»Steroids & Hormonal Science
»Stock & Forex Trading
»Surgery: Current Research
  
T
»Telecommunications System & Management
»Textile Science & Engineering
»Theoretical and Computational Chemistry:Open Access
»Thermodynamics & Catalysis
»Thyroid Disorders & Therapy
»Tissue Science & Engineering
»Translational Medicine
»Transplantation Technologies & Research
»Transcriptomics: Open Access
»Trauma & Treatment
»Tropical Diseases
»Tropical Medicine and Surgery
»Tourism & Hospitality
  
V
»Vaccines & Vaccination
»Vascular Medicine & surgery
»Veterinary Science & Technology
»Virology & Mycology
»Vitamins & Minerals
»Vortex Science and Technology
  
W
»Women's Health Care
  
Y
»Yoga & Physical Therapy
 
   Browse by Subjects
Clinical
» AIDS & Clinical Research
» Anesthesia & Clinical Research
» Angiology
» Cancer Science & Therapy
» Carcinogenesis & Mutagenesis
» Cell Science & Therapy
» Chemotherapy
» Child & Adolescent Behavior
» Clinical & Cellular Immunology
» Clinical Case Reports
» Clinical & Experimental Cardiology
» Clinical & Experimental Dermatology Research
» Clinical & Experimental Ophthalmology
» Clinical & Experimental Pharmacology
» Clinical & Experimental Pathology
» Clinical Microbiology: Open Access
» Clinical Research & Bioethics
» Clinical Research on Foot & Ankle
» Clinical Toxicology
» Clinical Trials
»Clinics in Mother and Child Health
» Communication Disorders, Deaf Studies & Hearing Aids
» Cytology & Histology
» Forensic Research
»Forensic Biomechanics
» Integrative Oncology
»Immunome Research
»JBR Journal of Clinical Diagnosis and Research
» Neurology & Neurophysiology
» Pulmonary & Respiratory Medicine
» Stem Cell Research & Therapy
» Transplantation Technologies & Research
   
Pharmaceutical Sciences
» Advances in Pharmacoepidemiology & Drug Safety
» Alcoholism and Drug Dependence
» Bioanalysis & Biomedicine
» Biochemical Pharmacology
» Bioequivalence & Bioavailability
» Cardiovascular Pharmacology: Open Access
» Clinical Pharmacology & Biopharmaceutics
» Developing Drugs
» Drug Designing
» Drug Metabolism & Toxicology
» Medicinal & Aromatic Plants
» Molecular Pharmaceutics & Organic Process Research
» Pharmaceutica Analytica Acta
» Pharmaceutical Regulatory Affairs
» Pharmacovigilance
» Vaccines & Vaccination
   
Chemistry
» Advanced Chemical Engineering
» Analytical & Bioanalytical Techniques
» Chemical Sciences Journal
» Chromatography & Separation Techniques
» Medicinal Chemistry
» Modern Chemistry & Applications
» Natural Products Chemistry & Research
» Organic Chemistry
» Physical Chemistry & Biophysics
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» Thermodynamics & Catalysis
» Theoretical and Computational Chemistry:Open Access
   
Environmental
» Anthropology
» Aquaculture Research & Development
» Astrobiology & Outreach
» Biodiversity & Endangered Species
» Earth Science & Climatic Change
» Ecosystem & Ecography
» Environmental & Analytical Toxicology
» Fisheries & Livestock Production
»Fundamentals of Renewable Energy and Applications
» Geography & Natural Disasters
» Hydrology: Current Research
»Innovative Energy Policies
»International Journal of waste resources
» Oceanography-Open Access
» Petroleum & Environmental Biotechnology
» Pollution Effects & Control
» Poultry, Fisheries & Wildlife Sciences
   
Omics
» Data Mining in Genomics & Proteomics
»Ergonomics
» Glycomics & Lipidomics
» Health & Medical Informatics
»JBR Journal of Young Scientist
» Metabolomics:Open Access
» OMICS Journal of Radiology
» Pharmacogenomics & Pharmacoproteomics
» Phylogenetics & Evolutionary Biology
» Proteomics & Bioinformatics
» Transcriptomics
   
Life Sciences
» Advanced Techniques in Biology & Medicine
»Advancements in Genetic Engineering
»Advances in Crop Science and Technology
»Advances in Dairy Research
» Aging Science
» Agrotechnology
» Air & Water Borne Diseases
» Antivirals & Antiretrovirals
» Autism-Open Access
» Bacteriology & Parasitology
» Biochemistry & Physiology
» Biochemistry and Analytical Biochemistry
» Bioenergetics
» Bioengineering & Biomedical Science
» Biofertilizers & Biopesticides
» Biological Systems
» Biometrics & Biostatistics
»Biomimetics Biomaterials and Tissue Engineering
» Biomolecular Research & Therapeutics
» Bioremediation & Biodegradation
» Biosafety
» Biosafety & Health Education
» Biosensors & Bioelectronics
» Biosensors Journal
» Biotechnology & Biomaterials
» Bioterrorism & Biodefense
» Cell & Developmental Biology
» Current Synthetic & Systems Biology
» Entomology, Ornithology & Herpetology
» Enzyme Engineering
» Fermentation Technology
» Fertilization: In Vitro - IVF-Worldwide
» Fisheries and Aquaculture Journal
» Forest Research
» Fungal Genomics & Biology
» Gene Technology
» Glycobiology
» Horticulture
» Homeopathy & Ayurvedic Medicine
»International Journal of Swarm Intelligence and Evolutionary Computation
» Marine Science: Research & Development
» Membrane Science & Technology
» Microbial & Biochemical Technology
» Molecular Biology
» Molecular Imaging & Dynamics
» Nanomedicine & Biotherapeutic Discovery
» Nanomedicine & Nanotechnology
» Nutrition & Food Sciences
» Plant Pathology & Microbiology
» Primatology
» Probiotics & Health
» Rice Research: Open Access
» Single Cell Biology
» Sociology and Criminology-Open Access
» Tissue Science & Engineering
» Tropical Diseases
» Veterinary Science & Technology
» Vitamins & Minerals
»Virology & Mycology
   
Engineering
» Advances in Automobile Engineering
» Advances in Robotics & Automation
» Aeronautics & Aerospace Engineering
» Applied & Computational Mathematics
» Applied Mechanical Engineering
» Architectural Engineering Technology
» Astrophysics & Aerospace technology
» Biochips & Tissue Chips
» Bioprocessing & Biotechniques
» Chemical Engineering & Process Technology
» Civil & Environmental Engineering
» Computer Science & Systems Biology
» Electrical & Electronics
» Food Processing & Technology
» Geology and Geosciences
» Geophysics & Remote sensing
»Global Journal of Technology and Optimization
» Industrial Engineering & Management
» Information Technology & Software Engineering
» International Journal of Advance Innovations, Thoughts & Ideas
»International Journal of Sensor Networks and Data Communications
» Irrigation and Drainage Systems Engineering
»Generalized Lie Theory and Applications
» Lovotics
» Material Sciences & Engineering
»Physical Mathematics
» Powder Metallurgy & Mining
» Telecommunications System & Management
» Textile Science & Engineering
»Vortex Science and Technology
   
Medical Sciences
» Addiction Research & Therapy
» Allergy & Therapy
» Alternative & Integrative Medicine
» Alzheimers Disease & Parkinsonism
» Anaplastology
» Anatomy & Physiology
» Ancient Diseases & Preventive Remedies
» Andrology
» Arthritis
» Autacoids
»Automatic Control of Physiological State and Function
» Bioceramics Development and Applications
» Biology and Medicine
» Biomusical Engineering
» Blood & Lymph
» Blood Disorders & Transfusion
» Bone Marrow Research
» Brain Disorders & Therapy
» Cardiovascular Diseases & Diagnosis
» Cloning & Transgenesis
» Community Medicine & Health Education
» Dentistry
» Depression and Anxiety
» Diabetes & Metabolism
» Emergency Medicine
» Endocrinology & Metabolic Syndrome
» Epidemiology: Open Access
» Family Medicine & Medical Science Research
» Gastrointestinal & Digestive System
» General Medicine
» General Practice
» Genetic Syndromes & Gene Therapy
» Gynecology& Obstetrics
» Gerontology & Geriatrics Research
» Hematology & Thromboembolic Diseases
» Hair: Therapy & Transplantation
» Health Care : Current Reviews
» Hereditary Genetics
» Human Genetics & Embryology
» Hypertension-Open Access
» Infectious Diseases & Therapy
» International Journal of Genomic Medicine
» Internal Medicine
»International Journal of Biomedical Data Mining
» International Journal of Physical Medicine & Rehabilitation
»JBR Journal of Interdisciplinary Medicine and Dental Science
» Leukemia
» Liver
»Malaria Chemotherapy, Control & Elimination
» Medical & Surgical Urology
» Medical Diagnostic Methods
» Medical Microbiology & Diagnosis
» Metabolic Syndrome
» Molecular Biomarkers & Diagnosis
» Molecular and Genetic Medicine
» Mycobacterial Diseases
» Neonatal Biology
» Nephrology & Therapeutics
»Neuroinfectious Diseases
» Neurological Disorders
» Novel Physiotherapies
» Nuclear Medicine & Radiation Therapy
» Nursing & Care
» Nutritional Disorders & Therapy
» Obesity & Weight Loss Therapy
» Occupational Medicine & Health Affairs
» Oral Health and Dental Management
» Oral Hygiene & Health
» Orthopedic & Muscular System
» Osteoporosis & Physical Activity
» Otolaryngology
» Pain & Relief
» Palliative Care & Medicine
» Pancreatic Disorders & Therapy
» Pediatrics & Therapeutics
» Primary Health Care
» Psychological Abnormalities in Children
» Psychology & Psychotherapy
» Reproductive System & Sexual Disorders
»Research and Development
» Rheumatology: Current Research
» Sleep Disorders & Therapy
» Spine
» Sports Medicine & Doping Studies
» Steroids & Hormonal Science
» Surgery: Current Research
» Thyroid Disorders & Therapy
» Translational Medicine
» Trauma & Treatment
» Tropical Medicine and Surgery
» Vascular Medicine & surgery
» Women's Health Care
» Yoga & Physical Therapy
 
Management
» Accounting & Marketing
» Arabian Journal Business and Management Review
» Arts and Social Sciences Journal
» Business and Economics Journal
» Business and Financial Affairs
» Civil & Legal Sciences
» Defense Management
» Entrepreneurship & Organization Management
» Global Economics
» Hotel & Business Management
» Intellectual Property Rights: Open Access
»International Journal of Accounting Research
» International Journal of Economics & Management Sciences
» Mass Communication & Journalism
» political Sciences & public affairs
»Review of Public Adminstration and Management
» Socialomics
» Stock & Forex Trading
» Tourism & Hospitality
 
   Conferences
Upcoming Conferences
»3rd International Conference and Exhibition on Biosensors & Bioelectronics August 11-13, 2014 San Antonio, USA
»2nd World Associations Congress August 11-13, 2014 San Antonio, USA
»International Meeting on Space- Open Debate August 12-13, 2014 San Antonio, USA
»5th International Conference and Exhibition on Analytical & Bioanalytical Techniques August 18-20, 2014 Beijing, China
»2nd International Conference on Epidemiology and Evolutionary Genetics August 18-19, 2014 Beijing, China
»2nd International Conference and Exhibition on Pharmacognosy, Phytochemistry & Natural Products August 25-27, 2014 Beijing, China
»2nd International Conference and Exhibition on Traditional & Alternative Medicine August 25-26, 2014 Beijing, China
»2nd International Conference and Exhibition on Mechanical & Aerospace Engineering September 08-10, 2014 Philadelphia, USA
»2nd International Conference and Exhibition on Lasers, Optics & Photonics September 08-10, 2014 Philadelphia, USA
»3rd International Conference and Exhibition on Neurology & Therapeutics September 08-10, 2014 Philadelphia, USA
»4th International Conference on Pharmaceutical Regulatory Affairs September 08-10, 2014 Raleigh, USA
»2nd International Conference on Radiology and Imaging September 08-09, 2014 Raleigh, USA
»2nd International Conference on Genomics & PharmacogenomicsSeptember 08-09, 2014 Raleigh, USA
»2nd International Conference on Alzheimer's Disease and Dementia September 23-25, 2014 Valencia Convention Centre, Valencia, Spain
»3rd International Conference and Exhibition on Nutrition & Food Sciences September 23-25, 2014 Valencia, Spain
»3rd International Conference on Clinical Microbiology & Microbial Genomics September 24-26, 2014 Valencia, Spain
»3rd International Conference on Tissue Science & Regenerative Medicine September 24-26, 2014 Valencia, Spain
»4th International Conference on Vaccines & Vaccination September 24-26, 2014 Valencia, Spain
»3rd International Summit on GMP, GCP & Quality Control September 25-26, 2014 Valencia, Spain
»5th World Congress on Bioequivalence and Bioavailability: Pharmaceutical R&D Summit September 29-October 01, 2014 Baltimore, USA
»2nd International Conference on Hematology & Blood Disorders September 29-October 01, 2014 Baltimore, USA
»3rd International Conference and Exhibition on Clinical & Cellular Immunology September 29-October 01, 2014 Baltimore, USA
»3rd International Conference and Exhibition on Materials Science & Engineering October 06-08, 2014 San Antonio, USA
»3rd International Conference on Forensic Research and Technology October 06-08, 2014 San Antonio, USA
»4th World Congress on Virology October 06-08, 2014 San Antonio, USA
»2nd International Conference on Endocrinology October 20-22, 2014 Chicago, USA
»3rd 3rd International Summit on Toxicology & Applied Pharmacology October 20-22, 2014 Chicago, USA
»3rd 4th World Congress on Cancer Science and Therapy October 20-22, 2014 Chicago, USA
»3rd 3rd International Conference and Exhibition on Cell & Gene Therapy October 27-29, 2014 Las Vegas, USA
»2nd International Conference on HIV/AIDS, STDs & STIs October 27-29, 2014 Chicago, USA
»2nd World Congress on Petrochemistry and Chemical Engineering October 27-29, 2014 Las Vegas, USA
»3rd International Conference and Exhibition on Pharmacovigilance & Clinical Trials October 27-29, 2014 Hyderabad, India
»3rd International Conference and Exhibition on Biowaivers and Biosimilars October 27-29, 2014 Hyderabad, India
»3rd International Conference on Translational Medicine November 03-05, 2014 Las Vegas, USA
»2nd International Conference on Predictive, Preventive and Personalized Medicine & Molecular Diagnostics November 03-05, 2014 Las Vegas, USA
»5th International Conference on Diabetes & Metabolism November 03-05, 2014 Las Vegas, USA
»2nd International Congress on Bacteriology and Infectious Diseases November 17-19, 2014 Chicago, USA
»2nd International Conference on Nursing & Healthcare November 17-19, 2014 Chicago, USA
»3rd International Conference on Surgery and Anesthesia November 17-19, 2014 Chicago, USA
»4th International Conference on Nanotek & Expo December 01-03, 2014 San Francisco, USA
»3rd International Conference and Exhibition on Obesity & Weight Management December 01-03, 2014 San Francisco, USA
»2nd International Summit on Clinical PharmacyDecember 02-03, 2014 San Francisco, USA
»3rd International Conference on Medicinal Chemistry & Computer Aided Drug Designing December 08-10, 2014 San Francisco, USA
»3rd International Conference and Exhibition on Probiotics & Functional Foods December 08-10, 2014 San Francisco, USA
Previous Conferences Organized/Co-organized
»Health Informatics & Technology Conference July 28-29, 2014 Baltimore, USA
»3rd International Conference on Gastroenterology & Urology July 28-30, 2014 San Francisco, USA
»3rd International Conference on Earth Science & Climate Change July 28-30, 2014 San Francisco, USA
»3rd International Conference and Exhibition on Orthopedics & Rheumatology July 28-30, 2014 San Francisco, USA
»International Conference on Business Economics of Broadcasting Media & Film Industry July 28-30, 2014, Baltimore, USA
»4th International Conference on Proteomics & Bioinformatics August 04-06, 2014 Chicago, USA
»3rd International Conference and Exhibition on Addiction Research & Therapy August 04-06, 2014 Chicago, USA
»2nd International Conference on Integrative Biology Summit August 04-05, 2014 Chicago, USA
»3rd International Conference and Exhibition on Cosmetology & Trichology July 21-23, 2014 Las Vegas, USA
»3rd International Conference and Exhibition on Food Processing & Technology July 21-23, 2014 Las Vegas, USA
»2nd International Conference on Oceanography July 21-23 , 2014 Las Vegas USA
»4th International Conference on Clinical & Experimental Ophthalmology July 14-16, 2014 Baltimore, USA
»3rd International Conference & Exhibition on Biometrics & Biostatistics July 14-16, 2014 Baltimore, USA
»2nd International Conference and Exhibition on Physical Medicine & Rehabilitation July 14-16, 2014 Baltimore, USA
»International Conference on Geriatrics & Gerentology July 08-10, 2014 Chicago , USA
»International Conference on Women's Health, Gynecology & Obstetrics July 08-10, 2014 Chicago, USA
»International Conference on Computer Graphics and Media Design July 08-10, 2014 Chicago, USA
»4th International Conference on Clinical & Experimental Cardiology April 14-16, 2014 San Antonio, USA
»4th International Conference on Clinical & Experimental Dermatology April 14-16, 2014 San Antonio, USA
»3rd International Conference and Exhibition on Pathology April 14-16, 2014 San Antonio, USA
»5th International Conference on Biomarkers and Clinical Research April 15-17, 2014 University of Oxford, UK
»2nd International Conference on Business Economics and Management April 21-23, 2014 Dubai, UAE
»2nd International Conference on Dental and Oral Health April 21-23, 2014 Dubai, UAE
»4th World Congress on Cell Science & Stem Cell Research June 24-26, 2014 Valencia, Spain
»3rd International Conference on Biodiversity & Sustainable Energy Development June 24-26, 2014 Valencia, Spain
»3rd International Conference and Exhibition on Occupational Health & Safety June 24-25, 2014 Valencia, Spain
»5th World congress on Biotechnology June 25-27, 2014 Valencia, Spain
»3rd International Conference on Nephrology & Therapeutics June 26-27, 2014 Valencia, Spain
»2nd International Conference on Bioprocess and Engineering June 26-27, 2014 Valencia, Spain
»2nd International Conference on Dental and Oral Health April 21-23, 2014 Dubai, UAE
»5th International Conference on Biomarkers and Clinical Research April 15-17, 2014 University of Oxford, UK
»3rd International Conference and Exhibition on Pathology April 14-16, 2014 San Antonio, USA
»4th International Conference on Clinical & Experimental Dermatology April 14-16, 2014 San Antonio, USA
»4th International Conference on Clinical & Experimental Cardiology April 14-16, 2014 San Antonio, USA
»4th International Conference and Exhibition on Pharmaceutics & Novel Drug Delivery Systems March 24-26, 2014 San Antonio, USA
»3rd International Conference and Exhibition on Metabolomics & Systems Biology March 24-26, 2014 San Antonio, USA
»2nd International Conference on Agricultural & Horticultural Sciences, February 03-05, 2014 Hyderabad, India
»International Conference and Exhibition on Traditional & Alternative Medicine, December 09-11, 2013 Hyderabad, India
»2nd International Conference and Exhibition on Obesity & Weight Management, December 02-04, 2013 Las Vegas, USA
»International Conference on Nursing & Emergency Medicine, December 02-04, 2013 Las Vegas, USA
»3rd International Conference on Nanotek & Expo, December 02-04, 2013 Las Vegas, USA
»3rd World Congress on Virology, November, 20-22, 2013 Baltimore, USA
»International Congress on Bacteriology and Infectious diseases, November 20-22, 2013 Baltimore, USA
»3rd World Congress on Cell Science & Stem Cell Research, November 20-22, 2013 San Antonio, USA
»2nd International Conference and Exhibition on Pharmacovigilance & Clinical Trials, November 18-19, 2013 San Antonio, USA
»International Summit on Clinical Pharmacy & Dispensing, November 18-20, 2013 San Antonio, USA
»World Congress on Petrochemistry and Chemical Engineering, November 18-20, 2013 San Antonio, USA
»International Conference on Functional and Comparative Genomics & Pharmacogenomics, November 12-14, 2013 Chicago, USA
»2nd International Conference and Exhibition on Cosmetology & Trichology, November 12-14, 2013 Chicago, USA
»2nd International Summit on GMP, QA & QC, November 12-14, 2013 Chicago, USA
» International Conference on Fermentation Technology, Bioprocess and Cell Culture, October 28-30, 2013 Kansas City, USA
»2nd International Conference and Exhibition on Food Processing & Technology, October 28-30, 2013 Kansas City, USA
»International Conference on HIV/AIDS, STDs, & STIs, October 24-25, 2013 Orlando-FL, USA
»2nd International Conference and Exhibition on Cell & Gene Therapy, October 23-25, 2013 Orlando, USA
»2nd International Conference and Exhibition on Probiotics & Functional Foods, October 23-25, 2013 Orlando, USA
»International Conference and Exhibition on Pharmacognosy, Phytochemistry and Natural Products, October 21-23, 2013 Hyderabad, India
» 3rd World Congress on Cancer Science & Therapy, October 21-23, 2013 California, USA
»3rd International Conference on Pharmaceutical Regulatory Affairs, October 21-23, 2013 California, USA
»2nd International Conference on Clinical & Cellular Immunology, October 15-17, 2013 Las Vegas, USA
»2nd International Conference on Medicinal Chemistry & Computer Aided Drug Designing, October 15-17, 2013 Las Vegas, USA
»4th International Conference and Exhibition on Analytical & Bioanalytical Techniques, October 15-17, 2013 Las Vegas, USA
»2nd International Summit on Toxicology, October 07-09, 2013 Las Vegas, USA
»International Conference and Exhibition on Lasers, Optics & Photonics, October 7-9, 2013 San Antonio, USA
»2nd International Conference and Exhibition on Materials Science & Engineering, October 07-09, 2013 Las Vegas, USA
»International Conference and Exhibition on Biochemical & Molecular Engineering, October 07-08, 2013 San Antonio, USA
»International Conference on Psychology, Autism and Alzheimer's Disease, September 30-October 01, 2013 San Antonio, USA
»International Conference and Exhibition on Mechanical & Aerospace Engineering, September 30-October 02, 2013 San Antonio, USA
»2nd International Conference and Exhibition on Biowaivers & Biosimilars, September 23-25, 2013 Raleigh, USA
»4th World Congress on Biotechnology, September 23-25, 2013 Raliegh, USA
»International Conference on Hematology & Blood Disorders, September 23-25, 2013 Raliegh, USA
»2nd International Conference on Surgery and Anesthesia, September 16-18, 2013 Las Vegas, USA
»2nd International Conference on Clinical Microbiology & Microbial Genomics, September 16-18, 2013 Las Vegas, USA
» International Conference on Omics Studies, September 04-06, 2013 Orlando-FL, USA
»International Symposia on Entomology, September 04-06, 2013 Miami, USA
» World Congress on Endocrinology, August 26-28, 2013 Raleigh, USA
»2nd International Conference on Hydrology and Groundwater Expo, August 26-27, 2013 Raleigh, USA
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Review Article Open Access
Effect of Thiamine Repletion on Cardiac Fibrosis and Protein o-Glycosylation in Diabetic Cardiomyopathy
Laboratory of Pharmacotherapy, Osaka University of Pharmaceutical Sciences, Nasahara, Takatsuki, Osaka, Japan
*Corresponding author: Yuka Kohda
Laboratory of Pharmacotherapy
Osaka University of Pharmaceutical Sciences 4-20-1 Nasahara
Takatsuki, Osaka 569-1094, Japan
Tel: +81-72-690-1047
Fax: +81-72-690-1047
E-mail: ykohda@gly.oups.ac.jp
 
Received November 24, 2011; Accepted February 11, 2012; Published February 16, 2012
 
Citation: Kohda Y, Tanaka T, Matsumura H (2012) Effect of Thiamine Repletion on Cardiac Fibrosis and Protein o-Glycosylation in Diabetic Cardiomyopathy. J Diabetes Metab S7:001. doi:10.4172/2155-6156.S7-001
 
Copyright: 2012 Kohda Y, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
 
Abstract
 
Once diagnosed with diabetes mellitus, the risk of diseases, such as nephropathy, neuropathy, retinopathy and heart disease also increases. The complication of diabetes accompanying myocardial disorder is known as diabetic cardiomyopathy, which is characterized by ventricular dilation that is usually asymptomatic as diabetes progresses. Myocardial fibrosis is closely related to diastolic dysfunction. Thiamine (vitamin B1), an essential micronutrient, has been reported to attenuate diabetic complications and all diabetics may be lacking in thiamine. Thiamine is a coenzyme utilized at multiple steps of glucose metabolism. We believe that thiamine repletion under hyperglycemia might activate glucose oxidation and reduce the overflow of glucose to the hexosamine biosynthesis pathway of glucose metabolism with concomitant reduction of diabetic lesions. The aim of this article is to highlight the role of thiamine, an important factor that combats diabetic complications, especially diabetic cardiomyopathy and also elucidate its impact on O-glycosylated protein in diabetes. Finally, we discuss the ability of thiamine repletion to prevent metabolic syndrome and obesity, which are considered prediabetic states, as well as prediabetic cardiomyopathy.
 
Keywords
 
Cardiac fibrosis; Diabetic cardiomyopathy; Thiamine repletion; Protein O-glycosylation; Pyruvate dehydrogenase; Metabolic syndrome
 
Introduction
 
Diabetes mellitus, a well recognized risk factor for the development of heart failure, was initially linked to heart disease 30 years ago with the Framingham Heart Study [1-7]. Cardiac failure in diabetes is primarily due to ischemic heart disease caused by coronary artery disease. However, it is proposed that the incidence of heart failure in diabetes, except for atherosclerotic coronary lesions, is 4-5 times higher compared to nondiabetics. Rubler et al. propounded the concept that diabetic cardiac failure without coronary lesions is classified as diabetic cardiomyopathy and it is caused by systolic and diastolic dysfunction due to diabetes itself [8]. Conversely, patients with heart failure are also at a higher risk of developing diabetes [9]. It has been revealed that there is a significant overlap in the development of both diabetes and cardiac failure. Diabetes is characterized by increased metabolism of free fatty acids due to reduced glucose utilization. The mutation of thiamine (vitamin B1) transporter gene SLC19A2 is linked to type 2 diabetes mellitus [10-12]. We believe that thiamine has the ability to increase carbohydrate metabolism and the amount of catalytic thiamine absorbed must necessarily increase if glucose is to be metabolized in large quantities.
 
Thiamine Status in Clinical Diabetes
 
Thiamine is a coenzyme that is involved in multiple steps of glucose metabolism and interacts with transketolase (TK) and pyruvate dehydrogenase (PDH) during decarboxylation [13]. It has been reported that thiamine is deficient in the blood of diabetic patients [14]. Thornalley et al. discussed that low plasma thiamine concentration in diabetes may be of limited significance if tissues can upregulate the gene expression and protein levels of thiamine transporters and maintain normal TK activity [15]. The above phenomenon occurs in the normoglycemic state [16,17]. However, Babaei-Jadidi et al. suggested that their findings in experimental diabetic models indicate that the phenomenon does not occur in renal glomeruli in the diabetic state in which the enhanced hexosamine biosynthetic pathway may block increased expression of the genes that encode thiamine transporter-1, thiamine transporter-2 and reduced folate carrier-1 and their proteins [18]. Previous studies have suggested that TK activity and level of TK protein decreases in renal glomeruli in diabetes [18]. Similar impairment of thiamine uptake and metabolism may occur in the retina and peripheral nerve in diabetes [19,20]. Therefore, reduced folate carrier-1 is associated with impaired gene expression and decreased protein levels in the retina of diabetic patients [20].
 
Thiamine deficiency in diabetes is caused by the excretion of thiamine in urine with osmotic diuresis, but the metabolic consumption may be due to increased glucose metabolism in hyperglycemia [21,22]. Renal clearance of thiamine has been reported to increase in diabetic patients. A link between low plasma thiamine concentration and a profound increase in renal clearance and fractional excretion of thiamine has also been suggested [15]. Thornalley et al. suggested that mechanisms of increased renal clearance of thiamine in diabetes probably involve decreased reuptake of thiamine in renal proximal tubules [15,18,23]. Thiamine clearance was dysfunctional in diabetic patients who had normal glomerular filtration rates that were assessed by creatinine clearance. Renal mishandling of thiamine in diabetic patients has been suggested to be an early marker of renal dysfunction in diabetes and, linked to the locus of renal thiamine reuptake, is indicative of proximal tubule dysfunction [15].
 
Diabetic complications and thiamine repletion
 
The pathogenesis of diabetic complications is caused by continuing hyperglycemia that cannot be handled by the glucose oxidation pathway as the main pathway of glucose metabolism. Instead, glucose enters the minor pathways of glucose metabolism, such as the hexosamine biosynthetic, diacylglycerol, advanced glycation end product and sorbitol pathways [24]. It is thought that cell function disorder is caused by various metabolic products based on an increase in the activity of these minor pathways [25].
 
Macrovascular and microvascular are general terms that refer to damaged larger (macrovascular) or smaller (microvascular) blood vessels. This damage results from a build-up of fat, blood clots and oxidation in the endothelium. Macrovascular disease is the most common cause of death among individuals with type 1 or type 2 diabetes. Macrovascular diseases include coronary artery disease, cerebrovascular disease and peripheral vascular disease. Some complications of macrovascular diseases are ischemic heart disease, heart attack (myocardial infarction), intermittent claudication, lower extremity ulcer and stroke. Complications of microvascular diseases are diabetic nephropathy, diabetic neuropathy and diabetic retinopathy. An increased plasma level of soluble vascular adhesion molecule (sVCAM)-1 acts as a marker of endothelial dysfunction and increased risk of atherosclerosis [26,27]. In diabetic patients with normal renal function, sVCAM-1 level was increased and linked to microvascular and macrovascular complications [28-31]. Thornalley et al. suggested that a decreased availability of thiamine in vascular cells in diabetes exacerbates metabolic dysfunction in hyperglycemia [15]. It has also been suggested that low plasma thiamine concentration may be a confounding factor linked to increased sVCAM-1 in diabetes [15]. In addition, thiamine deficiency in clinical diabetes may increase the fragility of vascular cells to the adverse effects of hyperglycemia and thereby, increase the risk of developing microvascular complications. Microvascular diseases damage the small blood vessels and can occur in long-term diabetic patients. Thornalley et al. suggested that correction of the low plasma thiamine concentration with thiamine supplements may decrease the risk of microvascular complications in diabetes [15]. As reported in diabetic nephropathy and retinopathy, to prevent pathogenesis and development of diabetic complications, the physiological concentration of thiamine must be sufficient to produce the desirable pharmacological effects [18,25]. It has previously been reported that high-dose thiamine supplementation counters diabetic dyslipidemia [32]. It has also been demonstrated that highdose application of benfotiamine as a derivative of thiamine inhibits increases in the hexosamine biosynthetic, diacylglycerol and advanced glycation end product pathways under the hyperglycemic state; prevents the pathogenesis of diabetic nephropathy and retinopathy; and delays the development of complications [25]. In streptozotocininduced diabetes, protein kinase C activation related to increased renal fibrosis is inhibited by the administration of thiamine and α-lipoic acid as another coenzyme of PDH that attenuates renal fibrosis in streptozotocin diabetes [18,33,34].
 
Effect of thiamine on diabetic cardiomyopathy
 
Our laboratory data have clearly demonstrated the effect of thiamine repletion on cardiac fibrosis, which contributes to heart failure in streptozotocin-induced diabetic rats [35]. Diabetes was induced in rats by an intraperitoneal injection of streptozotocin, which is a chemical that is selectively toxic in the insulin-producing β-cells of mammals, to obtain an animal model of diabetes [36]. In these rats, the thiamine levels are low both in plasma as well as red blood cells and as expected, supplemental thiamine enhances these levels (Table 1). Blood glucose levels were remarkably higher in thiamine-deficient, streptozotocin-induced diabetic rats compared with normal controls. Thiamine repletion did not influence blood glucose levels in diabetic rats that were not deficient in thiamine.
 
Table1 :Blood plasma and red blood cells thiamine levels in each experimental group. Each value represents the mean ± S.E. of five experiments. * p<0.01, compared with the control. # p<0.01, compared with “Streptozotocin diabetes”. Modified from Kohda et al. [23].
 
The key findings are summarized as follows:
 
1. Streptozotocin-induced diabetes resulted in left ventricular fractional shortening, as shown by echocardiography and this deficiency reduced the cardiac contractile activity.
 
2. The brain natriuretic peptide mRNA expression level in the left ventricle, a cardiac hormone that serves as a biochemical marker during heart failure, increased in streptozotocininduced diabetes.
 
3. Cardiac fibrosis, which is a characteristic of diabetic cardiomyopathy, was histologically shown using Sirius red stain to have a higher affinity for collagen.
 
4. The mRNA expression levels of thrombospondin, fibronectin, plasminogen activator inhibitor-1 and connective tissue growth factor increased, all of which promote cardiac fibrosis.
 
5. The O-glycosylated protein was higher in the left ventricle in streptozotocin-induced diabetic rats.
 
Thiamine repletion improved all of the above, suggesting that thiamine has the ability to protect against diabetic cardiomyopathy [35]. In support of this hypothesis, Ceylan-Isik et al. demonstrated that benfotiamine rescues cardiomyocyte contractile dysfunction [37]. Furthermore, thiamine may significantly suppress not only the cardiac fibrosis but also the O-glycosylated protein in the left ventricle, suggesting that activation of the hexosamine biosynthetic pathway also may be related to the pathogenesis and development of diabetic cardiomyopathy [35] (Figure 1).
 
Figure1 : Hypothetical scheme to explain the prevention of diabetic cardiomyopathy by thiamine repletion [23,33,37]. HBP: Hexosamine Biosynthetic Pathway; PDH: Pyruvate Dehydrogenase.
 
Protein O-glycosylation contributes to diabetic cardiomyopathy
 
Uncontrolled elevated blood glucose levels in diabetes produce chronic tissue damage. These occur largely due to a process called glycosylation, which adds a glucose molecule to protein thus modifying it and interfering with its function [38-40]. Activation of a minor pathway of glucose metabolism has been proposed as potentially contributing to the development of diabetic complications, such as the activation of the diacylglycerol, polyol or hexosamine biosynthesis pathways [24,41]. Among these, the diacylglycerol and hexosamine biosynthesis pathways most likely influence gene expression via post-translational modifications, such as phosphorylation and O-glycosylation of various transcriptional factors [42-44]. We have suggested that cardiac fibrosis and the level of protein O-glycosylation are elevated in diabetes [35]. Furthermore, we examined if the hexosamine biosynthesis pathway was involved in collagen expression in rat cardiac fibroblasts. The glucosamine treatment of rat cardiac fibroblasts caused an increase in collagen expression and enhanced O-glycosylated proteins [45]. These results suggest that O-glycosylation of protein induced by activation of the hexosamine biosynthesis pathway modifies collagen expression and contributes to diabetic cardiomyopathy [45] (Figure 1).
 
Effect of thiamine on diabetes-induced inhibition of PDH; the connection between PDH activity and O-glycosylation of PDH E1α
 
The activity of PDH is reduced in diabetic patients, which interferes with glucose metabolism [46,47]. PDH activity is regulated by reversible phosphorylation. It is dependent upon PDH kinase, which phosphorylates the PDH E1α subunit, contributing to the suppression of PDH activity [48]. It has been suggested that phosphorylation by PDH kinase renders PDH inactive.
 
We investigated the exact mechanism of diabetes-induced PDH inhibition and effect of thiamine upon rat cardiac fibroblasts. Thiamine dramatically restored high glucose-induced PDH inhibition. Interestingly, high glucose loads did not alter the phosphorylated PDH E1α. PDH inhibition in rat cardiac fibroblasts was not accompanied by an increase in PDH E1α phosphorylation. O-glycosylated protein levels markedly increased in rat cardiac fibroblasts exposed to high glucose and was inhibited by thiamine. These results suggest that thiamine ameliorates diabetes-induced PDH inhibition by suppressing increased expression of the O-glycosylated protein. O-glycosylation of PDH E1α may be involved in the regulation of PDH activity [49] (Figure 1). Discovering the exact mechanisms that lead to a reduction in PDH activity may enable the prevention of diabetes and diabetic cardiomyopathy.
 
Future prospects of thiamine repletion in prevention against metabolic syndrome
 
Associated with excess weight, metabolic syndrome is a dangerous precursor to heart disease and type 2 diabetes. Unfortunately, obesity is occurring in endemic numbers in many countries [50]. While metabolic syndrome has its own individual characteristics, it is really a cluster of symptoms that are markers of much greater health problems to come. Once diagnosed with diabetes, many other health issues, such as nephropathy, neuropathy, macular degeneration and foot ulcers can manifest. The risk of stroke, heart disease, including heart attack, angina, atherosclerosis, arteriosclerosis and postoperative complications also increase. Metabolic syndrome inevitably leads to insulin resistance, which is a risky condition that promotes a whole cascade of other health issues apart from diabetes and heart conditions [51]. We chose Otsuka Long–Evans Tokushima Fatty (OLETF) rats, developed by Kawano et al., as models for studying human obesity [52,53]. Cholecystokinin is associated with satiety control mechanisms and polyphagia-induced OLETF rats lack functional cholecystokinin-A receptors [54,55]. OLETF rats exhibit progressive obesity and metabolic disorders similar to human metabolic syndrome [56]. Fourweek- old OLETF rats were randomly divided into two groups; an untreated control group and a thiamine-treated group. OLETF rats were given water or water containing 0.2% thiamine. All rats were housed in cages and provided with standard rodent chow. Body weight and food intake were measured weekly throughout the experimental period. Thiamine repletion, which plays an important role in glucose metabolism, can prevent diabetic cardiomyopathy and nephropathy, including that which occurs in obesity. We found that thiamine intervention can impact metabolic abnormalities, such as progressive obesity and metabolic disorders similar to human metabolic syndrome in polyphagia-induced OLETF rats [57]. Thiamine intervention averted obesity, mainly resulting from a reduction in visceral adiposity and prevented metabolic disorders in OLETF rats. Thiamine has the potential to prevent obesity and metabolic disorders in OLETF rats. Although corroboration is necessary, the present findings indicate that thiamine may be beneficial in targeting composite physiological abnormalities rather than individual component criteria and can be used for preventive intervention. Epidemiological data have shown that few patients develop diabetes or coronary heart disease when they consume thiamine-containing brown rice or wheat germ, as opposed to white rice [58-62]. Absorption of thiamine from food might be important in preventing metabolic syndrome. However, if thiamine intake is insufficient, it can be increased by consuming dietary supplements or medicines. Thiamine is a soluble vitamin and seems to have no potential side effects even if consumed in excess due to urinary excretion of the quantities not used by the body.
 
Closing Notes
 
Diabetes may well be the paradigm for all chronic disease. It is a syndrome that affects every organ system in the body. Metabolic syndrome should be considered as a prediabetic or a pre-cardiovascular disease state. In metabolic syndrome, there is a cluster of imbalances which work simultaneously and when this occurs, degenerative disease can accelerate at an alarming rate. Metabolic syndrome is largely a disease of modern times which can be blamed on overconsumption of carbohydrate-rich foods and excess weight. Although it is a disorder that can be easily identified and eradicated with a few dietary and lifestyle changes, many people find it difficult to make these changes. Therefore, it is critical to develop a new preventive strategy against metabolic syndrome. Obesity frequently leads to type 2 diabetes mellitus that can progress to diabetic complications. Fortunately, recent years have seen a renaissance in the development of methods to treat diabetes effectively. Current pharmaceutical interventions are moderately effective in treating clinical symptoms of metabolic syndrome; nevertheless, a basic pharmaceutical method for preventing obesity and its related metabolic disorders remains to be established. Moreover, elucidation of the mechanisms concerning obesity and diabetes mellitus contributes to the prevention of metabolic syndrome and the appearance of effective new medications available to treat diabetic cardiomyopathy.
 
Acknowledgements
 
This article was supported by a “High Technology Research Center” Project for Private Universities: matching fund subsidy from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
 
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