leptin and Reperfusion-Injury

The present study aimed to assess the prevalence of symptoms of anxiety and depression among health professionals in the three most affected regions in Cameroon.. The study was a descriptive cross-sectional type. Participants were health care professionals working in the three chosen regions of Cameroon. The non_probability convinient sample technique and that of the snowball were valued via a web questionnaire. The non-exhaustive sample size was 292. The diagnosis of anxiety and depression was made by the HAD (Hospital Anxiety and Depression scale).. Les auteurs rapportent que le secteur médical est classé à un plus grand risque de contracter le COVID-19 et de le propager potentiellement à d’autres. Le nombre sans cesse croissant de cas confirmés et suspects, la pression dans les soins, l’épuisement des équipements de protection individuelle et le manque de médicaments spécifiques peuvent contribuer à un vécu anxio-dépressif significatif. La présente étude s’est donnée pour ambition d’évaluer la prévalence des symptômes de l’anxiété et de la dépression chez les professionnels de santé dans les trois Régions les plus concernées au Cameroun.. Le choix des trois Régions du Cameroun se justifie non seulement par le fait qu’elles totalisent 95,8 % des cas de coronavirus au pays depuis le début de la pandémie, mais aussi parce qu’elles disposent de plus de la moitié des personnels de santé (56 %). Il s’agit d’une étude transversale, descriptive et analytique. Les participants sont des professionnels de la santé en service dans les Régions du Centre, Littoral et de l’Ouest du Cameroun. La méthode d’échantillonnage non probabiliste de convenance couplée à celle de boule de neige via un web questionnaire a été adoptée. La collecte des données a duré du 5 au 19 avril 2020, intervalle de temps après lequel on n’avait plus eu de répondants. À la fin de cette période, la taille de l’échantillon non exhaustive était de 292 professionnels. Le diagnostic de l’état anxio-dépressive était posé via l’échelle de HAD (Hospital Anxiety and Depression scale). Dans le HAD, chaque réponse cotée évalue de manière semi-quantitative l’intensité du symptôme au cours de la semaine écoulée. Un score total est obtenu ainsi que des scores aux deux sous-échelles : le score maximal est de 42 pour l’échelle globale et de 21 pour chacune des sous-échelles. Le coefficient alpha de Cronbach est de 0,70 pour la dépression et de 0,74 pour l’anxiété. Certains auteurs après plusieurs travaux ont proposé qu’une note inférieure ou égale à 7 indique une absence d’anxiété ou de dépression ; celle comprise entre 8 et 10 suggère une anxiété ou une dépression faible à bénigne ; entre 11 et 14, pour une anxiété ou une dépression modérée ; enfin, une note comprise entre 15 et 21 est révélatrice d’une anxiété sévère. Le logiciel Excel 2013 et Epi Info version 7.2.2.6 ont été utilisés pour les traitements statistiques. Les liens entre les variables ont été considérées significatifs pour une valeur de. L’amélioration des conditions de travail et notamment la fourniture d’équipement de protection, la mise en place des cellules spéciales d’écoute pour le personnel de santé pourraient être proposées.. Taken together with satisfactory selectivity index (SI) values, the acetone and methanol extracts of. During a mean follow-up period of 25.6 ± 13.9 months, 38 (18.4%) VAs and 78 (37.7%) end-stage events occurred. Big ET-1 was positively correlated with NYHA class (. In primary prevention ICD indication patients, plasma big ET-1 levels can predict VAs and end-stage events and may facilitate ICD-implantation risk stratification.. Beyond age, cognitive impairment was associated with prior MI/stroke, higher hsCRP, statin use, less education, lower eGFR, BMI and LVEF.. These data demonstrate that even a short period of detraining is harmful for elderly women who regularly participate in a program of strength training, since it impairs physical performance, insulin sensitivity and cholesterol metabolism.. Exposure to PM. Respiratory sinus arrhythmia is reduced after PVI in patients with paroxysmal AF. Our findings suggest that this is related to a decrease in cardiac vagal tone. Whether and how this affects the clinical outcome including exercise capacity need to be determined.. BDNF and leptin were not associated with weight. We found that miR-214-5p exerted a protective role in I/R injured cardiac cells by direct targeting FASLG. The results indicated that the MGO injection reduced all CCl. The hepatoprotective effects of MGO might be due to histopathological suppression and inflammation inhibition in the liver.. OVEO showed moderate antifungal activity, whereas its main components carvacrol and thymol have great application potential as natural fungicides or lead compounds for commercial fungicides in preventing and controlling plant diseases caused by. PF trajectories were mainly related to income, pregestational BMI, birth weight, hospitalisation due to respiratory diseases in childhood, participant's BMI, report of wheezing, medical diagnosis and family history of asthma, gestational exposure to tobacco and current smoking status in adolescence and young adult age.. In chronic pain patients on opioids, administration of certain benzodiazepine sedatives induced a mild respiratory depression but paradoxically reduced sleep apnoea risk and severity by increasing the respiratory arousal threshold.. Quantitative measurements of sensory disturbances using the PainVision. The serum level of 20S-proteasome may be a useful marker for disease activity in AAV.. The electrophysiological data and MD simulations collectively suggest a crucial role of the interactions between the HA helix and S4-S5 linker in the apparent Ca. Invited for the cover of this issue are Vanesa Fernández-Moreira, Nils Metzler-Nolte, M. Concepción Gimeno and co-workers at Universidad de Zaragoza and Ruhr-Universität Bochum. The image depicts the reported bimetallic bioconjugates as planes directing the gold fragment towards the target (lysosomes). Read the full text of the article at 10.1002/chem.202002067.. The optimal CRT pacing configuration changes during dobutamine infusion while LV and RV activation timing does not. Further studies investigating the usefulness of automated dynamic changes to CRT pacing configuration according to physiologic condition may be warranted.

Topics: 3' Untranslated Regions; 5'-Nucleotidase; A549 Cells; Accidental Falls; Acetylcholinesterase; Acrylic Resins; Actinobacillus; Acute Disease; Acute Kidney Injury; Adaptor Proteins, Signal Transducing; Adenosine; Adenosine Triphosphate; Administration, Inhalation; Administration, Oral; Adolescent; Adult; Advance Care Planning; Africa, Northern; Age Factors; Aged; Aged, 80 and over; Air Pollutants; Air Pollution; Air Pollution, Indoor; Albendazole; Aluminum Oxide; Anastomosis, Surgical; Ancylostoma; Ancylostomiasis; Androstadienes; Angiogenesis Inhibitors; Angiotensin II; Animals; Anti-Bacterial Agents; Anti-Infective Agents; Antibodies, Bispecific; Antibodies, Viral; Anticoagulants; Antihypertensive Agents; Antinematodal Agents; Antineoplastic Agents; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Antioxidants; Antiporters; Antiviral Agents; Apoptosis; Aptamers, Nucleotide; Aromatase Inhibitors; Asian People; Astrocytes; Atrial Fibrillation; Auditory Threshold; Aurora Kinase B; Australia; Autophagy; Autophagy-Related Protein 5; Autotrophic Processes; Bacillus cereus; Bacillus thuringiensis; Bacterial Proteins; Beclin-1; Belgium; Benzene; Benzene Derivatives; Benzhydryl Compounds; beta Catenin; beta-Arrestin 2; Biliary Tract Diseases; Biofilms; Biofuels; Biomarkers; Biomarkers, Tumor; Biomass; Biomechanical Phenomena; Bioreactors; Biosensing Techniques; Biosynthetic Pathways; Bismuth; Blood Platelets; Bone and Bones; Bone Regeneration; Bortezomib; Botulinum Toxins, Type A; Brain; Brain Injuries; Brain Ischemia; Brain Neoplasms; Breast Neoplasms; Breath Tests; Bronchodilator Agents; Calcium Phosphates; Cannabis; Carbon Dioxide; Carbon Isotopes; Carcinogenesis; Carcinoma, Hepatocellular; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Cardiac Resynchronization Therapy; Cardiac Resynchronization Therapy Devices; Cardiomyopathies; Cardiovascular Diseases; Cariostatic Agents; Case Managers; Case-Control Studies; Catalysis; Cation Transport Proteins; CD8-Positive T-Lymphocytes; Cecropia Plant; Cell Adhesion; Cell Count; Cell Differentiation; Cell Division; Cell Line; Cell Line, Tumor; Cell Membrane; Cell Movement; Cell Proliferation; Cell Self Renewal; Cell Survival; Cells, Cultured; Cellular Reprogramming; Cellulose; Charcoal; Chemical and Drug Induced Liver Injury; Chemical Phenomena; Chemokines; Chemoradiotherapy; Chemoreceptor Cells; Child; Child Abuse; Child, Preschool; China; Chlorogenic Acid; Chloroquine; Chromatography, Gas; Chronic Disease; Clinical Competence; Coated Materials, Biocompatible; Cochlea; Cohort Studies; Color; Comorbidity; Computer Simulation; Computer-Aided Design; Contraception; Contraceptive Agents, Female; Contrast Media; COP-Coated Vesicles; Coronavirus Infections; Cost of Illness; Coturnix; COVID-19; Creatinine; Cross-Over Studies; Cross-Sectional Studies; Culex; Curriculum; Cyclic N-Oxides; Cytokines; Cytoplasm; Cytotoxicity, Immunologic; Cytotoxins; Databases, Factual; Deep Learning; Delivery, Obstetric; Denitrification; Dental Caries; Denture, Complete; Dexamethasone; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Dielectric Spectroscopy; Diet, High-Fat; Dietary Fiber; Disease Models, Animal; Disease Progression; DNA; DNA Copy Number Variations; DNA, Mitochondrial; Dog Diseases; Dogs; Dopaminergic Neurons; Double-Blind Method; Down-Regulation; Doxorubicin; Drug Carriers; Drug Design; Drug Interactions; Drug Resistance, Bacterial; Drug Resistance, Neoplasm; Drug-Related Side Effects and Adverse Reactions; Drugs, Chinese Herbal; Dry Powder Inhalers; Dust; E2F1 Transcription Factor; Ecosystem; Education, Nursing; Education, Nursing, Baccalaureate; Electric Impedance; Electricity; Electrocardiography; Electrochemical Techniques; Electrochemistry; Electrodes; Electrophoresis, Polyacrylamide Gel; Endoplasmic Reticulum; Endothelial Cells; Environmental Monitoring; Enzyme Inhibitors; Epithelial Cells; Epithelial-Mesenchymal Transition; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Estrogen Receptor Modulators; Europe; Evoked Potentials, Auditory, Brain Stem; Exosomes; Feasibility Studies; Female; Ferricyanides; Ferrocyanides; Fibrinogen; Finite Element Analysis; Fistula; Fluorescent Dyes; Fluorides, Topical; Fluorodeoxyglucose F18; Fluticasone; Follow-Up Studies; Food Contamination; Food Microbiology; Foods, Specialized; Forensic Medicine; Frail Elderly; France; Free Radicals; Fresh Water; Fungi; Fungicides, Industrial; Galactosamine; Gastrointestinal Neoplasms; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Frequency; Genetic Predisposition to Disease; Genotype; Gingival Hemorrhage; Glioblastoma; Glioma; Glomerular Filtration Rate; Glomerulosclerosis, Focal Segmental; Glucose; Glucose Transport Proteins, Facilitative; Glucosides; Glutamine; Glycolysis; Gold; GPI-Linked Proteins; Gram-Negative Bacteria; Gram-Positive Bacteria; Graphite; Haplotypes; HCT116 Cells; Healthy Volunteers; Hearing Loss; Heart Failure; Hedgehog Proteins; HEK293 Cells; HeLa Cells; Hemodynamics; Hemorrhage; Hepatocytes; Hippo Signaling Pathway; Histone Deacetylases; Homeostasis; Hospital Mortality; Hospitalization; Humans; Hydantoins; Hydrazines; Hydrogen Peroxide; Hydrogen-Ion Concentration; Hydrophobic and Hydrophilic Interactions; Hydroxylamines; Hypoglycemic Agents; Immunity, Innate; Immunoglobulin G; Immunohistochemistry; Immunologic Factors; Immunomodulation; Immunophenotyping; Immunotherapy; Incidence; Indazoles; Indonesia; Infant; Infant, Newborn; Infarction, Middle Cerebral Artery; Inflammation; Injections, Intramuscular; Insecticides; Insulin-Like Growth Factor I; Insurance, Health; Intention to Treat Analysis; Interleukin-1 Receptor-Associated Kinases; Interleukin-6; Intrauterine Devices; Intrauterine Devices, Copper; Iron; Ischemia; Jordan; Keratinocytes; Kidney; Kidney Diseases; Kir5.1 Channel; Klebsiella Infections; Klebsiella pneumoniae; Lab-On-A-Chip Devices; Laparoscopy; Lasers; Lasers, Semiconductor; Lenalidomide; Leptin; Lethal Dose 50; Levonorgestrel; Limit of Detection; Lipid Metabolism; Lipid Metabolism Disorders; Lipogenesis; Lipopolysaccharides; Liquid Biopsy; Liver; Liver Abscess, Pyogenic; Liver Cirrhosis; Liver Diseases; Liver Neoplasms; Longevity; Lung Neoplasms; Luteolin; Lymph Nodes; Lymphocyte Activation; Macaca fascicularis; Macrophages; Mad2 Proteins; Magnetic Resonance Imaging; Male; Mammary Glands, Human; Manganese; Manganese Compounds; MAP Kinase Signaling System; Materials Testing; Maternal Health Services; MCF-7 Cells; Medicaid; Medicine, Chinese Traditional; Melanoma; Membrane Proteins; Mental Health; Mercury; Metal Nanoparticles; Metals, Heavy; Metformin; Methionine Adenosyltransferase; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Inbred CBA; Mice, Knockout; Mice, Nude; Microalgae; Microbial Sensitivity Tests; Microglia; MicroRNAs; Microscopy, Atomic Force; Microscopy, Electron, Scanning; Middle Aged; Mitochondria; Mitochondrial Proteins; Mitral Valve; Mitral Valve Insufficiency; Models, Anatomic; Molecular Structure; Molybdenum; Monocarboxylic Acid Transporters; Moths; MPTP Poisoning; Multigene Family; Multiparametric Magnetic Resonance Imaging; Multiple Myeloma; Muscle, Skeletal; Mutagens; Mutation; Myeloid Cells; Nanocomposites; Nanofibers; Nanomedicine; Nanoparticles; Nanowires; Neoadjuvant Therapy; Neomycin; Neoplasm Grading; Neoplasm Recurrence, Local; Neoplasms; Neoplastic Stem Cells; Neostriatum; Neovascularization, Pathologic; Netherlands; Neuromuscular Agents; Neurons; NF-E2-Related Factor 2; NF-kappa B; Nickel; Nitrogen Oxides; Non-alcoholic Fatty Liver Disease; Nucleosides; Nucleotidyltransferases; Nutritional Status; Obesity, Morbid; Ofloxacin; Oils, Volatile; Oligopeptides; Oncogene Protein v-akt; Optical Imaging; Organic Cation Transport Proteins; Organophosphonates; Osteoarthritis; Osteoarthritis, Hip; Osteoarthritis, Knee; Osteoblasts; Osteogenesis; Oxidation-Reduction; Oxidative Stress; Oxides; Oxygen Isotopes; Pancreas; Pancreaticoduodenectomy; Pandemics; Particle Size; Particulate Matter; Patient Acceptance of Health Care; Patient Compliance; PC-3 Cells; Peptide Fragments; Peptides; Periodontal Attachment Loss; Periodontal Index; Periodontal Pocket; Periodontitis; Peroxides; Peru; Pest Control, Biological; Phosphatidylinositol 3-Kinase; Phosphatidylinositol 3-Kinases; Phylogeny; Pilot Projects; Piperidines; Plant Bark; Plant Extracts; Plant Leaves; Plasmids; Platelet Function Tests; Pneumonia, Viral; Podocytes; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerase Inhibitors; Polyethylene Terephthalates; Polymers; Polymorphism, Single Nucleotide; Porosity; Portugal; Positron-Emission Tomography; Postoperative Complications; Postural Balance; Potassium Channels, Inwardly Rectifying; Povidone; Powders; Precancerous Conditions; Precision Medicine; Predictive Value of Tests; Pregnancy; Prenatal Care; Prognosis; Promoter Regions, Genetic; Prospective Studies; Prostatectomy; Prostatic Neoplasms; Proteasome Inhibitors; Protective Agents; Protein Binding; Protein Kinase Inhibitors; Protein Serine-Threonine Kinases; Protein Transport; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins c-akt; Psychiatric Nursing; PTEN Phosphohydrolase; Pulmonary Embolism; Pyrimethamine; Radiopharmaceuticals; Rats; Rats, Sprague-Dawley; Rats, Wistar; Reactive Oxygen Species; Receptor, ErbB-2; Receptor, IGF Type 1; Receptors, Estrogen; Receptors, G-Protein-Coupled; Recombinational DNA Repair; Recovery of Function; Regional Blood Flow; Renal Dialysis; Renin; Renin-Angiotensin System; Reperfusion Injury; Reproducibility of Results; Republic of Korea; Respiratory Distress Syndrome; Retrospective Studies; Rhodamines; Risk Assessment; Risk Factors; RNA, Long Noncoding; RNA, Messenger; Running; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Salinity; Salmeterol Xinafoate; Sarcoma; Seasons; Shoulder Injuries; Signal Transduction; Silicon Dioxide; Silver; Sirtuin 1; Sirtuins; Skull Fractures; Social Determinants of Health; Sodium; Sodium Fluoride; Sodium Potassium Chloride Symporter Inhibitors; Sodium-Glucose Transporter 2 Inhibitors; Soil; Soil Pollutants; Spain; Spectrophotometry; Spectroscopy, Fourier Transform Infrared; Staphylococcal Protein A; Staphylococcus aureus; Stem Cells; Stereoisomerism; Stomach Neoplasms; Streptomyces; Strontium; Structure-Activity Relationship; Students, Nursing; Substance-Related Disorders; Succinic Acid; Sulfur; Surface Properties; Survival Rate; Survivin; Symporters; T-Lymphocytes; Temozolomide; Tensile Strength; Thiazoles; Thiobacillus; Thiohydantoins; Thiourea; Thrombectomy; Time Factors; Titanium; Tobacco Mosaic Virus; Tobacco Use Disorder; Toll-Like Receptor 4; Toluene; Tomography, X-Ray Computed; TOR Serine-Threonine Kinases; Toxicity Tests, Acute; Toxicity Tests, Subacute; Transcriptional Activation; Treatment Outcome; Troponin I; Tumor Cells, Cultured; Tumor Escape; Tumor Hypoxia; Tumor Microenvironment; Tumor Necrosis Factor Inhibitors; Tumor Necrosis Factor-alpha; Tyrosine; Ubiquitin-Protein Ligases; Ubiquitination; Ultrasonic Waves; United Kingdom; United States; United States Department of Veterans Affairs; Up-Regulation; Urea; Uric Acid; Urinary Bladder Neoplasms; Urinary Bladder, Neurogenic; Urine; Urodynamics; User-Computer Interface; Vemurafenib; Verbenaceae; Veterans; Veterans Health; Viral Load; Virtual Reality; Vitiligo; Water Pollutants, Chemical; Wildfires; Wnt Signaling Pathway; Wound Healing; X-Ray Diffraction; Xenograft Model Antitumor Assays; Xylenes; Young Adult; Zinc; Zinc Oxide; Zinc Sulfate; Zoonoses

The present study aimed to assess the prevalence of symptoms of anxiety and depression among health professionals in the three most affected regions in Cameroon.. The study was a descriptive cross-sectional type. Participants were health care professionals working in the three chosen regions of Cameroon. The non_probability convinient sample technique and that of the snowball were valued via a web questionnaire. The non-exhaustive sample size was 292. The diagnosis of anxiety and depression was made by the HAD (Hospital Anxiety and Depression scale).. Les auteurs rapportent que le secteur médical est classé à un plus grand risque de contracter le COVID-19 et de le propager potentiellement à d’autres. Le nombre sans cesse croissant de cas confirmés et suspects, la pression dans les soins, l’épuisement des équipements de protection individuelle et le manque de médicaments spécifiques peuvent contribuer à un vécu anxio-dépressif significatif. La présente étude s’est donnée pour ambition d’évaluer la prévalence des symptômes de l’anxiété et de la dépression chez les professionnels de santé dans les trois Régions les plus concernées au Cameroun.. Le choix des trois Régions du Cameroun se justifie non seulement par le fait qu’elles totalisent 95,8 % des cas de coronavirus au pays depuis le début de la pandémie, mais aussi parce qu’elles disposent de plus de la moitié des personnels de santé (56 %). Il s’agit d’une étude transversale, descriptive et analytique. Les participants sont des professionnels de la santé en service dans les Régions du Centre, Littoral et de l’Ouest du Cameroun. La méthode d’échantillonnage non probabiliste de convenance couplée à celle de boule de neige via un web questionnaire a été adoptée. La collecte des données a duré du 5 au 19 avril 2020, intervalle de temps après lequel on n’avait plus eu de répondants. À la fin de cette période, la taille de l’échantillon non exhaustive était de 292 professionnels. Le diagnostic de l’état anxio-dépressive était posé via l’échelle de HAD (Hospital Anxiety and Depression scale). Dans le HAD, chaque réponse cotée évalue de manière semi-quantitative l’intensité du symptôme au cours de la semaine écoulée. Un score total est obtenu ainsi que des scores aux deux sous-échelles : le score maximal est de 42 pour l’échelle globale et de 21 pour chacune des sous-échelles. Le coefficient alpha de Cronbach est de 0,70 pour la dépression et de 0,74 pour l’anxiété. Certains auteurs après plusieurs travaux ont proposé qu’une note inférieure ou égale à 7 indique une absence d’anxiété ou de dépression ; celle comprise entre 8 et 10 suggère une anxiété ou une dépression faible à bénigne ; entre 11 et 14, pour une anxiété ou une dépression modérée ; enfin, une note comprise entre 15 et 21 est révélatrice d’une anxiété sévère. Le logiciel Excel 2013 et Epi Info version 7.2.2.6 ont été utilisés pour les traitements statistiques. Les liens entre les variables ont été considérées significatifs pour une valeur de. L’amélioration des conditions de travail et notamment la fourniture d’équipement de protection, la mise en place des cellules spéciales d’écoute pour le personnel de santé pourraient être proposées.. Taken together with satisfactory selectivity index (SI) values, the acetone and methanol extracts of. During a mean follow-up period of 25.6 ± 13.9 months, 38 (18.4%) VAs and 78 (37.7%) end-stage events occurred. Big ET-1 was positively correlated with NYHA class (. In primary prevention ICD indication patients, plasma big ET-1 levels can predict VAs and end-stage events and may facilitate ICD-implantation risk stratification.. Beyond age, cognitive impairment was associated with prior MI/stroke, higher hsCRP, statin use, less education, lower eGFR, BMI and LVEF.. These data demonstrate that even a short period of detraining is harmful for elderly women who regularly participate in a program of strength training, since it impairs physical performance, insulin sensitivity and cholesterol metabolism.. Exposure to PM. Respiratory sinus arrhythmia is reduced after PVI in patients with paroxysmal AF. Our findings suggest that this is related to a decrease in cardiac vagal tone. Whether and how this affects the clinical outcome including exercise capacity need to be determined.. BDNF and leptin were not associated with weight. We found that miR-214-5p exerted a protective role in I/R injured cardiac cells by direct targeting FASLG. The results indicated that the MGO injection reduced all CCl. The hepatoprotective effects of MGO might be due to histopathological suppression and inflammation inhibition in the liver.. OVEO showed moderate antifungal activity, whereas its main components carvacrol and thymol have great application potential as natural fungicides or lead compounds for commercial fungicides in preventing and controlling plant diseases caused by. PF trajectories were mainly related to income, pregestational BMI, birth weight, hospitalisation due to respiratory diseases in childhood, participant's BMI, report of wheezing, medical diagnosis and family history of asthma, gestational exposure to tobacco and current smoking status in adolescence and young adult age.. In chronic pain patients on opioids, administration of certain benzodiazepine sedatives induced a mild respiratory depression but paradoxically reduced sleep apnoea risk and severity by increasing the respiratory arousal threshold.. Quantitative measurements of sensory disturbances using the PainVision. The serum level of 20S-proteasome may be a useful marker for disease activity in AAV.. The electrophysiological data and MD simulations collectively suggest a crucial role of the interactions between the HA helix and S4-S5 linker in the apparent Ca. Invited for the cover of this issue are Vanesa Fernández-Moreira, Nils Metzler-Nolte, M. Concepción Gimeno and co-workers at Universidad de Zaragoza and Ruhr-Universität Bochum. The image depicts the reported bimetallic bioconjugates as planes directing the gold fragment towards the target (lysosomes). Read the full text of the article at 10.1002/chem.202002067.. The optimal CRT pacing configuration changes during dobutamine infusion while LV and RV activation timing does not. Further studies investigating the usefulness of automated dynamic changes to CRT pacing configuration according to physiologic condition may be warranted.

Topics: 3' Untranslated Regions; 5'-Nucleotidase; A549 Cells; Accidental Falls; Acetylcholinesterase; Acrylic Resins; Actinobacillus; Acute Disease; Acute Kidney Injury; Adaptor Proteins, Signal Transducing; Adenosine; Adenosine Triphosphate; Administration, Inhalation; Administration, Oral; Adolescent; Adult; Advance Care Planning; Africa, Northern; Age Factors; Aged; Aged, 80 and over; Air Pollutants; Air Pollution; Air Pollution, Indoor; Albendazole; Aluminum Oxide; Anastomosis, Surgical; Ancylostoma; Ancylostomiasis; Androstadienes; Angiogenesis Inhibitors; Angiotensin II; Animals; Anti-Bacterial Agents; Anti-Infective Agents; Antibodies, Bispecific; Antibodies, Viral; Anticoagulants; Antihypertensive Agents; Antinematodal Agents; Antineoplastic Agents; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Antioxidants; Antiporters; Antiviral Agents; Apoptosis; Aptamers, Nucleotide; Aromatase Inhibitors; Asian People; Astrocytes; Atrial Fibrillation; Auditory Threshold; Aurora Kinase B; Australia; Autophagy; Autophagy-Related Protein 5; Autotrophic Processes; Bacillus cereus; Bacillus thuringiensis; Bacterial Proteins; Beclin-1; Belgium; Benzene; Benzene Derivatives; Benzhydryl Compounds; beta Catenin; beta-Arrestin 2; Biliary Tract Diseases; Biofilms; Biofuels; Biomarkers; Biomarkers, Tumor; Biomass; Biomechanical Phenomena; Bioreactors; Biosensing Techniques; Biosynthetic Pathways; Bismuth; Blood Platelets; Bone and Bones; Bone Regeneration; Bortezomib; Botulinum Toxins, Type A; Brain; Brain Injuries; Brain Ischemia; Brain Neoplasms; Breast Neoplasms; Breath Tests; Bronchodilator Agents; Calcium Phosphates; Cannabis; Carbon Dioxide; Carbon Isotopes; Carcinogenesis; Carcinoma, Hepatocellular; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Cardiac Resynchronization Therapy; Cardiac Resynchronization Therapy Devices; Cardiomyopathies; Cardiovascular Diseases; Cariostatic Agents; Case Managers; Case-Control Studies; Catalysis; Cation Transport Proteins; CD8-Positive T-Lymphocytes; Cecropia Plant; Cell Adhesion; Cell Count; Cell Differentiation; Cell Division; Cell Line; Cell Line, Tumor; Cell Membrane; Cell Movement; Cell Proliferation; Cell Self Renewal; Cell Survival; Cells, Cultured; Cellular Reprogramming; Cellulose; Charcoal; Chemical and Drug Induced Liver Injury; Chemical Phenomena; Chemokines; Chemoradiotherapy; Chemoreceptor Cells; Child; Child Abuse; Child, Preschool; China; Chlorogenic Acid; Chloroquine; Chromatography, Gas; Chronic Disease; Clinical Competence; Coated Materials, Biocompatible; Cochlea; Cohort Studies; Color; Comorbidity; Computer Simulation; Computer-Aided Design; Contraception; Contraceptive Agents, Female; Contrast Media; COP-Coated Vesicles; Coronavirus Infections; Cost of Illness; Coturnix; COVID-19; Creatinine; Cross-Over Studies; Cross-Sectional Studies; Culex; Curriculum; Cyclic N-Oxides; Cytokines; Cytoplasm; Cytotoxicity, Immunologic; Cytotoxins; Databases, Factual; Deep Learning; Delivery, Obstetric; Denitrification; Dental Caries; Denture, Complete; Dexamethasone; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Dielectric Spectroscopy; Diet, High-Fat; Dietary Fiber; Disease Models, Animal; Disease Progression; DNA; DNA Copy Number Variations; DNA, Mitochondrial; Dog Diseases; Dogs; Dopaminergic Neurons; Double-Blind Method; Down-Regulation; Doxorubicin; Drug Carriers; Drug Design; Drug Interactions; Drug Resistance, Bacterial; Drug Resistance, Neoplasm; Drug-Related Side Effects and Adverse Reactions; Drugs, Chinese Herbal; Dry Powder Inhalers; Dust; E2F1 Transcription Factor; Ecosystem; Education, Nursing; Education, Nursing, Baccalaureate; Electric Impedance; Electricity; Electrocardiography; Electrochemical Techniques; Electrochemistry; Electrodes; Electrophoresis, Polyacrylamide Gel; Endoplasmic Reticulum; Endothelial Cells; Environmental Monitoring; Enzyme Inhibitors; Epithelial Cells; Epithelial-Mesenchymal Transition; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Estrogen Receptor Modulators; Europe; Evoked Potentials, Auditory, Brain Stem; Exosomes; Feasibility Studies; Female; Ferricyanides; Ferrocyanides; Fibrinogen; Finite Element Analysis; Fistula; Fluorescent Dyes; Fluorides, Topical; Fluorodeoxyglucose F18; Fluticasone; Follow-Up Studies; Food Contamination; Food Microbiology; Foods, Specialized; Forensic Medicine; Frail Elderly; France; Free Radicals; Fresh Water; Fungi; Fungicides, Industrial; Galactosamine; Gastrointestinal Neoplasms; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Frequency; Genetic Predisposition to Disease; Genotype; Gingival Hemorrhage; Glioblastoma; Glioma; Glomerular Filtration Rate; Glomerulosclerosis, Focal Segmental; Glucose; Glucose Transport Proteins, Facilitative; Glucosides; Glutamine; Glycolysis; Gold; GPI-Linked Proteins; Gram-Negative Bacteria; Gram-Positive Bacteria; Graphite; Haplotypes; HCT116 Cells; Healthy Volunteers; Hearing Loss; Heart Failure; Hedgehog Proteins; HEK293 Cells; HeLa Cells; Hemodynamics; Hemorrhage; Hepatocytes; Hippo Signaling Pathway; Histone Deacetylases; Homeostasis; Hospital Mortality; Hospitalization; Humans; Hydantoins; Hydrazines; Hydrogen Peroxide; Hydrogen-Ion Concentration; Hydrophobic and Hydrophilic Interactions; Hydroxylamines; Hypoglycemic Agents; Immunity, Innate; Immunoglobulin G; Immunohistochemistry; Immunologic Factors; Immunomodulation; Immunophenotyping; Immunotherapy; Incidence; Indazoles; Indonesia; Infant; Infant, Newborn; Infarction, Middle Cerebral Artery; Inflammation; Injections, Intramuscular; Insecticides; Insulin-Like Growth Factor I; Insurance, Health; Intention to Treat Analysis; Interleukin-1 Receptor-Associated Kinases; Interleukin-6; Intrauterine Devices; Intrauterine Devices, Copper; Iron; Ischemia; Jordan; Keratinocytes; Kidney; Kidney Diseases; Kir5.1 Channel; Klebsiella Infections; Klebsiella pneumoniae; Lab-On-A-Chip Devices; Laparoscopy; Lasers; 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Renal ischemia and reperfusion (IR) injury introduces cellular stress and is the main cause of acute kidney damage. Renal cells exposed to noxious stress induce the expression of the pleiotropic hormone leptin. As we have previously revealed a deleterious stress-related role for leptin expression, these results suggested that leptin is also involved in pathological renal remodeling. The systemic functions of leptin preclude the study of its local effects using conventional approaches. We have therefore designed a method to locally perturb leptin activity in specific tissues without affecting its systemic levels. This study explores whether local anti-leptin strategy is renoprotective in a post-IR porcine kidney model.. We induced renal IR injury in pigs by exposing kidneys to ischemia and revascularization. Upon reperfusion, kidneys instantly received an intra-arterial bolus of either a leptin antagonist (LepA) or saline solution. Peripheral blood was sampled to assess systemic leptin, IL-6, creatinine, and BUN levels, and postoperative tissue samples were analyzed by hematoxylin and eosin histochemistry and immunohistochemistry.. Histology of IR/saline kidneys exhibited extensive necrosis of proximal tubular epithelial cells, as well as elevated levels of apoptosis markers and inflammation. In contrast, IR/LepA kidneys showed no signs of necrosis or inflammation with normal IL-6 and tall-like receptor 4 levels. LepA treatment led to upregulation in mRNA levels of leptin, leptin receptor, ERK1/2, STAT3, and transport molecule Na/H exchanger-3.. Local, intrarenal postischemic LepA treatment at reperfusion prevented apoptosis and inflammation and was renoprotective. Selective intrarenal administration of LepA at reperfusion may provide a viable option for clinical implementation.

Topics: Acute Kidney Injury; Animals; Inflammation; Interleukin-6; Ischemia; Kidney; Leptin; Necrosis; Reperfusion Injury; Swine

Despite the high prevalence of acute kidney injury (AKI), the therapeutic approaches for AKI are disappointing. This deficiency stems from the poor understanding of the pathogenesis of AKI. Recent studies demonstrate that αMUPA, alpha murine urokinase-type plasminogen activator (uPA) transgenic mice, display a cardioprotective pathway following myocardial ischemia. We hypothesize that these mice also possess protective renal pathways. Male and female αMUPA mice and their wild type were subjected to 30 min of bilateral ischemic AKI. Blood samples and kidneys were harvested 48 h following AKI for biomarkers of kidney function, renal injury, inflammatory response, and intracellular pathways sensing or responding to AKI. αMUPA mice, especially females, exhibited attenuated renal damage in response to AKI, as was evident from lower SCr and BUN, normal renal histology, and attenuated expression of NGAL and KIM-1. Notably, αMUPA females did not show a significant change in renal inflammatory and fibrotic markers following AKI as compared with wild-type (WT) mice and αMUPA males. Moreover, αMUPA female mice exhibited the lowest levels of renal apoptotic and autophagy markers during normal conditions and following AKI. αMUPA mice, especially the females, showed remarkable expression of PGC1α and eNOS following AKI. Furthermore, MUPA mice showed a significant elevation in renal leptin expression before and following AKI. Pretreatment of αMUPA with leptin-neutralizing antibodies prior to AKI abolished their resistance to AKI. Collectively, the kidneys of αMUPA mice, especially those of females, are less susceptible to ischemic I/R injury compared to WT mice, and this is due to nephroprotective actions mediated by the upregulation of leptin, eNOS, ACE2, and PGC1α along with impaired inflammatory, fibrotic, and autophagy processes.

Topics: Acute Kidney Injury; Animals; Female; Ischemia; Kidney; Leptin; Male; Mice; Mice, Transgenic; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Reperfusion; Reperfusion Injury

Brain reperfusion following an ischemic event is essential for tissue viability, however, it also involves processes that promote neuronal cell death. We have recently shown that local expression of the hormone leptin in cardiovascular organs drives deleterious remodeling. As cerebral ischemia-reperfusion (IR) lesions derive expression of both the leptin hormone and its receptor, we hypothesized that blocking leptin activity in the injured brain area will reduce the deleterious effects of IR injury.. C57BL6 male mice underwent bilateral common carotid artery and external carotid artery ligation. The right hemisphere was reperfused after 12 minutes, followed by intraarterial injection of either a low-dose leptin antagonist or saline solution via the ipsilateral ICA. The left common carotid artery remained ligated. Fifteen IR/leptin antagonist-injected and fourteen IR/saline-injected mice completed the experiment. Five days after surgery brains were collected and samples of the hippocampal CA1 region were analyzed for cell viability (H&E) and apoptosis (TUNEL and caspase3), for neuroinflammation (Iba1), and for signaling pathways of pSTAT3 and pSmad2.. The right hemisphere hippocampal CA1 region subjected to IR and saline injection exhibited increased apoptosis and necrosis of pyramidal cells. Also, increased density of activated microglia/macrophages was evident around the CA1 region. Comparatively, leptin antagonist treatment at reperfusion reduced apoptosis and necrosis of pyramidal cells, as indicated by increased number of viable cells (p < 0.01), and reduced TUNEL (p < 0.001) and caspase3-positive cells (p<0.05). Furthermore, this treatment reduced the density of activated microglia/macrophages (p < 0.001) in the CA1 region. Signaling pathway analysis revealed that while pSTAT3 and pSmad2-positive cells were found surrounding the stratum pyramidal in saline-treated animals, pSTAT3 signal was undetected and pSmad2 was greatly reduced in this territory following leptin antagonist treatment (p < 0.01).. Inhibition of leptin activity in hemispheric IR injury preserved the viability of ipsilateral hippocampal CA1 neurons, likely by preventing apoptosis and local inflammation. These results indicate that intraarterial anti-leptin therapy may have clinical potential in reducing hemispheric brain IR injury.

Topics: Animals; Apoptosis; CA1 Region, Hippocampal; Disease Models, Animal; Infusions, Intra-Arterial; Leptin; Macrophages; Male; Mice; Mice, Inbred C57BL; Microglia; Protective Agents; Reperfusion Injury; Signal Transduction; Smad2 Protein; STAT3 Transcription Factor

Neuroprotective effects of leptin have been shown in mouse model of cerebral ischemia/reperfusion injury and primary cortical neuronal culture with oxygen-glucose deprivation (OGD), while the underlying mechanisms are less understood. In the present study, we investigated whether leptin modulated mitochondrial function through JAK2/STAT3 in vivo mouse model of transient middle cerebral artery occlusion (MCAO) and in OGD-challenged primary neuronal cultures. JAK2/STAT3; mitochondrial biogenesis markers (PGC-1α); and apoptosis-associated proteins (caspase-3, BCL-2, BCL-XL, and cytochrome c) were detected by western blotting and reverse transcription-polymerase chain reaction at 1 h before and after ischemia/reperfusion. P-STAT3 and PGC-1α in neurons and astrocytes were detected. Moreover, mitochondrial morphology of the ischemic ipsilateral penumbra is examined using transmission electron microscopy. Primary cerebral cortical neurons were evaluated for viability, mitochondrial membrane potential (MMP), and apoptosis to assess whether dose-dependent neuroprotective effects of leptin during OGD were mitigated by the JAK2/STAT3 inhibitor AG490. Leptin activated JAK2/STAT3 signaling in neurons and astrocytes distributed in the ischemic ipsilateral penumbra, with peak p-STAT3 levels observed at 1 h after reperfusion. Leptin increased PGC-1α, BCL-2, and BCL-XL protein levels, cell viability, and MMP and decreased apoptosis both in vitro and in vivo; these effects were reversed by AG490 treatment. Our findings suggest that leptin-mediated neuroprotective effects in tMCAO may peak at 1 h to induce the transcription of its target gene PGC-1α, stabilization of MMP, inhibition of mitochondrial permeability transition pore opening, release of cytochrome c, and apoptosis.

Topics: Animals; Apoptosis; Brain; Brain Ischemia; Infarction, Middle Cerebral Artery; Janus Kinase 2; Leptin; Male; Membrane Potential, Mitochondrial; Mice; Mice, Inbred C57BL; Mitochondria; Neurons; Neuroprotective Agents; Proto-Oncogene Proteins c-bcl-2; Reperfusion Injury; Signal Transduction; STAT3 Transcription Factor; Stroke; Transcription Factors

The cellular and molecular mechanisms underlying leptin-mediated brain protection against cerebral ischemia were investigated at the blood-brain barrier (BBB) and neutrophil level. Through the ischemia/reperfusion (I/R) animal model, we found that leptin expression level was significantly decreased in ischemic hemisphere. Brain injection with leptin (15 μg/kg, intracisternally) could block the I/R-increased BBB permeability, activation of matrix metallopeptidase 9 (MMP-9) and brain infiltration of blood-borne neutrophils to reduce the infarct volume of ischemic brain. The brain expression level of tight junction protein ZO-1 as well as number and motility of neutrophils in blood was all increased by the same injection, indicating BBB stability (rather than reduction in neutrophils) played a major role in the leptin-inhibited brain infiltration of neutrophils. Leptin-mediated protection of BBB was further confirmed in vitro, through a BBB cellular model under the in vitro ischemic condition (G/R: glucose-oxygen-serum deprivation followed by GOS restoration). The results showed that leptin again could block the G/R-increased neutrophil adherence to EC layer as well as BBB permeability, likely by stimulating the endothelial expression of ZO-1 and VE-Cadherin. The study has demonstrated that leptin could protect ischemic brain via multiple ways (other than neuronal protection), by inhibiting the BBB permeability, brain infiltration of the blood-borne neutrophils and neutrophil adherence to vascular ECs. The role of leptin in vascular biology of stroke could further support its therapeutic potential in other neurodegenerative diseases, associated with BBB disorder.

Topics: Animals; Blood-Brain Barrier; Brain Ischemia; Infarction; Leptin; Neutrophils; Rats; Rats, Sprague-Dawley; Reperfusion; Reperfusion Injury

Our study aimed to investigate the possible modifying effects of leptin and combined use of resveratrol on rat renal I/R injury and their relationship on signal pathways and apoptosis-related mechanisms.. Renal ischemia-reperfusion (I/R) injury is an important cause of acute renal failure.. Male Sprague Dawley rats were divided into 5 groups: Control, I/R, I/R+leptin, I/R+resveratrol and I/R+leptin+resveratrol. Leptin (10 μg/kg BW) was administered (i.p.) 30 min prior to I/R. Resveratrol was administered by gavage at 20 mg/kg BW per d for 12 d prior to I/R. The left renal artery was exposed to 1 h of ischemia and 1 h of reperfusion.. Resveratrol treatment alone increased TNF-α, TNF-α R1, NF-κB, SIRT-1, STAT1 and STAT3 mRNA levels and decreased caspase 3 protein levels. Leptin treatment alone significantly decreased the caspase 3 protein levels. The combined use of resveratrol and leptin significantly increased STAT3, and caspase 3 mRNA levels, and decreased the caspase 3 protein levels. Apoptosis was significantly decreased especially in the leptin and leptin+resveratrol groups.. The present study suggest that a combined use of resveratrol and leptin has preventive and regulatory effects on renal I/R injury; the mechanism involves decreasing apoptosis, likely by altering the JAK/STAT pathway and SIRT1 expression (Fig. 8, Ref. 24).

Topics: Animals; Antioxidants; Apoptosis; Caspase 3; Gene Expression; Kidney; Leptin; Male; NF-kappa B; Rats; Rats, Sprague-Dawley; Receptors, Tumor Necrosis Factor; Reperfusion Injury; Resveratrol; RNA, Messenger; Signal Transduction; Sirtuin 1; STAT1 Transcription Factor; STAT3 Transcription Factor; Stilbenes; Tumor Necrosis Factor-alpha

To study the effect of leptin on neuron apoptosis in mice with cerebral ischemia injury.. In model group, most of the neurons in the central area of cerebral ischemia had necrosis obviously, and the amount of neuron apop-tosis was much higher than that in sham group (. Leptin could reduce neuron apoptosis through down-regulation the expression of caspase-3 and up-regulation the expression of bcl-2. It suggests that leptin could play a neuroprotective role in cerebral ischemia injury.

Topics: Animals; Apoptosis; Brain Ischemia; Caspase 3; Infarction, Middle Cerebral Artery; Leptin; Male; Mice; Neurons; Proto-Oncogene Proteins c-bcl-2; Reperfusion Injury

Short-term dietary restriction (DR) without malnutrition preconditions against surgical stress in rodents; however, the nutritional basis and underlying nutrient/energy-sensing pathways remain poorly understood.. We investigated the relative contribution of protein restriction (PR) vs. calorie restriction (CR) to protection from renal ischemia reperfusion injury (IRI) and changes in organ-autonomous nutrient/energy-sensing pathways and hormones underlying beneficial effects.. Mice were preconditioned on experimental diets lacking total calories (0-50% CR) or protein/essential amino acids (EAAs) vs. complete diets consumed ad libitum (AL) for 1 wk before IRI. Renal outcome was assessed by serum markers and histology and integrated over a 2-dimensional protein/energy landscape by geometric framework analysis. Changes in renal nutrient/energy-sensing signal transduction and systemic hormones leptin and adiponectin were also measured. The genetic requirement for amino acid sensing via general control non-derepressible 2 (GCN2) was tested with knockout vs. control mice. The involvement of the hormone leptin was tested by injection of recombinant protein vs. vehicle during the preconditioning period.. CR-mediated protection was dose dependent up to 50% with maximal 2-fold effect sizes. PR benefits were abrogated by EAA re-addition and additive with CR, with maximal benefits at any given amount of CR occurring with a protein-free diet. GCN2 was not required for functional benefits of PR. Activation and repression of nutrient/energy-sensing kinases, AMP-activated protein kinase (AMPK) and mechanistic target of rapamycin complex 1 (mTORC1), respectively, on PR reflected a state of negative energy balance, paralleled by 13% weight loss and an 87% decrease in leptin, independent of calorie intake. Recombinant leptin administration partially abrogated benefits of dietary preconditioning against renal IRI.. In male mice, PR and CR both contributed to the benefits of short-term DR against renal IRI independent of GCN2 but partially dependent on reduced circulating leptin and coincident with AMPK activation and mTORC1 repression.

Topics: Acute Kidney Injury; Animals; Area Under Curve; Caloric Restriction; Dietary Proteins; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Protein Serine-Threonine Kinases; Reperfusion Injury; Urea

Previous studies have demonstrated that both curcumin and leptin are protective factors against acute injuries. Here, we investigated whether leptin and its signaling pathway mediate the protective effects of curcumin.. A solid dispersion of curcumin-polyvinylpyrrolidone K30 was prepared and administered intraperitoneally. In vivo intestinal ischemia/reperfusion (I/R) injury in mice determined the effects of curcumin administration on inflammation, oxygen radical production, and leptin expression. In vitro studies using the venous epithelial cell line ECV-304 examined hypoxia/reoxygenation-induced leptin expression and release after curcumin administration. Furthermore, the effects on the leptin-regulated ERK1/2 and p38 MAPK signaling pathways were also explored.. Intestinal I/R induced marked bowel injuries. Curcumin treatment significantly improved animal survival and reduced the pathologic injuries in the intestines. Furthermore, the elevated intestinal water content and levels of malondialdehyde, interleukin 1β (IL-1β) and IL-6 were significantly decreased, but levels of superoxide dismutase increased. Interestingly, we found that the decreased leptin and its receptor Ob-Rb were restored by curcumin administration. In addition, in vitro studies showed that curcumin increased leptin expression and release after hypoxia/reoxygenation-induced cell injuries. Moreover, curcumin treatment restored decreased ERK1/2 phosphorylation (p-ERK1/2) and inhibited overactive p38 (p-p38) after injuries, and the effect was reversed by a leptin-specific antibody or Ob-R blocker.. These data suggest that leptin and Ob-Rb-dependent ERK and p38 MAPK signaling pathways may be involved in curcumin protection against intestinal I/R injury, and leptin may be a potential target of curcumin in intestinal I/R injury and other related acute diseases.

Topics: Acute Disease; Animals; Curcumin; Disease Models, Animal; Enzyme Inhibitors; Epithelial Cells; Intestines; Leptin; Male; Mice; Phosphorylation; Reperfusion Injury; Signal Transduction

The purpose of this study was to investigate the protective mechanism of leptin-mediated metabolic recovery against cerebral injury after ischemia and reperfusion. We determined the neurologic deficit score, extent of brain edema, and infarct volume after reperfusion. The histopathologic alterations and changes in glucose uptake in the brain were also observed. Moreover, the levels of lactate dehydrogenase (LDH), lactic acid, pyruvate, and ATP in brain tissue were detected. Leptin levels in serum were also detected. To further define leptin-induced neuroprotective signaling pathways, we examined the levels of phosphorylated Akt (p-Akt) in the brain and in cultured cells. After transient ischemia, leptin treatment markedly reduced the neurologic deficits, cerebral infarct volume, and brain edema. After leptin injection, ATP, leptin, and p-Akt levels were significantly increased, LDH levels and lactic acid/pyruvate ratio were noticeably reduced, and histopathologic injuries were alleviated, which were all reversed by the PI(3)K inhibitor LY294002. These data show that leptin ameliorates cerebral ischemia/reperfusion injury by enhancing p-Akt, which in turn improves the supply of energy. The PI(3)K/Akt pathway was found to be the critical pathway for the mediation of leptin-induced neuroprotection, a finding that may prove to be useful in the treatment of ischemic stroke.

Topics: Animals; Brain Edema; Brain Infarction; Chromones; Energy Metabolism; Enzyme Inhibitors; L-Lactate Dehydrogenase; Lactic Acid; Leptin; Male; Mice; Morpholines; Nerve Tissue Proteins; Phosphatidylinositol 3-Kinases; Phosphoinositide-3 Kinase Inhibitors; Phosphorylation; Proto-Oncogene Proteins c-akt; Pyruvic Acid; Reperfusion Injury; Signal Transduction

Recently, research has indicated that leptin plays a protective role in traumatic brain and liver injury. We studied the protective effect of leptin on intestinal I/R injury and examined its mechanism by using mice intestinal I/R model and murine peritoneal macrophage hypoxia/reoxygenation (H/R) injury model.. Leptin was intraperitoneally administrated at 45 minutes after ischemia, then reperfusion for two hours. Cells were treated with different concentrations of leptin at three hours after hypoxia, then reoxygenation for six hours. Mice intestines were harvested for histopathologic properties. The malondialdehyde, nitric oxide (NO), interleukin-6, and total antioxidative capacity were detected according to respective assay kit. Phosphorylated extracellular regulated kinase1/2 (p-ERK1/2) and phosphorylated cytosolic phospholipase A(2) (p-cPLA2) were determined by Western blot assay.. Here, we show that leptin reduced intestinal histologic alterations, malondialdehyde and interleukin-6 levels but increased the endogenous leptin expression and NO production in the intestines. Leptin also increased the NO and total antioxidative capacity levels in cells. We further demonstrated that leptin markedly activated ERK1/2 in the intestines and activated ERK1/2 and cPLA2 in the cells. Moreover, the protective effect of leptin against intestinal I/R injury and elevated NO production was attenuated by blocking the ERK1/2 pathway.. These data demonstrate that leptin ameliorated intestinal I/R and peritoneal macrophage H/R injury by enhancing ERK1/2 phosphorylation and promoting the NO production signaling pathway.

Topics: Animals; Antioxidants; Blotting, Western; Dose-Response Relationship, Drug; Interleukin-6; Intestinal Mucosa; Intestines; Leptin; Male; Malondialdehyde; MAP Kinase Signaling System; Mice; Nitric Oxide; Phospholipases A2; Phosphorylation; Reperfusion Injury; Signal Transduction

To explore the effect of leptin on expression of Cx43 after rat cerebral ischemia/ reperfusion injury and its related mechanism.. Forty-five male kunming mice were randomly divided into 3 groups: sham group, model group and leptin group. Mouse models of transient focal cerebral ischemia were established by occlusion of the right middle cerebral artery for 2 h followed by 24 h reperfusion in model and leptin group. Mice of leptin group were intraperitoneally injected with 1 mg/kg leptin at 0 minute after ischemia. The infarct volume and neurological deficit scores following leptin treatment were determined using TTC staining and the Longa's score, respectively, to evaluate the protective effect of leptin against ischemic cerebral injury. The histopathological changes in the brain were observed with HE staining. The astrocytes of SD rat cerebral cotex were cultured primaryly and purified, and then divided them into four groups: control, model, leptin 100 microg/L, and leptin 500 microg/L. The cerebral astrocytes with hypoxia/reoxygenation injury were induced. The cellular viability of injury was detected by MTT assay. The effect of leptin on Cx43 expression was detected by Western blot in brain tissues and astrocytes.. Compared with the model group, the neurological deficits and cerebral infarct volume of leptin group were reduced (P< 0.05), the histopathological injury in the brain tissues was alleviated and the expression of Cx43 was decreased markedly (P < 0.01). The survival rate of astrocytes was increased significantly in leptin 500 microg/L group (P < 0.01), whereas the Cx43 expression of astrocytes decreased (P < 0.01). But the difference of leptin 100 mcirog/L was not significant (P > 0.05).. Leptin can ameliorate cerebral pathological changes in the event of IR injury by suppressing the expression of Cx43 both in vivo and vitro experiments.

Topics: Animals; Astrocytes; Brain; Brain Ischemia; Cell Hypoxia; Cells, Cultured; Connexin 43; Leptin; Male; Mice; Rats; Rats, Sprague-Dawley; Reperfusion Injury

Leptin is an adipocytokine that reduces ischemic damage in several organs including brain and heart. STAT3 activation is a key step for the attainment of leptin effects in various tissues. We evaluated the possible effect of leptin on liver viability and STAT3 activation, in a rat model of ischemia-reperfusion injury. Rat livers, flushed and stored with Belzer solution (4° C for 24 h), were warmly reperfused (3.5 ml/min/g liver for 1 h at 37° C with O(2) ) with Krebs-Ringer bicarbonate. Treatment group underwent an identical protocol with the adjunct of Leptin (10 ng/ml). Liver effluent was harvested to assess LDH and AST output. Liver tissue was used for pSTAT3 expression (western blot and immunostaining), optical microscopy, TUNEL, and Cell Death Detection assays. The pSTAT3 expression was enhanced by administration of leptin. In parallel, LDH and AST output were reduced (P = 0.04 and P = 0.02 for LDH and AST, respectively). Optical microscopy, TUNEL, and Cell Death Detection assay results demonstrated increased viability in livers treated with leptin in comparison with others (Optical microscopy P = 0.02; TUNEL P = 0.01; Cell death Detection assay P = 0.003). In conclusion, cold storage and reperfusion with leptin reduce liver ischemia-reperfusion injury. This effect is associated with an increased expression of pSTAT-3.

Topics: Animals; Aspartate Aminotransferases; L-Lactate Dehydrogenase; Leptin; Liver; Male; Organ Preservation; Rats; Rats, Wistar; Reperfusion Injury; STAT3 Transcription Factor

To study the effect of Leptin on neuron apoptosis in mice with cerebral ischemia injury and its mechanism.. Seventy-five mice were randomly divided into three groups. Focal cerebral ischemia/reperfusion injury model in mice was reproduced by middle cerebral artery occlusion for 2 hours followed by reperfusion. In Leptin intervention group mice were given Leptin 1 μg/g during cerebral ischemia by intraperitoneal injection. Mice in the model group were given equal amount of phosphate buffer saline. After reperfusion for 24 hours, the neuron apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. The mRNA and protein expression of apoptosis relative gene caspase-3 and bcl-2 were determined by reverse transcription-polymerase chain reaction (RT-PCR) and immuno histochemistry.. Most of neuron necrosis was observed in cerebral ischemia center in model group. Compared with sham-operation group, neuron apoptosis rate, mRNA and protein expression of caspase-3 and bcl-2 in model group increased significantly [apoptosis rate: (68.65 ± 0.79)% vs. (4.40 ± 0.00)%, caspase-3 mRNA: 2.563 ± 0.250 vs. 0.153 ± 0.020, bcl-2 mRNA: 0.337 ± 0.100 vs. 0.125 ± 0.030, caspase-3 protein (absorbance value, A value): 0.57 ± 0.05 vs. 0.37 ± 0.03, bcl-2 protein (A value): 0.51 ± 0.04 vs. 0.35 ± 0.01, all P<0.01]. The apoptosis rate of penumbra neurons was reduced in Leptin intervention group significantly compared with model group [(42.30 ± 8.45)% vs. (68.65 ± 0.79)%, P<0.01]. Compared with model group, the mRNA and protein expression of caspase-3 in Leptin intervention group were reduced significantly [caspase-3 mRNA: 2.267 ± 0.040 vs. 2.563 ± 0.250, caspase-3 protein (A value): 0.45 ± 0.04 vs. 0.57 ± 0.05, P>0.05 and P<0.01], and the mRNA and protein expression of bcl-2 in Leptin intervention group upregulated significantly [bcl-2 mRNA: 0.662 ± 0.040 vs. 0.337 ± 0.100, bcl-2 protein (A value): 0.76 ± 0.09 vs. 0.51 ± 0.04, both P<0.01].. Leptin could reduce apoptosis of neurons through down-regulation of the expression of caspase-3 and up-regulation of the expression of bcl-2. The results suggest that Leptin plays a neuroprotective role in cerebral ischemia injury.

Topics: Animals; Apoptosis; Brain Ischemia; Caspase 3; Leptin; Male; Mice; Mice, Inbred Strains; Neurons; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-2; Reperfusion Injury

Ischemic stroke is a medical emergency triggered by a rapid reduction in blood supply to localized portions of the brain, usually because of thrombosis or embolism, which leads to neuronal dysfunction and death in the affected brain areas. Leptin is generally considered to be a strong and quick stress mediator after injuries. However, whether and how peripherally administered leptin performs neuroprotective potency in cerebral stroke has not been fully investigated. It has been reported that CGRP(8-37), an antagonist of the CGRP receptor, could reverse the protective effect of leptin on rats with CIP (caerulein-induced pancreatitis). However, the question remains: are leptin and CGRP associated in cerebral ischemia/reperfusion injury? The present study attempted to evaluate the relationship between CGRP expression and leptin neuroprotective effects (1mg/kg in 200 μL normal saline, i.p.) on focal cerebral ischemia/reperfusion injury in mice and the protective effect of leptin (500 μg/L) on neurons during hypoxia/reoxygenation injury. Peripheral administration of leptin alleviated injury-evoked brain damage by promoting CGRP expression, improving regional cerebral blood flow, and reducing local infarct volume and neurological deficits. Furthermore, leptin also promoted bcl-2 expression and suppressed caspase-3 in vivo and vitro after injury. Administration of CGRP(8-37) (4 × 10(-8)mol/L) partly abolished the beneficial effects of leptin, and restored the normal expression levels of bcl-2 and caspase-3 in neurons, which indicated that leptin-induced protection of neurons was correlated with release of CGRP. These results indicate that the neuroprotective effect of leptin against cerebral ischemia/reperfusion injury may be strongly relevant to the increase of CGRP expression.

Topics: Animals; Apoptosis; Brain; Brain Ischemia; Calcitonin Gene-Related Peptide; Caspase 3; Cell Hypoxia; Cerebrovascular Circulation; Gene Expression Regulation; Leptin; Male; Mice; Nervous System Diseases; Neurons; Neuroprotective Agents; Oxygen; Proto-Oncogene Proteins c-bcl-2; Rats; Regional Blood Flow; Reperfusion Injury; RNA, Messenger; Up-Regulation

To investigate the effect of leptin on apoptosis of rat cerebral astrocytes with ischemia/ hypoxia injury and its mechanism.. The cerebral astrocytes with ischemic/hypoxia injury were induced in neonatal SD rats. The cellular viability of injury of astrocytes was detected by MTT assay. The apoptosis of astrocyte were detected with Annexin V-FITC kit. The effect of leptin on the expression of apoptosis factor bcl-2, bax, caspase-3 was detected by RT-PCR and Western blot.. Compared with the ischemia group, the cellular viability of leptin intervention group increased significantly (P < 0.01), while the astrocytes apoptosis of leptin intervention group decreased significantly (P < 0.01). The mRNA and protein expression level of antiapoptosis factor bcl-2 in leptin intervention group was much higher than that of ischemia group (P < 0.01), whereas the mRNA and protein expression of bax and caspase-3 was much lower than that of ischemia group (P < 0.01).. Leptin could significantly decrease the apoptosis of astrocytes with ischemia/hypoxia injury, and it i relevant to the increase of bcl-2 expression and the decrease of bax caspase-3 expression level.

Topics: Animals; Animals, Newborn; Apoptosis; Astrocytes; bcl-2-Associated X Protein; Brain; Caspase 3; Hypoxia-Ischemia, Brain; Leptin; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Sprague-Dawley; Reperfusion Injury; RNA, Messenger

To evaluate the role of leptin in the internal disorders during hepatic ischemia/reperfusion injury.. A rat model of 70% hepatic ischemia/reperfusion injury was established, with groups of sham-operation (Sham), 60 min ischemia/60 min reperfusion (I60'R60'), I60'R150', I60'R240' and I60'R360'. Serum leptin was detected by a self-produced radioimmunoassay; serum glucose, total anti-oxidation capacity, myeloperoxidase, alanine transaminase and diamine oxidase were determined by relevant kits, while histological alterations and protein levels of leptin in the lung, liver and duodenum were examined by hematoxylin-eosin staining and immunohistochemistry. Spearman's rank correlation between leptin and other variables or grading of tissue impairment were analyzed simultaneously.. Serum leptin in I60'R360' was significantly higher than in Sham and I60'R240' groups (both P < 0.05), serum glucose in I60'R360' was higher than in Sham and I60'R150' (both P < 0.05), and serum total anti-oxidation capacity in I60'R240' and I60'R360' were higher than in Sham (both P < 0.05) and I60'R150'groups (both P < 0.01). Serum myeloperoxidase in groups of I60'R240' and I60'R360' were lower than in I60'R150'group (both P < 0.05), serum alanine transaminase in the four reperfusion groups were higher than in the Sham group (all P < 0.05), while serum DAO in I60'R360' was lower than in I60'R60' (P < 0.05). Histological impairment in the lung, liver and duodenum at the early phase of this injury was more serious, but the impairment at the later phase was lessened gradually. Protein levels of leptin in the lung in the four reperfusion groups were significantly lower than in the Sham group (all P < 0.01), decreasing in the order of I60'R150', I60'R60', I60'R360' and I60'R240'; the levels in the liver in I60'R60' and I60'R240' were higher than in the Sham group (both P < 0.01), while the levels in I60'R240' and I60'R360' were lower than in I60'R60' (both P < 0.01); the levels in duodenum in I60'R240' and I60'R360' were higher than in Sham, I60'R60' and I60'R150' (all P < 0.01), while the level in I60'R150' was lower than in I60'R60' (P < 0.05). There was a significantly positive correlation between serum leptin and alanine transaminase (ρ = 0.344, P = 0.021), a significantly negative correlation between the protein level of leptin in the lung and its damage scores (ρ = -0.313, P = 0.036), and a significantly positive correlation between the protein level of leptin in the liver and its damage scores (ρ = 0.297, P = 0.047).. Endogenous leptin fluctuates in hepatic ischemia/reperfusion injury, exerts a potency to rehabilitate the internal disorders and represents a potential target for supportive therapy.

Topics: Alanine Transaminase; Amine Oxidase (Copper-Containing); Animals; Blood Glucose; Duodenum; Leptin; Liver; Lung; Male; Models, Animal; Peroxidase; Rabbits; Rats; Rats, Sprague-Dawley; Reperfusion Injury

The aim of the study was to evaluate protective effects of exogenous leptin on ischemia/reperfusion (I/R)-induced injuries to the urinary bladder tissue and to investigate the effect on tumor necrosis factor alpha (TNF-alpha) levels and apoptotic cells during I/R injury. Bladder I/R injury was induced by abdominal aorta occlusion by ischemia for 45 min, followed by 60 min of reperfusion in rats. The rats were divided into three groups: control (n = 8 + 8), I/R (n = 8 + 8) and I/R+leptin group (n = 8 + 8). The rats in the I/R+leptin group were treated intraperitoneally with leptin (10 microg/kg) 60 min prior to ischemia induction. At the end of the reperfusion period, urinary bladders of the first eight rats from each group were removed for TUNEL staining processing while the others were removed for biochemical analyses for MDA and TNF-alpha levels. In the I/R group, the ratios of TUNEL-positive nuclei were higher than the control and the I/R+leptin groups. The MDA and TNF-alpha levels of the bladder tissue in the I/R group were higher than the control and leptin-treated groups. TUNEL-staining and biochemical studies revealed that leptin has a protective effect on urinary bladder I/R injury.

Topics: Animals; Apoptosis; Injections, Intraperitoneal; Ischemia; Leptin; Malondialdehyde; Models, Animal; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Tumor Necrosis Factor-alpha; Urinary Bladder

To investigate the protective effect of leptin against cerebral ischemia/reperfusion injury in mice.. Mouse models of transient focal cerebral ischemia were established by occlusion of the right middle cerebral artery for 2 h followed by 24 h reperfusion. The infarct volume and neurological deficit scores following leptin treatment were determined using TTC staining and the Longa's score, respectively, to evaluate the protective effect of leptin against ischemic cerebral injury. The levels of lactate dehydrogenase (LDH), malondialdehyde (MDA) and nitric oxide (NO) in the brain tissue were measured by colorimetry. The histopathological changes in the brain were observed with HE staining, and the expression of glial fibrillary acidicprotein (GFAP) was detected by immunohistochemistry.. Leptin treatment markedly reduced cerebral infarct volume and neurological deficits induced by transient ischemia. The LDH, MDA and NO levels in the brain tissues were significantly decreased after leptin treatment, which also alleviated the histopathological injury, maintained the normal morphology of the astrocytes and increased the expression of GFAP.. Leptin produces obvious protective effect against cerebral ischemia/reperfusion injury by inhibiting lipid peroxidation, stabilizing the internal environment and adjusting the activity of the astrocytes.

Topics: Animals; Brain; Brain Ischemia; Infarction, Middle Cerebral Artery; L-Lactate Dehydrogenase; Leptin; Male; Malondialdehyde; Mice; Nitric Oxide; Reperfusion Injury; Time Factors

We have previously shown that treatment of steatotic livers with vitamin E succinate decreases liver injury and increases survival after ischemia/reperfusion (I/R). It is now understood that compromised energy status is associated with increased injury following liver ischemia in the setting of hepatic steatosis at least partially as a result of increased reactive oxygen species (ROS) and induction of mitochondrial uncoupling protein-2 (UCP2). Given the association between ROS, mitochondrial function, and UCP2, it was our goal to determine whether the protective effects of vitamin E succinate were associated with decreased ROS injury, down-regulation of UCP2, or improvement of ATP levels following I/R. To test this, leptin deficient (ob/ob) mice with steatotic livers that had received other 50 IU of vitamin E succinate supplement per day or control chow for 7 days were subjected to total hepatic ischemia (15 minutes) followed by reperfusion. We measured liver expressions of ATP, glutathione (GSH), and UCP2 as well as mitochondrial DNA damage. Vitamin E treatment decreased hepatic UCP2 expression and increased ATP and GSH levels prior to I/R. These levels were maintained at 1 hour after I/R. At 24 hours, while hepatic UCP2 expression, ATP, and GSH levels were similar to those of mice not receiving vitamin E, mitochondrial DNA damage was blocked. These results revealed that vitamin E succinate decreased hepatic UCP2 expression, reduced oxidative stress, and improved mitochondrial function in mice with steatotic livers before and after I/R, identifying mechanisms of protection in this setting.

Topics: Animals; Blotting, Northern; DNA Damage; DNA, Mitochondrial; Fatty Liver; Glutathione; Ion Channels; Leptin; Liver; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Obese; Mitochondrial Proteins; Reperfusion Injury; RNA, Messenger; Succinates; Uncoupling Protein 2; Vitamin E

OBJECTIVE; To study the changes of leptin after hepatic ischemia/reperfusion (H-I/R) and its effects on H-I/R-induced hepatic injury.. A 70% H-I/R model of rats was established. The rats were divided into groups with different reperfusion times and sham-operation group. Radioimmunoassay was applied to measure protein levels of leptin in serum and adipose tissues of the rats. Enzyme-colorimetry was used to detect serum alanine transaminase. Hematoxylin-eosin staining and immunohistochemistry were applied to investigate pathological variations and protein expressions of leptin in livers, respectively. RT-PCR was used to detect leptin mRNA expressions in adipose tissues and livers.. Compared with the sham-operation group, serum leptin increased significantly in the 60 min ischemia/360 min reperfusion (I60' R360') group; protein level of leptin in adipose tissues increased significantly in the I60'R60' group; serum alanine transaminase increased significantly in all of the four reperfusion groups; protein expressions of leptin in livers increased significantly in the I60'R60' and 160'R240' groups; leptin mRNA expression in adipose tissues decreased significantly in the I60'R150' group; leptin mRNA expression in livers increased significantly in the 160'R60' group; leptin mRNA expressions in livers decreased significantly in the I60'R150', I60'R240' and I60'R360' groups. Pathological investigation showed that hepatic impairments at the early phase of H-I/R were more serious. The impairments at the later phase lessened gradually.. The change of leptin expressions after H-I/R may be a protective factor to withstand H-I/ R-induced hepatic injury.

Topics: Animals; Leptin; Liver; Male; Random Allocation; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

Although epidemiological studies reveal an increased incidence of obesity and an association between obesity and the prevalence/severity of ischemic stroke, little is known about the mechanisms that link obesity to ischemic stroke. This study tested the hypothesis that obesity exacerbates the cerebrovascular dysfunction and tissue injury induced by brain ischemia and reperfusion.. The adhesion of leukocytes and platelets in cerebral venules, blood-brain barrier permeability, brain water content, and infarct volume were measured in wild-type, obese (ob/ob), and leptin-reconstituted ob/ob mice subjected to 30 minutes middle cerebral artery occlusion and reperfusion. Tissue and plasma cytokine levels were determined by cytometric bead array, and a role for monocyte chemoattractant protein-1 and interleukin-6 was assessed using blocking antibodies.. Compared with wild-type mice, ob/ob exhibited larger increases in leukocyte and platelet adhesion, blood-brain barrier permeability, water content, and infarct volume after middle cerebral artery occlusion-reperfusion. Reconstitution of leptin in ob/ob mice tended to further enhance all reperfusion-induced responses. Ob/ob mice also exhibited higher plasma levels of monocyte chemoattractant protein-1 and interleukin-6 than wild-type mice. Immunoneutralization of monocyte chemoattractant protein-1, but not interleukin-6, reduced infarct volume in ob/ob mice.. Obesity worsens the inflammatory and injury responses to middle cerebral artery occlusion and reperfusion by a mechanism independent of leptin deficiency. monocyte chemoattractant protein-1 appears to contribute to the exaggerated responses to ischemic stroke in obese mice.

Topics: Animals; Blood-Brain Barrier; Brain Ischemia; Capillary Permeability; Cell Adhesion; Cerebral Infarction; Cerebrovascular Circulation; Chemokine CCL2; Encephalitis; Infarction, Middle Cerebral Artery; Interleukin-6; Leptin; Leukocytes; Male; Mice; Mice, Obese; Obesity; Platelet Adhesiveness; Reperfusion Injury; Stroke

Recent evidence suggests that the adipose tissue derived cytokine leptin (LEP) is involved in the modulation of growth and differentiation of normal small intestine. The purpose of the present study was to examine the effect of leptin on enterocyte turnover and intestinal recovery after ischemia-reperfusion (IR) injury in a rat. Male Sprague-Dawley rats were divided into three experimental groups: (1) sham rats underwent laparotomy, (2) IR-rats underwent occlusion of both superior mesenteric artery and portal vein for 30 min followed by 24 h of reperfusion, and (3) IR-LEP rats underwent IR and were treated with leptin given subcutaneously at a dose of 50 microg/kg once a day for 48 h before and 24 h following IR. Intestinal structural changes, enterocyte proliferation and enterocyte apoptosis were determined 24 h following IR. A non-parametric Kruskal-Wallis ANOVA test was used for statistical analysis with P < 0.05 considered statistically significant. Treatment with leptin resulted in a significant increase in bowel weight in ileum, mucosal weight in jejunum and ileum, mucosal DNA content in ileum, mucosal protein content in jejunum and ileum, villus height in jejunum and ileum, and crypt depth in jejunum compared to IR-animals. IR-LEP rats also had a significantly lower intestinal injury score as well as lower apoptotic index and higher cell proliferation index in jejunum and ileum compared to the IR-animals. In conclusion, pre-treatment with leptin prevents gut mucosal damage and improves intestinal rehabilitation following intestinal IR in a rat.

Topics: Analysis of Variance; Animals; Apoptosis; Cell Proliferation; Disease Models, Animal; Enterocytes; Intestinal Diseases; Intestinal Mucosa; Intestine, Small; Leptin; Male; Random Allocation; Rats; Rats, Sprague-Dawley; Recovery of Function; Reperfusion Injury

Leptin is the major adipose hormone that regulates body weight and energy expenditure by activating leptin receptors in the hypothalamus. Leptin receptors are also present in other cell types, and a potent antiapoptotic effect for leptin has recently been reported. We investigated whether leptin was neuroprotective against ischemic brain injury.. In vitro ischemic injury was induced in rat primary neuronal culture by oxygen-glucose deprivation for 90 minutes. In vivo ischemic brain injury was induced by middle cerebral artery occlusion in mice for 60 minutes.. Leptin receptors were detected in cultured rat cortical neurons, as well as in the mouse cortex, striatum, and hippocampus. In vitro results showed that leptin, 50 to 100 mug/mL, protected primary cortical neurons against death induced by oxygen-glucose deprivation in a concentration-dependent manner. In vivo studies in the mouse brain demonstrated that the intraperitoneal administration of leptin, 2 to 8 mg/kg, dose-dependently reduced infarct volume induced by middle cerebral artery occlusion. Leptin was effective when injected 5 minutes before or 30 to 90 minutes after reperfusion, but not 2 hours after reperfusion. Leptin improved animal body weight recovery and behavioral parameters after cerebral ischemia. Leptin enhanced the phosphorylation of extracellular signal-related kinase 1/2. Both extracellular signal-related kinase 1/2 activation and neuroprotection were abolished by the administration of PD98059 in vitro and in vivo.. Leptin is neuroprotective against ischemic neuronal injury. Our findings suggest that leptin is a legitimate candidate for the treatment of ischemic stroke.

Topics: Animals; Apoptosis; Body Weight; Brain; Brain Infarction; Cells, Cultured; Disease Models, Animal; Extracellular Signal-Regulated MAP Kinases; Glucose; Infarction, Middle Cerebral Artery; Ischemic Attack, Transient; Leptin; Male; Mice; Mice, Inbred C57BL; Neuroprotective Agents; Phosphorylation; Rats; Receptors, Cell Surface; Receptors, Leptin; Recovery of Function; Reperfusion Injury; Treatment Outcome

To explore the role and the rule of leptin levels in severe traumatism, an ischemia-reperfusion injury model was established to observe change of leptin levels, and platelet activating factor, noradrenaline, lipopolysaccharide, and endothelin-1 were utilized to induce vascular endothelial cells. Leptin concentrations in serum and supernatant were detected by murine and human leptin radioimmunoassay. The results showed that the first serum leptin level significantly decreased after an injury of 60 min ischemia and 30 min reperfusion versus pre-experimental serum values, and leptin level in serum showed a variational trend to increase as reperfusion time extended; the second, supernatant leptin level significantly decreased after PAF and ET-1 treatments of 6 and 24 h versus the control group. It can be concluded that leptin maybe an inflammatory cytokine to play a protection role in acute inflammation and traumatism.

Topics: Animals; Endothelial Cells; Intestines; Leptin; Male; Models, Biological; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Time Factors

To explore the effect of intestinal ischemia/reperfusion (I/R) injury on leptin and orexin-A levels in peripheral blood and central secretory tissues, and investigate the roles of leptin and orexin-A in acute inflammatory responses.. An intestinal I/R injury rat model was established, and the rats were grouped according to duration of the reperfusion time following a 60-min ischemia. Radioimmunoassay was used to examine the protein levels of leptin in the serum and adipose tissue, and the protein levels of orexin-A in the plasma and hypothalamus. Reverse transcriptase-polymerase chain reaction was also performed to detect the mRNA expressions of adipose leptin and hypothalamus orexin-A.. Compared with that before injury, serum leptin level of 60-min ischemia with 30-min reperfusion (I60'R30') group decreased significantly and that of I60'R360' increased significantly. Compared with the sham-operation group (sham) after injury, serum leptin level of I60'R360' group increased significantly, and adipose leptin protein levels of I60'R30' and I60'R90' groups decreased significantly, whereas that of I60'R360' group increased obviously. Compared with sham group after injury, adipose leptin mRNA expressions of I60'R30', I60'R240' and I60'R360' groups all increased significantly, while that of I60'R150' showed significant decrease. No significant changes were noted in the protein levels of orexin-A either in the plasma or hypothalamus after I/R injury. In comparison with sham group after injury, hypothalamus orexin-A mRNA expressions of I60'R30' and I60'R90' groups showed gradual but significant decrease, and till 150 min of reperfusion, the expression reached its lowest, followed then by slow recovery at 240 and 360 min, though still remaining significantly lower than that of sham group.. Leptin and orexin-A have a time-dependent response to intestinal I/R injury, but the former appears to exhibit a faster response, and they may play a certain role in the metabolic disorders of acute inflammation.

Topics: Animals; Female; Inflammation; Intestine, Small; Intracellular Signaling Peptides and Proteins; Leptin; Male; Neuropeptides; Orexins; Rabbits; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

To explore the effect of intestinal ischemia-reperfusion injury on protein levels of leptin and orexin-A in peripheral blood and their central secretory tissues and to find out the role leptin and orexin-A play in acute inflammatory responses.. An intestinal ischemia-reperfusion (I/R) injury model of rats was established and rats were divided randomly into six groups: sham-operation group, 60 min ischemia/30 min reperfusion group (I60'R30'), I60'R90', I60'R150', I60'R240' and I60'R360', 9 rats each group. Two highly-sensitive radioimmunoassays for leptin and orexin-A were established and used to check the change of their concentrations in peripheral blood and central secretory tissues before and after intestinal I/R injury.. Compared with the serum leptin level before injury, it decreased significantly in I60'R30' group and increased significantly in I60'R360' group; compared to sham-operation group after injury, serum leptin level increased significantly in I60'R360' group; compared to sham-operation group after injury, adipose leptin levels decreased significantly in I60'R30' and I60'R90' groups, while increased significantly in I60'R360' group. There was no significant difference between the expression levels of orexin-A before and after I/R injury.. Leptin has a time-dependent response and orexin-A has a delayed response to acute inflammatory stimuli such as intestinal I/R injury and they may participate in metabolic disorders in injury as inflammatory cytokines.

Topics: Adipose Tissue; Animals; Antibodies; Enteritis; Hypothalamus; Intestines; Intracellular Signaling Peptides and Proteins; Leptin; Male; Neuropeptides; Orexins; Rabbits; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Reperfusion Injury

The small intestine is extremely sensitive to ischemia-reperfusion (I/R) injury and a range of microcirculatory disturbances which contribute to tissue damage. Previous studies have shown that leptin plays an important physiological role in the microvasculature. The aim of this study was to evaluate the protective effects of leptin in I/R--induced mucosal injury in the small intestine.. Forty rats were divided into 5 groups (n = 8). Group I was subjected to a sham operation. Following mesenteric ischemia in group II (control); physiologic saline 1 cm3, in group III; leptin 100 microg/kg, and physiologic saline 1 cm3, in group IV; NG-L-arginine methyl ester (L-NAME) 20 mg/kg, and physiologic saline 1 cm3, in group V; leptin 100 microg/kg, L-NAME 20 mg/kg, and physiologic saline 1 cm3 were given intra-peritoneally. In these groups, an I/R procedure was performed by occlusion of the superior mesenteric artery for 45 min followed by 120 min reperfusion. After reperfusion, the small intestines were resected for malondialdehyde (MDA) and nitric oxide (NO) concentration and histopathologic properties. Mucosal lesions were scored between 0 and 5. Tissue MDA and NO concentration and histopathologic grades were compared statistically.. Tissue MDA level significantly increased (P < 0.05), tissue NO level significantly decreased in group V animals, compared to group III animals respectively (P < 0.001). Histopathologically, intestinal injury significantly decreased in the leptin treated ischemic group.. Leptin can be used safely in mesenteric occlusive diseases, since it induces NO formation and release in mesenteric vessels.

Topics: Animals; Drug Synergism; Enzyme Inhibitors; Intestinal Mucosa; Intestine, Small; Leptin; Male; Malondialdehyde; NG-Nitroarginine Methyl Ester; Nitric Oxide; Rats; Rats, Wistar; Reperfusion Injury

Tumor necrosis factor-alpha (TNF-alpha) has been established as an important mediator in renal ischemia-reperfusion (I/R) injury. Leptin, a product of the ob gene, has been known to exhibit cytoprotective effects on renal tissue, but its effect on renal tissue TNF-alpha level after renal I/R injury in rats remains unknown. The purpose of the study was to evaluate the effects of leptin on renal tissue TNF-alpha, malondialdehyde (MDA), protein carbonyls (PCs) and total sulfydryl group (SH) levels, and plasma nitrite levels after renal I/R injury in rats. The animals were divided into three groups: control, I/R and I/R+leptin. Rats were subjected to renal ischemia by clamping the left pedicle for 45 min, and then reperfused for 1 h. The I/R+leptin group was pretreated intraperitoneally with leptin (10 microg/kg) 30 min before the induction of ischemia. Our results indicate that MDA, TNF-alpha levels, and PCs were significantly higher in the I/R group than those in the control group (p < 0.05). The administration of leptin decreased these parameters (p < 0.05) significantly. The SH level was observed to significantly decrease after I/R injury when compared to the control group (p < 0.05). Leptin treatment significantly increased tissue SH and plasma nitrite levels when compared to the I/R group (p < 0.05). Plasma nitrite levels did not change significantly in I/R when compared to the control. These results suggest that leptin could exert a protective effect on I/R induced renal damage by decreasing TNF-alpha levels and increasing nitrite level.

Topics: Animals; Cryoprotective Agents; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Ischemia; Kidney Diseases; Leptin; Lipid Peroxidation; Malondialdehyde; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Tumor Necrosis Factor-alpha

To investigate the effect of intestinal ischemia/reperfusion injury on Leptin levels in serum and adipose tissue, and evaluate the potential role of Leptin in acute inflammatory response.. An intestinal ischemia/reperfusion injury model of rats was reproduced. Serum and adipose tissue Leptin concentrations and Leptin mRNA expression in adipose tissue were determined by a highly-sensitive murine Leptin radioimmunoassay and reverse transcription-polymerase chain reaction (RT-PCR), respectively.. Compared with animals prior to injury, serum Leptin level decreased significantly in ischemia for 60 minutes followed by reperfusion for 30 minutes (I60R30), but it tended to increase in I60R150 and significantly increased in I60R360. Compared with sham group, serum Leptin level tended to increase in I60R240 and elevated significantly in I60R360; Leptin levels in adipose tissue significantly decreased in I60R30 and I60R90, while they increased significantly in I60R360. Compared with sham group, Leptin mRNA levels elevated significantly in I60R30, I60R240 and I60R360, but lowered significantly in I60R150.. Leptin has a time-dependent response to acute inflammatory stimuli such as intestinal ischemia/reperfusion injury, and it migh play a role as an inflammatory cytokine.

Topics: Adipose Tissue; Animals; Disease Models, Animal; Female; Intestines; Leptin; Male; Random Allocation; Rats; Rats, Sprague-Dawley; Reperfusion Injury; RNA, Messenger

As leptin is an active mediator mainly secreted by adipose tissue and is closely related with energy metabolism, we evaluate both the changes of leptin levels in serum and adipose tissue with a concise radioimmunoassay and the changes of leptin mRNA expression in adipose tissue with RT-PCR, during the severe metabolic impediment in rat intestinal ischemia-reperfusion (I/R) injury. Results show that not only leptin levels in serum and adipose tissue but also its mRNA expression in adipose tissue undergo a fluctuation according to different injury times. Therefore, we conclude that leptin has a time-dependent response to acute inflammatory stimuli and acts as an anti-inflammatory cytokine.

Topics: Adipose Tissue; Animals; Anti-Inflammatory Agents; Base Sequence; Cytokines; Inflammation; Intestines; Leptin; Male; Rabbits; Radioimmunoassay; Rats; Reperfusion Injury; RNA, Messenger; Sensitivity and Specificity

The peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand-dependent nuclear receptor that has been implicated in the control of metabolism and numerous cellular processes, including cell cycle control, carcinogenesis, and inflammation. The present study was designed to investigate the effect of the specific PPARgamma ligand, pioglitazone, on the mucosal lesions induced by ischaemia and reperfusion (I/R) in rats.. I/R lesions were induced in Wistar rats by applying a small clamp to the coeliac artery for 30 min (ischaemic phase), followed by the removal of the clamp for 3 h (reperfusion phase). Vehicle (saline) or increasing doses of pioglitazone (2.5, 10, and 30 mg/kg i.g.) were given 30 min before exposure to I/R. The animals were killed immediately after the end of the reperfusion phase (time 0) and at 12 and 24h after I/R. The area of gastric lesions was measured by planimetry, and the gastric blood flow was determined by the H2 gas clearance method. The gastric mucosal gene expressions of PPARgamma, interleukin-1beta (IL-1beta), tumour necrosis factor alpha (TNF-alpha), leptin, cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) were examined by RT-PCR. In addition, protein expression of COX-2 and leptin was assessed by Western blot.. The pretreatment with pioglitazone reduced in a dose-dependent manner the mean lesion area induced by I/R, and this effect was accompanied by a significant increase in the gastric blood flow. The decrease in gastric ulcerations by pioglitazone was also observed 12 and 24 h after the I/R. The PPARgamma mRNA was weakly expressed in the intact gastric mucosa but significantly up-regulated after exposure to I/R at each time interval studied. The expression of IL-1beta was not changed significantly after pioglitazone applied i.g. at doses 2.5 and 10 mg/kg, but it was down-regulated at the dose 30mg/kg. TNFalpha mRNA was strongly increased after the exposure to I/R, but it was down-regulated after pioglitazone pretreatment. In contrast, both leptin and COX-2 mRNA and protein expression were increased in the gastric mucosa after exposure to I/R. The pretreatment with pioglitazone caused a significant up-regulation of mRNA and protein expression of leptin, reaching its peak at the dose 30 mg/kg i.g. In contrast, COX-2 expression did not change significantly after the 2.5 and 10 mg/kg of pioglitazone, but it significantly decreased after pioglitazone at dose 30 mg/kg given to rats before exposure to I/R.. Pioglitazone reduces the acute erosions and deeper gastric lesions induced by I/R. The beneficial effect of this PPARgamma ligand on I/R-induced gastric damage may be due to its anti-inflammatory properties, especially to the reduction in TNF-alpha expression and to up-regulation of leptin mRNA in the gastric mucosa. The inhibition of COX-2 expression by pioglitazone may reflect the anti-inflammatory properties of this compound.

Topics: Amino Acid Sequence; Animals; Cyclooxygenase 1; Cyclooxygenase 2; Gastric Mucosa; Hypoglycemic Agents; Interleukin-1; Isoenzymes; Leptin; Male; Membrane Proteins; Models, Animal; Pioglitazone; Prostaglandin-Endoperoxide Synthases; Rats; Rats, Wistar; Receptors, Cytoplasmic and Nuclear; Reperfusion Injury; Splanchnic Circulation; Stomach Ulcer; Thiazoles; Thiazolidinediones; Transcription Factors; Tumor Necrosis Factor-alpha

Leptin has cytoprotective effect to gastric mucosal injury in rats. We aimed to test the hypothesis that leptin induced histamine is involved in the prevention of ischemia-reperfusion (I/R) induced gastric mucosal injury in rats. At the end of the 30 min celiac artery occlusion and 12h reperfusion process, serum and gastric tissue samples were taken from three group of rats to measure oxidative status, histamine levels and for histological examinations. Leptin decreased ulcer and polymorphonuclear leukocyte (PMNL) index, and serum malondialdehyde (MDA) and protein carbonyl content but increased gastric tissue histamine levels. We concluded that leptin exerts a protective effect on gastric mucosa to I/R induced gastric injury probably through increasing tissue histamine content which, in turn, maintain the gastric mucosal blood flow.

Topics: Animals; Female; Gastric Mucosa; Histamine; Leptin; Oxidative Stress; Rats; Rats, Sprague-Dawley; Reperfusion Injury

To explore the effect of intestinal ischemia/reperfusion injury on Leptin concentrations in serum and adipose tissue, and to find out the role of Leptin in acute inflammatory responses.. An intestinal ischemia-reperfusion injury model of rats was established, and used a highly-sensitive murine Leptin radioimmunoassay to check the change of Leptin concentrations in serum and adipose tissue.. Serum Leptin level (10.82+/-0.83) microg/L significantly decreased after an injury of 60-minute ischemia and 30-minute reperfusion versus pre-experimental serum levels (16.46+/-3.21) microg/L; Leptin level in serum was higher than that in adipose tissue (4.466+/-2.63) mg/100g, and they both showed a similar changeable trend to increase step by step as reperfusion time extended (P=0.047).. Leptin may be an inflammatory cytokine and may play a role in inflammatory responses such as intestinal ischemia/reperfusion.

Topics: Animals; Female; Intestines; Ischemia; Leptin; Male; Rabbits; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Reperfusion Injury

Leptin is a hormone implicated in the regulation of the food intake and body weight, but also increasing number of evidence suggest that leptin participates in the regulation of inflammatory processes. The aim of our study was to examine the influence of exogenous leptin administration on the development and the course of acute ischemic pancreatitis. Acute pancreatitis was induced by temporary limitation of pancreatic blood flow, followed by reperfusion. Leptin was administered three times daily at the dose 10 or 50 micrograms/kg. Studies were terminated at 1, 3, 5, 10 and 21 days after induction of acute pancreatitis. Leptin administration reduced development of pancreatic damage and accelerated pancreatic regeneration. It was manifested by the decrease in serum lipase and amylase activity, the reduction in serum interleukin-1 beta concentration and the improvement of pancreatic histology. Additionally, treatment with leptin caused the increase in the pancreatic blood flow and pancreatic DNA synthesis. Serum interleukin-10 concentration was not effected by leptin administration. Leptin at the dose 50 micrograms/kg was more effective than 10 micrograms/kg. We conclude that leptin is able to limit the pancreatic damage in the course of ischemic pancreatitis and accelerates the pancreatic tissue repair. These effects of leptin seem to be dependent on the increase in pancreatic cell growth, the limitation of pro-inflammatory interleukin-1 beta release and the improvement of pancreatic blood flow.

Topics: Acute Disease; Animals; DNA; Dose-Response Relationship, Drug; Interleukin-1; Interleukin-10; Leptin; Male; Pancreas; Pancreatitis; Rats; Rats, Wistar; Regional Blood Flow; Reperfusion Injury; Time Factors

Leptin, a product of ob gene controlling food intake, has recently been detected in the stomach and shown to be released by CCK and implicated in gastroprotection against various noxious agents but it is unknown whether centrally applied leptin influences ischemia-reperfusion (I/R)-induced gastric erosions that progress into deeper gastric ulcerations. In this study we compared the effects of leptin and CCK-8 applied intracerebroventricularly (i.c.v.) or intraperitoneally (i.p.) on gastric mucosal lesions induced by I/R and topical application of 75% ethanol. Several major series of Wistar rats were used to examine the effects of leptin and CCK applied centrally on gastroprotection against I/R and ethanol in rats with A) vagotomy by cutting of vagal nerves, B) suppression of NO-synthase with L-NNA (20 mg/kg i.p.), C) inactivation of sensory nerves by capsaicin (125 mg/kg s.c.) and D) inhibition of CGRP receptors with CGR(8-37) (100 microg/kg i.p.) applied with or without the i.c.v. pretreatment with leptin or CCK-8. Rats were anesthetized 1 h after ethanol administration or at 3 h and 3 days upon the end of ischemia to measure the gastric blood flow (GBF) and then to determine the area of gastric lesions by planimetry. Blood was withdrawn for the measurement of plasma leptin and gastrin levels by radioimmunoassay (RIA). Leptin (0.1-20 microg/kg i.p.) dose-dependently attenuated gastric lesions induced by 75% ethanol and I/R; the dose reducing these lesions by 50% (ED50) was 8 microg/kg and 6 microg/kg, respectively and this protective effect was similar to that obtained with CCK-8 applied in a standard dose of 10 microg/kg i.p. This protective effect of leptin was accompanied by a significant increase in GBF and plasma gastrin levels whereas CCK-8 increased plasma leptin levels but failed to affect plasma gastrin levels. Leptin and CCK-8 applied i.c.v. in a dose of 625 ng/rat reduced significantly the area of I/R induced gastric lesions and raised the GBF and plasma leptin levels with the extent similar to those achieved with peripheral administration of leptin or CCK-8 (10 microg/kg i.p.). The protective and hyperemic effects of centrally administered leptin or CCK-8 (625 ng/rat i.c.v.) were completely abolished by vagotomy and significantly attenuated by sensory denervation with capsaicin or by CGRP antagonist, CGRP(8-37). The pretreatment with L-NNA to inhibit NO-synthase activity attenuated significantly the protective and hyperemic effects of CCK but

Topics: Animals; Brain; Calcitonin Gene-Related Peptide; Cytoprotection; Gastric Mucosa; Gastrins; Leptin; Male; Neurons, Afferent; Nitric Oxide; Rats; Rats, Wistar; Regional Blood Flow; Reperfusion Injury; Sincalide; Vagus Nerve