piperidines and nitroxyl

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

Spirocyclic nitroxyl radicals (SNRs) are stable paramagnetics bearing spiro-junction at a-, b-, or g-carbon atom of the nitroxide fragment, which is part of the heterocyclic system. Despite the fact that the first representatives of SNRs were obtained about 50 years ago, the methodology of their synthesis and their usage in chemistry and biochemical applications have begun to develop rapidly only in the last two decades. Due to the presence of spiro-function in the SNRs molecules, the latter have increased stability to various reducing agents (including biogenic ones), while the structures of the biradicals (SNBRs) comprises a rigid spiro-fused core that fixes mutual position and orientation of nitroxide moieties that favors their use in dynamic nuclear polarization (DNP) experiments. This first review on SNRs will give a glance at various strategies for the synthesis of spiro-substituted, mono-, and bis-nitroxides on the base of six-membered (piperidine, 1,2,3,4-tetrahydroquinoline, 9,9'(10

Topics: Imidazoles; Imidazolidines; Morpholines; Natural Science Disciplines; Nitrogen Oxides; Oxazoles; Piperidines; Pyrrolidines; Reducing Agents

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; 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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; 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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

Organophosphorus compounds occupy a significant position among the plethora of organic compounds, but a limited number of paramagnetic phosphorus compounds have been reported, including paramagnetic phosphonates. This paper describes the syntheses and further transformations of pyrroline and piperidine nitroxide phosphonates by well-established methods, such as the Pudovik, Arbuzov and Horner-Wadsworth-Emmons (HWE) reactions. The reaction of paramagnetic a-bromoketone produced a vinylphosphonate in the Perkow reaction. Paramagnetic a-hydroxyphosphonates could be subjected to oxidation, elimination and substitution reactions to produce various paramagnetic phosphonates. The synthesized paramagnetic phosphonates proved to be useful synthetic building blocks for carbon-carbon bond-forming reactions in the Horner-Wadsworth-Emmons olefination reactions. The unsaturated compounds achieved could be transformed into various substituted pyrroline nitroxides, proxyl nitroxides and paramagnetic polyaromatics. The Trolox

Topics: Alkenes; Carbon; Molecular Structure; Nitrogen Oxides; Organophosphonates; Piperidines; Pyrroles; Stereoisomerism

The cytotoxicity and antioxidant effects of chitosan-(poly)nitoxides of different molecular weights containing a nitroxide radical of the piperidine structure were studied on tumor (HeLa, A172, and HepG2) and normal (Vero) cell lines. The chitosan-(poly)nitroxides exhibited low cytotoxicity. Under conditions of oxidative stress induced with tert-butyl hydroperoxide, the most pronounced decrease in ROS levels in the presence of chitosan-(poly)nitroxides was observed in normal cells. In cell homogenates, the decrease in malondialdehyde levels was observed only in the presence of low-molecular-weight chitosan-(poly)nitroxide irrespective of the cell line. Our data demonstrate that the cell-specific antioxidant properties of chitosan-(poly)nitroxides are related to their penetration into cells and interaction with intracellular membranes.

Topics: Animals; Antioxidants; Cell Line, Tumor; Chitosan; Chlorocebus aethiops; HeLa Cells; Hep G2 Cells; Humans; Neuroglia; Nitrogen Oxides; Organ Specificity; Oxidative Stress; Piperidines; Reactive Oxygen Species; Structure-Activity Relationship; tert-Butylhydroperoxide; Vero Cells

Secondary piperidines are ideal pharmaceutical building blocks owing to the prevalence of piperidines in commercial drugs. Here, we report an electrochemical method for cyanation of the heterocycle adjacent to nitrogen without requiring protection or substitution of the N-H bond. The reaction utilizes ABNO (9-azabicyclononane N-oxyl) as a catalytic mediator. Electrochemical oxidation of ABNO generates the corresponding oxoammonium species, which promotes dehydrogenation of the 2° piperidine to the cyclic imine, followed by addition of cyanide. The low-potential, mediated electrolysis process is compatible with a wide range of heterocyclic and oxidatively sensitive substituents on the piperidine ring and enables synthesis of unnatural amino acids.

Topics: Cyanates; Electrochemical Techniques; Molecular Structure; Nitrogen Oxides; Oxidation-Reduction; Piperidines

Ascorbic acid (AsA), also known as vitamin C, is a vital small-molecule antioxidant with multiple functions in vivo. It's the major natural antioxidant found in plants and is also an essential component of human nutrition. AsA plays a key role in many diseases-related biological metabolism. Therefore, sensitive and selective detection of AsA is greatly important in pharmaceutical, clinical and food industry. Here a sensitive and selective sensor for ascorbic acid detection based on the recovered fluorescence of NAPS-NO (N-propyl-triethoxysilane-4-(4-ylamino-1-oxy-2,2,6,6-tetramethylpiperdine)- naphthalimide) probe is described. The fluorescence of the naphthalimide moiety of NAPS-NO is inhibited by the nitroxide group, which is covalently linked to the fluorophore. Then, ascorbic acid reacts rapidly with the nitroxide moiety of NAPS-NO to form hydroxylamine, and the fluorescence properties of the naphthalimide moiety are recovered and the ESR signal decayed. Over a wide range from 80 nM to 50 μM, a good linear relationship between the fluorescence intensity and the concentration of ascorbic acid was found and the detection limit was estimated to be as low as 20 nM. To confirm the practical usefulness of the fluorophore-nitroxide probe, we demonstrated the use of NAPS-NO for the measurement of AsA in human blood serum and also successfully determined the concentration of AsA in HEK 293 cell lysate. Results from confocal laser scanning microscopy experiments demonstrated that this chemosensor is cell permeable and can be used as a fluorescent probe for monitoring ascorbic acid in living cells.

Topics: Ascorbic Acid; Biological Transport; Cell Extracts; Fluorescence; HEK293 Cells; Humans; Limit of Detection; Molecular Probes; Naphthalimides; Nitrogen Oxides; Piperidines; Spectrometry, Fluorescence

Considering the role of oxidative stress in carcinogenesis, we investigated the effect of synthetic antioxidant Pirolin (3-carbamoyl-2,2,5,5-tetramethylpyrroline-1-oxyl) on breast cancer progression. Since the anticancer drugs may cause cardiotoxicity due to oxidative stress in the heart muscle, we also evaluated Pirolin performance in heart tissue and compared its effect with that of the natural dietary flavonoid quercetin.. Sprague-Dawley rats were administered with 7,12-dimethylbenz(a)anthracene (DMBA) and then treated ip with an antioxidant (each at a dose of 10mg/kg b.w.) for 14 days. The histopathology of tumors, their size and multiplicity were assesed. The effect of antioxidants on heart tissue was evaluated by the oxidative stress markers and poly (ADP-ribose) polymerase 1 (PARP 1) cleavage.. The median number of tumors and their volume, at the end of the study, were considerably smaller in both antioxidant-treated groups. We found a better antioxidative performance of quercetin in the heart, since a restoration of the GSH pool and decreased amount of hydroperoxides were observed. Antioxidants did not prevent cardiomyocytes from apoptosis.. The attenuation of tumor progression by Pirolin was comparable with the action of quercetin. No negative changes were observed in the heart of animals after Pirolin treatment. Thus, its use in targeting deregulated redox pathways should be further studied.

Topics: Animals; Anthracenes; Antineoplastic Agents; Cyclic N-Oxides; Female; Mammary Neoplasms, Experimental; Nitrogen Oxides; Piperidines; Quercetin; Rats; Rats, Sprague-Dawley

Stable nitroxide radical bearing organic polymer materials are attracting much attention for their application as next generation energy storage materials. A greater understanding of the inherent charge transfer mechanisms in such systems will ultimately be paramount to further advancements in the understanding of both intrafilm and interfacial ion- and electron-transfer reactions. This work is focused on advancing the fundamental understanding of these dynamic charge transfer properties by exploiting the fact that these species are efficient fluorescence quenchers. We systematically incorporated fluorescent perylene dyes into solutions containing the 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) radical and controlled their interaction by binding the TEMPO moiety into macromolecules with varying morphologies (e.g., chain length, density of radical pendant groups). In the case of the model compound, 4-oxo-TEMPO, quenching of the perylene excited state was found to be dominated by a dynamic (collisional) process, with a contribution from an apparent static process that is described by an ∼2 nm quenching sphere of action. When we incorporated the TEMPO unit into a macromolecule, the quenching behavior was altered significantly. The results can be described by using two models: (A) a collisional quenching process that becomes less efficient, presumably due to a reduction in the diffusion constant of the quenching entity, with a quenching sphere of action similar to 4-oxo-TEMPO or (B) a collisional quenching process that becomes more efficient as the radius of interaction grows larger with increasing oligomer length. This is the first study that definitively illustrates that fluorophore quenching by a polymer system cannot be explained using merely a classical Stern-Volmer approach but rather necessitates a more complex model.

Topics: Cyclic N-Oxides; Fluorescent Dyes; Molecular Conformation; Molecular Dynamics Simulation; Nitrogen Oxides; Perylene; Piperidines; Polymers; Spectrometry, Fluorescence

Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor mainly caused by mutations in the RET proto-oncogene. For MTC therapy, the U.S. Food and Drug Administration recently approved vandetanib and cabozantinib, multikinase inhibitors targeting RET and other tyrosine kinase receptors of vascular endothelial growth factor, epidermal growth factor, or hepatocyte growth factor. Nevertheless, not all patients with the progressive MTC respond to these drugs, requiring the development of additional therapeutic modalities that have distinct activity.. We aimed to evaluate mitochondria-targeted carboxy-proxyl (Mito-CP), a mitochondria-targeted redox-sensitive agent, for its tumor-suppressive efficacy against MTC.. In vitro cultures of 2 human MTC cell lines, TT and MZ-CRC-1, and TT xenografts in mice were treated with Mito-CP in comparison with vandetanib. The effects on cell survival/death, RET expression, mitochondrial integrity, and oxidative stress were determined.. Contrary to vandetanib, Mito-CP induced RET downregulation and strong cytotoxic effects in both cell lines in vitro, including caspase-dependent apoptosis. These effects were accompanied by mitochondrial membrane depolarization, decreased oxygen consumption, and increased oxidative stress in cells. Intriguingly, Mito-CP-induced cell death, but not RET downregulation, was partially inhibited by the reactive oxygen species scavenger, N-acetyl-cysteine, indicating that Mito-CP mediates tumor-suppressive effects via redox-dependent as well as redox-independent mechanisms. Orally administered Mito-CP effectively suppressed TT xenografts in mice, with an efficacy comparable to vandetanib and relatively low toxicity to animals.. Our results suggest that Mito-CP can effectively suppress MTC cell growth/survival via a mechanism distinct from vandetanib effects. Mitochondrial targeting may be a potential strategy for MTC therapy.

Topics: Animals; Antineoplastic Agents; Carcinoma, Neuroendocrine; Cell Line, Tumor; Cell Survival; Cyclic N-Oxides; Drug Delivery Systems; Female; Humans; Mice; Mice, Nude; Mitochondria; Nitrogen Oxides; Organophosphorus Compounds; Piperidines; Proto-Oncogene Mas; Quinazolines; Thyroid Neoplasms; Xenograft Model Antitumor Assays

Design of the new spin-labeled cyclodextrins can significantly extend the functionality of nitroxides. A series of new complexes based on fully methylated cyclodextrin (TRIMEB) covalently bound to the piperidine, pyrroline, pyrrolidine, and pH-sensitive imidazoline type nitroxides has been synthesized and studied using pulse and continuous wave electron paramagnetic resonance (EPR). The influence of the radical and linker properties on the structure of complexes formed has been investigated. Using the electron spin echo envelope modulation technique, we have analyzed quantitatively the accessibility of radicals to solvent molecules in studied complexes depending on the structure and length of the linkers. In all studied systems we observed different types of equilibria between conformations with radical fragment being outside the TRIMEB cavity and radical fragment capping the cavity of TRIMEB. The observed guest-induced shift of equilibrium toward the complex with radical capping TRIMEB cavity was explained by a change of macrocyclic configuration of TRIMEB. Complex with the -NH-CO- linker has been found most perspective for the applications requiring close location of nitroxide to the inclusion complex of TRIMEB. Using continuous wave EPR, we have shown that the pH-sensitive radical covalently bound to TRIMEB maintains its pH-sensitivity, but this complexation does not reduce radical reduction rate in the reaction with ascorbic acid.

Topics: Cyclodextrins; Electron Spin Resonance Spectroscopy; Hydrogen-Ion Concentration; Kinetics; Nitrogen Oxides; Piperidines; Pyrroles; Pyrrolidines; Spin Labels

Reactive oxygen species (ROS) scavengers have not been widely used for treatment of local inflammatory reactions such as arthritis and periodontal disease because they are rapidly eliminated from the inflamed site, which results in a low therapeutic effect. Therefore, to enhance the local retention time of ROS scavengers, we developed a redox-active injectable gel (RIG) system by using poly[4-(2,2,6,6-tetramethylpiperidine-N-oxyl)aminomethylstyrene]-b-poly(ethylene glycol)-b-poly[4-(2,2,6,6-tetramethylpiperidine-N-oxyl)aminomethylstyrene] (PMNT-PEG-PMNT) triblock copolymer, which possesses ROS scavenging nitroxide radicals as side chains of the PMNT segment. Cationic PMNT segment in PMNT-PEG-PMNT forms polyion complexes with anionic poly(acrylic acid) (PAAc) to form a flower-like micelle (ca. 79 nm), which exhibits in situ thermo-irreversible gelation under physiological conditions. We confirmed the prolonged site-specific retention time of RIG by performing in vivo noninvasive electron spin resonance imaging and quantitative evaluation. In contrast to low-molecular-weight nitroxide radical compounds that disappeared from injection sites in less than 1h after subcutaneous injection, 40% of the RIG remained even at 3 days. We also found that RIG inhibits neutrophil infiltration and cytokine production, which leads to suppression of hyperalgesia. These findings indicate the potential of RIG as an innovative approach for treatment of local inflammation.

Topics: Acrylic Resins; Animals; Antioxidants; Arthritis; Delayed-Action Preparations; Gels; Inflammation; Injections; Ions; Male; Mice; Micelles; Nitrogen Oxides; Oxidation-Reduction; Phase Transition; Piperidines; Polyethylene Glycols; Styrene; Temperature

EPR spectra of aqueous solutions of the singly charged surfactant nitroxide 4-[N,N-dimethyl-N-(ndodecyl) ammonium]-2,2,6,6-tetramethylpiperidinyl-N-oxy bromide-d16 (DCAT12) are studied as functions of the molar concentration, c = 0.1-8 mM, and the temperature from 273 to 353 K. This concentration range is below the critical micelle concentration, cmc, at which DCAT12 forms micelles. Spin-spin broadening of the EPR lines averaged over the three lines is separated into contributions due to spin exchange, , and dipolar, , interactions yielding values of the fractional broadening by spin exchange, Omega(T), that vary from near unity at 353 K to approximately 50% at 273 K. This compares with a variation from unity to approximately 77% for a neutral spin probe perdeuterated 2,2,6,6-tetramethyl-4-oxopiperidine-1-oxyl (PDT) over the same range. Unlike PDT and the Stokes-Einstein prediction, the broadening constant by spin exchange, d/dc, is not linear with T/eta, where eta is the shear viscosity, instead following a quadratic dependence. Nevertheless, d/dc is remarkably close to a hydrodynamic prediction using the Stokes-Einstein equation modified to take the spin probe charge into account. Compared with PDT, values of d/dc are decreased and d/dc increased at all temperatures, while the values of the re-encounter rate, tau(RE)(-1), deduced from line shifts, are reduced. Interestingly, values of d/dc, Omega(T), and tau(RE)(-1) are comparable for PDT and DCAT12 when compared at the same rotational diffusion rates.

Topics: Electron Spin Resonance Spectroscopy; Free Radicals; Micelles; Nitrogen Oxides; Piperidines; Protons; Quaternary Ammonium Compounds; Surface-Active Agents; Temperature; Water

EPR line shifts due to spin exchange of perdeuterated 2,2,6,6-tetramethyl-4-oxopiperidine-1-oxyl (14N-PDT) in aqueous solutions and the same probe isotopically substituted with 15N (15N-PDT) were measured from 293 to 338 and 287 to 353 K, respectively. Nonlinear least-squares fits of the EPR spectra yielded the resonance fields of the nitrogen hyperfine lines to high precision from which the shifts were deduced. The shifts are described by two terms: one linear and the other quadratic in the electron spin-exchange frequency, omegae. The quadratic term is due to spin exchange that occurs when two spin probes diffuse together and collide. A linear term is predicted for spin exchanges that occur upon re-encounter of the same two probes while they occupy the same "cage" before diffusing apart. The quadratic term has no adjustable parameters, while the linear term has one: the mean time between re-encounters, tauRE. The theory is cast in terms of the spin-exchange-induced line broadening that can be measured from each spectrum independently of the line shifts, thereby removing the explicit dependence of omegae on the temperature and the spin-probe concentration. In this form, theoretically, the value of the linear term is about a factor of 2 larger for 15N-PDT than for 14N-PDT for all temperatures; however, tauRE must be the same. Experimentally, we find that both of these expectations are fulfilled, providing strong support that the linear term is indeed due to re-encounter collisions. Values of tauRE derived from 14N-PDT and 15N-PDT are of the same order of magnitude and show the same trend with temperature as a hydrodynamic estimate based on the Stokes-Einstein equation.

Topics: Electron Spin Resonance Spectroscopy; Free Radicals; Least-Squares Analysis; Nitrogen Isotopes; Nitrogen Oxides; Piperidines; Triacetoneamine-N-Oxyl

Microsurgical procedures such as free tissue transfer or replantations of amputated digits involve an obligatory ischemic period leading to regional tissue oedema, rhabdomyolysis, systemic acidosis, hypercalcemia and multiple organ dysfunction syndrome reflecting ischemia-reperfusion (I/R) injury. Since nitroxide stable radicals act as antioxidants their potential protective effects were tested. Anaesthetized Sabra rats were subjected to regional ischemia of the hind limb for 2 h using a tourniquet. Upon reperfusion rats were injected with 4-OH-2,2,6,6-tetramethylpiperidine-1-oxyl (TPL). Systemic I/R-induced damage was assessed by sampling blood for differential count, lactate dehydrogenase (LDH) and creatine phosphokinase (CPK) serum levels. Regional injury was evaluated by analysing excised muscle samples for oedema (tissue water content) and inflammatory infiltrate (number of cell nuclei in histomorphometric analysis). I/R-induced changes of biomarkers reflecting systemic damage peaked about 8 h following the start of reperfusion and fully disappeared as the biomarkers relaxed to their pre-ischemic values after 24 h. TPL facilitated the recovery of some of these parameters and partially affected release of cellular CPK and LDH. The parameters of I/R-induced regional tissue injury did not demonstrate any recovery and were not inhibited by TPL.

Topics: Animals; Antioxidants; Blood Cell Count; Creatine Kinase; Disease Models, Animal; Electromyography; Hindlimb; Ischemia; L-Lactate Dehydrogenase; Male; Muscle, Skeletal; Nitrogen Oxides; Piperidines; Random Allocation; Rats; Reperfusion Injury

Two new analogues of the antiparkinsonian drug 1-aminoadamantane: 4-(1-adamantylamino)-2,2,6,6-tetramethylpiperidine-1-oxyl and 4-(1-adamantylammonio)-1-hydroxy-2,2,6,6-tetramethylpiperidinium dihydrochloride have been synthesized. Their antioxidant activity towards reactive oxygen species (ROS: (z.rad;)OH and O(2)(z.rad;-)) have been evaluated in three test systems. The compound with nitroxide substituent displays higher anti-oxidative capacity than those containing hydroxylamine. The in vivo study of ROS-involving 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-rat model of induced parkinsonism was undertaken to ascertain the neuroprotective ability of the novel synthesized compounds-antioxidants. The data clearly shows that the nitroxide free radical moiety of the molecule is necessary for their neuroprotective action on dopaminergic neurons under the applied conditions of deep oxidative stress caused by the neurotoxin (MPTP). The new synthesized analogues may find application in treatment of parkinsonian syndromes, either to block or to reduce the ROS-mediated neuronal damage and death.

Topics: Adamantane; Amantadine; Animals; Antioxidants; Antiparkinson Agents; Brain; Dopamine; Female; Free Radicals; Immunohistochemistry; Molecular Structure; Nitrogen Oxides; Parkinsonian Disorders; Piperidines; Rats; Rats, Inbred BUF; Reactive Oxygen Species; Spectrophotometry; Tyrosine 3-Monooxygenase

Reactive oxygen-derived species and redox-active metals are implicated in mediation of the pathogenesis of gastric mucosal damage and ulceration. Therefore, common strategies of intervention employ metal chelators, antioxidative enzymes, and low-molecular-weight antioxidants (LMWA). The aim of the present study was to elaborate the mechanism(s) responsible for the protection provided by nitroxide radicals in the experimental model of gastric ulceration. Fasted male rats were treated ig with 1 ml 96% ethanol, with or without ig pretreatment with nitroxide or hydroxylamine. In several experiments, rats were injected ip or iv with iron(III) or iron(II) prior to ethanol administration. Rats were sacrificed 10 min after ethanol administration, the stomach was removed, washed and lesion area measured. Pretreatment with iron(III) complexed to nitrilotriacetate or citrate, aggravated the extent of the gastric injury. Conversely, iron(II) inhibited the formation of lesions. The nitroxides were rapidly reduced to their respective hydroxylamines and demonstrated antiulcerative activity for rats treated with iron. However, injecting the hydroxylamine resulted in a similar tissue distribution of nitroxide/hydroxylamnine but did not provide protection. The results show that: (a) the nitroxide radicals, rather than their respective non-radical reduced form, are the active species responsible for protection; (b) nitroxides protect by dismutating O2*- and possibly indirectly increasing the NO level; (c) unlike classical LMWA which are reducing agents, nitroxides inhibit gastric damage by acting as mild oxidants, oxidizing reduced metals and pre-empting the Fenton reaction; and (d) the nitroxides act catalytically as recycling antioxidants.

Topics: Animals; Anti-Ulcer Agents; Antioxidants; Copper; Cyclic N-Oxides; Disease Models, Animal; Dose-Response Relationship, Drug; Ethanol; Gastric Mucosa; Hydroxylamines; Iron Compounds; Male; Nitrogen Oxides; Oxidants; Piperidines; Rats; Rats, Sprague-Dawley; Spin Labels; Stomach Ulcer

Reactive oxygen-derived species were previously implicated in mediation of post-traumatic brain damage; however, the efficacy of traditional antioxidants in preventing/reversing the damage is sometimes limited. The present work focused on the mechanisms underlying the neuroprotective activity of cell permeable, nontoxic, antioxidants, namely stable nitroxide radicals in an experimental model of rat closed-head injury. Brain damage was induced by the weight-drop method and the clinical status was evaluated according to a neurological severity score at 1 h and 24 h, where the difference between these scores reflects the extent of recovery. The metal chelator deferoxamine as well as three nitroxide derivatives, differing in hydrophilicity and charge, and one hydroxylamine (a reduced nitroxide) facilitated the clinical recovery and decreased the brain edema. The nitroxides, but neither the hydroxylamine nor deferoxamine, protected the integrity of the blood-brain barrier. Superoxide dismutase also improved the clinical recovery but did not affect brain edema or the blood-brain barrier. The results suggest that by switching back and forth between themselves, the nitroxide and hydroxylamine act catalytically as self-replenishing antioxidants, and protect brain tissue by terminating radical-chain reactions, oxidizing deleterious metal ions, and by removal of intracellular superoxide.

Topics: Animals; Antioxidants; Blood-Brain Barrier; Brain Diseases; Brain Edema; Deferoxamine; Head Injuries, Closed; Hydroxylamine; Male; Neuroprotective Agents; Nitrogen Oxides; Piperidines; Rats; Superoxide Dismutase

A series of dansylated sterically hindered amines designed to trapping reactive oxygen species, were synthesized. Compounds were tested in isolated thylakoid membranes subjected to photoinhibition by excess photosynthetically active radiation (400-700 nm). DanePy showed good selectivity for singlet oxygen and the formation of nitroxide was detected by appearance of ESR signal and quenching fluorescence.

Topics: Chloroplasts; Cyclic N-Oxides; Dansyl Compounds; Electron Spin Resonance Spectroscopy; Intracellular Membranes; Light; Nitrogen Oxides; Oxygen; Piperidines; Reactive Oxygen Species; Singlet Oxygen; Spectrometry, Fluorescence; Spin Labels; Spinacia oleracea

In plants experiencing environmental stress, the formation of reactive oxygen is often presumed. In this study, singlet oxygen was detected in broad bean (Vicia faba) leaves that were photoinhibited in vivo. Detection was based on the reaction of singlet oxygen with DanePy (dansyl-2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrole) yielding a nitroxide radical (DanePyO) which is EPR active and also features lower fluorescence compared to DanePy. The two (fluorescent and spin) sensor fuctions of DanePy are commensurate, which makes detecting singlet oxygen possible with a spectrofluorimeter in samples hard to measure with EPR spectroscopy [Kálai, T., Hideg, E., Vass, I., and Hideg, K. (1998) Free Radical Biol. Med. 24, 649-652]. We found that in leaves saturated with DanePy, the fluorescence of this double sensor was decreased when the leaves were photoinhibited by 1500 micromol m-2 s-1 photosynthetically active radiation. This fluorescence quenching is the first direct experimental evidence that photoinhibition of photosynthesis in vivo is accompanied by 1O2 production and is, at least partly, governed by the process characterized as acceptor side-induced photoinhibition in vitro.

Topics: Dansyl Compounds; Electron Spin Resonance Spectroscopy; Fabaceae; Fluorescence Polarization; Free Radicals; Nitrogen Oxides; Oxygen; Photochemistry; Photosynthesis; Photosynthetic Reaction Center Complex Proteins; Piperidines; Plant Leaves; Plants, Medicinal; Singlet Oxygen; Spectrometry, Fluorescence; Spin Labels; Time Factors

The effects of Cu(II) and the stable nitroxide radical 4-OH-2, 2, 6, 6-tetramethyl-piperidine-1-oxyl (TPL) on reperfusion injury following global myocardial ischemia have been studied using the isolated rat heart model in the Langendorff configuration. Hearts were equilibrated with Krebs-Henseleit buffer (KH-buffer) for 10 min and subjected to 18 min of normothermic global ischemia. After 20 min reperfusion, hemodynamic parameters recovered as follows: ventricular developed pressure (77%), dP/dt (71%) and -dP/dt (80%), heart rate (91%), and work index (70%). End-diastolic pressure was 16 mm Hg. When 10 microM Cu-nitrilotriacetate or Cu-(histidine)2 was included in the perfusate before, during, and following ischemia, the heart injury was more extensive and the work index only recovered to 17% of the preischemic value. The inclusion of 100 microM TPL during reperfusion abolished the copper-induced sensitization. In the absence of copper, TPL did not provide any protection against ischemia-reperfusion damage to the heart. The inclusion of 100 microM 1,4-dihydroxy-2,2,6,6-tetramethylpiperidine (TPL-H) during reperfusion, partially abolished the copper-induced sensitization. Since conversion between TPL and TPL-H takes place, the fact that both forms provide protection can increase their protective efficacy.

Topics: Animals; Antioxidants; Copper; Cyclic N-Oxides; Hydroxylamine; In Vitro Techniques; Male; Myocardial Reperfusion Injury; Nitrogen Oxides; Phosphates; Piperidines; Rats; Rats, Sprague-Dawley; Spin Labels

The reduction rates of five-membered pyrrolidine and pyrroline, and six-membered piperidine nitroxides (alternatively termed nitroxyls) containing various substituents were determined under homogeneous conditions using ascorbate, and electrochemically under heterogeneous conditions. The results were compared with data from the literature. It was shown that the increased rates of reduction of six-membered nitroxides, compared with those of the five-membered nitroxides, cannot be explained on the basis of differences in electrochemical potentials but, rather, can be ascribed to differences in the accessibility of the nitroxide group. A double bond in the five-membered nitroxyls increases the reduction rate. Within any ring system, the reduction rates of nitroxides using ascorbate can be correlated with the inductive substituent constants. The half-way potentials for electrochemical reduction within a series of nitroxides based on the same ring correlate with logarithms of the rates using ascorbate and with the inductive constants. The potentials for one-electron oxidation of the nitroxides were related to the inductive constants.

Topics: Ascorbic Acid; Carbon; Electrochemistry; Electrodes; Kinetics; Mercury; Nitrogen Oxides; Oxidation-Reduction; Piperidines; Pyrrolidines