interleukin-8 and Wounds-and-Injuries

Middle East Respiratory Syndrome (MERS) is a novel respiratory illness firstly reported in Saudi Arabia in 2012. It is caused by a new corona virus, called MERS corona virus (MERS-CoV). Most people who have MERS-CoV infection developed severe acute respiratory illness.. This work is done to determine the clinical characteristics and the outcome of intensive care unit (ICU) admitted patients with confirmed MERS-CoV infection.. This study included 32 laboratory confirmed MERS corona virus infected patients who were admitted into ICU. It included 20 (62.50%) males and 12 (37.50%) females. The mean age was 43.99 ± 13.03 years. Diagnosis was done by real-time reverse transcription polymerase chain reaction (rRT-PCR) test for corona virus on throat swab, sputum, tracheal aspirate, or bronchoalveolar lavage specimens. Clinical characteristics, co-morbidities and outcome were reported for all subjects.. Most MERS corona patients present with fever, cough, dyspnea, sore throat, runny nose and sputum. The presence of abdominal symptoms may indicate bad prognosis. Prolonged duration of symptoms before patients' hospitalization, prolonged duration of mechanical ventilation and hospital stay, bilateral radiological pulmonary infiltrates, and hypoxemic respiratory failure were found to be strong predictors of mortality in such patients. Also, old age, current smoking, smoking severity, presence of associated co-morbidities like obesity, diabetes mellitus, chronic heart diseases, COPD, malignancy, renal failure, renal transplantation and liver cirrhosis are associated with a poor outcome of ICU admitted MERS corona virus infected patients.. Plasma HO-1, ferritin, p21, and NQO1 were all elevated at baseline in CKD participants. Plasma HO-1 and urine NQO1 levels each inversely correlated with eGFR (. SnPP can be safely administered and, after its injection, the resulting changes in plasma HO-1, NQO1, ferritin, and p21 concentrations can provide information as to antioxidant gene responsiveness/reserves in subjects with and without kidney disease.. A Study with RBT-1, in Healthy Volunteers and Subjects with Stage 3-4 Chronic Kidney Disease, NCT0363002 and NCT03893799.. HFNC did not significantly modify work of breathing in healthy subjects. However, a significant reduction in the minute volume was achieved, capillary [Formula: see text] remaining constant, which suggests a reduction in dead-space ventilation with flows > 20 L/min. (ClinicalTrials.gov registration NCT02495675).. 3 组患者手术时间、术中显性失血量及术后 1 周血红蛋白下降量比较差异均无统计学意义（. 对于肥胖和超重的膝关节单间室骨关节炎患者，采用 UKA 术后可获满意短中期疗效，远期疗效尚需进一步随访观察。.. Decreased muscle strength was identified at both time points in patients with hEDS/HSD. The evolution of most muscle strength parameters over time did not significantly differ between groups. Future studies should focus on the effectiveness of different types of muscle training strategies in hEDS/HSD patients.. These findings support previous adverse findings of e-cigarette exposure on neurodevelopment in a mouse model and provide substantial evidence of persistent adverse behavioral and neuroimmunological consequences to adult offspring following maternal e-cigarette exposure during pregnancy. https://doi.org/10.1289/EHP6067.. This RCT directly compares a neoadjuvant chemotherapy regimen with a standard CROSS regimen in terms of overall survival for patients with locally advanced ESCC. The results of this RCT will provide an answer for the controversy regarding the survival benefits between the two treatment strategies.. NCT04138212, date of registration: October 24, 2019.. Results of current investigation indicated that milk type and post fermentation cooling patterns had a pronounced effect on antioxidant characteristics, fatty acid profile, lipid oxidation and textural characteristics of yoghurt. Buffalo milk based yoghurt had more fat, protein, higher antioxidant capacity and vitamin content. Antioxidant and sensory characteristics of T. If milk is exposed to excessive amounts of light, Vitamins B. The two concentration of ZnO nanoparticles in the ambient air produced two different outcomes. The lower concentration resulted in significant increases in Zn content of the liver while the higher concentration significantly increased Zn in the lungs (p < 0.05). Additionally, at the lower concentration, Zn content was found to be lower in brain tissue (p < 0.05). Using TEM/EDX we detected ZnO nanoparticles inside the cells in the lungs, kidney and liver. Inhaling ZnO NP at the higher concentration increased the levels of mRNA of the following genes in the lungs: Mt2 (2.56 fold), Slc30a1 (1.52 fold) and Slc30a5 (2.34 fold). At the lower ZnO nanoparticle concentration, only Slc30a7 mRNA levels in the lungs were up (1.74 fold). Thus the two air concentrations of ZnO nanoparticles produced distinct effects on the expression of the Zn-homeostasis related genes.. Until adverse health effects of ZnO nanoparticles deposited in organs such as lungs are further investigated and/or ruled out, the exposure to ZnO nanoparticles in aerosols should be avoided or minimised.

Topics: A549 Cells; Acetylmuramyl-Alanyl-Isoglutamine; Acinetobacter baumannii; Acute Lung Injury; Adaptor Proteins, Signal Transducing; Adenine; Adenocarcinoma; Adipogenesis; Administration, Cutaneous; Administration, Ophthalmic; Adolescent; Adsorption; Adult; Aeromonas hydrophila; Aerosols; Aged; Aged, 80 and over; Aging; Agriculture; Air Pollutants; Air Pollution; Airway Remodeling; Alanine Transaminase; Albuminuria; Aldehyde Dehydrogenase 1 Family; Algorithms; AlkB Homolog 2, Alpha-Ketoglutarate-Dependent Dioxygenase; Alzheimer Disease; Amino Acid Sequence; Ammonia; Ammonium Compounds; Anaerobiosis; Anesthetics, Dissociative; Anesthetics, Inhalation; Animals; Anti-Bacterial Agents; Anti-HIV Agents; Anti-Infective Agents; Anti-Inflammatory Agents; Antibiotics, Antineoplastic; Antibodies, Antineutrophil Cytoplasmic; Antibodies, Monoclonal, Humanized; Antifungal Agents; Antigens, Bacterial; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Antioxidants; Antitubercular Agents; Antiviral Agents; Apolipoproteins E; Apoptosis; Arabidopsis; Arabidopsis Proteins; Arsenic; Arthritis, Rheumatoid; Asthma; Atherosclerosis; ATP-Dependent Proteases; Attitude of Health Personnel; Australia; Austria; Autophagy; Axitinib; Bacteria; Bacterial Outer Membrane Proteins; Bacterial Proteins; Bacterial Toxins; Bacterial Typing Techniques; Bariatric Surgery; Base Composition; Bayes Theorem; Benzoxazoles; Benzylamines; beta Catenin; Betacoronavirus; Betula; Binding Sites; Biological Availability; Biological Oxygen Demand Analysis; Biomarkers; Biomarkers, Tumor; Biopsy; Bioreactors; Biosensing Techniques; Birth Weight; Blindness; Blood Chemical Analysis; Blood Gas Analysis; Blood Glucose; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Blood-Brain Barrier; Blotting, Western; Body Mass Index; Body Weight; Bone and Bones; Bone Density; Bone Resorption; Borates; Brain; Brain Infarction; Brain Injuries, Traumatic; Brain Neoplasms; Breakfast; Breast Milk Expression; Breast Neoplasms; Bronchi; Bronchoalveolar Lavage Fluid; Buffaloes; Cadherins; Calcification, Physiologic; Calcium Compounds; Calcium, Dietary; Cannula; Caprolactam; Carbon; Carbon Dioxide; Carboplatin; Carcinogenesis; Carcinoma, Ductal; Carcinoma, Ehrlich Tumor; Carcinoma, Hepatocellular; Carcinoma, Non-Small-Cell Lung; Carcinoma, Pancreatic Ductal; Carcinoma, Renal Cell; Cardiovascular Diseases; Carps; Carrageenan; Case-Control Studies; Catalysis; Catalytic Domain; Cattle; CD8-Positive T-Lymphocytes; Cell Adhesion; Cell Cycle Proteins; Cell Death; Cell Differentiation; Cell Line; Cell Line, Tumor; Cell Movement; Cell Nucleus; Cell Phone Use; Cell Proliferation; Cell Survival; Cell Transformation, Neoplastic; Cell Transformation, Viral; Cells, Cultured; Cellulose; Chemical Phenomena; Chemoradiotherapy; Child; Child Development; Child, Preschool; China; Chitosan; Chlorocebus aethiops; Cholecalciferol; Chromatography, Liquid; Circadian Clocks; Circadian Rhythm; Circular Dichroism; Cisplatin; Citric Acid; Clinical Competence; Clinical Laboratory Techniques; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Clostridioides difficile; Clostridium Infections; Coculture Techniques; Cohort Studies; Cold Temperature; Colitis; Collagen Type I; Collagen Type I, alpha 1 Chain; Collagen Type XI; Color; Connective Tissue Diseases; Copper; Coronary Angiography; Coronavirus 3C Proteases; Coronavirus Infections; Cost of Illness; Counselors; COVID-19; COVID-19 Testing; Creatine Kinase; Creatinine; Cross-Over Studies; Cross-Sectional Studies; Cryoelectron Microscopy; Cryosurgery; Crystallography, X-Ray; Cues; Cultural Competency; Cultural Diversity; Curriculum; Cyclic AMP Response Element-Binding Protein; Cyclin-Dependent Kinase Inhibitor p21; Cycloparaffins; Cysteine Endopeptidases; Cytokines; Cytoplasm; Cytoprotection; Databases, Factual; Denitrification; Deoxycytidine; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diagnosis, Differential; Diatoms; Diet; Diet, High-Fat; Dietary Exposure; Diffusion Magnetic Resonance Imaging; Diketopiperazines; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors; Disease Models, Animal; Disease Progression; Disease-Free Survival; DNA; DNA Damage; DNA Glycosylases; DNA Repair; DNA-Binding Proteins; DNA, Bacterial; DNA, Viral; Docetaxel; Dose Fractionation, Radiation; Dose-Response Relationship, Drug; Down-Regulation; Doxorubicin; Drosophila; Drosophila melanogaster; Drug Carriers; Drug Delivery Systems; Drug Liberation; Drug Repositioning; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Drug Synergism; Drug Therapy, Combination; Edema; Edible Grain; Education, Graduate; Education, Medical, Graduate; Education, Pharmacy; Ehlers-Danlos Syndrome; Electron Transport Complex III; Electron Transport Complex IV; Electronic Nicotine Delivery Systems; Emergency Service, Hospital; Empathy; Emulsions; Endothelial Cells; Endurance Training; Energy Intake; Enterovirus A, Human; Environment; Environmental Monitoring; Enzyme Assays; Enzyme Inhibitors; Epithelial Cells; Epithelial-Mesenchymal Transition; Epoxide Hydrolases; Epoxy Compounds; Erythrocyte Count; Erythrocytes; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Esophagectomy; Estrogens; Etanercept; Ethiopia; Ethnicity; Ethylenes; Exanthema; Exercise; Exercise Test; Exercise Tolerance; Extracellular Matrix; Extracorporeal Membrane Oxygenation; Eye Infections, Fungal; False Negative Reactions; Fatty Acids; Fecal Microbiota Transplantation; Feces; Female; Femur Neck; Fermentation; Ferritins; Fetal Development; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Fibroblasts; Fibroins; Fish Proteins; Flavanones; Flavonoids; Focus Groups; Follow-Up Studies; Food Handling; Food Supply; Food, Formulated; Forced Expiratory Volume; Forests; Fractures, Bone; Fruit and Vegetable Juices; Fusobacteria; G1 Phase Cell Cycle Checkpoints; G2 Phase Cell Cycle Checkpoints; Gamma Rays; Gastrectomy; Gastrointestinal Microbiome; Gastrointestinal Stromal Tumors; Gefitinib; Gels; Gemcitabine; Gene Amplification; Gene Expression; Gene Expression Regulation; Gene Expression Regulation, Bacterial; Gene Expression Regulation, Neoplastic; Gene Expression Regulation, Plant; Gene Knockdown Techniques; Gene-Environment Interaction; Genotype; Germany; Glioma; Glomerular Filtration Rate; Glucagon; Glucocorticoids; Glycemic Control; Glycerol; Glycogen Synthase Kinase 3 beta; Glycolipids; Glycolysis; Goblet Cells; Gram-Negative Bacterial Infections; Granulocyte Colony-Stimulating Factor; Graphite; Greenhouse Effect; Guanidines; Haemophilus influenzae; HCT116 Cells; Health Knowledge, Attitudes, Practice; Health Personnel; Health Services Accessibility; Health Services Needs and Demand; Health Status Disparities; Healthy Volunteers; 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Oocytes; Open Reading Frames; Osteoclasts; Osteogenesis; Osteoporosis; Osteoporosis, Postmenopausal; Outpatients; Ovarian Neoplasms; Ovariectomy; Overweight; Oxazines; Oxidants; Oxidation-Reduction; Oxidative Stress; Oxides; Oxidoreductases; Oxygen; Oxygen Inhalation Therapy; Oxygenators, Membrane; Ozone; Paclitaxel; Paenibacillus; Pain Measurement; Palliative Care; Pancreatic Neoplasms; Pandemics; Parasympathetic Nervous System; Particulate Matter; Pasteurization; Patient Preference; Patient Satisfaction; Pediatric Obesity; Permeability; Peroxiredoxins; Peroxynitrous Acid; Pharmaceutical Services; Pharmacists; Pharmacy; Phaseolus; Phenotype; Phoeniceae; Phosphates; Phosphatidylinositol 3-Kinases; Phospholipid Transfer Proteins; Phospholipids; Phosphorus; Phosphorylation; Photoperiod; Photosynthesis; Phylogeny; Physical Endurance; Physicians; Pilot Projects; Piperidines; Pituitary Adenylate Cyclase-Activating Polypeptide; Plant Extracts; Plant Leaves; Plant Proteins; Plant Roots; Plaque, Atherosclerotic; Pneumonia; Pneumonia, Viral; Point-of-Care Testing; Polyethylene Glycols; Polymers; Polysorbates; Pore Forming Cytotoxic Proteins; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Postprandial Period; Poverty; Pre-Exposure Prophylaxis; Prediabetic State; Predictive Value of Tests; Pregnancy; Pregnancy Trimester, First; Pregnancy, High-Risk; Prenatal Exposure Delayed Effects; Pressure; Prevalence; Primary Graft Dysfunction; Primary Health Care; Professional Role; Professionalism; Prognosis; Progression-Free Survival; Prolactin; Promoter Regions, Genetic; Proof of Concept Study; Proportional Hazards Models; Propylene Glycol; Prospective Studies; Prostate; Protein Binding; Protein Biosynthesis; Protein Isoforms; Protein Kinase Inhibitors; Protein Phosphatase 2; Protein Processing, Post-Translational; Protein Serine-Threonine Kinases; Protein Structure, Tertiary; Protein Transport; Proteoglycans; Proteome; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-myc; Proto-Oncogene Proteins c-ret; Proto-Oncogene Proteins p21(ras); Proton Pumps; Protons; Protoporphyrins; Pseudomonas aeruginosa; Pseudomonas fluorescens; Pulmonary Artery; Pulmonary Disease, Chronic Obstructive; Pulmonary Gas Exchange; Pulmonary Veins; Pyrazoles; Pyridines; Pyrimidines; Qualitative Research; Quinoxalines; Rabbits; Random Allocation; Rats; Rats, Sprague-Dawley; Rats, Wistar; Receptors, Histamine H3; Receptors, Immunologic; Receptors, Transferrin; Recombinant Proteins; Recurrence; Reference Values; Referral and Consultation; Regional Blood Flow; Registries; Regulon; Renal Insufficiency, Chronic; Reperfusion Injury; Repressor Proteins; Reproducibility of Results; Republic of Korea; Research Design; Resistance Training; Respiration, Artificial; Respiratory Distress Syndrome; Respiratory Insufficiency; Resuscitation; Retinal Dehydrogenase; Retreatment; Retrospective Studies; Reverse Transcriptase Inhibitors; Rhinitis, Allergic; Ribosomal Proteins; Ribosomes; Risk Assessment; Risk Factors; Ritonavir; Rivers; RNA Interference; RNA-Seq; RNA, Messenger; RNA, Ribosomal, 16S; RNA, Small Interfering; Rosuvastatin Calcium; Rural Population; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Salivary Ducts; Salivary Gland Neoplasms; San Francisco; SARS-CoV-2; Satiation; Satiety Response; Schools; Schools, Pharmacy; Seasons; Seawater; Selection, Genetic; Sequence Analysis, DNA; Serine-Threonine Kinase 3; Sewage; Sheep; Sheep, Domestic; Shock, Hemorrhagic; Signal Transduction; Silver; Silymarin; Single Photon Emission Computed Tomography Computed Tomography; Sirolimus; Sirtuin 1; Skin; Skin Neoplasms; Skin Physiological Phenomena; Sleep Initiation and Maintenance Disorders; Social Class; Social Participation; Social Support; Soil; Soil Microbiology; Solutions; Somatomedins; Soot; Specimen Handling; Spectrophotometry, Ultraviolet; Spectroscopy, Fourier Transform Infrared; Spectrum Analysis; Spinal Fractures; Spirometry; Staphylococcus aureus; STAT1 Transcription Factor; STAT3 Transcription Factor; Streptomyces coelicolor; Stress, Psychological; Stroke; Stroke Volume; Structure-Activity Relationship; Students, Medical; Students, Pharmacy; Substance Abuse Treatment Centers; Sulfur Dioxide; Surface Properties; Surface-Active Agents; Surveys and Questionnaires; Survival Analysis; Survival Rate; Survivin; Sweden; Swine; Swine, Miniature; Sympathetic Nervous System; T-Lymphocytes, Regulatory; Talaromyces; Tandem Mass Spectrometry; tau Proteins; Telemedicine; Telomerase; Telomere; Telomere Homeostasis; Temperature; Terminally Ill; Th1 Cells; Thiamethoxam; Thiazoles; Thiophenes; Thioredoxin Reductase 1; Thrombosis; Thulium; Thyroid Cancer, Papillary; Thyroid Carcinoma, Anaplastic; Thyroid Neoplasms; Time Factors; Titanium; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed; TOR Serine-Threonine Kinases; Transcription Factor AP-1; Transcription Factors; Transcription, Genetic; Transcriptional Activation; Transcriptome; Transforming Growth Factor beta1; Transistors, Electronic; Translational Research, Biomedical; Transplantation Tolerance; Transplantation, Homologous; Transportation; Treatment Outcome; Tretinoin; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary; Tubulin Modulators; Tumor Microenvironment; Tumor Necrosis Factor Inhibitors; Tumor Necrosis Factor-alpha; Twins; Ultrasonic Therapy; Ultrasonography; Ultraviolet Rays; United States; Up-Regulation; Uranium; Urethra; Urinary Bladder; Urodynamics; Uromodulin; Uveitis; Vasoconstrictor Agents; Ventricular Function, Left; Vero Cells; Vesicular Transport Proteins; Viral Nonstructural Proteins; Visual Acuity; Vital Capacity; Vitamin D; Vitamin D Deficiency; Vitamin K 2; Vitamins; Volatilization; Voriconazole; Waiting Lists; Waste Disposal, Fluid; Wastewater; Water Pollutants, Chemical; Whole Genome Sequencing; Wine; Wnt Signaling Pathway; Wound Healing; Wounds and Injuries; WW Domains; X-linked Nuclear Protein; X-Ray Diffraction; Xanthines; Xenograft Model Antitumor Assays; YAP-Signaling Proteins; Yogurt; Young Adult; Zebrafish; Zebrafish Proteins; Ziziphus

Most authorities believe that the greatest need for blood substitutes is in patients with unanticipated acute blood loss, and trauma is the most likely scenario. The blood substitutes reaching advanced clinical trials today are red blood cell (RBC) substitutes, derived from hemoglobin. The hemoglobin-based oxygen carriers (HBOCs) tested currently in FDA Phase III clinical trials are polymerized hemoglobin solutions. The standard approach to restoring oxygen delivery in hemorrhagic shock has been crystalloid administration to expand intravascular volume, followed by stored RBCs for critical anemia. However, allogenic RBCs may have adverse immunoinflammatory effects that increase the risk of postinjury multiple organ failure (MOF). Phase II clinical trials, as well as in vitro and in vivo work, suggest that resuscitation with a HBOC--in lieu of stored RBCs--attenuates the systemic inflammatory response invoked in the pathogenesis of MOF. Specifically, an HBOC has been shown to obviate stored RBC provoked neutrophil priming, endothelial activation, and systemic release of interleukins 6, 8, and 10. Based on this background and work by others, we have initiated a multicenter prehospital trial in which severely injured patients with major blood loss (systemic blood pressure <90 mmHg) are randomized to initial field resuscitation with crystalloid versus HBOC. During the hospital phase, the control group is further resuscitated with stored RBCs, whereas the study group receives HBOC (up to 6 units) in the first 12 h. The primary study endpoint is 30-day mortality, and secondary endpoints include reduction in allogenic RBCs, hemoglobin levels <5 g/dL, uncrossmatched RBCs, and MOF. The potential efficacy of HBOCs extends beyond the temporary replacement for stored RBCs. Hemoglobin solutions might ultimately prove superior in delivering oxygen to ischemic or injured tissue. The current generation of HBOCs can be lifesaving for acute blood loss today, but the next generation might be biochemically tailored for specific clinical indications.

Topics: Blood Substitutes; Blood Transfusion; Clinical Trials as Topic; Erythrocytes; Hemoglobins; Humans; Inflammation; Interleukin-10; Interleukin-6; Interleukin-8; Multicenter Studies as Topic; Neutrophils; Nitric Oxide; Oxygen; Polymers; Shock, Hemorrhagic; Wounds and Injuries

It has been suggested that beneficial bacteria may stimulate wound healing. The aim was to investigate the effect of topical applications of probiotic lactobacilli on the healing of standardised oral wounds. This pilot study employed a randomised, placebo-controlled, double-blind cross-over design. Standardised biopsies were punched in the oral mucosa of 10 healthy volunteers, with and without exposure to two strains of Lactobacilli reuteri administrated as lozenges and topical oil. The healing was scored clinically after 2, 5 and 8 days. The amount of exudate was quantified through filter papers and the levels of selected cytokines and chemokines were determined with multiplex immunoassays. Saliva samples were collected before the biopsy and after healing for determination of oxytocin with ELISA. Subjectively perceived pain and discomfort was reported through a daily logbook. There was a clear tendency of improved healing in test group at the 2-and 5-day check-ups but the difference compared with the placebo intervention was not statistically significant (P=0.08). Higher but non-significant expressions of the tumour necrosis factor (TNF) superfamily ligand members 13 (APRIL) and 13B (BAFF), as well as the chemokine interleukin 8 (IL-8), were displayed in wound exudates from the probiotic group as compared with placebo, particularly after 5 and 8 days. The salivary levels of oxytocin were significantly lower (P<0.05) in the placebo group at the 8-day follow-up. The mean number of days with pain and/or discomfort after the biopsies was similar in both groups. No side-effects were reported. The findings of this pilot study justify a larger clinical trial to elucidate the possible role of probiotic supplements on oral wound healing.

Topics: Adult; Aged; B-Cell Activating Factor; Double-Blind Method; Female; Humans; Interleukin-8; Limosilactobacillus reuteri; Male; Middle Aged; Mouth Diseases; Pilot Projects; Probiotics; Tumor Necrosis Factor Ligand Superfamily Member 13; Wound Healing; Wounds and Injuries; Young Adult

Middle East Respiratory Syndrome (MERS) is a novel respiratory illness firstly reported in Saudi Arabia in 2012. It is caused by a new corona virus, called MERS corona virus (MERS-CoV). Most people who have MERS-CoV infection developed severe acute respiratory illness.. This work is done to determine the clinical characteristics and the outcome of intensive care unit (ICU) admitted patients with confirmed MERS-CoV infection.. This study included 32 laboratory confirmed MERS corona virus infected patients who were admitted into ICU. It included 20 (62.50%) males and 12 (37.50%) females. The mean age was 43.99 ± 13.03 years. Diagnosis was done by real-time reverse transcription polymerase chain reaction (rRT-PCR) test for corona virus on throat swab, sputum, tracheal aspirate, or bronchoalveolar lavage specimens. Clinical characteristics, co-morbidities and outcome were reported for all subjects.. Most MERS corona patients present with fever, cough, dyspnea, sore throat, runny nose and sputum. The presence of abdominal symptoms may indicate bad prognosis. Prolonged duration of symptoms before patients' hospitalization, prolonged duration of mechanical ventilation and hospital stay, bilateral radiological pulmonary infiltrates, and hypoxemic respiratory failure were found to be strong predictors of mortality in such patients. Also, old age, current smoking, smoking severity, presence of associated co-morbidities like obesity, diabetes mellitus, chronic heart diseases, COPD, malignancy, renal failure, renal transplantation and liver cirrhosis are associated with a poor outcome of ICU admitted MERS corona virus infected patients.. Plasma HO-1, ferritin, p21, and NQO1 were all elevated at baseline in CKD participants. Plasma HO-1 and urine NQO1 levels each inversely correlated with eGFR (. SnPP can be safely administered and, after its injection, the resulting changes in plasma HO-1, NQO1, ferritin, and p21 concentrations can provide information as to antioxidant gene responsiveness/reserves in subjects with and without kidney disease.. A Study with RBT-1, in Healthy Volunteers and Subjects with Stage 3-4 Chronic Kidney Disease, NCT0363002 and NCT03893799.. HFNC did not significantly modify work of breathing in healthy subjects. However, a significant reduction in the minute volume was achieved, capillary [Formula: see text] remaining constant, which suggests a reduction in dead-space ventilation with flows > 20 L/min. (ClinicalTrials.gov registration NCT02495675).. 3 组患者手术时间、术中显性失血量及术后 1 周血红蛋白下降量比较差异均无统计学意义（. 对于肥胖和超重的膝关节单间室骨关节炎患者，采用 UKA 术后可获满意短中期疗效，远期疗效尚需进一步随访观察。.. Decreased muscle strength was identified at both time points in patients with hEDS/HSD. The evolution of most muscle strength parameters over time did not significantly differ between groups. Future studies should focus on the effectiveness of different types of muscle training strategies in hEDS/HSD patients.. These findings support previous adverse findings of e-cigarette exposure on neurodevelopment in a mouse model and provide substantial evidence of persistent adverse behavioral and neuroimmunological consequences to adult offspring following maternal e-cigarette exposure during pregnancy. https://doi.org/10.1289/EHP6067.. This RCT directly compares a neoadjuvant chemotherapy regimen with a standard CROSS regimen in terms of overall survival for patients with locally advanced ESCC. The results of this RCT will provide an answer for the controversy regarding the survival benefits between the two treatment strategies.. NCT04138212, date of registration: October 24, 2019.. Results of current investigation indicated that milk type and post fermentation cooling patterns had a pronounced effect on antioxidant characteristics, fatty acid profile, lipid oxidation and textural characteristics of yoghurt. Buffalo milk based yoghurt had more fat, protein, higher antioxidant capacity and vitamin content. Antioxidant and sensory characteristics of T. If milk is exposed to excessive amounts of light, Vitamins B. The two concentration of ZnO nanoparticles in the ambient air produced two different outcomes. The lower concentration resulted in significant increases in Zn content of the liver while the higher concentration significantly increased Zn in the lungs (p < 0.05). Additionally, at the lower concentration, Zn content was found to be lower in brain tissue (p < 0.05). Using TEM/EDX we detected ZnO nanoparticles inside the cells in the lungs, kidney and liver. Inhaling ZnO NP at the higher concentration increased the levels of mRNA of the following genes in the lungs: Mt2 (2.56 fold), Slc30a1 (1.52 fold) and Slc30a5 (2.34 fold). At the lower ZnO nanoparticle concentration, only Slc30a7 mRNA levels in the lungs were up (1.74 fold). Thus the two air concentrations of ZnO nanoparticles produced distinct effects on the expression of the Zn-homeostasis related genes.. Until adverse health effects of ZnO nanoparticles deposited in organs such as lungs are further investigated and/or ruled out, the exposure to ZnO nanoparticles in aerosols should be avoided or minimised.

Topics: A549 Cells; Acetylmuramyl-Alanyl-Isoglutamine; Acinetobacter baumannii; Acute Lung Injury; Adaptor Proteins, Signal Transducing; Adenine; Adenocarcinoma; Adipogenesis; Administration, Cutaneous; Administration, Ophthalmic; Adolescent; Adsorption; Adult; Aeromonas hydrophila; Aerosols; Aged; Aged, 80 and over; Aging; Agriculture; Air Pollutants; Air Pollution; Airway Remodeling; Alanine Transaminase; Albuminuria; Aldehyde Dehydrogenase 1 Family; Algorithms; AlkB Homolog 2, Alpha-Ketoglutarate-Dependent Dioxygenase; Alzheimer Disease; Amino Acid Sequence; Ammonia; Ammonium Compounds; Anaerobiosis; Anesthetics, Dissociative; Anesthetics, Inhalation; Animals; Anti-Bacterial Agents; Anti-HIV Agents; Anti-Infective Agents; Anti-Inflammatory Agents; Antibiotics, Antineoplastic; Antibodies, Antineutrophil Cytoplasmic; Antibodies, Monoclonal, Humanized; Antifungal Agents; Antigens, Bacterial; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Antioxidants; Antitubercular Agents; Antiviral Agents; Apolipoproteins E; Apoptosis; Arabidopsis; Arabidopsis Proteins; Arsenic; Arthritis, Rheumatoid; Asthma; Atherosclerosis; ATP-Dependent Proteases; Attitude of Health Personnel; Australia; Austria; Autophagy; Axitinib; Bacteria; Bacterial Outer Membrane Proteins; Bacterial Proteins; Bacterial Toxins; Bacterial Typing Techniques; Bariatric Surgery; Base Composition; Bayes Theorem; Benzoxazoles; Benzylamines; beta Catenin; Betacoronavirus; Betula; Binding Sites; Biological Availability; Biological Oxygen Demand Analysis; Biomarkers; Biomarkers, Tumor; Biopsy; Bioreactors; Biosensing Techniques; Birth Weight; Blindness; Blood Chemical Analysis; Blood Gas Analysis; Blood Glucose; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Blood-Brain Barrier; Blotting, Western; Body Mass Index; Body Weight; Bone and Bones; Bone Density; Bone Resorption; Borates; Brain; Brain Infarction; Brain Injuries, Traumatic; Brain Neoplasms; Breakfast; Breast Milk Expression; Breast Neoplasms; Bronchi; Bronchoalveolar Lavage Fluid; Buffaloes; Cadherins; Calcification, Physiologic; Calcium Compounds; Calcium, Dietary; Cannula; Caprolactam; Carbon; Carbon Dioxide; Carboplatin; Carcinogenesis; Carcinoma, Ductal; Carcinoma, Ehrlich Tumor; Carcinoma, Hepatocellular; Carcinoma, Non-Small-Cell Lung; Carcinoma, Pancreatic Ductal; Carcinoma, Renal Cell; Cardiovascular Diseases; Carps; Carrageenan; Case-Control Studies; Catalysis; Catalytic Domain; Cattle; CD8-Positive T-Lymphocytes; Cell Adhesion; Cell Cycle Proteins; Cell Death; Cell Differentiation; Cell Line; Cell Line, Tumor; Cell Movement; Cell Nucleus; Cell Phone Use; Cell Proliferation; Cell Survival; Cell Transformation, Neoplastic; Cell Transformation, Viral; Cells, Cultured; Cellulose; Chemical Phenomena; Chemoradiotherapy; Child; Child Development; Child, Preschool; China; Chitosan; Chlorocebus aethiops; Cholecalciferol; Chromatography, Liquid; Circadian Clocks; Circadian Rhythm; Circular Dichroism; Cisplatin; Citric Acid; Clinical Competence; Clinical Laboratory Techniques; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Clostridioides difficile; Clostridium Infections; Coculture Techniques; Cohort Studies; Cold Temperature; Colitis; Collagen Type I; Collagen Type I, alpha 1 Chain; Collagen Type XI; Color; Connective Tissue Diseases; Copper; Coronary Angiography; Coronavirus 3C Proteases; Coronavirus Infections; Cost of Illness; Counselors; COVID-19; COVID-19 Testing; Creatine Kinase; Creatinine; Cross-Over Studies; Cross-Sectional Studies; Cryoelectron Microscopy; Cryosurgery; Crystallography, X-Ray; Cues; Cultural Competency; Cultural Diversity; Curriculum; Cyclic AMP Response Element-Binding Protein; Cyclin-Dependent Kinase Inhibitor p21; Cycloparaffins; Cysteine Endopeptidases; Cytokines; Cytoplasm; Cytoprotection; Databases, Factual; Denitrification; Deoxycytidine; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diagnosis, Differential; Diatoms; Diet; Diet, High-Fat; Dietary Exposure; Diffusion Magnetic Resonance Imaging; Diketopiperazines; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors; Disease Models, Animal; Disease Progression; Disease-Free Survival; DNA; DNA Damage; DNA Glycosylases; DNA Repair; DNA-Binding Proteins; DNA, Bacterial; DNA, Viral; Docetaxel; Dose Fractionation, Radiation; Dose-Response Relationship, Drug; Down-Regulation; Doxorubicin; Drosophila; Drosophila melanogaster; Drug Carriers; Drug Delivery Systems; Drug Liberation; Drug Repositioning; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Drug Synergism; Drug Therapy, Combination; Edema; Edible Grain; Education, Graduate; Education, Medical, Graduate; Education, Pharmacy; Ehlers-Danlos Syndrome; Electron Transport Complex III; Electron Transport Complex IV; Electronic Nicotine Delivery Systems; Emergency Service, Hospital; Empathy; Emulsions; Endothelial Cells; Endurance Training; Energy Intake; Enterovirus A, Human; Environment; Environmental Monitoring; Enzyme Assays; Enzyme Inhibitors; Epithelial Cells; Epithelial-Mesenchymal Transition; Epoxide Hydrolases; Epoxy Compounds; Erythrocyte Count; Erythrocytes; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Esophagectomy; Estrogens; Etanercept; Ethiopia; Ethnicity; Ethylenes; Exanthema; Exercise; Exercise Test; Exercise Tolerance; Extracellular Matrix; Extracorporeal Membrane Oxygenation; Eye Infections, Fungal; False Negative Reactions; Fatty Acids; Fecal Microbiota Transplantation; Feces; Female; Femur Neck; Fermentation; Ferritins; Fetal Development; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Fibroblasts; Fibroins; Fish Proteins; Flavanones; Flavonoids; Focus Groups; Follow-Up Studies; Food Handling; Food Supply; Food, Formulated; Forced Expiratory Volume; Forests; Fractures, Bone; Fruit and Vegetable Juices; Fusobacteria; G1 Phase Cell Cycle Checkpoints; G2 Phase Cell Cycle Checkpoints; Gamma Rays; Gastrectomy; Gastrointestinal Microbiome; Gastrointestinal Stromal Tumors; Gefitinib; Gels; Gemcitabine; Gene Amplification; Gene Expression; Gene Expression Regulation; Gene Expression Regulation, Bacterial; Gene Expression Regulation, Neoplastic; Gene Expression Regulation, Plant; Gene Knockdown Techniques; Gene-Environment Interaction; Genotype; Germany; Glioma; Glomerular Filtration Rate; Glucagon; Glucocorticoids; Glycemic Control; Glycerol; Glycogen Synthase Kinase 3 beta; Glycolipids; Glycolysis; Goblet Cells; Gram-Negative Bacterial Infections; Granulocyte Colony-Stimulating Factor; Graphite; Greenhouse Effect; Guanidines; Haemophilus influenzae; HCT116 Cells; Health Knowledge, Attitudes, Practice; Health Personnel; Health Services Accessibility; Health Services Needs and Demand; Health Status Disparities; Healthy Volunteers; Heart Failure; Heart Rate; Heart Transplantation; Heart-Assist Devices; HEK293 Cells; Heme; Heme Oxygenase-1; Hemolysis; Hemorrhage; Hepatitis B; Hepatitis B e Antigens; Hepatitis B Surface Antigens; Hepatitis B virus; Hepatitis B, Chronic; Hepatocytes; Hexoses; High-Throughput Nucleotide Sequencing; Hippo Signaling Pathway; Histamine; Histamine Agonists; Histidine; Histone Deacetylase 2; HIV Infections; HIV Reverse Transcriptase; HIV-1; Homebound Persons; Homeodomain Proteins; Homosexuality, Male; Hospice and Palliative Care Nursing; HSP70 Heat-Shock Proteins; Humans; Hyaluronan Receptors; Hydrogen; Hydrogen Peroxide; Hydrogen-Ion Concentration; Hydrolysis; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypoglycemia; Hypoglycemic Agents; Hypoxia; Idiopathic Interstitial Pneumonias; Imaging, Three-Dimensional; Imatinib Mesylate; Immunotherapy; Implementation Science; Incidence; INDEL Mutation; Induced Pluripotent Stem Cells; Industrial Waste; Infant; Infant, Newborn; Inflammation; Inflammation Mediators; Infliximab; Infusions, Intravenous; Inhibitory Concentration 50; Injections; Insecticides; Insulin-Like Growth Factor Binding Protein 5; Insulin-Secreting Cells; Interleukin-1; Interleukin-17; Interleukin-8; Internship and Residency; Intestines; Intracellular Signaling Peptides and Proteins; Ion Transport; Iridaceae; Iridoid Glucosides; Islets of Langerhans Transplantation; Isodon; Isoflurane; Isotopes; Italy; Joint Instability; Ketamine; Kidney; Kidney Failure, Chronic; Kidney Function Tests; Kidney Neoplasms; Kinetics; Klebsiella pneumoniae; Knee Joint; Kruppel-Like Factor 4; Kruppel-Like Transcription Factors; Lactate Dehydrogenase 5; Laparoscopy; Laser Therapy; Lasers, Semiconductor; Lasers, Solid-State; Laurates; Lead; Leukocyte L1 Antigen Complex; Leukocytes, Mononuclear; Light; Lipid Peroxidation; Lipopolysaccharides; Liposomes; Liver; Liver Cirrhosis; Liver Neoplasms; Liver Transplantation; Locomotion; Longitudinal Studies; Lopinavir; Lower Urinary Tract Symptoms; Lubricants; Lung; Lung Diseases, Interstitial; Lung Neoplasms; Lymphocyte Activation; Lymphocytes, Tumor-Infiltrating; Lymphoma, Mantle-Cell; Lysosomes; Macrophages; Male; Manganese Compounds; MAP Kinase Kinase 4; Mass Screening; Maternal Health; Medicine, Chinese Traditional; Melanoma, Experimental; Memantine; Membrane Glycoproteins; Membrane Proteins; Mesenchymal Stem Cell Transplantation; Metal Nanoparticles; Metalloendopeptidases; Metalloporphyrins; Methadone; Methane; Methicillin-Resistant Staphylococcus aureus; Mexico; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred ICR; Mice, Knockout; Mice, Nude; Mice, SCID; Mice, Transgenic; Microarray Analysis; Microbial Sensitivity Tests; Microbiota; Micronutrients; MicroRNAs; Microscopy, Confocal; Microsomes, Liver; Middle Aged; Milk; Milk, Human; Minority Groups; Mitochondria; Mitochondrial Membranes; Mitochondrial Proteins; Models, Animal; Models, Molecular; Molecular Conformation; Molecular Docking Simulation; Molecular Dynamics Simulation; Molecular Epidemiology; 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Pneumonia; Pneumonia, Viral; Point-of-Care Testing; Polyethylene Glycols; Polymers; Polysorbates; Pore Forming Cytotoxic Proteins; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Postprandial Period; Poverty; Pre-Exposure Prophylaxis; Prediabetic State; Predictive Value of Tests; Pregnancy; Pregnancy Trimester, First; Pregnancy, High-Risk; Prenatal Exposure Delayed Effects; Pressure; Prevalence; Primary Graft Dysfunction; Primary Health Care; Professional Role; Professionalism; Prognosis; Progression-Free Survival; Prolactin; Promoter Regions, Genetic; Proof of Concept Study; Proportional Hazards Models; Propylene Glycol; Prospective Studies; Prostate; Protein Binding; Protein Biosynthesis; Protein Isoforms; Protein Kinase Inhibitors; Protein Phosphatase 2; Protein Processing, Post-Translational; Protein Serine-Threonine Kinases; Protein Structure, Tertiary; Protein Transport; Proteoglycans; Proteome; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-myc; Proto-Oncogene Proteins c-ret; Proto-Oncogene Proteins p21(ras); Proton Pumps; Protons; Protoporphyrins; Pseudomonas aeruginosa; Pseudomonas fluorescens; Pulmonary Artery; Pulmonary Disease, Chronic Obstructive; Pulmonary Gas Exchange; Pulmonary Veins; Pyrazoles; Pyridines; Pyrimidines; Qualitative Research; Quinoxalines; Rabbits; Random Allocation; Rats; Rats, Sprague-Dawley; Rats, Wistar; Receptors, Histamine H3; Receptors, Immunologic; Receptors, Transferrin; Recombinant Proteins; Recurrence; Reference Values; Referral and Consultation; Regional Blood Flow; Registries; Regulon; Renal Insufficiency, Chronic; Reperfusion Injury; Repressor Proteins; Reproducibility of Results; Republic of Korea; Research Design; Resistance Training; Respiration, Artificial; Respiratory Distress Syndrome; Respiratory Insufficiency; Resuscitation; Retinal Dehydrogenase; Retreatment; Retrospective Studies; Reverse Transcriptase Inhibitors; Rhinitis, Allergic; Ribosomal Proteins; Ribosomes; Risk Assessment; 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STAT3 Transcription Factor; Streptomyces coelicolor; Stress, Psychological; Stroke; Stroke Volume; Structure-Activity Relationship; Students, Medical; Students, Pharmacy; Substance Abuse Treatment Centers; Sulfur Dioxide; Surface Properties; Surface-Active Agents; Surveys and Questionnaires; Survival Analysis; Survival Rate; Survivin; Sweden; Swine; Swine, Miniature; Sympathetic Nervous System; T-Lymphocytes, Regulatory; Talaromyces; Tandem Mass Spectrometry; tau Proteins; Telemedicine; Telomerase; Telomere; Telomere Homeostasis; Temperature; Terminally Ill; Th1 Cells; Thiamethoxam; Thiazoles; Thiophenes; Thioredoxin Reductase 1; Thrombosis; Thulium; Thyroid Cancer, Papillary; Thyroid Carcinoma, Anaplastic; Thyroid Neoplasms; Time Factors; Titanium; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed; TOR Serine-Threonine Kinases; Transcription Factor AP-1; Transcription Factors; Transcription, Genetic; Transcriptional Activation; Transcriptome; Transforming Growth Factor beta1; Transistors, Electronic; Translational Research, Biomedical; Transplantation Tolerance; Transplantation, Homologous; Transportation; Treatment Outcome; Tretinoin; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary; Tubulin Modulators; Tumor Microenvironment; Tumor Necrosis Factor Inhibitors; Tumor Necrosis Factor-alpha; Twins; Ultrasonic Therapy; Ultrasonography; Ultraviolet Rays; United States; Up-Regulation; Uranium; Urethra; Urinary Bladder; Urodynamics; Uromodulin; Uveitis; Vasoconstrictor Agents; Ventricular Function, Left; Vero Cells; Vesicular Transport Proteins; Viral Nonstructural Proteins; Visual Acuity; Vital Capacity; Vitamin D; Vitamin D Deficiency; Vitamin K 2; Vitamins; Volatilization; Voriconazole; Waiting Lists; Waste Disposal, Fluid; Wastewater; Water Pollutants, Chemical; Whole Genome Sequencing; Wine; Wnt Signaling Pathway; Wound Healing; Wounds and Injuries; WW Domains; X-linked Nuclear Protein; X-Ray Diffraction; Xanthines; Xenograft Model Antitumor Assays; YAP-Signaling Proteins; Yogurt; Young Adult; Zebrafish; Zebrafish Proteins; Ziziphus

There are no current pharmacological therapies for the prevention or treatment of acute respiratory distress syndrome. Early dysregulated inflammation likely plays a role in acute respiratory distress syndrome development and possibly acute respiratory distress syndrome outcomes. p38 mitogen-activated protein kinase is central to the regulation of multiple inflammatory mediators implicated in acute organ dysfunction and is the target for a novel class of cytokine-suppressive anti-inflammatory drugs. In preclinical models, p38 inhibitors reduce lung injury following pancreatitis and burn injury.. We conducted a phase IIa, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the safety and tolerability of dilmapimod, a novel p38 mitogen-activated protein kinase inhibitor, in patients at risk for developing acute respiratory distress syndrome admitted with an Injury Severity Score more than 16, excluding head trauma. Enrolled patients received 4- or 24-hour IV dilmapimod infusions at different doses or placebo, daily for 3 days, in four separate cohorts.. Multicenter randomized clinical trial of large, academic trauma centers.. Seventy-seven patients were enrolled. Although adverse events were common in this critically ill population, dilmapimod was well tolerated, with no clinically relevant safety findings. Pharmacokinetic models indicated that the higher dose of 10 mg given as continuous infusion over 24 hours had the most favorable plasma concentration profile. Likewise, measures of soluble inflammatory markers including interleukin-6, C-reactive peptide, interleukin-8, and soluble tumor necrosis factor receptor 1 were most different between this dosing arm and placebo. Although the study was not specifically designed with acute respiratory distress syndrome as an outcome, the number of patients who developed acute respiratory distress syndrome was small (2/77).. The novel p38 mitogen-activated protein kinase inhibitor dilmapimod appears well tolerated and may merit further evaluation for prevention of acute respiratory distress syndrome and other organ injury in larger clinical trials. Furthermore, results of this early-phase trial may aid in design of future studies aimed at prevention of acute respiratory distress syndrome and other organ injury.

Topics: Adult; C-Reactive Protein; Dose-Response Relationship, Drug; Double-Blind Method; Female; Hospital Mortality; Humans; Inflammation Mediators; Interleukin-6; Interleukin-8; Male; Middle Aged; p38 Mitogen-Activated Protein Kinases; Pyridones; Pyrimidines; Receptors, Tumor Necrosis Factor, Type I; Respiratory Distress Syndrome; Trauma Severity Indices; Wounds and Injuries

Inhaled nitric oxide is used to treat hypoxia associated with acute lung injury. Endogenous nitric oxide regulates inflammatory responses, but the effect of inhaled nitric oxide therapy is unknown. We hypothesized that inhaled nitric oxide may alter inflammatory responses and endogenous nitric oxide synthase activity.. A randomized, prospective interventional study.. A university hospital's general intensive care unit.. Thirty-two patients with acute lung injury.. Patients who responded to test doses of nitric oxide were randomized to ventilator therapy with and without inhaled nitric oxide. The inhaled concentration of nitric oxide was determined by dose titration at 0, 2, 10, and 40 ppm and the minimum concentration used, which resulted in an increase in the PaO2/FIO2 ratio of at least 25%.. Patients were followed up for 30 days or until death, and bronchoalveolar lavage (BAL) was performed at 0, 24, and 72 hrs. Nitric oxide synthase activity was measured spectrophotometrically, and myeloperoxidase, elastase, interleukin-8, and leukotrienes were measured in BAL fluid by enzyme immunoassay. Total nitrite and lipid peroxides in serum were measured colorimetrically. Nitric oxide synthase activity decreased (p = .01) and total nitrite increased (p = .02) in patients receiving inhaled nitric oxide. Other markers of inflammation in BAL fluid did not change. Lipid peroxide concentrations also did not alter.. The decrease in activity of nitric oxide synthase in patients receiving nitric oxide is likely to be the result of feedback inhibition of the enzyme. This study shows that inhaled nitric oxide has no effect on several markers of the inflammatory response system and does not lead to increased oxidant stress.

Topics: Acute Disease; Administration, Inhalation; Adolescent; Adult; Aged; Aged, 80 and over; Female; Humans; Inflammation; Interleukin-8; Leukotrienes; Lipid Peroxides; Lung; Lung Injury; Male; Middle Aged; Nitric Oxide; Nitric Oxide Synthase; Nitrites; Pancreatic Elastase; Peroxidase; Prospective Studies; Wounds and Injuries

Seven key inflammatory biomarkers were recently found to be associated with the risk of mortality in a multicenter study of massively transfused patients. The aim of this prospective single-center study was to determine which of these early inflammatory markers could predict 30-d mortality among all critically injured trauma patients.. Serum samples were collected at 6, 24, and 72 h from 238 consecutive patients admitted to the intensive care unit following traumatic injury. Inflammatory markers syndecan-1, eotaxin, IL-1ra, IL-6, IL-8, IL-10, IP-10, and MCP-1 were analyzed via multiplex enzyme-linked immunosorbent assay. Subgroup analysis was performed for patients undergoing massive transfusion (≥5 red blood cells), submassive transfusion (1-4 red blood cells), or no transfusion during the first 4 h postinjury. The primary outcome of 30-d survival was modeled as a function of each biomarker and confounders using repeat measures logistic regression.. Patients had a median age of 51.3 y [33.7, 70.2], 70.6% were male, 17.4% experienced penetrating trauma, and had a median injury severity score of 22 [14, 33]. IL-1ra, IL-8, IL-10, and MCP-1 were significantly increased during the first 72 h in nonsurvivors (n = 31). Elevated IL-1ra, IL-8, IL-10, and MCP-1 at 6 h postinjury were associated with 30-d mortality. By contrast, serum syndecan-1 and eotaxin levels were not associated with mortality at any time point. IL-8 and lactate were increased at 6 h in 30-d nonsurvivors for patients receiving submassive transfusion (n = 78).. Early evaluations of IL-1ra, IL-8, IL-10, and IP-10 within 6 h of injury are useful predictors of 30-d mortality. Subgroup analysis suggests that transfusion status does not significantly affect early inflammatory markers.. Level III, prognostic/epidemiological.

Topics: Biomarkers; Chemokine CXCL10; Female; Humans; Interleukin 1 Receptor Antagonist Protein; Interleukin-10; Interleukin-8; Male; Prospective Studies; Syndecan-1; Wounds and Injuries

Traumatic injury is the leading cause of mortality in patients under 50. It is associated with a complex inflammatory response involving hormonal, immunologic, and metabolic mediators. The marked elevation of cytokines and inflammatory mediators subsequently correlates with the development of posttraumatic complications. The aim was to determine whether elevated cytokine levels provide a predictive value for orthopedic trauma patients. A prospective cohort study of patients with New Injury Severity Score (NISS) > 5 was undertaken. IL-6, IL-8, IL-10, and migration inhibitory factor levels were measured within 24-h of presentation. Demographic covariates and clinical outcomes were obtained from the medical records. Fifty-eight patients (83% male, 40 years) were included. Addition of IL-6 to baseline models significantly improved prediction of pulmonary complication (LR = 6.21, p = 0.01), ICU (change in R

Topics: Adult; Cytokines; Female; Humans; Injury Severity Score; Intensive Care Units; Interleukin-6; Interleukin-8; Length of Stay; Male; Predictive Value of Tests; Prospective Studies; Wounds and Injuries

Emerging evidence has manifested that many microRNAs (miRNAs) exert crucial roles in the responses and remission process of traumatic spinal cord injury (TSCI). The present study aimed to investigate clinical significance of miR-34a concerning the assessment of neurological remission and prognosis after TSCI.. We examined the serum levels of miR-34a in patients with TSCI and healthy controls through real-time polymerase chain reaction (RT-qPCR) assay. Then, receiver operating characteristic (ROC) curve was used to determine the diagnostic value of miR-34a in TSCI. Finally, we detected the expression levels of miR-34a from serum samples over a 12-week period.. The results of our study demonstrated that miR-34a was significantly down-regulated in TSCI patients compared with healthy controls. miR-34a may function a potential biomarker for TSCI diagnosis with an area under curve (AUC) of 0.8020. The expression of miR-34a was increased in the remission group compared to the non-remission group after 12 weeks post-injury. The expression of miR-34a was negatively related to TNF-alpha, IL-6, and IL-8.. Measuring serum expression level of miR-34a over time may be used in tracking the process and neurological remission of TSCI.

Topics: Biomarkers; Down-Regulation; Gene Expression; Humans; Interleukin-6; Interleukin-8; MicroRNAs; Prognosis; Reverse Transcriptase Polymerase Chain Reaction; ROC Curve; Spinal Cord Injuries; Time Factors; Tumor Necrosis Factor-alpha; Wounds and Injuries

Topics: Animals; Disease Models, Animal; Extremities; Femur; Inflammation; Interleukin-10; Interleukin-8; Liver; Lung; Lung Injury; Male; Multiple Trauma; Swine; Wounds and Injuries

This study aims to explore whether positive end-expiratory pressure (PEEP) guided by esophageal pressure is better than the acute respiratory distress syndrome network (ARDSNet) during the treatment of traumatic acute respiratory distress syndrome (ARDS) patients.. The use of the oxygenation method of inhaled oxygen concentration titration PEEP is suggested.. This study takes traumatic ARDS patients as the research object. The data of 23 patients were included in this study. The patients were randomly divided into two groups: the esophageal pressure titration PEEP group (n= 12), and the ARDSNet (PEEP-FiO2 table) titration PEEP group (n= 11). All patients were given mechanical ventilation, and changes in oxygenation index, respiratory mechanics, hemodynamics and inflammatory reaction index were recorded when titrating the best PEEP with the two methods on the current day of grouping and after grouping for 24, 48 and 72 hours.. The PEEP titration value in the esophageal pressure group was 12 ± 4 cm H2O, and this value was significantly higher than the PEEP titration value in the ARDSNet group (8 ± 3 cm H2O) (P< 0.05). The end-expiratory transpulmonary pressure of titrating the best PEEP with the esophageal pressure method and ARDSNet method is 0.5 ± 0.7 cm H2O vs.-1.1 ± 3.3 cm H2O (P< 0.05). When titrating the best PEEP with the esophageal pressure method, lung tissue compliance, end-expiratory transpulmonary pressure and the oxygenation index are higher than those obtained through the ARDSNet method (P< 0.05). (2) In the esophageal pressure group, with the extension of treatment time, high-sensitivity C reactive protein (hs-CRP) and procalcitonin (PCT) exhibited a trend of significant decrease (P< 0.05). In the ARDSNet group, with the extension of treatment time, PCT also exhibited a significant decrease (P< 0.05), while the decrease in hs-CRP was not significant (P> 0.05). After comparing these two treatment groups at each monitoring time point, we found that the difference in hs-CRP and PCT was not statistically significant (P> 0.05). During the 72-hour treatment of interleukin-6 (IL-6) and interleukin-8 (IL-8), we found that these two were significantly lower in the esophageal pressure group than in the ARDSNet group (P< 0.05).. The PEEP selection of mechanical ventilation of patients with traumatic ARDS guided by transpulmonary pressure and calculated by measuring intrapleural pressure can realize the individual adjustment of PEEP, identify ARDS patients benefiting from high PEEP, and provide a PEEP setting that can better meet the needs of traumatic patients.

Topics: Adult; C-Reactive Protein; Esophagus; Female; Humans; Interleukin-6; Interleukin-8; Male; Oxygen; Positive-Pressure Respiration; Procalcitonin; Respiratory Distress Syndrome; Wounds and Injuries

The aim of the study was to investigate the time-course of serum and wound fluids interleukin (IL)-6 and IL-8 levels in dogs with cutaneous wounds and their relationship with some haematologic parameters. The experimental group comprised of six adult dogs that underwent surgery with wounds (n = 6) on the mid lateral aspect of the right antebrachium; and control group of six, apparently, healthy intact (free from cutaneous wounds) adult dogs, comprising equal number of both sexes. Vital signs evaluated were within normal limits. Samples of blood, serum and wound fluids harvested pre- and at 12 h, 36 h, 60 h, 156 h and 324 h post-injury, were utilised for IL-6 and IL-8 assay and haematology. Peak concentrations of IL-6 in wound fluid (1.33. ± 0.33 ng/mL) and serum (0.82 ± 0.24 ng/mL) of the experimental group at 12 h post-operation were higher (P < 0.01) than the control (0.30 ± 0.05 ng/mL). Concentrations of IL-8 at 12 h and 60 h in wound fluid (0.21 ± 0.05 ng/mL and 0.22 ± 0.11 ng/mL) respectively were lower (P < 0.05) than serum (0.71 ± 0.21 ng/mL and 0.73 ± 0.24 ng/mL) respectively in the experimental group and corresponding values recorded in controls (0.34 ± 0.09 ng/mL and 0.36 ± 0.14 ng/mL). The haematological and biochemical parameters exhibited minimum fluctuations, but values were within normal ranges. Significant correlations were obtained between serum and wound fluid IL-6 (r = 0.827, P < 0.05); wound fluid IL-6 and monocyte count (r = 0.818, P < 0.04); wound fluid IL-6 and haematocrit (r = -0.894, P < 0.05). There was a positive correlation between serum IL-8 and serum IL-6 (r = 0.622, P > 0.05) and serum IL-8 and wound fluid IL-8 (r = 0.718, P > 0.05) in the experimental group. In conclusion, IL-6 and IL-8 exerted modulated inflammatory processes following cutaneous wounds in dogs. Further studies are required to investigate the expression patterns of IL-6 and IL-8 in cutaneous wounds in order to improve the quality of management of cutaneous wounds.

Topics: Animals; Dogs; Female; Hematology; Interleukin-6; Interleukin-8; Male; Skin Diseases; Tumor Necrosis Factor-alpha; Wound Healing; Wounds and Injuries

Topics: Aged; APACHE; Cardiovascular Diseases; Cohort Studies; Critical Illness; Disseminated Intravascular Coagulation; Extracellular Traps; Female; Gastrointestinal Diseases; Humans; Intensive Care Units; Interleukin-8; Kidney Diseases; Male; Middle Aged; Mitogen-Activated Protein Kinases; Mortality; Multivariate Analysis; Nervous System Diseases; Neutrophils; Organ Dysfunction Scores; Prospective Studies; Reproducibility of Results; Respiratory Tract Diseases; Risk Assessment; Sepsis; Wounds and Injuries

The autotransfusion of unwashed (or unprocessed) shed hemothorax blood (USHB) in trauma patients is widely assumed to be beneficial; however, the inflammatory potential of shed pleural blood has not been thoroughly studied. Since previous studies have documented marked changes in coagulation function of shed pleural blood, we hypothesized that its level of inflammatory cytokines would be elevated.. A prospective observational study of trauma patients in whom cytokine levels from USHB were compared to venous samples from healthy volunteers was conducted. Differences between the cytokine content of patient-derived samples were compared to those from healthy subjects.. There was a statistically significant increase in pro-inflammatory cytokines (IL-6, IL-8, TNFα, GM-CSF), a pro-inflammatory Th-1 cytokine (IFNγ), and anti-inflammatory Th-2 cytokines (IL-4 and IL-10) in shed pleural blood over four hours when compared with samples from healthy controls (P <0.05). Cytokine levels in USHB are approximately 10- to 100-fold higher compared with healthy control venous samples.. USHB, even collected within the accepted four-hour window, contains significantly elevated cytokine levels, suggesting the potential for deleterious effects from autotransfusion. Randomized trials are needed to determine the safety and efficacy of autotransfusion in trauma patients.

Topics: Adult; Blood Transfusion, Autologous; Cytokines; Female; Hemothorax; Humans; Interleukin-10; Interleukin-4; Interleukin-6; Interleukin-8; Male; Middle Aged; Prospective Studies; Thoracic Injuries; Tumor Necrosis Factor-alpha; Wounds and Injuries

In this study, we developed horseradish peroxidase (HRP)-catalyzed sprayable gelatin hydrogels (GH) as a bioactive wound dressing that can deliver cell-attracting chemotactic cytokines to the injured tissues for diabetic wound healing. We hypothesized that topical administration of chemokines using GH hydrogels might improve wound healing by inducing recruitment of the endogenous cells. Two types of chemokines (interleukin-8; IL-8, macrophage inflammatory protein-3α; MIP-3α) were simply loaded into GH hydrogels during in situ cross-linking, and then their wound-healing effects were evaluated in streptozotocin-induced diabetic mice. The incorporation of chemokines did not affect hydrogels properties including swelling ratio and mechanical stiffness, and the bioactivities of IL-8 and MIP-3α released from hydrogel matrices were stably maintained. In vivo transplantation of chemokine-loaded GH hydrogels facilitated cell infiltration into the wound area, and promoted wound healing with enhanced re-epithelialization/neovascularization and increased collagen deposition, compared with no treatment or the GH hydrogel alone. Based on our results, we suggest that cell-recruiting chemokine-loaded GH hydrogel dressing can serve as a delivery platform of various therapeutic proteins for wound healing applications.. Despite development of materials combined with therapeutic agents for diabetic wound treatment, impaired wound healing by insufficient chemotactic responses still remain as a significant problem. In this study, we have developed enzyme-catalyzed gelatin (GH) hydrogels as a sprayable dressing material that can deliver cell-attracting chemokines for diabetic wound healing. The chemotactic cytokines (IL-8 and MIP-3α) were simply loaded within hydrogel during in situ gelling, and wound healing efficacy of chemokine-loaded GH hydrogels was investigated in STZ-induced diabetic mouse model. These hydrogels significantly promoted wound-healing efficacy with faster wound closure, neovascularization, and thicker granulation. Therefore, we expect that HRP-catalyzed in situ forming GH hydrogels can serve as an injectable/sprayable carrier of various therapeutic agents for wound healing applications.

Topics: Animals; Chemokine CCL20; Diabetes Mellitus, Experimental; Drug Delivery Systems; Gelatin; Humans; Hydrogels; Interleukin-8; Mice; Mice, Inbred ICR; Wound Healing; Wounds and Injuries

Mice engrafted with human CD34

Topics: Animals; Cells, Cultured; Disease Models, Animal; Flow Cytometry; Hematopoietic Stem Cell Transplantation; Humans; Immunohistochemistry; Inflammation; Interleukin-10; Interleukin-6; Interleukin-8; Mice; Mice, Inbred NOD; Myeloid-Derived Suppressor Cells; Signal Transduction; Wound Healing; Wounds and Injuries

Traumatic injury results in a systemic inflammatory response syndrome (SIRS), a phenomenon characterised by the release of pro-inflammatory cytokines into the circulation and immune cell activation. Released from necrotic cells as a result of tissue damage, damage associated molecular patterns (DAMPs) are thought to initiate the SIRS response by activating circulating immune cells through surface expressed pathogen recognition receptors. Neutrophils, the most abundant leucocyte in human circulation, are heavily implicated in the initial immune response to traumatic injury and have been shown to elicit a robust functional response to DAMP stimulation. Here, we confirm that mitochondrial DAMPs (mtDAMPs) are potent activators of human neutrophils and show for the first time that signalling through the mitogen-activated-protein-kinases p38 and extracellular-signal-related-kinase 1/2 (ERK1/2) is essential for this response. At 40 and/or 100 μg/ml, mtDAMPs activated human neutrophils, indicated by a significant reduction in the surface expression of L-selectin, and triggered a number of functional responses from both resting and tumour necrosis factor-α primed neutrophils, which included reactive oxygen species (ROS) generation, degranulation, secretion of interleukin-8 and activation of p38 and ERK1/2 MAPKs. Pre-treatment of neutrophils with Cyclosporin H, a selective inhibitor of formyl peptide receptor-1 (FPR-1), significantly inhibited mtDAMP-induced L-selectin shedding as well as p38 and ERK1/2 activation, suggesting that N-formyl peptides are the main constituents driving mtDAMP-induced neutrophil activation. Indeed, no evidence of L-selectin shedding or p38 and ERK1/2 activation was observed in neutrophils challenged with mitochondrial DNA alone. Interestingly, pharmacological inhibition of p38 or ERK1/2 either alone or in combination significantly inhibited L-selectin shedding and IL-8 secretion by mtDAMP-challenged neutrophils, revealing for the first time that MAPK activation is required for mtDAMP-induced neutrophil activation and function. Our findings demonstrate that signalling through FPR-1 and activation of p38 and ERK1/2 MAPKs are key events in mtDAMP-induced neutrophil activation. Gaining an understanding of the signalling pathways involved in mtDAMP-induced neutrophil activation may assist in the development of future therapeutic strategies aimed at targeting the SIRS response to improve the outcome of the hospitalised trauma patient. Reducin

Topics: Humans; Interleukin-8; L-Selectin; MAP Kinase Signaling System; Mitochondria; Mitochondrial Proteins; Neutrophil Activation; Neutrophils; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Signal Transduction; Systemic Inflammatory Response Syndrome; Tumor Necrosis Factor-alpha; Wounds and Injuries

Much research is now being conducted in order to understand the role of cytokines in the development of the inflammatory response following trauma. The purpose of this study was to evaluate whether serum levels of certain cytokines, measured immediately after initial injury, can be used as potential biomarkers for predicting the development and the degree of severity of the systemic inflammatory response (SIRS) in patients with moderate and severe trauma.. We conducted a prospective study with 71 individuals of whom 13 (18.3 %) were healthy controls and 58 (81.7 %) were traumatized orthopaedic patients who were categorized into two groups: 31 (43.6 %) with moderate injuries and 27 (38.1 %) patients with severe orthopaedic trauma. Thirty cc of heparinized blood were drawn from each individual within a few hours after the injury. Serum levels of pro-inflammatory, regulatory and anti-inflammatory cytokines were measured in each individual participant.. High levels of pro-inflammatory cytokines IL-1β,-6,-8,-12, tumour necrosis factor alpha and interferon gamma were found in all injured patients compared to healthy controls. Only IL-6 and IL-8 were significantly higher in the injured patients. Levels of the regulatory cytokines, transformed growth factor beta (TGF-β) and IL-10 were higher in the injured patients, but significant only for TGF-β. Levels of IL-4 were significantly lower in the injured groups as compared to the controls.. Secretion of large amounts of pro-inflammatory cytokines and decreased level of anti-inflammatory cytokines during the acute phase of trauma may lead to the development of systemic inflammatory response syndrome (SIRS) in unstable polytraumatized patients. SIRS may result in life threatening conditions as acute respiratory distress syndrome (ARDS) and multiple organ failure (MOF). High levels of IL-6, IL-8, TGFβ and low levels of IL-4 were found to be reliable markers for the existence of immune reactivity in trauma patients. More research is needed to study pattern of cytokine levels along the acute period of injury, after surgical interventions and during recovery.

Topics: Adult; Biomarkers; Cytokines; Female; Fractures, Bone; Humans; Interleukin-4; Interleukin-6; Interleukin-8; Male; Middle Aged; Prospective Studies; Systemic Inflammatory Response Syndrome; Transforming Growth Factor beta; Wounds and Injuries; Young Adult

Burn wound infections are often difficult to treat due to the presence of multidrug-resistant bacterial strains and biofilms. Currently, mupirocin is used to eradicate methicillin-resistant Staphylococcus aureus (MRSA) from colonized persons; however, mupirocin resistance is also emerging. Since we consider antimicrobial peptides to be promising candidates for the development of novel anti-infective agents, we studied the antibacterial activities of a set of synthetic peptides against different strains of S. aureus, including mupirocin-resistant MRSA strains. The peptides were derived from P60.4Ac, a peptide based on the human cathelicidin LL-37. The results showed that peptide 10 (P10) was the only peptide more efficient than P60.4Ac, which is better than LL-37, in killing MRSA strain LUH14616. All three peptides displayed good antibiofilm activities. However, both P10 and P60.4Ac were more efficient than LL-37 in eliminating biofilm-associated bacteria. No toxic effects of these three peptides on human epidermal models were detected, as observed morphologically and by staining for mitochondrial activity. In addition, P60.4Ac and P10, but not LL-37, eradicated MRSA LUH14616 and the mupirocin-resistant MRSA strain LUH15051 from thermally wounded human skin equivalents (HSE). Interestingly, P60.4Ac and P10, but not mupirocin, eradicated LUH15051 from the HSEs. None of the peptides affected the excretion of interleukin 8 (IL-8) by thermally wounded HSEs upon MRSA exposure. In conclusion, the synthetic peptides P60.4Ac and P10 appear to be attractive candidates for the development of novel local therapies to treat patients with burn wounds infected with multidrug-resistant bacteria.

Topics: Amino Acid Sequence; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Biofilms; Burns, Electric; Cathelicidins; Epidermis; Epithelial Cells; Fibroblasts; Humans; Interleukin-8; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Mitochondria; Models, Biological; Molecular Sequence Data; Mupirocin; Skin, Artificial; Solid-Phase Synthesis Techniques; Wounds and Injuries

Once a patient is in septic shock, survival rates drop by 7.6% for every hour of delay in antibiotic therapy. Biomarkers based on the molecular mechanism of sepsis are important for timely diagnosis and triage. Here, we study the potential roles of a panel of cellular and viral miRNAs as sepsis biomarkers. We performed genome-wide microRNA (miRNA) expression profiling in leukocytes from septic patients and nonseptic controls, combined with quantitative RT-PCR in plasmas from two cohorts of septic patients, two cohorts of nonseptic surgical patients and healthy volunteers. Enzyme-linked immunosorbent assay, miRNA transfection and chromatin immunoprecipitation were used to study the effects of Kaposi sarcoma herpes virus (KSHV) miRNAs on interleukin's secretion. Differences related to sepsis etiology were noted for plasma levels of 10 cellular and 2 KSHV miRNAs (miR-K-10b and miR-K-12-12*) between septic and nonseptic patients. All the sepsis groups had high KSHV miRNAs levels compared with controls; Afro-American patients had higher levels of KSHV-miR-K12-12* than non-Afro-American patients. Both KSHV miRNAs were increased on postoperative day 1, but returned to baseline on day 7; they acted as direct agonists of Toll-like receptor 8 (TLR8), which might explain the increased secretion of the IL-6 and IL-10. Cellular and KSHV miRNAs are differentially expressed in sepsis and early postsurgical patients and may be exploited for diagnostic and therapeutic purposes. Increased miR-K-10b and miR-K12-12* are functionally involved in sepsis as agonists of TLR8, forming a positive feedback that may lead to cytokine dysregulation.

Topics: Aged; APACHE; Black or African American; Case-Control Studies; Feedback, Physiological; Female; Gene Expression Profiling; Gene Expression Regulation; Herpesvirus 8, Human; Humans; Interleukin-6; Interleukin-8; Leukocytes, Mononuclear; Male; MicroRNAs; Middle Aged; Sarcoma, Kaposi; Sepsis; Signal Transduction; Survival Analysis; Toll-Like Receptor 8; Wounds and Injuries

Clinical evidence supports the existence of a trauma-induced secondary cardiac injury. Experimental research suggests inflammation as a possible mechanism. The study aimed to determine if there was an early association between inflammation and secondary cardiac injury in trauma patients.. A cohort study of critically injured patients between January 2008 and January 2010 was undertaken. Levels of the cardiac biomarkers troponin I and heart-specific fatty acid-binding protein and the cytokines tumor necrosis factor α (TNF-α), interleukin (IL)-6, IL-1β, and IL-8 were measured on admission to hospital, and again at 24 and 72 h. Participants were reviewed for adverse cardiac events (ACEs) and in-hospital mortality.. Of 135 patients recruited, 18 (13%) had an ACE. Patients with ACEs had higher admission plasma levels of TNF-α (5.4 vs. 3.8 pg/mL; P = 0.03), IL-6 (140 vs. 58.9 pg/mL, P = 0.009), and IL-8 (19.3 vs. 9.1 pg/mL, P = 0.03) compared with those without events. Hour 24 cytokines were not associated with events, but IL-8 (14.5 vs. 5.8 pg/mL; P = 0.01) and IL-1β (0.55 vs. 0.19 pg/mL; P = 0.04) were higher in patients with ACEs at 72 hours. Admission IL-6 was independently associated with heart-specific fatty acid-binding protein increase (P < 0.05). Patients who presented with an elevated troponin I combined with either an elevated TNF-α (relative risk [RR], 11.0; 95% confidence interval [CI], 1.8-66.9; P = 0.015), elevated IL-6 (RR, 17.3; 95% CI, 2.9-101.4; P = 0.001), or elevated IL-8 (RR, 15.0; 95% CI, 3.1-72.9; P = 0.008) were at the highest risk of in-hospital death when compared with individuals with normal biomarker and cytokine values.. There is an association between hyperacute elevations in inflammatory cytokines with cardiac injury and ACEs in critically injured patients. Biomarker evidence of cardiac injury and inflammation on admission is associated with a higher risk of in-hospital death.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Cytokines; Fatty Acid-Binding Proteins; Female; Heart Injuries; Humans; Interleukin-1; Interleukin-1beta; Interleukin-6; Interleukin-8; Male; Middle Aged; Troponin I; Tumor Necrosis Factor-alpha; Wounds and Injuries; Young Adult

Hyperbaric oxygen (HBO) therapy involves the inhalation of 100% oxygen, whilst inside a chamber at greater than atmospheric pressure. It is an effective treatment for chronic diabetic wounds, although the molecular mechanisms involved remain unclear. We hypothesised that HBO could alter inflammatory gene expression in human endothelial cells via a reactive oxygen/nitrogen species-mediated pathway. Endothelial cells were exposed to a chronic wound model comprising hypoxia (2% O(2) at 1 atmosphere absolute (ATA); PO(2) ~2 kPa) in the presence of lipopolysaccharide and TNF-α for 24h, then treated with HBO for 90 min (97.5% O(2) at 2.4 ATA; PO(2) ~237 kPa). 5h post-HBO, 19 genes involved in adhesion, angiogenesis, inflammation and oxidative stress were downregulated. Notably, only angiogenin gene expression, which promotes both angiogenesis and nitric oxide production (reflected by increased eNOS protein expression in this study), was upregulated. This led to a decrease in endothelial IL-8 mRNA and protein, which could help alleviate inflammatory processes during chronic wound healing. This was no longer evident 22.5h post-HBO, demonstrating the importance of daily exposures in HBO treatment protocols. These studies indicate that elevated oxygen transiently regulates inflammatory gene expression in endothelial cells, which may enhance chronic wound healing.

Topics: Cell Survival; Cells, Cultured; Chronic Disease; Endothelial Cells; Gene Expression; Human Umbilical Vein Endothelial Cells; Humans; Hyperbaric Oxygenation; Inflammation; Inflammation Mediators; Interleukin-8; Nitric Oxide Synthase Type III; Up-Regulation; Wound Healing; Wounds and Injuries

Cytokines are central mediators of the immune-inflammatory response to injury and subsequent multiple organ dysfunction syndrome (MODS). Although previous studies evaluated cytokine levels after trauma, differences between patients with burn and non-burn trauma have not been assessed systematically.. A prospective database of trauma patients admitted between May 2004 and September 2007 to the burn or surgical intensive care units within 24 h of injury with an anticipated stay of at least 72 h was analyzed. Sequential clinical and laboratory parameters were collected in the first week, including multiplex analysis data for plasma levels of inflammatory cytokines (IL-6, and IL-8). Patients with known pre-injury coagulopathy were excluded. A Marshall score of 10 or greater was defined as MODS.. A total of 179 patients were enrolled (67 burn and 112 non-burn). Plasma IL-6 and IL-8 levels were markedly elevated in both burn and non-burn patients compared to healthy volunteers. Burn subjects had higher levels of IL-6 and IL-8 than the non-burn on days 1 through 7 after injury. Subjects with burns and at least 30% total body surface area were older and had a lower injury severity score, a higher prevalence of MODS, and correspondingly higher mortality. Multivariate analysis of injury type, MODS, and time did not demonstrate an influence of MODS.. Burns were associated with a greater and more sustained immune-inflammatory response than non-burn trauma as evidenced by elevated plasma IL-6 and IL-8 levels during the first week. There was no association between MODS and plasma cytokine levels.

Topics: Adult; Burns; Female; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Multiple Organ Failure; Multivariate Analysis; Prospective Studies; Systemic Inflammatory Response Syndrome; Wounds and Injuries

Red blood cell (RBC) transfusion is associated with alterations in systemic concentrations of IL-8/CXCL8 functional homologs in a murine model. Whether RBC transfusion alters systemic neutrophil chemokine concentrations in individuals sustaining traumatic injury is not known. We conducted a retrospective, single-center study of severely injured trauma patients presenting within 12 h of injury with a base deficit greater than 6 and hypotension in the field. Plasma concentrations of 25 chemokines, cytokines, and growth factors were obtained from both transfused (n = 22) and nontransfused (n = 33) groups in the first 48 h following admission. The transfused group (mean RBC units, 2.7 [SD, 1.7]) tended to be older (49.9 [SD, 21.1] vs. 40.4 [SD, 19.9] years, P = 0.10), with a higher percentage of females (40.9% vs. 18.2%, P = 0.06) and a higher Injury Severity Score (27.1 [SD, 12.7] vs. 21.4 [SD, 10.2], P = 0.07). In univariate and multivariate analyses, transfusion was associated with increased hospital and intensive care unit length of stay but not ventilator-free days. Plasma CXCL8 concentrations were higher in the transfused (84 [SD, 88] pg/mL) than the nontransfused group (31 [SD, 21] pg/mL, P = 0.003). Using a linear prediction model to calculate bioanalyte concentrations standardized for age, sex, Injury Severity Score, and admission SBP, we observed that CXCL8 concentrations diverged within 12 h following injury, with the transfused group showing persistently elevated CXCL8 concentrations by contrast to the decay observed in the nontransfused group. Other bioanalytes showed no differences across time. Red blood cell transfusion is associated with persistently elevated neutrophil chemokine CXCL8 concentrations following traumatic injury.

Topics: Adult; Aged; Cohort Studies; Erythrocyte Transfusion; Female; Humans; Interleukin-8; Male; Middle Aged; Retrospective Studies; Wounds and Injuries

Toll-like receptor 2 (TLR2) signaling plays a critical role in orchestrating the innate immune response and the development of sepsis and subsequent organ dysfunction after trauma. The objectives of this prospective study were to identify haplotype tag single-nucleotide polymorphisms (htSNPs) within the entire TLR2 gene and to investigate their clinical relevance in patients with major trauma. A total of 410 patients with major trauma were prospectively recruited. The htSNPs of the TLR2 gene was determined using HapMap database and linkage disequilibrium analysis. The htSNPs were genotyped using polymerase chain reaction-restriction fragment length polymorphism method. The whole peripheral blood samples obtained immediately after admission were stimulated with bacterial lipoprotein and then determined for production of tumor necrosis factor-α, interleukin 8, and interleukin 10. Sepsis morbidity rate and multiple organ dysfunction (MOD) scores were accessed. Three SNPs (rs1898830, rs3804099, and rs7656411) were identified as htSNPs for the TLR2 gene. All of them were shown to be high-frequency SNPs in this study cohort. Two of them (rs1898830 and rs3804099) and the haplotype ATT were significantly associated with cytokine production by peripheral blood leukocytes in response to bacterial lipoprotein stimulation. Only rs3804099, however, was significantly associated with higher sepsis morbidity rate and MOD scores in patients with major trauma. In addition, the patients with the haplotype ATT had lower sepsis morbidity rate than those without the haplotype ATT. Therefore, three SNPs might act as htSNPs for the entire TLR2 gene in the Chinese population. The rs3804099 and the haplotype ATT might be used as relevant risk estimates for the development of sepsis and MOD in patients with major trauma.

Topics: Asian People; Genotype; Haplotypes; Humans; Interleukin-10; Interleukin-8; Multiple Organ Failure; Polymorphism, Restriction Fragment Length; Polymorphism, Single Nucleotide; Prospective Studies; Sepsis; Toll-Like Receptor 2; Tumor Necrosis Factor-alpha; Wounds and Injuries

Posttrauma apoptosis resistance of neutrophils (PMN) is related to overshooting immune responses, systemic inflammatory response syndrome (SIRS) and multiple organ failure (MOF). Recently, we have shown that the apoptosis resistance in circulating PMN from severely injured patients which is known to be mediated by high serum levels of pro-inflammatory cytokines can be overcome by the activation of Fas death receptor. Here, we aimed to study whether stimulation of surface Fas leads to the inactivation of hyperactivated PMN from critically ill patients with SIRS. PMN from 23 multiple trauma patients (mean injury severity score (ISS) 34±1.9) were isolated at day 1 after admission to the trauma center. PMN from 17 volunteer blood donors served as controls. Neutrophil activity has been determined after ex vivo short (1 h) and long-term (4 h) stimulation of freshly isolated PMN with immobilized agonistic anti-Fas antibodies. We found neutrophil chemotactic migration in response to IL-8, phagocytosis and oxidative burst to be significantly inhibited in control cells already after short-term (1 h) Fas stimulation. In contrast, inactivation of trauma PMN by agonistic anti-Fas antibodies was found to be efficient only after long-term (4 h) incubation of cells with agonistic antibodies. Thus, in trauma PMN down-regulation of neutrophil activity seems to be delayed when compared to cells isolated from healthy controls, suggesting impaired susceptibility for Fas stimulation in these cells. Interestingly, whereas Fas-mediated inhibition of phagocytosis and oxidative burst could be prevented by the broad range caspase inhibitor t-butoxycarbonyl-aspartyl(O-methyl)-fluoromethyl ketone (BocD-fmk), the chemotactic activity in response to IL-8 was unaffected. In conclusion, we demonstrate that stimulation of neutrophil Fas does not only initiate apoptosis but also induces inhibition of neutrophil functions, partially by non-apoptotic signaling.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Apoptosis; Chemotaxis, Leukocyte; Fas Ligand Protein; fas Receptor; Female; Flow Cytometry; Humans; Interleukin-8; Male; Middle Aged; Multiple Organ Failure; Neutrophils; Phagocytosis; Respiratory Burst; Signal Transduction; Systemic Inflammatory Response Syndrome; Wounds and Injuries

The diagnosis of acute lung injury (ALI) is based on a consensus clinical definition. Despite the simplicity of this definition, ALI remains underdiagnosed and undertreated. Severe trauma is a well-described cause of ALI that represents a relatively homogeneous subset of patients with ALI. The aims of this study were to develop a panel of plasma biomarkers to facilitate diagnosis of trauma-induced ALI and to enhance our understanding of the pathogenesis of human ALI.. A retrospective nested case control of 192 patients admitted to the trauma intensive care unit at a university hospital between 2002 and 2006. We compared 107 patients with ALI to 85 patients without ALI. Plasma was collected within 72 hours of intensive care unit admission. Twenty-one plasma biomarkers were measured in duplicate in each plasma sample.. Patients with ALI had higher severity of illness scores, more days of mechanical ventilation, longer hospital stays, and higher mortality versus controls. Seven biomarkers (receptor for advanced glycation end products, procollagen peptide III, brain natriuretic peptide, angiopoietin-2, interleukin-10, tumor necrosis factor alpha, and interleukin-8) had a high diagnostic accuracy as reflected by the area under the receiver operating characteristic curve of 0.86 (95% confidence interval, 0.82-0.92) in differentiating ALI from controls.. A model using seven plasma biomarkers had a high diagnostic accuracy in differentiating patients with trauma-induced ALI from trauma patients without ALI. In addition, use of a panel of biomarkers provides insight into the likely importance of alveolar epithelial injury in the pathogenesis of early ALI.

Topics: Acute Lung Injury; Adult; Angiopoietin-2; Biomarkers; Case-Control Studies; Causality; Collagen Type III; Discriminant Analysis; Female; Hospitals, University; Humans; Interleukin-10; Interleukin-8; Length of Stay; Logistic Models; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Predictive Value of Tests; Receptor for Advanced Glycation End Products; Receptors, Immunologic; Respiration, Artificial; Retrospective Studies; Sensitivity and Specificity; Severity of Illness Index; Statistics, Nonparametric; Tumor Necrosis Factor-alpha; Wounds and Injuries

Severe trauma may induce alternations of cytokine response and polymorphonuclear cell (PMN) activity in patients. This study investigated the correlation of plasma migration inhibitory factor (MIF) level and PMN activation after severe injury, and their relationship with clinical outcomes.. A prospective observational study was performed at the emergency department and intensive care unit of a university hospital. Thirty-two severe blunt trauma patients (Injury Severity Score greater than 16) with systemic inflammatory response syndrome (SIRS) were enrolled. Age- and gender-matched healthy persons were the controls. Patient blood samples were obtained within 24 hours of and at 72 hours after injury. PMNs were isolated and measured for NF-kBp65 translocation and respiratory burst. Plasma MIF, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-8, and IL-10 concentrations were measured. Control PMNs were incubated with patient plasma preincubated with anti-MIF antibody or anti-IL-6 antibody; cytokine blockade effects were evaluated.. Twelve patients developed organ failure. Compared with patients without organ failure, patients with organ failure had lower blood pressure and a higher base deficit on admission, higher NF-kBp65 translocation and respiratory burst of PMNs, and higher plasma MIF (968 ± 246 pg/mL vs 564 ± 299 pg/mL) and IL-6 (202 ± 91 pg/mL vs 119 ± 84 pg/mL) levels within 24 hours after injury. Plasma MIF had significant positive correlation with NF-kB translocation of PMNs within 24 hours of incurring trauma (R = 0.668). The presence of anti-MIF antibody in patients' plasma obtained within 24 hours, but not at 72 hours, after injury could significantly partially block the NF-kBp65 translocation and respiratory activity of PMNs in the controls.. An early increase of plasma MIF associates with NF-kB translocation and respiratory burst in PMNs of severe trauma patients and correlates with higher morbidity. MIF is one of the important factors responsible for early PMN activation and may provide a target of immunomodulation after injury.

Topics: Adult; Case-Control Studies; Confounding Factors, Epidemiologic; Female; Humans; Injury Severity Score; Interleukin-10; Interleukin-6; Interleukin-8; Macrophage Migration-Inhibitory Factors; Male; Middle Aged; Morbidity; Multiple Organ Failure; Neutrophils; NF-kappa B; Prospective Studies; Research Design; Respiratory Burst; Time Factors; Translocation, Genetic; Tumor Necrosis Factor-alpha; Wounds and Injuries

Clinical observations are suggesting accelerated granulation tissue formation in traumatic wounds treated with vacuum-assisted closure (VAC). Aim of this study was to determine the impact of VAC therapy versus alternative Epigard application on local inflammation and neovascularization in traumatic soft tissue wounds.. Thirty-two patients with traumatic wounds requiring temporary coverage (VAC n = 16; Epigard n = 16) were included. At each change of dressing, samples of wound fluid and serum were collected (n = 80). The cytokines interleukin (IL)-6, IL-8, vascular endothelial growth factor (VEGF), and fibroblast growth factor-2 were measured by ELISA. Wound biopsies were examined histologically for inflammatory cells and degree of neovascularization present.. All cytokines were found to be elevated in wound fluids during both VAC and Epigard treatment, whereas serum concentrations were negligible or not detectable. In wound fluids, significantly higher IL-8 (p < 0.001) and VEGF (p < 0.05) levels were detected during VAC therapy. Furthermore, histologic examination revealed increased neovascularization (p < 0.05) illustrated by CD31 and von Willebrand factor immunohistochemistry in wound biopsies of VAC treatment. In addition, there was an accumulation of neutrophils as well as an augmented expression of VEGF (p < 0.005) in VAC wound biopsies.. This study suggests that VAC therapy of traumatic wounds leads to increased local IL-8 and VEGF concentrations, which may trigger accumulation of neutrophils and angiogenesis and thus, accelerate neovascularization.

Topics: Adult; Amputation, Traumatic; Arm Injuries; Biopsy; Female; Fibroblast Growth Factor 2; Fluorocarbon Polymers; Fractures, Open; Humans; Injury Severity Score; Interleukin-6; Interleukin-8; Leg Injuries; Leukocyte Count; Male; Middle Aged; Negative-Pressure Wound Therapy; Neovascularization, Pathologic; Neutrophils; Platelet Endothelial Cell Adhesion Molecule-1; Skin Transplantation; Soft Tissue Injuries; Surgical Flaps; Vascular Endothelial Growth Factor A; von Willebrand Factor; Wound Healing; Wounds and Injuries

Systemic inflammation subsequent to polytrauma is connected to neutrophil (PMN) dysregulation characterized by reduced NF-kB-translocation and cytokine expression. The dynamics of NF-kB-activation as well as its down-stream regulation of IL-8-expression in PMN following major trauma remain unclear. The aim of this pilot study was to analyse NF-kB nuclear translocation in relation to IL- 8-mRNA-expression in PMN after major trauma.. PMN were isolated from blood samples of 15 major trauma patients (New Injury Severity Score, NISS > 16) drawn within 90 min and subsequently 6, 12, 24, 48, 72 h after trauma. NF-kB-translocation was analysed by Electrophoretic Mobility Shift Assay, EMSA and quantified by densitometry [arbitrary units], IL-8-mRNA-expression by RT-PCR, [copies/50 ng RNA]. Additionally, NF-kB-translocation and IL-8-expression in PMN of healthy volunteers were analysed natively (-control) and after LPS stimulation (+control).. NF-kB-translocation and IL-8-mRNA-expression was significantly increased in polytrauma patients (n=15; NISS: 34 +/- 8 [mean +/- SEM]) initially. In non-survivors, NFkB- translocation was significantly increased on admission and subsequently reduced within 6 h, while it increased in the survivors group. After 24 h, a second significant increase in NF-kB-activity and IL-8-expression was found in survivors that was subsequently reduced in both groups.. This pilot study has shown that a concomitant initial increase in transcriptional NF-kB-activity and IL-8 mRNA expression was observed in the early posttraumatic period which preceded the down-regulation of the innate immune system.

Topics: Adolescent; Adult; Aged; Female; Humans; Interleukin-8; Male; Middle Aged; Multiple Organ Failure; Neutrophils; NF-kappa B; Protein Transport; RNA, Messenger; Wounds and Injuries

Severe injury may lead to immunosuppression, multiple organ failure, and death. The aim of the study was to investigate the direct impact of soft tissue destruction on the development of trauma-associated immunomodulation. Hip surgery was considered to represent an isolated soft tissue trauma that allowed for the examination of changes taking place locally at the site of trauma or systemically with regard to monocyte function and leukocyte redistribution. Peripheral blood and wound fluid collected from the drains of 21 patients after hip surgery were analyzed to determine the cellular composition and/or the responsiveness of mononuclear cells (MNCs) to lipopolysaccharide (LPS). Different factors present in the wound fluids were tested for their capacity to modulate the MNC of healthy individuals with regard to cytokine and chemokine secretion. We found that various factors, including heat-shock protein (HSP) 60 and HSP70, were locally released at the site of soft tissue trauma and could be detected in wound fluids. The wound fluid-derived MNC (but not the peripheral blood-derived MNC) showed an impaired capacity to release TNF-alpha after LPS stimulation. Cell-free wound fluid suppressed in healthy individuals the LPS-induced TNF-alpha secretion by MNC. After surgery, granulocytosis was found in peripheral blood and in wound fluids, but monocytopenia was restricted to wound fluids. In parallel, wound fluids induced in healthy individuals the release by MNC of distinct chemokines specific for granulocytes and monocytes. These wound fluid-mediated effects of TNF-alpha suppression and chemokine induction could be mimicked by recombinant human HSP70 and, in part, by HSP60. Thus, tissue-derived factors, such as HSP70 released after injury, suppress monocyte function and, therefore, might favor the development of immunosuppression after severe injury.

Topics: Aged; Aged, 80 and over; Arthroplasty, Replacement, Hip; Blotting, Western; Cytokines; Female; Flow Cytometry; Heat-Shock Proteins; HSP70 Heat-Shock Proteins; Humans; Interleukin-10; Interleukin-8; Lipopolysaccharides; Male; Middle Aged; Monocytes; Muscle, Skeletal; Recombinant Proteins; Soft Tissue Injuries; Tumor Necrosis Factor-alpha; Wounds and Injuries

The lung produces a localized immunologic response to systemic trauma, characterized by an initial proinflammatory period with production of interleukin (IL)-8 and IL-18, followed by an anti-inflammatory phase with elevated levels of IL-10. Recent studies have shown a correlation between alveolar IL-10 and the rate of local neutrophil apoptosis. The aim of the present study was to further characterize the association of alveolar IL-8 and IL-10 after trauma with neutrophil activation, apoptosis, and phagocytic capacity.. Bronchoalveolar lavage fluid (BALF) was obtained from 17 trauma patients with an Injury Severity Score >/=16 who required mechanical ventilation. Neutrophils from venous blood of healthy volunteers were incubated in either (1) cell culture media (control), (2) culture media + BALF, (3) culture media + BALF + anti-IL-8 neutralizing antibody, or (4) culture media + BALF + anti-IL-10. Surface CD11b expression, ability to phagocytose fluorescent bacteria, and neutrophil apoptosis were determined by flow cytometry.. Phagocytosis and CD11b expression were both augmented on postinjury day 1 when compared with controls. Neutralization of IL-10 or IL-8 produced no significant differences in phagocytosis or CD11b expression. However, neutralization of IL-10 significantly decreased the rate of apoptosis in samples from postinjury day 1.. Phagocytosis and CD11b expression on neutrophils are IL-8 and IL-10 independent. However, our data indicate that alveolar neutrophil apoptosis is dependent on IL-10 at early time points after injury. Elucidation of this pathway may allow novel interventions to prevent posttraumatic pulmonary dysfunction.

Topics: Adolescent; Adult; Apoptosis; Bronchoalveolar Lavage Fluid; Female; Humans; Interleukin-10; Interleukin-8; Male; Middle Aged; Neutrophils; Pulmonary Alveoli; Reference Values; Wounds and Injuries

Severe injury after trauma is associated with a diminished production of different proinflammatory cytokines after stimulation with bacterial cell wall components. The cellular mechanisms, leading to a decreased responsiveness especially of monocytes after multiple injuries have not yet been elucidated in detail. The expression of Toll-like receptors (TLR) on leukocytes is essential for recognition of bacterial components. We investigated the expression of TLR2 and 4 in correlation with gram-negative and gram-positive stimuli-dependent cytokine liberation after severe injury in comparison with that in healthy volunteers.. In a prospective clinical experimental study, 12 trauma patients with an Injury Severity Score above 21 points and 14 healthy volunteers were analyzed. Heparinized whole blood samples of patients were collected within 48 hours after trauma and incubated in vitro with or without lipopolysaccharide (LPS) and peptidoglycan (PGN). TLR2 and TLR4 expression on monocytes was analyzed by flow cytometry. LPS- and PGN-induced tumor necrosis factor alpha (TNFalpha) and interleukin-8 production was measured by means of enzyme-linked immunosorbent assay.. Both LPS- and PGN-induced TNFalpha liberation were significantly reduced in severely injured patients. The surface expression of TLR2 was also significantly decreased on monocytes collected from trauma patients, whereas the expression of TLR4 remained unchanged. There was only a negative correlation between TLR2 expression and the liberation of TNFalpha after stimulation with LPS or PGN.. We conclude that diminished cytokine production after trauma cannot be explained simply by changes in TLR2 or TLR4 expression and that subsequent signaling cascades or additional receptors are involved in the blunted cytokine response after trauma.

Topics: Adolescent; Adult; Aged; Cytokines; Female; HLA-DR Antigens; Humans; Immunity, Innate; Interleukin-8; Lipopolysaccharide Receptors; Lipopolysaccharides; Male; Middle Aged; Monocytes; Peptidoglycan; Prospective Studies; Reference Values; Toll-Like Receptor 2; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha; Wounds and Injuries

Although multiple organ failure (MOF) remains the leading cause of death after trauma, the pathogenic cellular and molecular mechanisms underlying MOF are poorly understood. In addition to proinflammatory and anti-inflammatory mediator cascades, the temporal onset of MOF has generated recent interest because the organ systems involved into MOF seem to deteriorate in a time-dependent fashion after trauma. We therefore investigated the temporal course of MOF in traumatized human patients and evaluated and compared the distribution patterns of cytokine expression, including interleukin (IL) 6, IL-8, IL-10, and the soluble tumor necrosis factor-[alpha] receptors sTNF-R p55 and sTNF-R p75 in early-onset versus late-onset MOF. In addition, we analyzed the predictive value of cytokine biomarkers of MOF and lethal outcome. In a prospective observational cohort study conducted at three trauma centers, all patients (n = 352) admitted to two level 1 trauma centers in Germany were enrolled in the study based on the following inclusion criteria: severe traumatic brain injury (TBI) with a Glasgow Coma Scale (GCS) score of 8 or lower and/or distinct changes in cranial computed tomography and/or multiple injuries (MT) to the body (at least two regions had Abbreviated Injury Scale score of 3 or higher). The incidence of MOF was evaluated using the modified Goris-MOF score. The temporal onset of MOF was divided into early-onset MOF (EMOF, developing on days 0-3), late-onset MOF (LMOF, developing on days 4-10), combined early-onset and late-onset MOF (CMOF), and patients never showing signs of MOF during the observation period. In addition, the levels of the serum cytokine markers IL-6, IL-8, IL-10, sTNF-R p55, and sTNF-R p75 were analyzed at specific posttraumatic time points using established enzyme-linked immunosorbent assay techniques. A total of 352 patients (274 men and 78 women; TBI, 101; TBI + MT, 125; MT, 126) were enrolled into the study. Patients assigned to the EMOF group showed specific disruption of pulmonary and cardiocirculatory function, whereas LMOF was significantly associated with hepatic failure. The patients without signs of MOF and the EMOF patients had the same risk of lethal outcome (8.2% vs. 7.5%); LMOF and CMOF were found to be associated with a 3- to 4-fold increase in mortality (38.5% vs. 30.6%, respectively). Analysis of cytokine serum biomarkers revealed that patients with LMOF showed a biphasic elevation of IL-6 and significantly higher sTNF-

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; Humans; Injury Severity Score; Interleukin-10; Interleukin-6; Interleukin-8; Male; Middle Aged; Multiple Organ Failure; Multiple Trauma; Receptors, Tumor Necrosis Factor, Type I; Survival Rate; Time Factors; Trauma Severity Indices; Tumor Necrosis Factor Decoy Receptors; Wounds and Injuries

The relationship between postmortem serum cytokine levels and severity of traumatic injuries was studied. The postmortem serum levels of interleukin-6 (IL-6) and interleukin-8 (IL-8) of 131 victims who died from traumatic injury were measured by an enzyme-linked immunosorbent assay method and compared with scores of total abbreviated injury scale (total AIS) and injury severity score (ISS) calculated from detailed autopsy reports. A significant positive correlation was observed between IL-6 and total AIS (rs=0.4508, p<0.0001), between IL-6 and ISS (rs=0.3337, p<0.0001), between IL-8 and total AIS (rs=0.6593, p<0.0001), and between IL-8 and ISS (rs=0.5305, p<0.0001). The significant correlation between cytokine levels and anatomical traumatic severity indicated that the cytokine levels are useful objective indexes of traumatic severity. In addition, the total AIS is a suitable marker to evaluate traumatic severity as the coefficient of correlation between the cytokine levels and the total AIS was higher than that for the ISS values.

Topics: Abbreviated Injury Scale; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Female; Forensic Pathology; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Postmortem Changes; Wounds and Injuries

In experimental settings, the increased intestinal permeability (IP) following severe trauma is associated with increased serum concentrations of cytokines. Multiply injured patients are susceptible to the development of multiple organ failure (MOF). The aim of this study was to determine if altered IP after trauma was associated with upregulation of cytokines and if cytokines and IP influenced the development of MOF. In 30 multiply injured patients, IP was measured on days 2 and 4 after injury using the lactulose-mannitol (L-M) test, and the levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and IL-8 were determined simultaneously. The L-M ratio increased significantly from 0.049 (0.017-0.133) on day 2 to 0.150 (0.059-0.339) on day 4 (p < 0.02) On day 4, a significant correlation was also found between the L-M ratio and IL-6 (r = 0.43, p < 0.03). The IL-6 level on days 2 and 4 was significantly (p < 0.01 and p < 0.03, respectively) higher in MOF patients than in those without MOF, as was the TNF-alpha level on day 4 significantly higher (p < 0.04) in MOF patients. IP increases following multiple trauma, and on day 4 it correlates with the IL-6 level. However, in patients who develop MOF only cytokines are invariably increased, with IL-6 alone being significantly increased on both measurements in these patients.

Topics: Adult; Cytokines; Female; Humans; Interleukin-6; Interleukin-8; Intestinal Mucosa; Lactulose; Male; Mannitol; Middle Aged; Multiple Organ Failure; Permeability; Tumor Necrosis Factor-alpha; Wounds and Injuries

To assess in patients with multiple trauma the relevance of the following as predictive markers for infections: the inflammation parameters white blood count, body temperature, blood polymorphonuclear leukocyte (PMN) migration; blood levels of C-reactive protein, PMN elastase, procalcitonin, neopterin, interleukin 6, interleukin 8, malondialdehyde, total antioxidative status; the stress parameters cortisol and lactate.. Prospective observational cohort study.. Intensive Care Unit of a university surgical department.. Twenty-six patients with multiple trauma of differing severity.. Trauma severity was estimated by the ISS. PMN migration upon F-Met-Leu-Phe stimulation was determined in fresh whole blood in a ready-for-use, one-way membrane filter assay and evaluated by automated image analysis. The other parameters were measured with commercially available tests. During hospitalization, nine patients developed infections, and 17 patients were free of infection. PMN migration below a critical minimum preceded infections in eight of the infected, but occurred in only three of the non-infected patients (positive/negative predictive values 0.72/0.93; sensitivity/specificity 0.88/0.82; likelihood ratio 5.0). Fever (> or =38.0 degrees C) had predictive values of 0.83/0.80 and a high likelihood ratio of 9.4, but a low sensitivity/specificity of 0.55/0.94. The other parameters were without significance. Procalcitonin, elastase, C-reactive protein, neopterin and lactate correlated positively with the injury severity score.. PMN migration proved to be a highly sensitive predictive marker for infections. The whole-blood PMN migration test may facilitate early aggressive antimicrobial therapy.

Topics: Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Cell Movement; Cohort Studies; Humans; Infections; Interleukin-1; Interleukin-8; Leukocyte Count; Neutrophils; Predictive Value of Tests; Prospective Studies; Protein Precursors; Wounds and Injuries

Topics: Adolescent; Adult; Female; Humans; Interleukin-8; Male; Middle Aged; Respiratory Distress Syndrome; Tumor Necrosis Factor-alpha; Wounds and Injuries; Young Adult

G protein-coupled chemoattractants recruit neutrophils (PMN) to sites of injury and infection. The leukotrienes (LT) and CXC chemokines (CXC) and their receptors (BLT1/BLT2 and CXCR1/CXCR2) are all known to play roles in these responses. Each system has been studied separately in vitro, but in vivo they act concurrently, and the clinical interactions between the two systems are unstudied. We prospectively studied calcium mobilization and chemotactic responses to LTB(4) in PMN from major trauma patients. The responses of the high affinity BLT1 receptor were suppressed at the 3-day postinjury time point, but recovered by 1 wk. Trauma patients had transient elevations of plasma LT and CXC levels. Functional deficits identical with those in trauma PMN were reproduced in vitro by exposing healthy PMN to CXCs at the elevated plasma concentrations found. Functional responses to LTB(4) were suppressed by cross-talk with CXC and BLT2 receptors that desensitize BLT1. Since the suppression of intracellular calcium mobilization was prominent, we also studied the role of suppressed cell calcium mobilization in the defective chemotactic responses to LTB(4). We noted that PMN chemotaxis to LTB(4) showed far more dependence on store-operated calcium entry than on the release of cellular calcium stores, and that store-operated calcium responses to BLT1 activation were markedly inhibited during the same time period as was chemotaxis. The intermittent release of inflammatory mediators after injury can blunt PMN responses to LTs by suppressing BLT1 as well as downstream calcium entry. Diminished LT receptor activity due to cross-talk with CXC receptors can inhibit PMN recruitment to infective sites. This may predispose injured patients to septic complications.

Topics: Adolescent; Adult; Aged; Calcium; Calcium Signaling; Chemotaxis, Leukocyte; Female; Humans; Inflammation Mediators; Interleukin-8; Leukotriene B4; Male; Middle Aged; Neutrophils; Prospective Studies; Receptor Cross-Talk; Receptors, Chemokine; Receptors, Interleukin-8A; Receptors, Interleukin-8B; Receptors, Leukotriene B4; Wounds and Injuries

The lung's immune response to trauma is biphasic with an initial proinflammatory and a subsequent anti-inflammatory cytokine response that alters cell function. Apoptosis, programmed cell death, is regulated by cytokines, and alteration of this important cellular function has been associated with end-organ dysfunction. We hypothesize that the lung's immune response to trauma alters alveolar inflammatory cell apoptosis and may contribute to posttrauma pulmonary dysfunction.. Bronchoalveolar lavage specimens were obtained from trauma patients with an injury severity score of 16 or more compared with patients who underwent elective surgery. Interleukin (IL)-8 and IL-10 were measured in the supernatant. Apoptosis and HLA-DR expression were measured in the cellular content, and Pao(2)/Fio(2) ratios were calculated as a measure of pulmonary function.. After trauma, the alveolar inflammatory cell population was composed primarily of neutrophils. Apoptosis was suppressed initially after injury but increased to control levels by 72 hours after injury in parallel to alveolar concentrations of IL-10. Levels of IL-8 remained elevated, and HLA-DR expression remained suppressed throughout the study period. Pao(2)/Fio(2) ratios demonstrated pulmonary dysfunction by 72 hours.. The lung's biphasic cytokine response to injury significantly alters both alveolar inflammatory cell apoptosis and HLA-DR expression. The alteration of alveolar inflammatory cell apoptosis may be dependent on the local production of IL-10. A reduction in apoptosis immediately preceded the onset of clinically significant pulmonary dysfunction.

Topics: Adult; Apoptosis; Bronchoalveolar Lavage Fluid; Female; HLA-DR Antigens; Humans; Inflammation; Interleukin-10; Interleukin-8; Lung Injury; Male; Neutrophils; Oxygen; Pulmonary Alveoli; Pulmonary Artery; Respiration; Time Factors; Trauma Severity Indices; Wounds and Injuries

Estimation of trauma severity currently relies on clinical diagnoses and scoring systems. However, the early estimation of the severity of chest trauma and overall soft tissue trauma (STT) remains insufficient. Traditional trauma scoring systems fail to reflect the individual trauma pattern and severity, neglecting the different outcomes after injuries in different body regions. Therefore, the aim of this prospective study was to detect laboratory markers that may reflect the pattern and extent of individual trauma in the very early phase after injury.. In 107 non-selected trauma patients, blood samples were collected almost immediately and then at short intervals after the trauma. In addition to the biochemical analysis of 20 different mediators viewed as potential trauma markers, the following data were correlated with the laboratory results: injury severity score (ISS), polytrauma score (PTS), Ulmer score HTAPE (trauma pattern specific: head (H), thorax (T), abdomen (A), pelvis (P), extremities (E); 0-3 degrees each), multiple organ failure score (MOF), overall, primary and secondary lethality.. ISS and the severity of head injury were clearly higher in non-survivors (n=17) than in survivors (n=90) (median ISS: 35 versus 18; median severity of head injury (H): 3 versus 1). Whereas head injury was correlated with early death (3 days post-trauma) was influenced by thoracic trauma (r=0.15) as well as by soft tissue trauma (STT, r=0.12). Of all investigated mediators, interleukin-6 (IL-6) displayed the highest correlations (r=0.66, P<0.00001) with the extent of chest trauma, followed by correlations with PTS, STT, fracture trauma (FT) and ISS during the first hour after trauma. There was no correlation between IL-6 and head injury. The extent of STT was correlated best to IL-8 (r=0.75), IL-6 (r=0.54), and creatine kinase (CK, r=0.49) plasma concentrations.. In the very early stage after an accident the severity of chest trauma is strongly correlated with the plasma concentration of IL-6, and the extent of overall soft tissue trauma (STT) to plasma concentrations of IL-8, IL-6, and CK.

Topics: Adolescent; Adult; Aged; Biomarkers; Craniocerebral Trauma; Creatine Kinase; Female; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Multiple Organ Failure; Prospective Studies; Soft Tissue Injuries; Statistics, Nonparametric; Survival Rate; Thoracic Injuries; Trauma Severity Indices; Wounds and Injuries

While clinical observations suggest that trauma to the skin plays a critical role in the induction of skin lesions in some skin diseases, the mechanism by which these lesions are induced is not known. We have postulated that minor trauma to the skin may lead to the expression of critical adhesion molecules on epidermal endothelial cells (E-selectin) and pro-inflammatory cytokines, which would predispose these areas to the development of skin lesions. In order to test this hypothesis normal inner arm skin of 11 normal subjects was gently rubbed with a pencil eraser for 2 min. Four hours after rubbing, skin biopsies were obtained from the rubbed site and from adjacent normal, unrubbed inner arm skin. Expression of E-selectin, intercellular adhesion molecules (ICAM-1) and the mRNA of selected cytokines was studied utilizing real time polymerase chain reactions. Biopsies were also examined for the presence of an inflammatory infiltrate and for the presence of E-selectin and ICAM-1. No clinical or histologic changes were seen in the skin expression/unrubbed skin expression = 9.0; (median ratio rubbed skin expression/unrubbed skin expression range 0.9-161.0), ICAM-1 (median rubbed skin expression/unrubbed skin expression = 3.2; range 0.9-19.8), IL-8 (median rubbed skin expression/unrubbed skin expression = 6.6; range 2.6-57.3) and IL-10 (median rubbed skin expression/unrubbed skin expression = 13.1; range 2.4-29.0) was noted. Immunohistochemistry revealed the presence of E-selectin in the dermal blood vessels in three of four subjects 4 h after rubbing but not in the unrubbed skin. Changes in ICAM -1 or HLA-DR deposits were seen in the rubbed compared with the unrubbed skin. These findings demonstrated that minor trauma to skin may induce expression of E-selectin, ICAM-1 and IL-8, which may make the skin a more permissive site for the development of inflammatory reactions. These findings may play an important role in the development of skin lesions in areas of minor trauma.

Topics: Biopsy; DNA, Complementary; E-Selectin; Female; Gene Expression Regulation; Humans; Immunohistochemistry; Inflammation; Intercellular Adhesion Molecule-1; Interleukin-10; Interleukin-8; Male; Models, Biological; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Skin; Time Factors; Wounds and Injuries

We investigated the usefulness of cytokine measurement in the field of forensic medicine. In this study, the levels of Interleukin (IL)-1beta, IL-6, IL-8, IL-10 in serum collected within 2 days after death were used to estimate the cause of death. In seventy-one victims, mean age 55.5 +/- 17.7 (S.D.) years, the cases were classified as traumatic death (24 cases, trauma group), unnatural deaths by other than traumatic causes (31 cases, unnatural death group), and deaths due to natural causes (16 cases, natural death group). The Kruskal-Wallis test showed that IL-6 and IL-8 were good indices of trauma. According to the Scheffé test, IL-6 and IL-8 levels of the traumatic death group were significantly higher than those of the unnatural death group (p < 0.05), but there was no significant difference in IL-6 levels between the traumatic death and natural death groups. Further, IL-6 levels showed considerable variability even among similar cases. However, IL-8 measurement of postmortem samples is useful to evaluate non-quantitative damage received before death.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Autopsy; Biomarkers; Cause of Death; Female; Forensic Medicine; Humans; Interleukin-1; Interleukin-10; Interleukin-6; Interleukin-8; Interleukins; Male; Middle Aged; Wounds and Injuries

Immunohistochemical studies on the time-dependent expression of the chemokines such as interleukin (IL)-8, monocyte chemoattractant protein (MCP)-1 and macrophage inflammatory protein (MIP)-1alpha were performed on 50 human skin wounds with different wound ages (group I 0-12 h, group II 1-4 days, group III 7-14 days and group IV 17-21 days). In the wound specimens with wound ages between 4 and 12 h, neutrophils mainly showed positive reactions for IL-8, MCP-1 and MIP-1alpha. With increasing wound ages, macrophages and fibroblasts were positively stained with anti-IL-8, MIP-1alpha and MCP-1 antibodies. Morphometrically, there was a similar distribution in the positive ratios of the inflammatory cells among IL-8, MCP-1 and MIP-alpha. The positive ratios of each chemokine were very low in group I and a considerable increase of the positive ratios in each chemokine was observed in group II (mean +/- standard error IL-8: 59.8 +/- 2.1%, MCP-1: 42.4 +/- 3.1% and MIP-1alpha: 50.4 +/- 3.7%). Although the positive ratios for each chemokine gradually decreased according to the wound age, the mean positive ratios in groups III and IV were significantly higher than those in group I. From the forensic aspect, these chemokines are considered useful markers for wound age determination. Thus, ratios of > 50% for IL-8, > 30% for MCP-1 or > 40% for MIP-1alpha indicate a wound age of at least I day. Moreover, the combined investigation of these three chemokines can make wound age determination more objective and accurate.

Topics: Adolescent; Adult; Aged; Chemokine CCL2; Chemokine CCL3; Chemokine CCL4; Chemokines; Child; Forensic Medicine; Humans; Immunohistochemistry; Interleukin-8; Macrophage Inflammatory Proteins; Middle Aged; Skin; Wound Healing; Wounds and Injuries

Chemotaxins from inflammatory sites prime or activate neutrophils (PMN) by using cytosolic calcium ([Ca2+]i) fluxes as second messengers. [Ca2+]i can be mobilized rapidly by receptor-mediated entry or store-release, or more slowly by store-operated calcium influx (SOCI). We studied [Ca2+]i mobilization by chemotaxins and how trauma impacts the calcium entry mechanisms used by chemotaxins.. [Ca2+]i flux was studied by spectrofluorometry. The contributions of early and late [Ca2+]i currents to net calcium flux were compared after stimulation by more potent (fMLP, C5a, PAF) or less potent (IL-8, GRO-alpha, and LTB4) agonists. Store operated [Ca2+]i mobilization was reflected by the ratio of area under the [Ca2+]i efflux curve to peak [Ca2+]i (efflux curve). PMN from trauma patients (ISS > 25) and pair-matched volunteer (n = 7 pairs) were then primed and stimulated with thapsigargin to compare cell calcium stores and SOCI.. Late [Ca2+]i mobilization made more important contributions to fMLP, PAF, and C5a signals than to IL-8, GRO-alpha, or LTB4 (p < 0.01 all comparisons). Calcium stores and store release were only marginally lower after injury (p = not significant), but trauma PMN showed far higher [Ca2+]i influx after thapsigargin (p = 0.007), and greater net SOCI (p = 0.034).. SOCI may play an important role in PMN activation, and trauma increases PMN SOCI. Prolonged elevations of [Ca2+]i due to enhanced SOCI may alter stimulus-response coupling to chemotaxins and contribute to PMN dysfunction after injury.

Topics: Adult; Calcium; Complement C5a; Female; Humans; In Vitro Techniques; Interleukin-8; Leukotriene B4; Male; N-Formylmethionine Leucyl-Phenylalanine; Neutrophils; Platelet Activating Factor; Spectrophotometry; Wounds and Injuries

Wound healing is a sequential biological process that involves the integration of chemotaxis of neutrophils, mitosis and migration of keratinocytes, and remodeling of the scar, all of which are regulated by specific soluble mediators. To modulate wound healing specific mediators have to be identified and functionally characterized. Therefore we addressed this study on the polymorphonuclear leukocyte (PMN) attractant interleukin-8 (IL-8) and its function in epidermal wound healing.. Peptide purification, bioassays for PMN chemotaxis, and sequential IL-8 measurements were performed on human wound fluid from burn blisters and skin graft donor sites. Histology for IL-8 immunoreactivity was included. In vitro human keratinocytes were assayed for proliferation, migration, and integrin expression after IL-8 treatment. Wounding experiments with topical IL-8 were performed in a chimeric mouse model.. IL-8 was found to be the major bioactive chemoattractant for PMNs in human blister and skin graft donor site wound fluids (mean levels ranging from 173 ng/ml Postoperative Day (POD) 1 to 2130 ng/ml (POD 5)). Released intracellular epidermal IL-8 immunoreactivity at the wound edge was considered as an immediate source of IL-8 while NH(2)-terminal analysis revealed the 77-amino-acid residue form as a second source of IL-8 possibly PMN derived. In vitro experiments on the effect of recombinant human (rh) IL-8 on keratinocyte proliferation revealed a rise in cell number (4.8-fold, ED(50) = 0.6 ng/ml), which was accompanied by an increase in cells in S phase and overexpression of the integrin subunit alpha6. In vivo topically applied IL-8 (1 microg/ml) on human skin grafts in a chimeric mouse model enhanced reepithelialization in IL-8 treated animals over controls due to elevated numbers of mitotic keratinocytes. Wound contraction was significantly diminished by topical IL-8.. These results indicate the sequential function of endogenous IL-8 in all phases of human wound healing. Topical IL-8 may be useful in impaired wound healing.

Topics: Animals; Antibodies, Monoclonal; Antigens, CD; Cell Division; Humans; Integrin alpha6; Interleukin-8; Keratinocytes; Mice; Mice, Nude; S Phase; Skin; Tumor Necrosis Factor-alpha; Wound Healing; Wounds and Injuries

Trauma modulates polymorphonuclear neutrophil (PMN) function, predisposing to organ failure and infection. Many chemoattractants released by injury activate PMNs via G-protein-coupled (GPC) receptors, which elevate PMN cytosolic calcium ([Ca2+]i). Nonetheless, PMN GPC receptor function after injury is unstudied.. PMNs from 11 major trauma patients (Injury Severity Score = 31 +/- 3, eight men and three women, age = 38 +/- 3) were obtained on days 1, 3, and 7 after injury. Nine developed organ failure and one died. PMNs were exposed to interleukin-8 (IL-8), growth regulated oncogene-alpha (GRO-alpha), and platelet-activating factor (PAF) to stimulate the CXCR1, CXCR2, and PAF receptors. [Ca2+]i flux measurements were used to quantify receptor responses. Receptor responses to individual as well as serial GPC agonists were studied over the week after injury and compared with the responses of PMNs from healthy volunteers (n = 10-23). Results were evaluated by one-way analysis of variance, and paired and unpaired t tests.. Responses to GRO-alpha and PAF were significantly depressed early after injury (p < 0.01). Responses to all agonists tested tended to be lowest on day 1, to peak on day 3, and to decrease again by day 7, but variations in response to GRO-alpha were the most marked (p < 0.03, analysis of variance). Whereas GRO-alpha primed IL-8 and IL-8 primed PAF in normal PMNs, GRO-alpha paradoxically suppressed IL-8 responses and IL-8 suppressed PAF responses in trauma PMNs. PAF priming of IL-8 responses was unaffected by injury.. Receptor responses to individual GPC agonists are suppressed early after trauma, but increase by day 3. Normal chemokine priming of PMN calcium mobilization is reversed by injury; priming by PAF is intact. PMN GPC responses depend on the sequence in which agonists are encountered. Injury appears to alter these interactions, thus priming some aspects of PMN function while simultaneously suppressing others.

Topics: Adult; Area Under Curve; Calcium; Case-Control Studies; Chemokine CXCL1; Chemokines, CXC; Chemotactic Factors; Female; Growth Substances; Humans; Injury Severity Score; Intercellular Signaling Peptides and Proteins; Interleukin-8; Male; Middle Aged; Neutrophils; Platelet Activating Factor; Platelet Membrane Glycoproteins; Receptors, Cell Surface; Receptors, Cytokine; Receptors, G-Protein-Coupled; Receptors, Interleukin-8A; Receptors, Interleukin-8B; Spectrometry, Fluorescence; Wounds and Injuries

Postinjury neutrophil (PMN) priming identifies the injured patient at risk for the subsequent development of multiple organ failure (MOF). PMN priming has previously been shown to cause enhanced release of proteases and superoxide. PMNs, however, are a rich source of proinflammatory cytokines, such as interleukin (IL)-8 and tumor necrosis factor (TNF), which have been implicated in the development of MOF. PMNs also make IL-1ra, which is an anti-inflammatory cytokine that inhibits IL-1. It is our hypothesis that postinjury PMNs are primed for increased stimulated release of the proinflammatory cytokines IL-8 and TNF but not the anti-inflammatory cytokine IL-1ra.. Twelve trauma patients with a mean Injury Severity Score of 24 (+/-4.6) and 10 elective surgical patients were studied. Postinjury PMNs were isolated from blood obtained at presentation (within 2 hours after injury) and 24 hours after trauma. PMNs from elective surgical patients were obtained preoperatively, immediately postoperatively, and at 24 hours. The PMNs were stimulated with platelet-activating factor (200 nM)/N-formyl-methionyl-leucyl-phenylalanine (1 micromol/L) or lipopolysaccharide (100 ng/mL) incubated for 24 hours in RPMI-1640, and release of IL-8, TNF, and IL-1ra were measured.. Postinjury PMNs were primed for both platelet-activating factor/N-formyl-methionyl-leucyl-phenylalanine-stimulated and lipopolysaccharide-stimulated IL-8 and TNF release at 2 hours after injury (fourfold increase of IL-8 release and fivefold increase of TNF release), whereas elective surgical patients demonstrated no priming. In contrast, postinjury patients were not primed for increased release of the counterinflammatory cytokine IL-1ra, suggesting a specific postinjury up-regulation of IL-8 and TNF.. After injury, PMNs are primed for proinflammatory cytokine release in addition to superoxide and elastase. This augmented release of IL-8 and TNF may be involved in the subsequent development of organ dysfunction and ultimately MOF.

Topics: Adult; Case-Control Studies; Cytokines; Female; Humans; Injury Severity Score; Interleukin-1; Interleukin-8; Male; Multiple Organ Failure; Neutrophils; Tumor Necrosis Factor-alpha; Wounds and Injuries

The cytokine production in endotoxin stimulated blood of patients immediately after polytrauma with high risk for developing sepsis or multi organ failure was analysed. Forty patients sustaining traumatic injury with >/=317 pts according to the Injury Severity Score (ISS), 10 of whom developed severe sepsis (ACCP/SCCM conference 1992) were included in the study. Levels of interleukin 8 (IL-8), IL-6 and tumour necrosis factor (TNF) were measured by ELISA in endotoxin-stimulated whole blood and IL-10 and IL-6 in serum. The allotype for the bi-allelic Nco I restriction length polymorphism in the TNF locus was determined for each patient.Two to four hours after polytrauma endotoxin-stimulated synthesis of TNF and IL-6 was found to be reduced in whole blood from patients compared to healthy donors, whereas no such differences were found for IL-8 synthesis. At this time, however, the patients who developed sepsis at a later stage (day 4-6) showed significantly (P<0.05) enhanced IL-8 synthesis in endotoxin stimulated whole blood in comparison to healthy donors. The IL-6 and TNF production of their blood was significantly enhanced compared to patients with uncomplicated recovery. Ninety per cent of the patients developing sepsis were of the TNFB2/TNFB2 allotype, whereas this was the case for only 30% of the non-septic group. Assessment of endotoxin-stimulated cytokine synthesis may provide a prognostic indicator for patients at high risk for developing a sepsis syndrome.

Topics: Adolescent; Adult; Biomarkers; Blood Cells; Cytokines; Female; Gene Frequency; Humans; Immunoglobulin Allotypes; Interleukin-10; Interleukin-6; Interleukin-8; Lipopolysaccharides; Male; Middle Aged; Polymorphism, Genetic; Polymorphism, Restriction Fragment Length; Sepsis; Time Factors; Tumor Necrosis Factor-alpha; Wounds and Injuries

Trauma and adult respiratory distress syndrome (ARDS) are associated with increased CXC chemokine (CXC) activity. CXCs such as interleukin (IL)-8 activate polymorphonuclear neutrophils (PMNs) in the lung by means of calcium signals ([Ca2+]i). We studied CXC effects on PMN [Ca2+]i in ARDS and trauma.. Isolated PMNs were loaded with Fura-2 dye. Normal PMNs were incubated in ARDS plasma or volunteer plasma, with or without blocking antibodies to IL-8, growth-related oncogene alpha (GRO-alpha), or both (n = 6 pairs), and then stimulated with 1 to 10 nmol/L IL-8. PMNs from trauma patients or volunteers (n = 10 pairs) were stimulated with GRO-alpha, or with sequential GRO-alpha/IL-8. [Ca2+]i was measured with spectrofluorometry.. [Ca2+]i responses to IL-8 were higher after being incubated in ARDS plasma than in volunteer plasma (251 +/- 33 vs 218 +/- 33 nmol/L, P = .03). Blockade of GRO-alpha or IL-8 reversed ARDS plasma effects. After GRO-alpha/IL-8, PMNs from trauma patients demonstrated more Ca2+ store release than did PMNs from volunteers (235 +/- 13 vs 170 +/- 10 nmol/L, P < .01). Conversely, PMNs from trauma patients lost receptor-operated Ca2+ influex to GRO-alpha.. In traumatic ARDS, plasma CXCs prime PMNs for higher [Ca2+]i flux, making PMN activation more likely. IL-8 and GRO-alpha interact to modulate these PMN [Ca2+]i responses.

Topics: Adult; Calcium Signaling; Chemokine CXCL1; Chemokines, CXC; Chemotactic Factors; Growth Substances; Humans; Intercellular Signaling Peptides and Proteins; Interleukin-8; Male; Neutrophils; Respiratory Distress Syndrome; Wounds and Injuries

To evaluate the role of interleukin 8 (IL-8) in the regulation of neutrophil (PMN) apoptosis in normal plasma and plasma from patients with early, fulminant acute respiratory distress syndrome (ARDS).. Experimental study using cultured human PMNs.. University hospital, level I trauma center.. Plasma was obtained from 6 patients with early, fulminant posttraumatic ARDS (mean Injury Severity Score, 26). All samples were drawn within 24 hours after injury. Plasma was also taken from 13 healthy control subjects. These controls were also used as sources of PMNs.. Effect of early, fulminant ARDS and normal plasma on spontaneous apoptosis, CD16, and CD11-b expression in PMNs in vitro; levels of IL-8 in plasma; correlation of extracellular IL-8 concentration with rate of PMN apoptosis; and effect of IL-8 blockade on PMN apoptosis, CD16, and CD11-b expression in ARDS and normal plasma.. Plasma from patients with early, fulminant ARDS inhibited spontaneous PMN apoptosis at 24 hours (35%+/-5% vs 54%+/-5%; P=.01). Neither CD16 nor CD1l-b differed significantly between the 2 groups. The mean plasma level of IL-8 in patients with early, fulminant ARDS was 359+/-161 pg/mL vs 3.0+/-0.4 pg/mL in healthy controls (P<.05). Interleukin 8 inhibited apoptosis in plasma-free medium at low doses (1-50 pg/mL) but had no significant effect at higher doses (100-5000 pg/mL) (P<.05). Interleukin 8 blockade with monoclonal antibody suppressed apoptosis in normal plasma (28%+/-5% with monoclonal antibody vs 51%+/-5% without monoclonal antibody; P=.008) but not in plasma from patients with early, fulminant ARDS (29%+/-5% with monoclonal antibody vs 34%+/-6% without monoclonal antibody; P=.67). It had no effect on CD16 or CD11-b expression in either plasma.. Plasma from patients with early, fulminant ARDS contains soluble factors that inhibit PMN apoptosis in vitro. Low levels of IL-8 inhibit PMN apoptosis in normal plasma. Although plasma levels of IL-8 are markedly elevated in early, fulminant ARDS, IL-8 is not directly responsible for the antiapoptotic effect of plasma from patients with early, fulminant ARDS.

Topics: Apoptosis; Case-Control Studies; CD11 Antigens; Cells, Cultured; Humans; Injury Severity Score; Interleukin-8; Neutrophil Activation; Neutrophils; Receptors, IgG; Respiratory Distress Syndrome; Time Factors; Wounds and Injuries

1) To determine whether tumor necrosis factor (TNF) up-regulation occurs in the first hours following severe injury. 2) To determine whether the time from injury to blood sampling affects the probability of detecting TNF.. A prospective, cross-sectional study was performed using a convenience sample of adult major trauma patients ("patients") treated at a university hospital ED (Level-1 trauma center) and 20 healthy volunteers ("controls"). The time interval from injury to specimen collection (delta T), the injury severity scale (ISS) score, patient demographics, and quantitative cytokine [TNF and interleukin (IL-6, IL-8)] levels were measured. In the patients, cytokine levels were analyzed as a function of delta T (using first hourly cutoff points and then the median T as an arbitrary cutoff point) with and without potential confounders (e.g., ISS, age, gender).. The mean delta T was 92.8 +/- 49.2 min (range 10-210 min, median 82 min). In the controls, TNF activity was present in 96%, with a mean level of 125 pg/mL. The controls showed no baseline IL-6 activity and only 10% had a measurable baseline IL-8 level. In the patients, TNF was present in 93%, with a mean level of 628 +/- 138 pg/mL. When the patients' specimens were divided at the median to obtain roughly equal-sized groups, more TNF levels were elevated > 2.5 SD above the controls in the early vs late group (51% vs 30%; p = 0.07). The mean levels of TNF and IL-8 also were higher in the early vs late group (756 vs 530 and 287 vs 135, respectively; p < 0.05).. TNF levels are elevated in the immediate 4 hours post-injury. Previous investigators' inability to detect TNF activity increases may be related to delays in sampling. These results are consistent with the theory that increased TNF activity occurs early after major trauma and may initiate subsequent cytokine activity.

Topics: Adult; Cross-Sectional Studies; Humans; Interleukin-6; Interleukin-8; Prospective Studies; Time Factors; Tumor Necrosis Factor-alpha; Up-Regulation; Wounds and Injuries

In 17 patients plasma TNF-alpha and IL-8 were assayed with enzyme-linked immunosorbent assay. IL-6 activity in plasma was determined by bioassay with IL-6-dependent cell line 7TD1. The limulus amoebocyte lysate chromogenic test was used for plasma endotoxin assay. Plasma cytokine levels in injured patients were significantly increased. Plasma TNF-alpha was shown to be increased earlier, while an increase in plasma IL-6 and IL-8 levels occurred late, all of which were shown to be significantly positively correlated with ISS, cardiac and hepatic enzyme activities, and index of renal function. In addition, obvious endotoxaemia occurred at an early stage of injuries, which was respectively significantly correlated with ISS and plasma TNF-alpha, IL-6 and IL-8 levels. Severe injuries could induce increased successive release of TNF-alpha, IL-6 and IL-8, and obvious endotoxaemia. The post injury release of cytokines might be related to endotoxaemia, and may play an important role in the development of organ damage after injury.

Topics: Adolescent; Adult; Aged; Cytokines; Endotoxemia; Endotoxins; Enzymes; Female; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Multiple Organ Failure; Tumor Necrosis Factor-alpha; Wounds and Injuries

We investigated kinetics of plasma TNF, IL-6 and IL-8 and their relationship with organ dysfunction and endotoxemia in 17 patients with severe trauma in order to further elucidate the role of cytokines in the development of organ damage and their production mechanism after trauma. Plasma cytokine levels significantly increased in trauma patients, and their plasma TNF was increased earlier. The cytokines were positively correlated with ISS, cardiac and hepatic enzyme activities, index of renal function, and plasma endotoxin levels. It is suggested that TNF, IL-6 and IL-8 may participate in the development of organ damage after trauma, and its release might be related to massive endotoxin translocation into body at the early stage of trauma.

Topics: Adolescent; Adult; Aged; Endotoxins; Female; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Multiple Organ Failure; Tumor Necrosis Factor-alpha; Wounds and Injuries

We measured the levels of soluble intercellular adhesion molecule-1 (sICAM-1), CD11a, CD11b, CD18, endotoxin, and various inflammatory cytokines to clarify the relationship between adhesive molecules and cytokines in sepsis. We studied 21 patients with sepsis (sepsis group) and 13 patients with trauma not complicated by infection (trauma group). The mean sICAM-1 level was significantly higher in the sepsis group than in the trauma group. No significant difference was observed in the CD11a, CD11b, and CD18 levels between the two groups. The sICAM-1 levels significantly correlated with the levels of endotoxin, tumor necrosis factor alpha (TNF-alpha), and IL-8, but CD11a, CD11b, and CD18 levels did not correlate with endotoxin or cytokine levels. These findings suggest that ICAM-1 production is induced by endotoxins and cytokines produced in excess by inflammatory reactions and that endotoxins and cytokines are involved in qualitative, but not quantitative changes in LFA-1 (CD11a/CD18) and Mac-1 (CD11b/CD18).

Topics: Adult; Aged; Aged, 80 and over; Antigens, CD; Cell Adhesion Molecules; Cytokines; Endothelium, Vascular; Female; Humans; Interleukin-8; Male; Middle Aged; Sepsis; Tumor Necrosis Factor-alpha; Wounds and Injuries

Interleukin-6 (IL-6), interleukin-8 (IL-8), and adhesion molecules have been implicated as mediators in neutrophil (PMN) and endothelial cell (EC) interactions leading to postinjury multiple organ failure (MOF). Our hypothesis was that circulating levels of IL-6, IL-8, and soluble intercellular adhesion molecule-1 (sICAM-1) would discriminate patients at risk for postinjury MOF.. Serial plasma levels of IL-6, IL-8, and sICAM-1 were measured in 27 high-risk trauma patients.. The IL-6 and IL-8 levels were significantly elevated in MOF patients compared with non-MOF patients at 12 and 36 hours postinjury. The IL-6 level was also elevated at 84 and 132 hours, and IL-8 at 84 hours. The sICAM-1 level did not become elevated in MOF patients until 132 hours postinjury.. Interleukin-6 and IL-8 are elevated early after trauma and discriminate patients who will develop MOF. Late elevation of sICAM-1 likely results from PMN cytotoxicity leading to EC injury or inflammation.

Topics: Adult; Awards and Prizes; Female; Humans; Intercellular Adhesion Molecule-1; Interleukin-6; Interleukin-8; Male; Multiple Organ Failure; Prospective Studies; Risk Factors; Wounds and Injuries

Plasma from 33 patients at risk of multiple organ failure (MOF) after major trauma was tested for a priming effect on neutrophils, and for the presence of platelet-activating factor (PAF) activity and interleukin (IL) 8. Plasma sampled at 3, 6, 12 and 24 h after injury significantly primed normal neutrophils to release mean(s.e.m.) 1.26(0.19), 1.33(0.26), 1.04(0.14) and 0.86(0.13) nmol superoxide per min per 1.3 x 10(6) neutrophils respectively (P < 0.05). Priming at 3 h after injury was inhibited by mean(s.e.m.) 63.8(7.0) per cent by the PAF antagonist, WEB 2170 (P < 0.01). Mean(s.e.m.) plasma IL-8 was raised at 6 and 12 h after injury to 785(183) and 836(175) pg/ml (P < 0.01). At 12 h after injury the plasma IL-8 level correlated directly with the number of units of red blood cells transfused (r = 0.64, P < 0.01), and was significantly higher in the group of six patients who developed MOF (P < 0.05). These data suggest that after trauma the mediators PAF and IL-8 appear sequentially in the circulation, are potential mechanisms of circulating neutrophil priming, and that IL-8 may also be an early biochemical marker predicting the onset of MOF.

Topics: Adolescent; Adult; Aged; Female; Humans; Injury Severity Score; Interleukin-8; Male; Middle Aged; Multiple Organ Failure; Neutrophils; Platelet Activating Factor; Time Factors; Wounds and Injuries

The precondition for the systematic modulation of host impairing behavior of hyperactivated monocytes following trauma is to fully understand the mechanistic basis of cellular dysfunction. It was the objective of this study to scrutinize the synthesis patterns and the level of regulation of the functionally related inflammatory cytokines interleukin (IL)-1 beta and IL-8 under stressful conditions. We compared the quantity of cytokine protein release in lipopolysaccharide-stimulated in vitro cultures of peripheral blood mononuclear leukocytes with the signal intensity of the corresponding detectable mRNAs. Fourteen patients with major burn or multiple trauma on consecutive days post-trauma and healthy volunteers were studied. We saw an almost identical pattern of synthesis for both monokines during the time of observation, with a considerable impairment until day 5 post-trauma and recovery thereafter. In contrast to IL-1 beta, a clear concurrence between mRNA signal intensity and the quantity of protein release was found in the majority of patients for IL-8. From these data we conclude that the launching mechanisms for the de novo synthesis for both monokines under stress differ greatly, with IL-8 being clearly regulated on the transcriptional level, whereas the downregulation of IL-1 beta occurs, most likely, on the post-transcriptional level.

Topics: Adolescent; Adult; Aged; Burns; Female; Humans; In Vitro Techniques; Inflammation Mediators; Interleukin-1; Interleukin-8; Lipopolysaccharides; Male; Middle Aged; Monocytes; RNA, Messenger; Time Factors; Transcription, Genetic; Wounds and Injuries

IL-8 is a recently described chemokine that increases polymorphonuclear neutrophil infiltration and has been implicated in inflammatory pathology. This study assesses monocyte (M phi) interleukin-8 (IL-8) levels in severe trauma patients (injury severity score > 16) who have elevated levels of M phi cell-associated tumor necrosis factor alpha (TNF alpha), a major marker for systemic inflammatory response syndrome after injury. We demonstrate elevated (p = .0007) levels of M phi IL-8 only in those trauma patients who also have increased (p = .0001) M phi-secreted TNF alpha whereas the patients having normal M phi-secreted TNF alpha levels have normal or even decreased M phi IL-8 production. There is no association between M phi IL-8 production and cell-associated TNF alpha levels. M phi induction by Fc gamma RI cross-linking, a common induction pathway in trauma patients' M phi that increases the production of both cell-associated and secreted TNF alpha, can also increase (p = .0022) M phi IL-8 levels. Therefore, post-trauma elevation of M phi IL-8 levels may be associated with increased secreted TNF alpha resulting from, at least in part, Fc gamma RI cross-linking stimulation in vivo.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-8; Male; Middle Aged; Monocytes; Receptors, IgG; Tumor Necrosis Factor-alpha; Wounds and Injuries

Trauma patients with positive Candida antigen titers have high mortality rates. Death is the result of sepsis and multi-organ system failure. Considerations of host immunity to Candida led us to concurrently study the function of neutrophils (PMNs) from severely injured adults with positive titers (n = 20), patients with negative titers matched for age, sex, and injury (n = 20), and volunteers (n = 20). Anticandidal PMN function was determined using a 3H-glucose incorporation assay. RESULTS are expressed as mean percentage of growth inhibition +/- SEM.. PMN, from all groups inhibited Candida growth, although PMNs from titer-positive patients demonstrated less growth inhibition. In vitro cytokines granulocyte macrophage-colony stimulating factor [(GM-CSF), interferon-gamma (IFN-gamma), and interleukin 8 (IL-8)] improved function of PMNs from each group and corrected the impaired anticandidal function of PMNs from titer-positive patients, with GM-CSF being most effective.. Seriously injured patients with positive Candida antigen titers have PMNs with impaired anticandidal function, which can be restored by cytokines. These findings begin to explain why seriously injured patients with positive Candida antigen titers have increased mortality and to offer hope of therapeutic intervention.

Topics: Adult; Antigens, Fungal; Biomarkers; Candida albicans; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Interferon-gamma; Interleukin-8; Male; Middle Aged; Neutrophils; Wounds and Injuries

To investigate the effect of surgical trauma and other factors on the postoperative elevation of serum interleukin 6 (IL-6), we examined changes in IL-6 concentration after major thoracoabdominal surgery. Serum IL-6 levels reached the maximum concentration on the first postoperative day in all 38 patients, with peak ranging from 1400.8 +/- 383.4 pg/ml (mean +/- SEM) to 29.8 +/- 3.8 among six groups who underwent surgery at different sites. The IL-6 peak was significantly correlated with surgical trauma as defined by the operation length and the volume of blood loss during surgery (r = 0.554, P < 0.01 and r = 0.427, P < 0.01, respectively). The peak concentration of serum IL-6 in patients undergoing esophagectomy was significantly higher than in those undergoing pancreaticoduodenectomy (P < 0.05), despite a similar degree of surgical trauma defined by the operation length and volume of blood loss during surgery. Peak IL-6 concentration observed in a patient who underwent esophagectomy was about 100-fold greater in fluid drained from the thorax than in the peripheral blood. IL-6 mRNA was demonstrated in leukocytes from thoracic and abdominal exudate at 6, 24 and 48 h after surgery. In contrast, IL-6 mRNA could not be detected in leukocytes from the peripheral blood. Similar findings were also observed for interleukin 8 (IL-8). However, interleukin 1 beta (IL-1 beta) and tumour necrosis factor-alpha (TNF-alpha) were detected only once after surgery in the drainage fluid.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Blotting, Northern; Cytokines; Elective Surgical Procedures; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-1; Interleukin-6; Interleukin-8; Male; Middle Aged; Postoperative Period; Time Factors; Tumor Necrosis Factor-alpha; Wounds and Injuries

This study was designed to further differentiate monocyte behavior in critically ill patients with operative or accidental trauma. The patient population studied consisted of 39 patients (17 patients undergoing elective surgery [ES], seven patients with major multiple injuries [MI], and 15 patients in an acute septic state [S]). Immunologic parameters assessed included monocyte phenotyping with the monoclonal antibody LeuM3, measurement of the cytokines interleukin (IL)-1, IL-6, and IL-8 in lipopolysaccharide-stimulated in vitro cultures of mononuclear leukocytes (PBMCs), and determination of neopterin in gamma-interferon-stimulated in vitro cultures and corresponding serum samples. Serum neopterin levels were very high in S patients (89.0 nmol/L; p less than 0.05) compared with control values (4.6 nmol/L), with a rise to 16.4 nmol/L in ES patients on day 7 and 13.4 nmol/L in MI patients on day 7. The concentrations of gamma-interferon-induced neopterin in the supernatants of the PBMC cultures were elevated in all patient groups. Severe impairment of IL-1 synthesis was seen in MI and S patients. IL-8 synthesis (818 +/- 150 units/ml, control value) was also suppressed (p less than 0.05) in MI patients; the values were 135 +/- 65 units/ml on day 1,231 +/- 110 units/ml on day 3,347 +/- 131 units/ml on day 7, and 355 +/- 107 units/ml in S patients. The kinetic patterns of synthesis were comparable for IL-1 and IL-8 in all patient groups. Lipopolysaccharide-induced IL-6 synthesis (9.4 +/- 1.5 x 10(3) units/ml, control value) was significantly elevated in the PBMC cultures of all patient groups, with the exception of the early phase after accidental trauma. Maximum amounts of IL-6 synthesis after surgery were 19.6 +/- 7 x 10(3) units/ml in S patients and 19.0 +/- 2.2 x 10(3) units/ml in ES patients. These results demonstrate (1) the impairment of the functional capacity of circulating monocytes and (2) that the degree of functional impairment is proportional to the severity of the injury.

Topics: Adolescent; Adult; Aged; Biopterins; Critical Care; Humans; Infections; Interleukin-1; Interleukin-6; Interleukin-8; Interleukins; Middle Aged; Monocytes; Neopterin; Phenotype; Postoperative Period; Wounds and Injuries

It has been suggested that platelet-derived growth factor (PDGF) plays a central role in wound healing. Analysis of human wound fluid revealed the presence of PDGF AA (30 kd) and monocyte/macrophage-derived growth factor (MDGF) (12 to 14 kd) in the immediate postoperative period.. The amount of PDGF AA present was assayed by Western blot analysis. The chemotactic and mitogenic potential of purified wound fluid containing PDGF AA and MDGF was determined on a responsive cell line. The biologic activity of MDGF was assayed with a cell line that is unresponsive to the PDGF AA found in wound fluid.. Both the concentration and the biologic activity were highest in the immediate postoperative period and declined to negligible levels by 24 hours after surgery. The chemotactic activity of MDGF was highest in the immediate postoperative period and declined during the first 24 hours in a manner similar to that of the combined PDGF AA and MDGF activity.. These data demonstrate the changing levels of PDGF and MDGF in human wound fluid over time, supporting the cascade model of wound repair. By demonstrating that MDGF acts on cell lines unresponsive to the PDGF AA found in wound fluid, these data suggest that MDGF may also play an important role in wound healing.

Topics: 3T3 Cells; Adolescent; Animals; Antibodies; Blotting, Western; Cell Division; Chemotaxis; DNA Replication; Humans; Interleukin-8; Kinetics; Mice; Orthopedics; Platelet-Derived Growth Factor; Wounds and Injuries