Impact of chronic wounds of various etiology on systemic profiles of key inflammatory cytokines, chemokines and growth factors, and their interplay.

BACKGROUND: Non-healing wounds are becoming a growing concern for public health as a result of their increasing prevalence in progressively aging societies. OBJECTIVES: The aim of this article is to evaluate the effects of wound etiology on a panel of circulating cytokines in patients with non-healing wounds of the lower extremities. MATERIAL AND METHODS: This prospective case-control study involved 104 individuals: healthy elderly people (n = 46) and patients with diabetes and/or cardiovascular disease (n = 58; among them 38 with chronic wounds of venous, ischemic or neurotrophic etiology). Selected serum cytokines - i.e. IL-1ß, IL-4, IL-6, IL-8, FGF-2, G-CSF, GM-CSF, MCP-1, MIP-1α, TNF-α, VEGF-A, and PDGF-BB - were measured using the Luminex platform. RESULTS: Compared to healthy elderly people, presence of diabetes and/or cardiovascular disease was associated with elevated IL-6, IL-8, MCP-1 and G-CSF while non-healing wounds coexisted with the increase in the levels of all examined cytokines/growth factors except for G-CSF and GM-CSF. Among diseased elderly people, having wounds was associated with increased levels of IL-1ß, IL-4, IL-6, IL-8, FGF-2, MIP-1α, PDGF-BB, and VEGF-A. Interleukin 1ß elevation was a sole independent predictor of chronic wounds with an odds ratio (OR) of 6.3. Cytokines in healthy seniors were loosely interrelated, while the levels of cytokines in diseased patients with wounds displayed a tight pattern of association. When stratified by their etiology, the association pattern for IL-6, IL-8, MCP-1, and VEGF-A was disrupted in neurotrophic wounds. CONCLUSIONS: The results presented herein may improve our understanding of the pathomechanisms which lead to chronic wounds and of the effects they exert on a systemic level, as well as providing potential targets for more effective therapies.

Quantitative indices of dynamics in concentrations of lipopolysaccharide-binding protein (LBP) as prognostic factors in severe sepsis/septic shock patients--comparison with CRP and procalcitonin.

OBJECTIVES: To devise and evaluate quantitative indices of dynamics in lipopolysaccharide-binding protein (LBP), CRP, and procalcitonin concentrations as prognostic markers in sepsis. DESIGN AND METHODS: Prospective observational cross-sectional study with 5-day follow-up. Simple (Δ(5-1)) and relative (chain indices-based) rates for LBP (ELISA), procalcitonin (immunoluminometry), and CRP were devised. RESULTS: Admission concentrations of all markers were higher in septic patients than controls. Not the admission levels but markers' time-courses differed between survivors (declining) and non-survivors (persistently high). Simple and relative rates were greater in survivors than non-survivors. Their accuracies as outcome predictors were comparable, higher for LBP and CRP than PCT. At ~95% sensitivity, the highest specificity had LBP relative and simple rates. Except for sepsis severity scores, only LBP was independently associated with lethal outcome. CONCLUSIONS: For outcome prediction, the evaluation of dynamics of sepsis mediators, expressed by simple or relative rates, is a more suitable alternative to markers' peak values.

Circulating adipocyte fatty acid-binding protein, juvenile obesity, and metabolic syndrome.

Adipocyte fatty acid-binding protein (A-FABP) links obesity and metabolic syndrome (MetS) and might be targeted in future therapies. Its utility as a MetS biomarker has been suggested in adults but has not been examined in children/adolescents. Our objectives were to identify metabolic parameters associated with A-FABP elevation in children and adolescents and to evaluate the effect of obesity intervention and A-FABP diagnostic utility. A-FABP and anthropometric, metabolic, and inflammatory indices were measured in 31 lean and 114 overweight/obese children and adolescents and reassessed after obesity intervention (1 year; diet and enhanced physical activity, with or without metformin). A-FABP was significantly higher in overweight/ obese than lean individuals, where it correlated with insulin, waist circumference (WC), and 2-h glucose independent of body mass index (BMI), age, gender, and developmental stage. The pattern of A-FABP associations differed between sexes. As a MetS indicator, A-FABP had 68% accuracy. The weight reduction program was effective in reducing A-FABP, BMI%, WC, triglycerides, and cholesterol. In conclusion, elevation in A-FABP is associated with MetS components independent of BMI status and can be reduced by diet and enhanced physical activity. A-FABP as a single MetS biomarker has a moderate accuracy.

Midkine, a multifunctional cytokine, in patients with severe sepsis and septic shock: a pilot study.

The objective of the study was to evaluate whether severe sepsis and septic shock are related to alterations in midkine concentrations, to identify disease-related factors associated with these alterations, and to initially appraise whether midkine might serve as a biomarker in sepsis. Prospective observational cross-sectional study with 5-day follow-up. Circulating midkine was measured (enzyme-linked immunosorbent assay) in 38 septic (13 with severe sepsis, 25 with septic shock), 82 active inflammatory bowel disease (IBD) (26 with systemic inflammatory response syndrome [SIRS]) patients, and 87 healthy subjects. Midkine significantly increased along with a sequence: health-inflammation (IBD)-systemic inflammation (IBD-SIRS)-severe sepsis/septic shock. High midkine levels (>1,000 ng/L) were found in 63% of septic and in 19% of IBD-SIRS patients, whereas extremely high concentrations (>5,000 ng/L) were found in 16% vs. 4%. Although not different at admission, midkine gradually decreased in severe sepsis and remained high in shock. Similarly, persistently high midkine was observed in patients with cardiovascular insufficiency (CVI) and in mechanically ventilated as compared with normalizing levels in patients without CVI and not requiring ventilation. The differences in devised simple rates (Δ5th-1st) were significant in all these cases. Accordingly, admission midkine was higher in patients with metabolic acidosis. Concerning pathogen, gram-positive infections were associated with the highest midkine levels. In conclusion, sepsis and septic shock are associated with midkine elevation, substantially more pronounced than in inflammation, even systemic, revealing a new potential mediator of deregulation of neutrophil migration. Sepsis-related global hypoxia seems to contribute to midkine elevation. Our results substantiate further research on possible midkine application as a sepsis biomarker: in differentiating SIRS from sepsis and identifying gram-positive sepsis and septic patients at risk of CVI and shock.

[The composition, biochemical properties and toxicity of snake venoms]. / Sklad i wlasciwosci biochemiczne oraz toksycznosc jadów wezy.

2.5 million cases of snake bites are noticed in the world every year (within 100,000 is mortal). These bites occur frequently in Asia and Africa. Some reports proved the toxicity and composition changes of well-known venoms from the same snake species according to the climatic zone. Snake venom is a natural source of many biologically active substances, including those with potential therapeutic properties. These substances contain peptides, proteins, and enzymes which are divided into five subfamilies: three-finger toxins, serine protease inhibitors of the Kunitz type, phospholipases A2, serine proteases, and metalloproteases. All snake venoms are grouped depending on their mode of action. They usually cause neurotransmission disorders, cardiotoxic action, hemostasis disorders, and have central nervous system and necrotic activity.

The effect of packed red blood cell storage on arachidonic acid and advanced glycation end-product formation.

INTRODUCTION: The transfusion of packed red blood cells (PRBCs) is a significant risk to blood recipients. Blood banking procedures permit the storage of PRBCs for up to 42 days. Storage of PRBCs can cause polymorphonuclear granulocytes (PMNs) activation and the development of neutrophil-mediated transfusion-related acute lung injury. The aim of our study was to determine if PRBC storage has an influence on the formation of arachidonic acid (AA) and advanced glycation end products (AGEs). MATERIALS AND METHODS: Twenty units of PRBCs were used to measure AA and AGE levels. The samples were taken on the 0th, 14th, 28th, and 42nd days of PRBC storage. The AA level was analyzed by gas-liquid chromatography-mass spectrometry and AGE level by an immunoenzymatic test. RESULTS: During the first 14 days of PRBC storage, the AA level significantly increased and then slowly decreased. The AGE level increased continuously during the whole time of the study. In a model experiment, the AA glycoxidation product trans-2-nonenal (T2N) formed adducts in reaction with hemoglobin which were detectable with the test for AGE. CONCLUSIONS: It is highly probable that the observed increase in AGE level is related to the decrease in AA in PRBCs, which can be associated with the formation of toxic aldehydes, especially T2N and 4-hydroxynonenal (HNE), from AA. Glucose in the PRBCs (preservative solution) can contribute to AGE formation as well. The formation of AGEs, HNE, and T2N in PRBCs, their influence on PMNs in vitro, and confirmation of our assumption need further studies.

[Severe sepsis or clinical view of autoaggressive disease. Wegener's granulomatosis--case report]. / Ciezka sepsa czy obraz kliniczny choroby z autoagresji. Ziarniniak Wegenera - opis przypadku.

Each factor infection or non-infection (surgery, burn) can be the cause of inflammatory reaction development and in turn releasing of pro- and antiinflammatory mediators. Excessive or/and uncontrol releasing of these mediators leads to endothelium damage and organ dysfunction. Standard analysis of common infection markers, i.e. peripheral blood leukocytes, C-reactive protein, reaction of Biernacki measurements, do not allow to distinguish infection and noninfection reason of systemic inflammatory response. Procalcitonin is the specific marker for bacterial and fungal infection. Its level is low during local bacterial and virus infection, autoimmunological diseases, but it is increased at the patients with sepsis, severe sepsis. In described case (patient with Wegener's granulomatosis) applying procalcitonin measurement and sensitive and specific microbiological diagnostic by using bronchio-alveolal lavage leads to successful treatment.

Structural and serological characterization of the major glycolipid from Rothia mucilaginosa.

Structural studies on the major glycolipid isolated from Rothia mucilaginosa were carried out utilising specific chemical degradation, NMR spectroscopy and matrix-assisted laser-desorption/ionization time of flight mass spectrometry (MALDI TOF-MS). The glycolipid was found to be a dimannosylacylmonoglyceride in which the carbohydrate part was the glycerol-linked dimannoside alpha-D-Manp-(1-->3)-alpha-D-Manp-(1-->3)-sn-Gro (Man A-Man B-Gro), of which Man B was esterified at O-6 by a fatty acid residue. A second fatty acid substituted the secondary methylene position of the glycerol residue, in contrast to the glycolipid previously found in R. dentocariosa and Saccharopolyspora strains, in which the second fatty acid esterified the primary methylene position of glycerol. Results of the ELISA experiment with rabbit specific antibacterial sera indicate that these two major glycolipids are antigenic, and the patterns of serological reactivity are similar but not identical.