Serum levels of MMP-3 and cathepsin K in patients with ankylosing spondylitis: effect of TNFalpha antagonist therapy

ObjectiveTo measure serum levels of MMP-3 and cathepsin K in patients with ankylosing spondylitis (AS) and in controls and to look for changes in these variables during TNFα antagonist therapy.MethodsWe prospectively studied a group of patients who met New York criteria for AS and a group of healthy volunteers. We recorded age, disease duration, main features of the disease, BASDAI, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Serum MMP-3 and cathepsin K were assayed in duplicate using ELISA kits (Quantikine MMP-3, R&;D Systems; and Cathepsin K, Biomedica). We also assayed IL-17 (Quantikine IL-17, R&;D Systems) and BMP-7 (human BMP-7 DuoSet, R&;D Systems). In patients treated with TNFα antagonists, the assays were repeated 10 weeks after treatment initiation. The Mann–Whitney test was used for between-group comparisons and the Wilcoxon test for evaluations of changes under treatment. Correlation testing was performed. P-values less than 0.05 were considered significant.ResultsWe studied 23 outpatients with AS and 21 controls, with mean age of 39.9 years and 41.2 years, respectively (NS). Disease duration was 10.1 years (1.3); most patients had axial disease (n = 21) and carried HLA-B27 (n = 19). At baseline, the mean BASDAI was 44.1 mm (4.1) and the mean CRP level was 22.3 mg/L (4.7). Serum MMP-3 levels were significantly higher in the patients than in the controls (4.71 vs. 2.79 ng/ml, P = 0.04); levels were also higher for cathepsin K (6.4 vs. 3.6 pg/ml) and IL-17 (60.4 vs. 32 pg/ml), but the differences were not statistically significant. No difference was noted for BMP-7. The only positive correlation was between the ESR and the CRP level (P = 0.0002). Thirteen patients were evaluated 10 weeks into TNFα antagonist therapy (adalimumab, n = 7; etanercept, n = 4; or infliximab, n = 2). Serum MMP-3 decreased significantly (P = 0.04); significant decreases were also noted for the ESR, CRP, and BASDAI.ConclusionMMP-3 is significantly increased in patients with active AS but fails to correlate significantly with conventional variables used to assess disease activity. TNFα antagonist therapy induces a significant decrease in MMP-3 levels, together with decreases in conventional variables (ESR, CRP, and BASDAI). MMP-3 may be a biomarker for disease activity in AS but supplies no additional information to the clinician.     

The optimal time for early burn wound excision to reduce pro-inflammatory cytokine production in a murine burn injury model

BackgroundA potential solution to prevent post-burn deleterious inflammatory responses is early burn wound excision. However, the most beneficial time point remains controversial. This animal study investigated the optimal time point for burn wound excision to reduce pro-inflammatory cytokines production after burn.MethodsForty-eight male Sprague-Dawley rats received scald burns with third-degree burns of 30% body surface area, and were then divided into eight groups by day of operation for excision. Group 1 (n = 6) received burn eschar excision on post-burn day (PBD) 1. Group 2 received excision on PBD2 (n = 6) and so on, while group 8 was the control group (n = 6) that did not undergo excision. The skin defect after excision was covered with a bovine-derived collagen dressing. Interleukin-1 (IL-1), IL-6, IL-10 and tumour necrosis factor-α were serially analysed by enzyme-linked immunosorbent assay (ELISA).ResultsWe found that levels of all pro-inflammatory cytokines appeared to be lower after excision of full-thickness burns, but as the excision time was delayed from group 1 to group 7, the differences showed progressive decline.ConclusionsWe believe that the earlier the excision is performed, the more the level of pro-inflammatory cytokines can be lowered, and the better the post-burn inflammatory process can be modulated.     

Mast cells activation contribute to small intestinal ischemia reperfusion induced acute lung injury in rats

BackgroundSmall intestinal ischemia-reperfusion (IIR) injury may lead to severe local and remote tissue injury, especially acute lung injury (ALI). Mast cell activation plays an important role in IIR injury. It is unknown whether IIR mediates lung injury via mast cell activation.MethodsAdult SD rats were randomized into sham operated group (S), sole IIR group (IIR) in which rats were subjected to 75 min of superior mesenteric artery occlusion followed by 4 h reperfusion, or IIR being respectively treated with the mast cell stabilizer Cromolyn Sodium (IIR + CS group), with the tryptase antagonist Protamine (IIR + P group), with the histamine receptor antagonist Ketotifen (IIR + K group), or with the mast cell degranulator Compound 48/80 (IIR + CP group). The above agents were, respectively, administrated intravenously 5 min before reperfusion. At the end of experiment, lung tissue was obtained for histologic assessment and assays for protein expressions of tryptase and mast cell protease 7(MCP7). Pulmonary mast cell number and levels of histamine, TNF-α and IL-8 were quantified.ResultsIIR resulted in lung injury evidenced as significant increases in lung histological scores (P < 0.05 IIR vs. S), accompanied with concomitant increases of mast cell counts and elevations in TNF-α and IL-8 concentrations and reductions in histamine levels (all P < 0.05 IIR vs. S). IIR also increased lung tissue tryptase and MCP7 protein expressions (all P < 0.05, IIR vs. S). Cromolyn Sodium, Ketotifen and Protamine significantly reduced whilst Compound 48/80 aggravated IIR mediated ALI and the above biochemical changes (P < 0.05).ConclusionsMast cells activation play a critical role in IIR mediated ALI.     

Early protein C activation is reflective of burn injury severity and plays a critical role in inflammatory burden and patient outcomes

BackgroundNavigating the complexities of a severe burn injury is a challenging endeavour where the natural course of some patients can be difficult to predict. Straddling both the coagulation and inflammatory cascades that feature strongly in the burns systemic pathophysiology, we propose the pleiotropic protein C (PC) system may produce a viable biomarker to assist traditional evaluation methods for diagnostic and prognostic purposes.MethodsWe enrolled 86 patients in a prospective observational cohort study. Over three weeks, serial blood samples were taken and measured for PC, activated (A)PC, their receptor endothelial protein C receptor (EPCR), and a panel of inflammatory cytokines including C-reactive protein (CRP), tumour necrosis factor-α, interleukin (IL)-1β, IL-6, IL-8, and IL-17. Their temporal trends were analysed alongside clinical factors including burn size, burn depth, presence of inhalational injury, and a composite outcome of requiring increased support.Results(i) APC increased from a nadir on Day 3 (2.3 ± 2.1 ng/mL vs 4.1 ± 2.5 ng/mL by Day 18, p < 0.0005), only becoming appropriately correlated to PC from Day 6 onwards (r = 0.412–0.721, p < 0.05 for all Days 6–21). (ii) This early disturbance in the PC system was amplified in the more severe burns (≥30% total body surface area, predominantly full thickness, or with inhalational injury), which were characterised by a marked fall in PC activation (approximated by APC/PC ratio) and APC levels during Days 0–3 with low unchanged PC levels. Critically low levels of this cytoprotective agent was associated with greater inflammatory burden, as reflected by significantly elevated CRP, IL-6, and IL-8 levels in the more severe compared to less severe burns, and by negative correlations between both PC and APC with most inflammatory cytokines. (iii) Alongside clinical markers of severity at admission (burn size, burn depth, and presence of inhalational injury), only Day 0 APC/PC ratio (OR 1.048 (1.014–1.083), p = 0.006), APC (OR 1.364 (1.032–1.803), p = 0.029), PC (OR 0.899 (0.849–0.953), p < 0.0005), and not any inflammatory cytokines were predictive markers of requiring increased support. Uniquely, decreased Day 0 PC was further individually associated with each increased total length of stay, ICU length of stay, intravenous fluid resuscitation, and total surgeries, as well as possibly mortality.ConclusionAn early functional depletion of the cytoprotective PC system provides a physiological link between severe burns and the cytokine storm, likely contributing to worse outcomes. Our findings on the changes in APC, PC and PC activation during this pathological state support APC and PC as early diagnostic and prognostic biomarkers, and provides a basis for their therapeutic potential in severe burn injuries.     

No differences of carotid intima-media thickness between young patients with ankylosing spondylitis and healthy controls

ObjectiveAccelerated atherosclerosis in inflammatory rheumatic diseases such as ankylosing spondylitis (AS) stands out among the leading causes of morbidity and mortality. We assessed the correlation between subclinical carotid atherosclerosis and its related clinical parameters in AS patients.MethodsTwenty-eight patients (23 males, 5 females) with AS and 27 sex- and age-matched controls were consecutively recruited to this study. We estimated the carotid intima–media thickness (IMT) and parameters related to arterial elastic properties, including the distensibility coefficient (DC), stiffness index (β), and incremental elastic modulus (E_inc) using high-resolution ultrasonography. Serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1) were measured using enzyme-linked immunosorbent assay (ELISA).ResultsCarotid IMT values and arterial elastic parameters in AS patients showed no statistical significance compared to those of controls (0.57 ± 0.07 vs 0.55 ± 0.05, p = 0.387 for IMT, 28.45 ± 9.23 vs 31.93 ± 9.52, p = 0.175 for DC, 2.32 ± 0.18 vs 2.29 ± 0.15, p = 0.559 for stiffness index (β), and 0.14 ± 0.05 vs 0.12 ± 0.03, p = 0.116 for E_inc). The serum level of IL-6 in AS patients was significantly different compared with controls (p = 0.001), but not in serum levels of TNF-α and MCP-1 (p = 0.162, p = 0.087, respectively). Carotid IMT and all arterial elastic parameters calculated in this study were not found to be associated with serum levels of TNF-α, IL-6, and MCP-1.ConclusionThis cross-sectional study showed that carotid IMT and parameters related with arterial elastic properties in young AS patients without clinically evident cardiovascular risk factors were not different from those of sex- and age-matched healthy controls. Serum levels of TNF-α, IL-6, and MCP-1 did not reflect the degree of carotid subclinical atherosclerosis. However, these findings should be confirmed further in a larger population.     

Impact of orally administered tramadol combined with self-selected music on adult outpatients with burns undergoing dressing change: A randomized controlled trial

ObjectiveTo investigate the effects of music and/or tramadol on pain and anxiety in burn outpatients undergoing dressing changes.DesignRandomized controlled trial.SettingBurns and Plastic Reconstruction Unit.ParticipantsPatients (N = 180) with burns on up to 10%–30% of the total body surface area (TBSA).InterventionsThe patients were randomly allocated to 4 equal-sized groups as follows: (1) tramadol group (TG), patients received 100 mg of tramadol orally 20 min before the dressing change; (2) music group (MG), patients listened to self-selected music during the dressing change; (3) music-plus-tramadol group (MTG), patients received tramadol and listened to self-selected music; and (4) control group (CG), patients received a routine dressing change only. All patients underwent the interventions once per day for 2 days.Main outcome measuresMcGill Pain Questionnaire Short Form (MPQ-SF) (primary outcome), McGill Pain Persian version of Burn Specific Pain Anxiety Scale (BSPAS) (primary outcome), and heart rate (HR) and overall patient satisfaction (secondary outcomes).ResultsThe results showed that music-plus-tramadol group (MTG) had better outcomes with respect to pain and anxiety management during dressing changes.ConclusionsIn comparison with music or tramadol alone, the integration of music and tramadol offers a secure and favorable treatment choice to relieve pain and anxiety, ultimately improving the satisfaction levels of burn outpatients during dressing changes.     

Nano-silver modified porcine small intestinal submucosa for the treatment of infected partial-thickness burn wounds

Background and aimSilver has been widely used as a topical antimicrobial agent in burn wound care. In a previous study, we demonstrated the introduction of nano-silver particles to porcine small intestinal submucosa (NS-PSIS) led to significant enhancement in antibacterial property in repairing contaminated abdominal defect. In this study, we explored the efficacy of NS-PSIS in the treatment of Pseudomonas aeruginosa-infected partial-thickness burn wounds.Methods48 male Sprague-Dawley rats were divided into four groups of equal number. Standardized and reproducible Pseudomonas aeruginosa-infected partial-thickness thermal burns wound model were created using these rats. NS-PSIS, PSIS (porcine small intestinal submucosa) or lipido-colloid dressingss (Urgotul?) were tested for 14 days to assess their ability to heal the rats’ burn wounds. Control group was without any treatment after the establishment of infected burn-wound. The wound contraction rate, animal body weight change, histological examination, and the quantification of IL-6 and C-reactive protein (CRP) were measured to evaluate the healing effects.ResultsNS-PSIS significantly promoted wound healing and recovered the normal growth of rats. There were significantly lower expression levels of pro-inflammatory cytokine (IL-6) and CRP in NS-PSIS group as compared with the PSIS or Urgotul group in the treatment of infected partial-thickness burn wounds. Histological exams revealed significant less inflammatory cells infiltrating, more re-epithelization and neovascularization in NS-PSIS group. There were also less inflammatory cells infiltrations in the major organs in NS-PSIS group.ConclusionsNano-silver modified porcine small intestinal submucosa (NS-PSIS) can be used as a biological derivative dressing for the treatment of infected partial-thickness burn wounds.     

Changes of serum Tau, GFAP, TNF-α and malonaldehyde after blast-related traumatic brain injury

Objective： To determine the changes of serum Tau protein, glial fibrillary acidic protein （GFAP）, tumor necrosis factor alpha （TNF-α）, and malonaldehyde （MDA） in rats after blast-related traumatic brain injury （BTBI） and to provide relative information for further studies on BTBI mechanism and seek specific biomarkers for BTBI. Methods： Ninety male Sprague-Dawley rats were randomly assigned into three groups： control group, moderate blast injury group, and severe blast injury group （n=30 for each）. Rats in the moderate and severe blast injury groups were respectively exposed to corresponding levels of BTBI. After explosion, serum levels of Tau, GFAP, TNF-α, and MDA in each group were determined by Elisa assay at different time points after injury （8 h, 24 h, 3 d, and 6 d）. The extent of brain damage was detected by Nissl staining and TUNEL assay. Results： Serum levels of Tau and GFAP rapidly increased and reached the peak at 24 h after either moderate or severe blast injury. All the values were significantly higher than control group at all time points （P〈0.05）. Serum TNF-α level of both injury groups peaked at 8 h after BTBI and stayed significantly higher than control group at all time points （P〈0.05）. Serum MDA of two injury groups began to significantly increase at 3 d and the level stayed significantly higher than control group until 6 d （P〈0.05）. Moreover, unlike the other biomarkers, serum MDA of severe blast injury group was significantly higher than moderate blast injury group at 6 d （P〈0.05）. Conclusion： The changes of serum Tau, GFAP, and TNF-α showed a good sensitivity at the acute phase after BTBI （within 24 h）. However, their specificity and correlation with the extent of injury were limited in this experiment. Moreover, although the change of serum MDA showed a poor sensitivity and specificity to the diagnosis of BTBI during the first few days, it can reflect the injury degree at 6 d after injury. Therefore, further studies are nee     

Prediction of response to disease modifying antirheumatic drugs in rheumatoid arthritis

AimTo investigate potential predictors of response to conventional DMARDs in RA.MethodsStudy design – 6-month follow-up prospective study.ParticipantsRA patients with active disease.Intervention and follow-upIntroduction of one DMARD. Response to treatment evaluated at 6 months (ACR20 criteria).AnalysisPotential predictors of response, patients’ demographics, disease activity, percentages of PBMC subsets expressing P-gp, serum IL-1β, IL-6, IL-8, IL-10, IL-12, TNF-α levels, were evaluated using univariate and multivariate logistic regression analysis. ROC curve analyses were performed in order to obtain thresholds allowing the prediction of response.ResultsForty-two patients (mean age = 57 ± 13 years, mean disease duration = 5.4 ± 7.2 years) were included. MTX was given to 30. The response to therapy was predicted by the baseline serum level of TNF-α (mean = 30.2 pg/ml ± 18 in non-responders vs. 11.9 pg/ml ± 11.2 in responders). The threshold, which predicted with the best accuracy the response to treatment, was 20.1 pg/ml (sensitivity, specificity, positive and negative predictive values of 75, 78.9, 83.3, and 69.2%, respectively; AUC = 80.3%, 95% CI = 62.8–97.7%). Similar results were obtained in the subgroups of patients treated with MTX and patients with early RA of less than 3 years duration.ConclusionIn the present work, the serum concentration of TNF-α was related to further response to DMARDs. Other works are needed for confirmation and to assess whether such biomarker could be used to predict the response to DMARDs at the individual level.     

Brain natriuretic peptide induces CD8+ T cell death via a caspase 3 associated pathway--implications following heart transplantation

BackgroundBrain natriuretic peptide (BNP) remains elevated after cardiac transplantation despite replacement of the failing ventricle. Serum peaks are also seen during acute rejection episodes independent of intracardiac hemodynamic disturbance. High BNP levels are also reported during bacterial sepsis, burns, stroke and myocardial infarction. Given all of these conditions are linked by immune activation processes, we hypothesised that BNP is an immunoactive agent.MethodsPeripheral blood mononuclear cells (PBMCs) were isolated from whole blood of 40 cardiac transplant recipients. Cells were co-cultured for 72 h in the presence or absence of BNP. Cells were then immunophenotyped using flow cytometry. Cell death pathways were determined using caspase 3 quantification and mitochondrial membrane assessment. Supernatants were analysed for cytokine, chemokine and growth factor production using luminex.ResultsCo-culture of CD8 + T cells with BNP reduced cell number, and increased intracellular caspase 3. Supernatant analysis revealed that BNP reduced the expression of inflammatory cytokines including TNF-α, IL-1α and IL-6. However it preserved the production of anti-inflammatory and regulatory cytokines such as IL-4, 5 and 13.ConclusionOur findings provide evidence that BNP directly induces CD8 + T cell apoptosis via a caspase 3 associated mechanism from cardiac transplant patients. This may impart significant consequences on immune mediated disease processes, such as allograft rejection.     

Inflammatory response to orthopedic biomaterials after total hip replacement

BackgroundThe aim of the present study was to investigate early inflammatory response in the first 3 days after the implantation of hip prostheses, and to compare the early inflammation responses associated with the use of different combinations of bearing materials.Methods34 patients were enrolled, all of whom underwent unilateral total hip replacement and had identical hip prostheses, except for the bearing materials. These consisted of polyethylene on alumina (n = 8), polyethylene on CoCr (n = 11), or alumina on alumina (n = 15). Blood samples were collected preoperatively in the morning of the day of surgery, and at 6 h, 1 day, 2 days, and 3 days postoperatively. CK, CRP, and IL-6 in peripheral blood were measured. Pain score was obtained at 2 days after surgery.ResultsThere were no significant differences in the pre- and postoperative background variables among the groups. Pain scores of different groups were not significantly different either (P > 0.05). There were also no significant differences in the levels of CK, CRP, and IL-6 when patients with the three combinations of bearing materials were compared.ConclusionsWe concluded that varying the bearing materials used in the hip prosthesis did not influence the early inflammatory response after prosthesis implantation.     

Impact of polyclonal anti-thymocyte globulins on the expression of adhesion and inflammation molecules after ischemia–reperfusion injury

BackgroundPolyclonal anti-thymocyte globulins (ATGs) are immunosuppressive agents used for the treatment and prevention of acute organ rejection after transplantation. ATGs induce apoptosis and complement-mediated cell death in peripheral T-lymphocytes and have shown a reduction of leukocyte adhesion after ischemia–reperfusion (IRI). We analyzed the impact of different ATGs upon the expression of adhesion and inflammation molecules after IRI.Materials and methodsThe major arteries and veins of the extremities of cynomolgus monkeys were surgically isolated and flushed with Ringer's lactate at 4 °C. After 60 min of ischemia the limbs were reperfused with matching human blood. ATGs were added to the blood 30 min prior to the reperfusion, forming four groups: Tecelac-ATG group (n = 16), Fresenius(S)-ATG group (n = 16), Thymoglobulin-ATG group (n = 12) and a control group (n = 16). Biopsies from muscular tissue were obtained after the experiments. The expression of adhesion (ICAM-1, VCAM, PECAM, CD11b, CD62E) and inflammation (IL-1, IL-6, TNF-α) molecules on endothelium, leukocytes, and reperfused tissue was analyzed by means of immunohistochemistry.ResultsThe expression of the studied adhesion molecules (ICAM-1, VCAM, PECAM, CD11b, and CD62E) was significantly increased in the control group when compared with the treated groups. The expression of IL-1, IL-6, and TNF-α was reduced in the ATG-groups in comparison to the control group.DiscussionOur results showed that ATGs caused a reduction of the expression of adhesion and inflammation molecules both in endothelium and reperfused tissue. The inhibition of the expression of molecules required for firm cellular adhesion, may contribute to decreasing cellular graft infiltration after post-ischemic reperfusion.     

Glucocorticoids suppress fibroblast apoptosis in an in vitro thermal injury model

The wounds of full- and deep partial-thickness burns result in hypertrophic scars and lead to skin contracture more severely than those of superficial partial-thickness burns. Therefore, preventing burn progression may help improve the aesthetic and functional outcomes after healing. Although a number of studies have focused on elucidating the underlying mechanisms of and preventing burn wound progression, it is still difficult to rescue burned dermis unless early tangential excision is performed. To investigate the underlying mechanisms of and prevent cell death of heat-injured fibroblasts, we developed an in vitro experimental model of heat-injured fibroblasts. We confirmed that heating at 55 °C for 30 s caused fibroblast necrosis immediately after heating, whereas heating at 46 °C for 30 s induced apoptosis 24 h after heating. We also found that the supplementation of 100 ng/ml betamethasone to the culture medium after heating decreased the number of apoptotic cells and increased that of live cells. Our studies suggest that glucocorticoids suppress apoptosis of heat-injured fibroblasts and may be useful for preventing burn wound progression.     

Linking systemic angiogenic factors (VEGF,angiogenin, TIMP-2) and Doppler ultrasound to anti-inflammatory treatment in rheumatoid arthritis

ObjectiveTo evaluate an association between synovial Doppler flow and serum levels of vascular endothelial growth factor (VEGF), angiogenin and TIMP-2 in patients with rheumatoid arthritis during anti-inflammatory treatment with glucocorticoids and TNF-α inhibitors.MethodsInflamed wrists of 15 patients with rheumatoid arthritis (RA) were examined by two independent ultrasound investigators prior to and at days 3, 7, 14 and 42 after the initiation of treatment with glucocorticoids in therapy-naïve patients or after the beginning of a therapy with a TNF-α inhibitor in patients with DMARD failure. Quantitative three-dimensional power Doppler ultrasonographic assessment of synovial vascularization was compared at each visit with serum levels of VEGF, angiogenin and TIMP-2.ResultsIn the glucocorticoid group, synovial Doppler signals decreased significantly at day 3 (?44%; P = 0.003) in comparison to a delayed decrease in the TNF-α inhibitor group after 6 weeks (?46%; P = 0.001). A significant reduction of serum VEGF levels could be determined with a delay of 1 week after the decrease of Doppler activity but no correlation was found between both parameters (rho: P = 0.7; r = ?0.03). Angiogenin concentrations decreased in the TNF group and increased in the GC group. Levels of TIMP-2 did not change significantly in both groups.ConclusionThe decrease of serum VEGF levels under treatment with glucocorticoids or TNF-α inhibitors followed the reduction of the intra-articular synovial Doppler flow. This result supports the idea that the reduction of synovial perfusion due to anti-inflammatory treatment is not regulated by systemic VEGF, but that the inflamed joints are the source for circulating VEGF.     

Atherosclerosis progression in psoriatic arthritis patients despite the treatment with tumor necrosis factor-alpha blockers: A two-year prospective observational study

ObjectiveTo evaluate the progression of subclinical atherosclerosis in Psoriatic Arthritis (PsA) patients treated with anti-tumor necrosis factor (TNF)-α agents.MethodsThirty-two PsA patients classified according to the CASPAR criteria and attending the Rheumatology Unit of the University of Padua Medical Center were enrolled in a two-year prospective, observational study. In accordance with the ASAS/EULAR recommendations on the management of these patients, those studied were prescribed biological agents [etanercept (n = 21), adalimumab (n = 6), infliximab (n = 5)]. Plasma lipids, inflammatory biomarkers, including C-reactive protein (CRP), interleukin-6 (IL-6), vessel endothelium growth factor (VEGF), osteoprotegerin (OPG), and TNF-α, as well as Disease Activity Score 28 calculated with CRP (DAS 28-CRP) were evaluated at baseline and after two years of treatment. Bilateral carotid B-mode ultrasound measurements [the mean-intima media thickness (mean-IMT), the mean maximum-IMT (M-Max)] of each carotid artery segment (common, bulb, and internal carotid artery) and the post-occlusion flow-mediated dilation (FMD) of the brachial artery were also assessed at baseline and after two years.ResultsDespite an improvement in the DAS 28-CRP score (P < 0.0005) and lower low-density lipoprotein cholesterol (P < 0.013) and triglyceride (P < 0.036) values, there was a significant progression in both the mean-IMT (P < 0.0005) and M-Max (P < 0.0005). Moreover, no recovery in FMD (P = ns) was observed after two years of anti TNF-α treatment. Serum TNF-α levels were increased (P = 0.003) and OPG values were decreased (P = 0.011) at the end of follow- up with respect to baseline values.ConclusionsDespite improvement in clinical status, arterial remodelling was observed in the PsA patients who were treated with anti TNF-α agents for two years.     

Protective effect of immunosuppressive treatment before orthotopic kidney autotransplantation

BackgroundIschemia reperfusion injury (IRI) is one of the risk factors for delayed graft function, acute rejection and long term allograft survival after kidney transplantation. IRI is an independent antigen inflammatory process that produces tissue damage. Our objective was to study the impact of immunosuppressive treatment (IS) on IRI applying only one dose of IS before orthotopic kidney autotransplantation.MethodsTwenty-four rats allocated in four groups were studied. One group served as control (G1: autotransplanted rats without IS) and the rest received IS 12 h before kidney autotransplantation (G2: Rapamycin, G3: Mycophenolate mofetil and G4: Tacrolimus).ResultsImproved renal function and systemic inflammatory response were found among IS groups compared to the control group (Delta Urea p < 0.0001; Delta Creatinine p < 0.0001; Delta C3 p < 0.001). The number of apoptotic nuclei in renal medulla in G1 was higher than in IS groups (p < 0.0001). Tubular damage was less severe in IS groups respecting G1 (p < 0.001). C3, TNF-α and IL-6 expression in kidney samples was reduced when IS was used compared to the control group. No differences were observed among the different immunosuppressive drugs tested. However, Heme oxygenase-1(HO-1) was increased only in Rapamycin treatment.ConclusionsThese data suggest that the use of IS administered before transplant attenuates the IRI process after kidney transplantation in an animal model.     

Fibrin sealant improves graft adherence in a porcine full-thickness burn wound model

IntroductionAutograft take and rapid wound closure is essential for the survival of severely burned patients. Loss of skin grafts typically occurs during the first few days after coverage, mainly due to shear forces and inadequate contact with the wound bed. Slow-clotting fibrin sealant, applied with a spray-on device, has been shown to improve healing of skin grafts in large wounds. However, its use in burn wounds has not been studied so far.Study aimTo evaluate the effectiveness of sprayed fibrin sealant in excised and grafted full-thickness burns.Material and methodsTen female Yorkshire pigs (30–45 kg) received a full-thickness contact burn of approximately 15% total body surface area. The burns were excised to the level of the muscular fascia after 24 h and covered with meshed skin autograft (mesh ratio 1:3). Wounds were randomized to either fibrin sealant (n = 20) or standard skin staples (n = 16) for graft fixation. Fibrin sealant was used as a slow-clotting spray (4 IU thrombin/ml). Outcome measurements included clinical scoring at days 2, 5, 9 and 14 postoperatively, planimetric analysis of wound closure, and histological examination of epidermal and dermal thickness 14 days after autografting.ResultsIn the fibrin sealant group, graft adherence scores were significantly increased (p < 0.02) and graft dislocation scores significantly decreased (p < 0.01) at days 2 and 5 postoperatively, when compared to controls. Planimetric analysis of remaining open mesh interstices showed acceleration of wound closure in the fibrin sealant group but did not reach statistical significance (day 14 p = 0.04 at significance level p < 0.025). Wound contraction, occurrence of hematoma, and dermal as well as epidermal thickness were not different between the groups at 14 days postoperatively.ConclusionThe results indicate that the use of slow-clotting fibrin sealant spray for autograft fixation is advantageous over skin staples. Easy handling and reduced graft dislocation at early time points are key qualities of this method.     

Influences of purposeful activity versus rote exercise on improving pain and hand function in pediatric burn

PurposeTo explore the influences of purposeful activities versus rote exercises on pain, range of motion and hand function in children with hand burn.MethodsThirty patients had superficial and deep partial and full-thickness burns, including hand and wrist with less than 25% total body surface area (TBSA) was included in this study. The patients were randomly allocated to one of the two groups; purposeful activity group (PA-group, n = 15) and rote exercises group (Rex-group, n = 15). Outcomes measured were pain severities using the self-report faces scale and analogue scale (VAS), total active motion (TAM) using standard dorsal hand goniometer, and hand function using Jebsen–Taylor hand function test (JTHFT). Measurements were recorded 72 h post-burn, after 1, 2, and 3 weeks, at the time of discharge and at 3 months follow up.ResultsIn PA-group, results regarding to pain modulation (p < 0.05), TAM (p < 0.01), and JTHFT (p < 0.01) was statistically significance in comparison to Rex-group.ConclusionThis study supports the belief that the purposeful activity based on playing, and games can reduce pain, improve hand movement and functions better than rote exercise. As well as its reusability and versatility, suggesting another option in the rehabilitation of children with hand burn.     

The association between plasma gelsolin level and prognosis of burn patients

ObjectiveTo observe the change in plasma gelsolin levels among burn patients, and explore its impact on patient prognosis.MethodsThis prospective cohort study includes 98 burn patients with burns ≥30% TBSA, who were admitted to our institution between January 2010 and June 2013. Patients were grouped according to burn sizes, development and severity of sepsis, and survival from sepsis. The plasma gelsolin levels among different groups were compared by repeated measure ANOVA. The relationship between plasma gelsolin levels and the presence of sepsis and prognosis was examined by logistic regression.ResultsThe plasma gelsolin levels decreased with increasing burn sizes and increasing sepsis severity, with the lowest gelsolin level observed at 7 days after the burn. The plasma gelsolin concentrations were significantly lower among patients with sepsis than those without (P < 0.001), and were lower among those who died after sepsis than those who survived (P < 0.001). Logistic regression suggested that plasma gelsolin level was inversely associated with the occurrence of sepsis [OR 0.873 (95%CI 0.693–0.993)] and survival after sepsis [OR 0.939 (95%CI 0.859–0.992)].DiscussionPlasma gelsolin levels decrease after burn. The level is significantly lower among those with large burns and those with combined sepsis. Plasma gelsolin levels can be used to predict the prognosis of burn patients.