Markers Of Tissue Injury Research Articles

Effects of Acupuncture in Anesthesia for Craniotomy: A Meta-Analysis.

Acupuncture treatment has been used in China for >2500 years, and at present it is used worldwide as a form of analgesia in patients with acute and chronic pain. Furthermore, acupuncture is regularly used not only as a single anesthetic technique but also as a supplement or in addition to general anesthesia (GA). The aim of this systematic review and meta-analysis was to assess the level of evidence for the clinical use of acupuncture in addition to GA in patients undergoing craniotomy. This is a systematic review of randomized controlled trials with meta-analyses. The literature search (PubMed, Cochrane Library, and Web of Science) yielded 56 citations, published between 1972 and March 01, 2015. No systematic review or meta-analyses on this topic matched our search criteria. Each article of any language was assessed and rated for the methodological quality of the studies, using the recommendation of the Oxford Centre for Evidence Based Medicine. Ten prospective randomized controlled clinical trials with a total of 700 patients were included. Included in the meta-analysis were studies that involved any craniotomy under GA compared with a combination of GA and acupuncture. Exclusion criteria were no acupuncture during surgery, no GA during surgery, only postoperative data available, animal studies, and low grade of evidence. The use of acupuncture significantly reduced the amount of volatile anesthetics during surgery (P<0.001) and led to faster extubation time (P=0.001) and postoperative patient recovery (P=0.003). In addition, significantly reduced blood levels of the brain tissue injury marker S100β 48 hours after operation (P=0.001) and occurrence of postoperative nausea and vomiting (P=0.017) were observed. No patient studied suffered from awareness. The analysis suggests that the complementary use of acupuncture for craniotomy has additional analgesic effects, reduces the needed amount of volatile anesthetic, reduces the onset of postoperative nausea and vomiting, and might have protective effects on brain tissue. Our findings may stimulate future randomized controlled trials to provide definitive recommendations.

Early diagnostics of temporomandibular joint structural elements injures caused by traumatic mandibular bone fractures

A rapidly increasing number of mandibular condylar fractures and some complications related to injuries of temporomandibular elements make this study important. Intra-articular disorders lead to secondary pathological findings such as osteoarthritis, deforming osteoarthrosis, and temporomandibular joint ankylosis that limits mouth opening, mastication, swallowing, breathing, and decreased/lost working capacity or disability. Early diagnosis of intra-articular disorders can prevent from long-lasting functional complications caused by temporomandibular joint injuries. This study was performed for the purpose of early detection and investigation of organic pathological changes in the cartilaginous and osseous tissues of the temporomandibular joint caused by traumatic fractures of the mandibular condyle. Twenty patients underwent a general clinical examination, magnetic resonance imaging (MRI), and immune-enzyme testing for biochemical markers of connective tissue injury (pyridinoline and deoxypyridinoline) in urine. Disk dislocation, deformation, adhesion, perforation or squeeze, tension or disruption of ligaments, and injury of articular surfaces are among complications of mandibular fractures that can be revealed on MRI. As regards biochemical findings, we revealed a sharp rise in the levels of pyridinoline and deoxypyridinoline before treatment and a lack of stabilization within 21 days of treatment.

Zingerone reduces HMGB1-mediated septic responses and improves survival in septic mice

High mobility group box 1 (HMGB1) is considered a late mediator of sepsis and the inhibition of HMGB1-mediated severe inflammatory responses and restoration of endothelial integrity have emerged as attractive therapeutic strategies for the management of sepsis. Zingerone (ZGR), a phenolic alkanone isolated from ginger, has been reported to possess various pharmacological activities. We examined the effects of ZGR on HMGB1-mediated septic responses and survival rate in a mouse model of sepsis. ZGR was administered after HMGB1 challenge. The antiseptic activity of ZGR was determined from the measurements of permeability, leukocyte adhesion and migration, activation of pro-inflammatory proteins, and the production of tissue injury markers in HMGB1-activated HUVECs and mice. ZGR significantly reduced HMGB1 release in LPS-activated HUVECs via the SIRT1-mediated deacetylation of HMGB1. And, ZGR suppressed the production of TNF-α and IL-6 and the activation of NF-κB and ERK 1/2 by HMGB1. ZGR also inhibited HMGB1-mediated hyperpermeability and leukocyte migration in mice. In addition, treatment with ZGR reduced the CLP-induced release of HMGB1, sepsis-related mortality, and tissue injury in vivo. Our results indicated that ZGR might be useful in the treatment of sepsis by targeting HMGB1.

The role of interleukin-1β as a predictive biomarker and potential therapeutic target during clinical ex vivo lung perfusion

BackgroundExtended criteria donor lungs deemed unsuitable for immediate transplantation can be reconditioned using ex vivo lung perfusion (EVLP). Objective identification of which donor lungs can be successfully reconditioned and will function well post-operatively has not been established. This study assessed the predictive value of markers of inflammation and tissue injury in donor lungs undergoing EVLP as part of the DEVELOP-UK study.MethodsLongitudinal samples of perfusate, bronchoalveolar lavage, and tissue from 42 human donor lungs undergoing clinical EVLP assessments were analyzed for markers of inflammation and tissue injury. Levels were compared according to EVLP success and post-transplant outcomes. Neutrophil adhesion to human pulmonary microvascular endothelial cells (HPMECs) conditioned with perfusates from EVLP assessments was investigated on a microfluidic platform.ResultsThe most effective markers to differentiate between in-hospital survival and non-survival post-transplant were perfusate interleukin (IL)-1β (area under the curve = 1.00, p = 0.002) and tumor necrosis factor-α (area under the curve = 0.95, p = 0.006) after 30 minutes of EVLP. IL-1β levels in perfusate correlated with upregulation of intracellular adhesion molecule-1 in donor lung vasculature (R2 = 0.68, p < 0.001) and to a lesser degree upregulation of intracellular adhesion molecule-1 (R2 = 0.30, p = 0.001) and E-selectin (R2 = 0.29, p = 0.001) in conditioned HPMECs and neutrophil adhesion to conditioned HPMECs (R2 = 0.33, p < 0.001). Neutralization of IL-1β in perfusate effectively inhibited neutrophil adhesion to conditioned HPMECs (91% reduction, p = 0.002).ConclusionsDonor lungs develop a detectable and discriminatory pro-inflammatory signature in perfusate during EVLP. Blocking the IL-1β pathway during EVLP may reduce endothelial activation and subsequent neutrophil adhesion on reperfusion; this requires further investigation in vivo.

Cerebral Gray Matter Atrophy Is Associated with the CSF IgG index in African American with Multiple Sclerosis

African American (AA) patients with multiple sclerosis (MS) have been reported to have a more aggressive disease course compared to their white counterparts. We explored the relation of gray matter (GM) volume, a marker of tissue injury, and cerebrospinal fluid (CSF) IgG index in both AA and white MS patients. This was a cross-sectional study of 150 self-identified AA and 150 white patients with MS who underwent magnetic resonance imaging scan of brain and CSF sampling. Intrathecal IgG synthesis was quantified as IgG index. The Spearman test was used for univariate correlation analysis, followed by generalized linear model (GLM) to assess the effect of race on the correlation between IgG index and GM volume. The GM volume was inversely related to the IgG index for the entire group (rho = -.57, P < .0004). The AA group showed a stronger correlation (rho = -.893, P < .00004), as compared to whites (rho = -.019, P = .85), between GM and IgG index. Furthermore, GLM analysis showed a significant effect of race on the relation between IgG index and GM volume (P < .0005). AA patients with MS have lower GM volume and a stronger inverse correlation between GM volume and CSF IgG index, compared to the whites. These findings suggest a potentially prominent role of humoral immunity in mediating tissue injury in AA patients with MS.

Mycophenolate mofetil improves renal haemodynamics, microvascular oxygenation, and inflammation in a rat model of supra-renal aortic clamping-mediated renal ischaemia reperfusion injury.

Ischaemia/reperfusion (I/R) is one of the main causes of acute kidney injury (AKI), which is characterized by sterile inflammation and oxidative stress. Immune cell activation can provoke overproduction of inflammatory mediators and reactive oxygen species (ROS), leading to perturbation of the microcirculation and tissue oxygenation associated with local and remote tissue injury. This study investigated whether the clinically employed immunosuppressant mycophenolate mofetil (MMF) was able to reduce I/R-induced renal oxygenation defects and oxidative stress by preventing sterile inflammation. Rats were divided into three groups (n=6/group): (1) a sham-operated control group; (2) a group subjected to renal I/R alone (I/R); and (3) a group subjected to I/R and MMF treatment (20mg/kg prior to I/R) (I/R+MMF). Ischaemia was induced by a vascular occluder placed on the abdominal aorta for 30minutes, followed by 120minutes of reperfusion. Renal I/R deteriorated renal oxygenation (P<.001) and oxygen delivery (P<.01), reduced creatinine clearance (P<.01) and tubular sodium reabsorption (P<.001), and increased iNOS, renal tissue injury markers (P<.001), and IL-6 (P<.001). Oral MMF administration prior to insult restored renal cortical oxygenation (P<.05) and iNOS, renal injury markers, and inflammation parameters (P<.001) to near-baseline levels without affecting renal function. MMF exerted a prophylactic effect on renal microvascular oxygenation and abrogated tissue inflammation and renal injury following lower body I/R-induced AKI. These findings may have clinical implications during major vascular or renal transplant surgery.

Profiling inflammation and tissue injury markers in perfusate and bronchoalveolar lavage fluid during human ex vivo lung perfusion.

OBJECTIVES: Availability of donor lungs suitable for transplant falls short of current demand and contributes to waiting list mortality. Ex vivo lung perfusion (EVLP) offers the opportunity to objectively assess and recondition organs unsuitable for immediate transplant. Identifying robust biomarkers that can stratify donor lungs during EVLP to use or non-use or for specific interventions could further improve its clinical impact. METHODS: In this pilot study, 16 consecutive donor lungs unsuitable for immediate transplant were assessed by EVLP. Key inflammatory mediators and tissue injury markers were measured in serial perfusate samples collected hourly and in bronchoalveolar lavage fluid (BALF) collected before and after EVLP. Levels were compared between donor lungs that met criteria for transplant and those that did not. RESULTS: Seven of the 16 donor lungs (44%) improved during EVLP and were transplanted with uniformly good outcomes. Tissue and vascular injury markers lactate dehydrogenase, HMGB-1 and Syndecan-1 were significantly lower in perfusate from transplanted lungs. A model combining IL-1β and IL-8 concentrations in perfusate could predict final EVLP outcome after 2 h assessment. In addition, perfusate IL-1β concentrations showed an inverse correlation to recipient oxygenation 24 h post-transplant. CONCLUSIONS: This study confirms the feasibility of using inflammation and tissue injury markers in perfusate and BALF to identify donor lungs most likely to improve for successful transplant during clinical EVLP. These results support examining this issue in a larger study.

Diosmin Attenuates Methotrexate‐Induced Hepatic, Renal, and Cardiac Injury: A Biochemical and Histopathological Study in Mice

The current study was designed to investigate the beneficial role of diosmin, a biologically active flavonoid, against methotrexate- (MTX-) induced hepatic, renal, and cardiac injuries in mice. Male Swiss albino mice received a single intraperitoneal injection of MTX (at 20 mg/kg, body weight) either alone or in combination with oral diosmin (at 50 or 100 mg/kg body weight, for 10 days). Serum was used to evaluate tissue injury markers, while hepatic, renal, and cardiac tissue samples were obtained for determination of antioxidant activity as well as histopathological examination. Diosmin treatment ameliorated the MTX-induced elevation of serum alkaline phosphatase, aminotransferases, urea, creatinine, lactate dehydrogenase, and creatine kinases as well as plasma proinflammatory cytokines (interleukin-1-beta, interleukin-6, and tumor necrosis factor-alpha). Additionally, both diosmin doses significantly reduced tissue levels of malondialdehyde and nitric oxide and increased those of glutathione, glutathione peroxidase, glutathione reductase, glutathione S-transferase, superoxide dismutase, and catalase, compared to the MTX-intoxicated group. Histopathological examination showed that diosmin significantly minimized the MTX-induced histological alterations and nearly restored the normal architecture of hepatic, renal, and cardiac tissues. Based on these findings, diosmin may be a promising agent for protection against MTX-induced cytotoxicity in patients with cancer and autoimmune diseases.

Markers of muscle damage for comparing soft tissue injury following proximal femur nail and dynamic hip screw operations for intertrochanteric hip fractures

BackgroundFemoral neck fractures are the most common fractures among the elderly. The two operative approaches used for the treatment of AO/OTA 31 intertrochanteric fractures include an intramedullary device (proximal femoral nail [PFN]) or an extramedullary device (sliding/dynamic hip screw [DHS]). The aim of this study was to provide objective evidence of local soft tissue injury by measuring serum creatine phosphokinase (CPK), a biochemical marker, to quantify muscle damage and inflammation in patients treated by the two approaches. Patients and methodsMedical data of 359 patients operated for intertrochanteric fractures with PFN (156 patients) or DHS (193 patients) were retrospectively reviewed. The fractures were classified according to AO/OTA classification. Perioperative and radiographic data were collected to ensure cohorts with similar characteristics. Serum CPK and serum hemoglobin (Hb) levels were measured preoperatively and on postoperative day 1 (POD1). Independent predictors of elevation in the levels of markers of inflammation and muscle damage were determined by a multivariate linear regression model. ResultsThe demographics were similar for the two groups. Our study population included 64.2% female patients. Preoperative serum CPK levels were available for 89 patients and POD1 serum CPK levels were available for all patients. One-hundred and thirteen of the 193 DHS patients (58%) and 14 of the 156 PFN patients (9%) had a stable fracture (AO/OTA 31A1, p<0.0001). The DHS patients had a greater increase between pre- and postoperative CPK levels compared to the PFN patients (DHS, δ=368 versus PFN, δ=65, p<0.0002). The PFN patients had a greater decrease in both the pre- and postoperative Hb levels compared to the DHS patients (Diff_Hb 0.27g/dl). The older the patient, the greater decreases in Diff_CPK compared to the younger ones. ConclusionsImplementation of POD1 CPK blood levels as a biochemical marker of soft tissue injury provided quantitative evidence that patients whose intertrochanteric fracture was stabilized by a DHS suffered greater soft tissue injury compared to patients whose fracture was stabilized by a PFN.

Estimation of Serum Uric Acid as an Indicator of Severity of Preeclampsia and Perinatal Outcome.

Uric acid is a marker of oxidative stress tissue injury and renal dysfunction, hence a correlation hypothesized. (1) To evaluate severity of preeclampsia with raised serum uric acid. (2) To evaluate perinatal outcome in preeclampsia with raised serum uric ccid. 50 pregnant women withsevere preeclampsia and 50 normotensive womenwere included in the study and maternal serum uric acid was estimated in both the groups. In the study group comprising of 50 cases of preeclampsia, there is a positive correlation (r=0.695 & +0.359) between the variables in study group, and as the SBP or DBP increases, the MSUA concentration also increases. In control group, there is a negative correlation (r=-0.083 & -0.095). Perinatal complication was more in study group, 54% were preterm compared to 4% in control group also as MSUA value increased average gestational age decreased. Mean birth weight in study group was 1.8kg study group of which 13 (26%) babies were VLBW, 28 (56%) were LBW, and 9 (18%) babies had normal birth weight, in control group mean birth weight was 2.99kg. There were 6 cases of ELBW babies in study group which were included in VLBW group for statistical calculation. The difference was found to be statistically significant (p<0.05). In the study group, the MSUA concentration is found higher in LBW and VLBW babies compared to normal birth weight babies. There is a positive correlation between SUA & severity of preeclampsia, and a significant adverse fetal outcome is observed with raised MSUA in preeclamptic patients.

Tributyltin-mediated hepatic, renal and testicular tissue damage in male Syrian hamster (Mesocricetus auratus): a study on impact of oxidative stress

Organotin compounds are a versatile group of organometallic chemicals that are used in a variety of industrial and agricultural applications. Tributyltin (TBT), a common organotin, brings about severe spermatotoxic and organotoxic effects. However, information about the adverse effects of TBT on liver, kidney and testis is scanty. Hence, the present study was undertaken to elucidate the TBT-mediated oxidative stress-induced impairments in these organs. Administration of TBT through oral route at increasing doses of 50, 100 and 150 ppm for 65 days to male Syrian hamsters resulted in drastically decreased activities of antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase and decreased mean levels of non-enzymatic antioxidants (reduced glutathione, vitamin C, and vitamin E) followed by a dramatic increase in the levels of lipid peroxidation in the liver, kidney and testis as compared to the control animals. Significantly high levels of serum urea, creatinine, uric acid and bilirubin were observed in TBT-treated hamsters. Also, TBT treatment induced drastic histopathological changes in the liver, kidney and testis combined with remarkable changes in serum levels of tissue injury marker enzymes Aspartate transaminases, Alkaline phosphatase and Alanine transaminase. These data affirm that exposure to TBT can lead to oxidative stress-induced damage to liver, kidney and testis.

Nanovesicular liposome-encapsulated hemoglobin (LEH) prevents multi-organ injuries in a rat model of hemorrhagic shock

The goals of resuscitation in hemorrhagic shock are to correct oxygen deficit and to maintain perfusion pressure to the vital organs. We created liposome-encapsulated hemoglobin (LEH) as a nanoparticulate oxygen carrier (216±2nm) containing 7.2g/dl hemoglobin, and examined its ability to prevent the systemic manifestations of hemorrhagic shock (45% blood loss) in a rat model. We collected plasma after 6h of shock and LEH resuscitation, and determined the circulating biomarkers of systemic inflammation and functions of liver, gut, heart, and kidney. As is typical of the shock pathology, a significant increase in the plasma levels of cardiac troponin, liver function enzymes, soluble CD163 (macrophage activation), and creatinine, and the liver/gut myeloperoxidase activity was observed in the hemorrhaged rats. The plasma levels of TNF-α, IL-6, IL-1α, CINC-1, and IL-22 also increased after hemorrhagic shock. LEH administration prevented the hemorrhagic shock-induced accumulation of the markers of injury to the critical organs and pro-inflammatory cytokines. LEH also decreased the plasma levels of stress hormone corticosterone in hemorrhaged rats. Although saline also reduced the circulating corticosterone and a few other tissue injury markers, it was not as effective as LEH in restraining the plasma levels of creatinine, alanine transaminase, CD163, TNF-α, IL-6, and IL-1α. These results indicate that resuscitation with nanoparticulate LEH creates a pro-survival phenotype in hemorrhaged rats, and because of its oxygen-carrying capacity, LEH performs significantly better than saline in hemorrhagic shock.

The Association of Plasma Fractalkine and Inflammation After Ischemic Stroke

BACKGROUND: Inflammation affects the brain after stroke with main functions to rapidly eliminate the source of the disturbance, remove damaged tissue and then restore tissue homeostasis. High sensitive C-reactive protein (hsCRP) is a sensitive marker of inflammation and tissue injury in the arterial wall, while fractalkine is a distinct chemokine that promotes inflammatory signaling after neuronal death on ischemic stroke. We aim to investigate the association of fractalkine with hsCRP as a marker of inflammation in ischemic stroke patients.METHODS: This study was designed as a cross-sectional study. Soon after patients with ischemic stroke admitted to hospital, plasma fractalkine and hsCRP concentrations were assesed. Subjects had to be at least 30 years old and maximum 30 days of stroke onset. High inflammation was defined as hsCRP value &gt;3 mg/L.RESULTS: High fractalkine levels were found on 24 ischemic stroke patients (49%) and mean of fractalkine 0.719 ng/mL on patients with stroke onset &lt;7 days was higher than patients with stroke onset 7-30 days. Low fractalkine levels (&lt;0.527 ng/mL) were found on ischemic stroke patients with onset 7-30 days accompanied by high inflammation (hsCRP &gt;3 mg/L), but no significant correlation between fractalkine and hsCRP (p=0.613).CONCLUSION: High inflammation and low plasma fractalkine profile was found after 7 days of onset in ischemic stroke patients. No significant correlation between fractalkine and hsCRP in ischemic stroke patients.KEYWORDS: CRP, fractalkine, inflammation, ischemic stroke

Neutrophil infiltration and activation in bronchiolitic airways are independent of viral etiology.

Hospitalization with bronchiolitis is linked to the development of early childhood chronic wheeze and asthma. Viral etiology and severity of inflammation are potential contributing factors. Previously we observed reduced airway neutrophil infiltration in breastfed bronchiolitic infants, with a corresponding reduction in disease severity. This study aimed to examine whether respiratory viral etiology and co-infection alters the pattern of neutrophil influx, and the inflammatory mediator profile, resulting in epithelial damage in bronchiolitis. Nasopharyngeal aspirates (NPAs) collected from hospitalized infants were assessed for viruses, soluble protein, cellular infiltrate, interleukin (IL)-6, -8, and myeloperoxidase (MPO). NPAs were collected from 228 bronchiolitic and 14 non-bronchiolitic infants. In the bronchiolitic cohort, human rhinovirus was most prevalent (38%), followed by respiratory syncytial virus (36%), adenovirus (10%), and human metapneumovirus (6%), with 25% positive for viral co-infections and 25% negative for all screened viruses. Viral-induced bronchiolitis was associated with increased cellular infiltrate and protein, above control, and virus-negative infants (P < 0.05). Cellular infiltrate correlated to IL-6, -8, and MPO (r = 0.331, 0.669, and 0.661; P < 0.01). Protein, IL-6, -8, and MPO differed significantly between viral groups; however, the majority of marker values for all groups fall within an overlapping, indistinguishable range, precluding their use as biomarkers of viral etiology. No significant difference was found between single and viral co-infections for any parameter. Bronchiolitic infants presenting with a detectable respiratory virus during hospitalization demonstrated elevated markers of airway tissue inflammation and injury. In this cohort, viral etiology did not discernibly modulate chemokine-mediated neutrophil infiltration and activation. Pediatr Pulmonol. 2017;52:238-246. © 2016 Wiley Periodicals, Inc.

Sustained Elevation of Vascular Endothelial Growth Factor and Angiopoietin-2 Levels After Transcatheter Aortic Valve Replacement

BackgroundTranscatheter aortic valve replacement (TAVR) exposes the systemic vasculature to increased mechanical forces. Endothelial adaptation to mechanical stimuli is associated with angiogenic activation through various growth factors. We studied the potential angiogenic shift evoked by TAVR. MethodsFrom a cohort of 69 consecutive patients undergoing TAVR, we excluded patients with conditions known to affect angiogenic factors, and serum vascular endothelial growth factor (VEGF) and angiopoietin (Ang)-1 and Ang-2 were assessed by ELISA. We assessed in vitro the properties of endothelial cells after exposure to serum collected from patients undergoing TAVR using adhesion, migration, and Matrigel angiogenesis assays. The correlation between changes in angiogenic factors and cardiac functions was evaluated on 30- day echocardiograms. ResultsThe study population consisted of 46 patients (82 ± 5 years). Two days after TAVR the post/pre TAVR ratio of VEGF, Ang-1, and Ang-2 was 5.38 ± 4 (P < 0.001), 1.05 ± 0.49 (P = 0.27), and 4.65 ± 2.01 (P < 0.001), respectively. The increase in VEGF and Ang-2 showed a significant correlation (r = 0.609; P < 0.001), but no correlation was found with hemolysis or tissue injury markers. Patients with relatively low levels of VEGF or an Ang-2 rise had more severe aortic stenosis and coronary disease at baseline. Exposure of endothelial cells to post-TAVR serum induced adhesion, migration, and tube formation compared with pre-TAVR serum. An increase in VEGF levels correlated with improvement in pulmonary systolic pressure and a right ventricular fractional area change at 30 days, (r = 0.54 and r = 0.48, respectively; P < 0.01). ConclusionsSustained elevation of VEGF and Ang-2 levels occur after TAVR, reflecting a systemic angiogenic shift. A rise in VEGF levels is associated with a decrease in pulmonary blood pressure in patients undergoing TAVR.

Inflammatory Profiling of Patients Undergoing Lumbar Interbody Fusion by Different Approaches: In Search for Markers of Mini-invasiveness

Introduction Minimally-invasive surgeries have become routinely adopted due to reduced tissue trauma and damage. In spine surgery, and particularly lumbar interbody fusion (LIF) procedures, several minimal invasive approaches are available.1–3 Although these approaches are thought to be less traumatic, and thus less pro-inflammatory, currently there are no scientific evidences about it.4 Creatin kinase (CK), C-reactive protein (CRP), interleukin (IL)-6 and IL-10, have been proposed as molecular discriminants between mini-invasive and conventional procedures.5 The aim of this work was to investigate how different approaches in LIF differed in inflammatory profiles over the immediate peri-surgical period. Material and Methods Seventy consecutive patients affected by degenerative discopathy were prospectively enrolled. To better characterize the approach-dependent effects, very strict inclusion (single-level discopathy L3-to-S1, healthy status) and exclusion criteria (chronic pathologies, or recent illnesses) were applied. Seventeen patients underwent to anterior LIF (ALIF), 20 to transforaminal posterior LIF (TLIF), and 26 to far-lateral LIF (XLIF). Patients were sampled, by standard venipuncture, 24h pre-surgery (T0), and 24h (T1) and 72h (T2) post-surgery. Blood was collected into serum and plasma (Becton Dickinson &amp; Co., Franklin Lakes, NJ, USA) tubes. Serum and plasma, obtained by centrifugation (1200 g, 10 minute, 4°C), were stored at -80°C until assayed for a panel of 37 molecules involved in inflammation (including cytokines, soluble cytokine receptors and metalloproteinases) were tested by a fluorescent bead-based multiplex system (Bio-Plex®, Bio-Rad Laboratories, Inc., Hercules, CA, USA). One-way ANOVA was used to study within-group time-dependent changes (repeated measures) and between-groups changes, at each time points (Prism v6, GraphPad Software, La Jolla, CA, USA). Significance was set at p &lt; 0.05. Results At baseline no differences were found in any of the subgroup, indicating homogeneity in pre-surgical conditions. In general, the inflammatory responses to ALIF and TLIF were comparable being characterized by an increase from T0 to T1 and a decrease from T1 to T2. Instead, in XLIF we found a stabilization, or even an increase, from T1 to T2. Interestingly, in all the procedure IL-10, IL-26, osteocalcin, osteopontin, pentraxin, and sTNFR-1 showed a linear increase, although delayed in XLIF. By comparing the amplitude of changes between the time-points, both ALIF and TLIF induced significantly much more sCD163, MMP-2, MMP-3, compared with XLIF. XLIF, instead, was more effective in inducing sCD30, IFN-α2, IFN-γ, IL-2, sIL-6R, sIL-6Rβ, IL-8, IL-10, IL-12p40, MMP-1, osteopontin, sTNFR-1, and sTNFR-2. Conclusion Our preliminary results indicate that: i) ALIF and TLIF are comparable in terms of inflammatory profile; ii) the amplitude of changes induced by surgery is greater in XLIF for the majority of the tested molecules; iii) XLIF is more effective in inducing anti-inflammatory mediators. Additional work is evaluating the relationship between the changes observed in these parameters and those recorded in analytes routinely measured in these settings (martial status, muscular enzymes). To have a panel of markers predicting the response of the patients to different surgical approaches could give the surgeon a valuable additional tool in deciding the optimal approach. References Foley KT, Holly LT, Schwender JD. Minimally invasive lumbar fusion. Spine 2003; 28(15, Suppl)S26–S35 Berjano P, Damilano M, Lamartina C. Sagittal alignment correction and reconstruction of lumbar post-traumatic kyphosis via MIS lateral approach. Eur Spine J 2012;21(12):2718–2720 Berjano P, Balsano M, Buric J, Petruzzi M, Lamartina C. Direct lateral access lumbar and thoracolumbar fusion: preliminary results. Eur Spine J 2012;21(1, Suppl 1):S37–S42 Lombardi G, Grasso D, Berjano P, Banfi G, Lamartina C. Is minimally invasive spine surgery also pro-inflammatory? Muscular markers, inflammatory parameters and cytokines to quantify the operative invasiveness assessment in spine fusion. Eur J Inflam 2014;2:237–249 Kim KT, Lee SH, Suk KS, Bae SC. The quantitative analysis of tissue injury markers after mini-open lumbar fusion. Spine 2006;31(6):712–716

Original Research: Diametric effects of hypoxia on pathophysiology of sickle cell disease in a murine model.

Hypoxia causes erythrocyte sickling invitro; however, its role in the pathophysiology of sickle cell disease is poorly understood. We report that hypoxia rapidly decreased oxygen saturation in transgenic sickle cell disease mice, but this effect was immediately buffered by a robust ventilatory response. The initial hypoxemia improved steadily throughout the duration of hypoxia without any detectable acute pulmonary adverse effect. Furthermore, the mice suffered acute anemia that ironically was associated with lowering of both plasma hemoglobin and heme. These results were corroborated by increased plasma haptoglobin and hemopexin levels. Markers of ischemic tissue injury increased spatiotemporally following repeated hypoxia exposures. This variation was supported by organ-specific induction of hypoxia-responsive genes. Our results show that hypoxia exerts diametric effects on sickle cell disease by promoting ischemic injury while enhancing the expression of hemolysis scavenger molecules. This phenomenon may help to understand the disparate clinical syndromes associated with hemolysis and vaso-occlusion in sickle cell disease.

Beneficial Immune Effects of Myeloid-Related Proteins in Kidney Transplant Rejection.

Acute rejection is a risk factor for inferior long-term kidney transplant survival. Although T cell immunity is considered the main effector in clinical acute rejection, the role of myeloid cells is less clear. Expression of S100 calcium-binding protein A8 (S100A8) and S100A9 was evaluated in 303 biopsies before and after transplantation from 190 patients. In two independent cohorts of patients with acute rejection (n = 98 and n = 11; mostly cellular rejections), high expression of S100 calcium-binding protein A8 (S100A8) and A9 (S100A9) was related to improved graft outcome. Mechanisms of action of the S100 molecules were investigated. In the graft and peripheral blood cells, S100A8 and S100A9 expression correlated with myeloid-derived suppressor markers. In line with this finding, recombinant S100A8 and S100A9 proteins inhibited maturation and the allogeneic T cell stimulatory capacity of dendritic cells. S100A9 enhanced the production of reactive oxygen species by macrophages, which suppressed T cell activity at low concentrations in the form of hydrogen peroxide. Intragraft S100A8 and S100A9 expression linked to reduced expression of T cell immunity and tissue injury markers and higher expression of immune regulatory molecules. This study sheds new light on the importance of myeloid cell subsets in directing the outcome of T cell-mediated acute rejection.

Burn encephalopathy and syndrome of hypermetabolism-hypercatabolism: is there an interrelation?

Aim : To define an influence of hypermetabolism-hypercatabolism syndrome on the burn encephalopathy development on the base of study of metabolic changes on the background of an acute period of burn disease. Materials and methods : there were examined 104 patients separated in 2 groups depending on heaviness of injury. There were defined the levels of cortisol, neurospecific enolase (NSE), glucose and blood protein. There were assessed memory, thinking and psychological state of patients. Results : At admission to hospital the cortisol level in patients of 1 and 2 groups was 270,5±29,2 ng/ml and 330,3±17,4 ng/ml, glucose level - 6,0±0,4 mmol/l and 7,7±0,5 mmol/l in 1 and 2 groups respectively. The protein level of blood maximally decreased at 3 day and was 53,6±1,1 g/l in patients of the 1 group and 48,9±1,1 g/l in patients of the 2 group. An increase of cortisol level depended on heaviness of thermal trauma. There was defined correlation between the levels of cortisol and neuron specific enolase in patients of the 1 group at 3 day (R=0.638, p=0.006), in patients of the 2 group at 7 day (R=0.488, p=0.002). In patients of the 1 group sleep disorder and delirium development did not depended on the level of metabolic changes. At the 7 day there was defined correlative connection between cortisol level and memory (R=-0,681, p=0,071) and thinking (R=-0,520, p=0,038). In patients of the 2 group cortisol level at 1 day determined the memory and thinking disorders to the septic-toxemia stage. Sleep disorder correlated with expressed hypoproteinomia at 3 day (R=-0,483, p=0,001). The delirium development was caused with an increase of blood serum cortisol at 1 day after thermal trauma (R=0,467, p=0,058). Conclusion : The one of mechanisms of nerve tissue injury was the development of metabolic changes caused by stress on the background of heavy thermal trauma. The dynamics of cortisol level to the burn shock stage corresponded with the changes of neurospecific enolase level of blood serum as a marker of the nerve tissue injury

Inhibition of fatty acid synthase with C75 decreases organ injury after hemorrhagic shock

Hemorrhagic shock is the primary cause of morbidity and mortality in the intensive care units in patients under the age of 35. Several organs, including the lungs, are seriously affected by hemorrhagic shock and inadequate resuscitation. Excess free fatty acids have shown to trigger inflammation in various disease conditions. C75 is a small compound that inhibits fatty acid synthase, a key enzyme in the control of fatty acid metabolism that also stimulates fatty acid oxidation. We hypothesized that C75 treatment would be protective against hemorrhagic shock. Adult male Sprague-Dawley rats were cannulated with a femoral artery catheter and subjected to controlled bleeding. Blood was shed to maintain a mean arterial pressure of 30mm Hg for 90minutes, then resuscitated over 30minutes with a crystalloid volume equal to twice the volume of shed blood. Fifteen minutes into the 30-minute resuscitation, the rats received either intravenous infusion of C75 (1mg/kg body weight) or vehicle (20% dimethyl sulfoxide). Blood and tissue samples were collected 6hours after resuscitation (ie, 7.5hours after hemorrhage) for analysis. After hemorrhage and resuscitation, C75 treatment decreased the increase in serum free fatty acids by 48%, restored adenosine triphosphate levels, and stimulated carnitine palmitoyl transferase-1 activity. Administration of C75 decreased serum levels of markers of injury (aspartate aminotransferase, lactate, and lactate dehydrogenase) by 38%, 32%, and 78%, respectively. Serum creatinine and blood urea nitrogen were also decreased significantly by 38% and 40%, respectively. These changes correlated with decreases in neutrophil infiltration in the lung, evidenced by decreases in Gr-1-stained cells and myeloperoxidase activity and improved lung histology. Finally, administration of C75 decreased pulmonary mRNA levels of cyclooxygenase-2 and interleukin-6 by 87% and 65%, respectively. Administration of C75 after hemorrhage and resuscitation decreased the increase in serum free fatty acids, decreased markers of tissue injury, downregulated the expression of inflammatory mediators, and decreased neutrophil infiltration and lung injury. Thus, the dual action of inhibiting fatty acid synthesis and stimulating fatty acid oxidation by C75 could be developed as a promising adjuvant therapy strategy to protect against hemorrhagic shock.