Inflammatory Response Biomarkers Research Articles

A study of IL-6, IL-8, and TNF-α as inflammatory markers in COPD patients

To assess the diagnostic value of interleukin 6 (IL-6), IL-8 and tumor necrosis factor-α (TNF-α) as inflammatory markers in chronic obstructive pulmonary disease (COPD) patients. IL-6, IL-8 and TNF-α levels were measured by ELISA in the serum and the bronchoalveolar lavage (BAL) in 10 control participants and 25 mild and moderate COPD patients, whereas 25 patients with severe COPD were studied for the serum level of these inflammatory biomarkers. The mean value and SD of BAL and serum IL-6, IL-8 and TNF-α levels were significantly higher in COPD patients when compared with control participants; the serum level of these biomarkers were also significantly higher in severe compared with mild and moderate COPD patients. Increased srum and/or BAL IL-6, IL-8 and TNF-α can be used as biomarkers of the systemic inflammatory response in COPD patients, and their levels are correlated with the severity of COPD. Egypt J Broncho 2014 8:91–99

Pentraxin 3 as a biomarker of local inflammatory response to vascular injury in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disorder with organ injury related to vasculitis. Inflammation of blood vessels results from auto-immunological activation of endothelial cells. The pentraxin 3 (PTX3), might act as an indicator of vasculitides in many diseases. The aim of this study was to determine whether PTX3 might be useful as a marker of vascular injury in SLE. This study was carried out in a group of 56 SLE women, and in the 28 female volunteers control group. All participants’ plasma and serum samples were collected to estimate concentrations (ELISA) of PTX3, soluble thrombomodulin, soluble E-selectin (sE-selectin), soluble P-selectin (sP-selectin), soluble form of vascular cell adhesion molecule 1 (sVCAM-1), soluble inter-cellular adhesion molecule-1 (sICAM-1), soluble platelet endothelial cell adhesion molecule 1, monocyte chemotactic protein-1 (MCP-1) and von Willebrand factor (vWF) activity. Anthropometric, demographic and lifestyle characteristics of SLE patients were also performed. The SLE patients had higher PTX3, vWF, MCP-1, sE-selectin and sVCAM-1 levels than the controls (1.82 ± 1.56 ng/mL, 237 ± 101%, 70.05 ± 18.31 ng/mL, 111.16 ± 49.15 ng/mL and 978.78 ± 462.35 ng/mL vs. 0.86 ± 0.40 ng/mL, 138 ± 43%, 58.56 ± 13.91 ng/mL, 66.04 ± 27.18 ng/mL and 499.07 ± 125.67 ng/mL, respectively). The independent factors affecting PTX3 expression included Systemic Lupus Erythematosus Disease Activity Index, prednisone dose and anemia severity. Moreover, the PTX3 areas under the curve–receiver operating characteristics curves 0.717 ± 0.056 with cut-off level of 1.96 ng/mL was comparable to vWF, MCP-1, sE-selectin, sP-selectin and sICAM-1. PTX3 and sVCAM-1 were the only factors related to SLE activity. Other vascular injury indicators associated with PTX3 were vWF and sVCAM-1. In conclusion, PTX3 concentrations in SLE patients might serve as a indicator of the activation/dysfunction of vascular endothelium.

Could Pentraxin 3 Be a New Diagnostic Marker for Excessive Inflammatory Response in Cardiac Surgery?

The aim of this study was to compare the dynamics of two inflammatory response biomarkers pentraxin 3 (PTX3) and C-reactive protein (CRP) after cardiac surgery with particular regard to different postoperative clinical manifestation of inflammatory response. In this study, 42 patients undergoing open heart surgery with the use of cardiopulmonary bypass were included and divided in two groups according to the extent of clinical manifestation of inflammatory response: Group A (n=21)-patients with different severity of systemic inflammatory response syndrome (SIRS) and Group B (n=21)-patients with uneventful postoperative period (no SIRS). The serum levels of PTX3 and CRP were evaluated and compared at the following time points: before and at the end of surgery, 6 hours, 1st, 3rd, and 7th day after surgery. The dynamics of CRP levels were comparable between both groups and showed the classical characteristics after cardiac surgery with a peak on the 3rd postoperative day (113 vs. 132 mg/L). In contrast, the dynamics of PTX3 showed an earlier increase of serum levels with the peak on the 1st postoperative day in both groups (36.3 vs. 42.7 ng/mL). Importantly, a significant difference of PTX3 levels was found on the 3rd postoperative day (31.1 vs. 7.0 ng/mL; p<0.006) between the two groups showing significantly delayed decrease of PTX3 levels in patients with SIRS (Group A). This study demonstrates considerably different dynamics of PTX3 levels after cardiac surgery in patients with SIRS and patients without SIRS, thus it may be indicative to start the appropriate therapy.

Dexmedetomidine reduces intestinal and hepatic injury after hepatectomy with inflow occlusion under general anaesthesia: a randomized controlled trial

We compared intestinal, hepatic, and other organ function after hepatic portal occlusion with or without dexmedetomidine administration under general anaesthesia. In this prospective, randomized double-blind investigation, 44 patients undergoing elective hepatectomy with inflow occlusion were randomized into a dexmedetomidine group or a control group. The dexmedetomidine group received an initial dexmedetomidine loading dose of 1 μg kg(-1) over 10 min followed by a maintenance dose of 0.3 μg kg(-1) h(-1). In the control group, 0.9% sodium chloride was administered. The primary outcome was serum diamine oxidase (DAO) activity reflecting intestinal injury. The secondary outcomes included variables reflecting intestinal, hepatic, kidney, and cardiopulmonary function, and biomarkers of oxidative stress and systemic inflammatory response. DAO activity was lower in the dexmedetomidine group than in the control group at 6 and 24 h after liver reperfusion [9.77 (1.07) vs14.29 (1.43) units ml(-1), P=0.021; 9.67 (0.98) vs 13.97 (1.31) units ml(-1), P=0.017]. d-lactate acid levels were lower during 1-72 h after liver reperfusion compared with the control group (all P<0.05). Also, the intestinal injury severity grade was decreased by dexmedetomidine (P=0.038). The biomarkers reflecting liver injury increased over time, but were lower in the dexmedetomidine group (all P<0.05), while the variables reflecting cardiopulmonary and renal function showed no differences between the groups (all P>0.05). Dexmedetomidine administered perioperatively attenuates intestinal and hepatic injury in patients undergoing elective liver resection with inflow occlusion without any potential risk. ChiCTR-TRC-11001530, September 2011.

Salivary biomarkers of bacterial burden, inflammatory response, and tissue destruction in periodontitis

Chronic periodontitis has an episodic and multifactorial character, with fluctuations in bacterial burden, inflammatory response, and tissue destruction. We investigated the association of selected salivary biomarkers with periodontal parameters and validated the use of a novel salivary diagnostic approach, the cumulative risk score (CRS), in detection of periodontitis in subjects with angiographically verified coronary artery disease diagnosis. The concentrations of matrix metalloproteinase (MMP)-8, interleukin (IL)-1β, and Porphyromonas gingivalis were analysed from saliva of 493 subjects. The subjects participated in a detailed clinical and radiographic oral examination. The CRS index, combining the three salivary biomarkers, was calculated for each subject. High salivary concentrations of MMP-8, IL-1β, and P. gingivalis were associated with deepened periodontal pockets and alveolar bone loss, and MMP-8 and IL-1β with bleeding on probing. The CRS index had a stronger association with moderate to severe periodontitis (OR 6.13; 95% CI 3.11-12.09) than any of the markers alone. Salivary concentrations of MMP-8, IL-1β, and P. gingivalis are associated with various clinical and radiographic measures of periodontitis. The CRS index, combining the three salivary biomarkers, is associated with periodontitis more strongly than any of the markers alone regardless of the coronary artery disease status of the patients.

Cytokine Levels (IL-4, IL-6, IL-8 and TGFβ) as Potential Biomarkers of Systemic Inflammatory Response in Trauma Patients

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.

Changes in breath carbon isotope composition as a potential biomarker of inflammatory acute phase response in mechanically ventilated pediatric patients

Sepsis is a leading cause of mortality in intensive care units.

Associations between Maternal and Infant Morbidities and sRAGE within the First Week of Life in Extremely Preterm Infants

BackgroundSoluble RAGE (sRAGE) has been associated with multiple inflammatory responses including maternal chorioamnionitis and preeclampsia. Analysis of umbilical cord blood levels have also indicated that sRAGE levels in the infant are affected by maternal inflammation. S100b is a ligand for RAGE and increases in circulating S100b levels are associated with poor neurological outcome in preterm infants. The objective of this study was to determine whether sRAGE or s100b levels in plasma samples from extremely preterm infants at the end of the first week of life were correlated with infant morbidities and whether sRAGE and s100b levels at this time point were still associated with maternal inflammation. MethodsPlasma samples were collected from 130 preterm infants (≤28 weeks) at days of life 5, 6, or 7. sRAGE and s100b levels were measured by ELISA and data were analyzed by Pearson’s correlation or Generalized Estimating Equations. ResultssRAGE was negatively correlated with development of sepsis (p=0.024), the FiO2 requirement of the infant at the time of sampling (p=0.030), as well as maternal preeclampsia (p=0.046), and positively correlated with maternal chorioamnionitis (p=0.006). s100b levels were positively associated with maternal chorioamnionitis (p=0.039). No correlations were observed with other infant morbidities. ConclusionThese data indicate that sRAGE could potentially be a biomarker of early severe inflammatory responses in the preterm infant. However, more studies are needed to confirm the present findings.

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Anti-TWEAK Monoclonal Antibody in Patients With Rheumatoid Arthritis

Persistent upregulation of signaling by cytokine tumor necrosis factor-like weak inducer of apoptosis (TWEAK) through its receptor fibroblast growth factor-inducible molecule-14 (Fn14) promotes chronic inflammation and tissue destruction. The aim of this study was to explore the safety and tolerability of the TWEAK-blocking monoclonal antibody BIIB023 and determine its pharmacokinetics and effects on TWEAK pathway pharmacodynamic markers in rheumatoid arthritis (RA). Phase I, first-in-human, 2-part, multicenter, double-blind, dose-escalation study. Patients were randomized to a single dose of BIIB023 (0.03-20 mg/kg) (n = 38) or placebo (n = 15) as an add-on to methotrexate. Three open-label cohorts of RA patients taking background disease-modifying antirheumatic drugs and stable tumor necrosis factor (TNF) inhibitor therapy (n = 12) received a single-dose of BIIB023 of 2, 10, or 20 mg/kg and were assessed over 70 days. The incidence of treatment-emergent adverse events for the BIIB023 monotherapy cohorts and open-label cohorts of BIIB023 as add-on therapy to TNF inhibitors compared with placebo were 47% and 50% versus 33%, respectively. Serum exposure to BIIB023 increased in a dose-dependent manner from 0.03 to 20 mg/kg, but not in direct proportion to dose level. After administration, the time course of BIIB023 serum concentration was multiphasic and showed expedited elimination when levels decreased to < 10 µg/mL. Serum-soluble TWEAK levels were suppressed at all dose levels by 6 hours post-dose and recovered to baseline between days 7 and 28. A trend toward downward modulation of serum biomarkers of inflammatory response was suggested in monocyte chemoattractant protein 1, inducible protein 10, macrophage inflammatory protein 1β, and tissue inhibitor of metalloproteinase 1 in the BIIB023 group versus placebo. Single-dose BIIB023 showed a favorable safety and tolerability profile in RA. Suppression of serum-soluble TWEAK for ≤ 28 days was observed and downward trends in serum biomarkers suggested.

Role of adiponectin and other inflammatory biomarkers in COPD patients

BackgroundAdiponectin (APN) is a secretory protein synthesized by adipocytes and plays a potential role in regulating the inflammatory response by many of autocrine or paracrine. The mechanism of APN participation in the inflammation of COPD remains unknown. So, we investigated serum and induced sputum adiponectin as a biomarker of systemic inflammatory response and to find its relation with other inflammatory biomarkers like, IL-8, IL-6 and TNF-α. The aim of the work was also to find out its role in the pathogenesis of cachexia in COPD patients. Patients and methodsThe study included 80 subjects including 60 COPD patients (20 stable and 40 exacerbated) and 20 age and sex-matched healthy control subjects. The adiponectin, interleukin-8, interleukin-6 and tumor necrosis factor-alpha levels were measured in serum, induced sputum by enzyme-linked immunosorbent assay. Serum CRP level was measured using the nephelometric method. Body mass index (BMI) was estimated for COPD patients and its relation to the inflammatory biomarkers was studied. ResultsAdiponectin levels in COPD patients were significantly higher than those in control subjects (P<0.001). CRP, APN, IL-8, IL-6, TNF-α were significantly higher in the exacerbated COPD patients compared to the stable group (P<0.001, P<0.001, P<0.001, P<0.001 and P<0.001, respectively). The ratio of APN level in serum to induced sputum was (3.1) in AECOPD patients and (2.4) in stable COPD patients while for IL-8, IL-6 & TNF-α the ratios were all <(1). ConclusionAdiponectin could play a role as a biomarker of systemic inflammatory response in COPD patients. Also, its rise in the exacerbation period denotes that this may also be a biomarker of the exacerbation phase. While IL-8, IL-6, TNF-α could be used to reflect the airway inflammation in induced sputum. Adiponectin serum level is higher in underweight COPD patients which may reflect its role in the pathogenesis of cachexia in COPD patients.

Acute inflammatory response to transgastric natural orifice transluminal endoscopic surgery peritoneoscopy: An experimental study in swine

OBJECTIVE:To investigate the impact of transgastric peritoneal access on plasma biomarkers of acute inflammatory response in comparison to laparoscopy.METHODS:This was a prospective and comparative study in a porcine model. Transgastric peritoneal access performed by natural orifice transluminal endoscopic surgery was compared with laparoscopy. Laparotomy and sham groups were used as positive and negative controls, respectively. Thirty-four pigs were assigned to receive transgastric natural orifice transluminal endoscopic surgery (n = 12), laparoscopy (n = 8), laparotomy (n = 8) or a sham procedure involving only anesthesia (n = 6). In the natural orifice transluminal endoscopic surgery group, peritoneoscopy was performed with a gastroscope via transgastric access. Blood samples were collected at baseline and 1, 3, 6, 9 and 24 h after the surgical procedure for measurement of interleukins 1β, 6 and 10 and tumor necrosis factor-α. A complete blood count was performed, and C-reactive protein levels were measured at baseline and at 24 h.RESULTS:All surgical and endoscopic procedures were performed without major complications. Peritoneal cavity inventory showed no signs of peritonitis in any animal. Interleukin 1β, interleukin 10 and tumor necrosis factor-α levels were below the threshold of detection. The mean level of interleukin 6 was statistically significantly higher in the laparotomy group than in the other groups (p<0.05), with no significant differences among the sham, laparoscopy and natural orifice transluminal endoscopic surgery groups (p>0.05). C-reactive protein analysis indicated significant increases in all groups, with no differences among the groups. Complete blood count analysis showed no differences among the groups.CONCLUSIONS:Based on the observed interleukin 6 patterns, the systemic inflammatory response resulting from transgastric peritoneal access by natural orifice transluminal endoscopic surgery is similar in intensity to the response that occurs after laparoscopy.

Anacardic Acids from Cashew Nuts Ameliorate Lung Damage Induced byExposureto Diesel Exhaust Particles in Mice

Anacardic acids from cashew nut shell liquid, a Brazilian natural substance, have antimicrobial and antioxidant activities and modulate immune responses and angiogenesis. As inflammatory lung diseases have been correlated to environmental pollutants exposure and no reports addressing the effects of dietary supplementation with anacardic acids on lung inflammation in vivo have been evidenced, we investigated the effects of supplementation with anacardic acids in a model of diesel exhaust particle- (DEP-) induced lung inflammation. BALB/c mice received an intranasal instillation of 50 μg of DEP for 20 days. Ten days prior to DEP instillation, animals were pretreated orally with 50, 150, or 250 mg/kg of anacardic acids or vehicle (100 μL of cashew nut oil) for 30 days. The biomarkers of inflammatory and antioxidant responses in the alveolar parenchyma, bronchoalveolar lavage fluid (BALF), and pulmonary vessels were investigated. All doses of anacardic acids ameliorated antioxidant enzyme activities and decreased vascular adhesion molecule in vessels. Animals that received 50 mg/kg of anacardic acids showed decreased levels of neutrophils and tumor necrosis factor in the lungs and BALF, respectively. In summary, we demonstrated that AAs supplementation has a potential protective role on oxidative and inflammatory mechanisms in the lungs.

Elevated immunoreactivity of RANTES and CCR1 correlate with the severity of stages and dysmenorrhea in women with deep infiltrating endometriosis

Deep infiltrating endometriosis (DIE) is typically characterized by multifocal locations. It has been shown that CCR1, combined highly with RANTES, contributes to the enhanced recruitment of inflammatory cells at endometriotic sites. As an estrogen-dependent disorder, estrogen receptors are also crucial to the growth of endometriotic tissues. In this study we report the immunohistochemical analysis of RANTES, CCR1, ER-α and ER-β in 48 histological lesions prepared from women with DIE undergoing surgery. Immunohistochemical analysis of RANTES, CCR1, ER-α and ER-β was conducted at different sites of DIE lesions. RANTES was immunolocalized in the cytoplasm and CCR1 in cytomembranes of endometriotic cells. ER-α and ER-β extensively immunostained the nuclei of endometrial glandular, and stromal cells. Immunoreactivity in DIE lesions, similar to the widespread ERs, showed higher expression of RANTES and CCR1 in three types of DIE lesions. There was a significant correlation, independent of cyclic changes, between the expression of RANTES/CCR1 and DIE lesions. RANTES/CCR1 increased significantly according to the severity of dysmenorrhea. RANTES and CCR1 together may provide a potential biomarker for DIE-related pain and inflammatory response in endometriotic lesions of patients with DIE.

Evidence of oxidative damage and inflammation associated with low glutathione redox status in the autism brain

Despite increasing evidence of oxidative stress in the pathophysiology of autism, most studies have not evaluated biomarkers within specific brain regions, and the functional consequences of oxidative stress remain relatively understudied. We examined frozen samples from the cerebellum and temporal cortex (Brodmann area 22 (BA22)) from individuals with autism and unaffected controls (n=15 and n=12 per group, respectively). Biomarkers of oxidative stress, including reduced glutathione (GSH), oxidized glutathione (GSSG) and glutathione redox/antioxidant capacity (GSH/GSSG), were measured. Biomarkers of oxidative protein damage (3-nitrotyrosine; 3-NT) and oxidative DNA damage (8-oxo-deoxyguanosine; 8-oxo-dG) were also assessed. Functional indicators of oxidative stress included relative levels of 3-chlorotyrosine (3-CT), an established biomarker of a chronic inflammatory response, and aconitase activity, a biomarker of mitochondrial superoxide production. Consistent with previous studies on plasma and immune cells, GSH and GSH/GSSG were significantly decreased in both autism cerebellum (P<0.01) and BA22 (P<0.01). There was a significant increase in 3-NT in the autism cerebellum and BA22 (P<0.01). Similarly, 8-oxo-dG was significantly increased in autism cerebellum and BA22 (P<0.01 and P=0.01, respectively), and was inversely correlated with GSH/GSSG in the cerebellum (P<0.01). There was a significant increase in 3-CT levels in both brain regions (P<0.01), whereas aconitase activity was significantly decreased in autism cerebellum (P<0.01), and was negatively correlated with GSH/GSSG (P=0.01). Together, these results indicate that decreased GSH/GSSG redox/antioxidant capacity and increased oxidative stress in the autism brain may have functional consequence in terms of a chronic inflammatory response, increased mitochondrial superoxide production, and oxidative protein and DNA damage.

Changes in circulating biomarkers during a single hemodialysis session

The hemodialysis (HD) procedure induces an inflammatory response potentially contributing to cardiovascular disease. Here we investigated the acute impact of HD on circulating biomarkers. Circulating biomarkers (small solutes, middle molecular-sized peptides, and proteins) related to inflammation, oxidative stress, and vascular calcification (VC) were measured before and after a single session of HD in 45 clinically stable patients. Concentrations were corrected for ultrafiltration-induced hemoconcentration. Among vascular calcification-related biomarkers, osteoprotegerin and fetuin-A remained unchanged while fibroblast growth factor-23 (FGF23) decreased by -19%. Changes of FGF23 and changes of phosphate correlated (ρ = 0.61, P < 0.001). While C-reactive protein did not change, interleukin-6 (IL-6) increased by 14% and pentraxin 3 (PTX3) increased by 45%. IL-6 and PTX3 appear to be valid biomarkers of the intradialytic inflammatory response. VC-related markers were in general not affected by the single HD session; however, the observed correlation between acute changes of FGF-23 and phosphate during HD warrants further studies.

Association of Progranulin and High Sensitivity CRP Concentrations in Gingival Crevicular Fluid and Serum in Chronic Periodontitis Subjects with and without Obesity

Background: Obesity is considered as a strong risk factor of inflammatory periodontal tissue destruction. The purpose of this study is to determine presence of progranulin (PGRN) and high sensitivity C reactive protein (hs CRP) levels in serum and gingival crevicular fluid (GCF) in obese subjects with chronic periodontitis and to find an association, if any.Material and methods: 40 subjects (20 males and 20 females) were selected based on their clinical parameters into four groups (10 subjects in each group): group 1 (healthy non obese), group 2 (healthy obese), group 3 (non obese with chronic periodontitis) and group 4 (obese with chronic periodontitis). Serum and GCF PGRN levels were estimated by enzyme linked immunosorbant assay (ELISA) and hs CRP levels were estimated by immunoturbidimetry method.Results: The mean PGRN and hs CRP concentration both in serum and GCF were highest for group 4 followed by group 3, group 2 and least in Group 1.Conclusion: PGRN and hs CRP may be novel biomarkers of the chronic inflammatory response in obesity and chronic periodontitis.

Association of progranulin and high sensitivity CRP concentrations in gingival crevicular fluid and serum in chronic periodontitis subjects with and without obesity.

Background: Obesity is considered as a strong risk factor of inflammatory periodontal tissue destruction. The purpose of this study is to determine presence of progranulin (PGRN) and high sensitivity C reactive protein (hs CRP) levels in serum and gingival crevicular fluid (GCF) in obese subjects with chronic periodontitis and to find an association, if any. Material and methods: 40 subjects (20 males and 20 females) were selected based on their clinical parameters into four groups (10 subjects in each group): group 1 (healthy non obese), group 2 (healthy obese), group 3 (non obese with chronic periodontitis) and group 4 (obese with chronic periodontitis). Serum and GCF PGRN levels were estimated by enzyme linked immunosorbant assay (ELISA) and hs CRP levels were estimated by immunoturbidimetry method. Results: The mean PGRN and hs CRP concentration both in serum and GCF were highest for group 4 followed by group 3, group 2 and least in Group 1. Conclusion: PGRN and hs CRP may be novel biomarkers of the chronic inflammatory response in obesity and chronic periodontitis.

Protective effect of a novel peptide against methylmercury-induced toxicity in rat primary astrocytes

Methylmercury (MeHg) is an environmental neurotoxicant associated with aberrant central nervous system (CNS) functions. In this study, we examined the protective effect of a novel anti-inflammatory and cytoprotective nonapeptide, termed IIIM1, against MeHg-induced toxicity in cultured rat neonatal primary astrocytes. Astrocytes were pretreated for 66h with 5μg/ml IIIM1 (4.95μM) followed by 6h exposure to MeHg (5μM). MeHg significantly increased F2-isoprostane generation, a lipid peroxidation biomarker of oxidative injury and this effect was significantly reduced upon pre-treatment with IIIM1. The MeHg-induced increase in levels of prostaglandin E2 (PGE2), biomarkers of inflammatory responses, was also decreased in the peptide-treated cells. Mass spectrometry analysis revealed no chemical or binding interaction between MeHg and IIIM1, indicating that intracellular cytoprotective mechanism of action accounts for the neuroprotection rather than direct intracellular neutralization of the neurotoxicant with the peptide. These findings point to therapeutic potential for IIIM1 in a plethora of conditions associated with reactive oxygen species (ROS) generation. The implication of these findings may prove beneficial in designing new treatment modalities that efficiently suppress neurotoxicity, triggered not only by MeHg, but also by other metals and environmental agents, as well as chronic disease conditions that inherently increase reactive radical production and inflammatory signaling.

MP-10.16 Cystatin-C, Interleukin-18 and N-GAL Levels as Biomarkers of Inflammatory Response After Extracorporeal Shock Wave Lithotripsy

MP-10.16 Cystatin-C, Interleukin-18 and N-GAL Levels as Biomarkers of Inflammatory Response After Extracorporeal Shock Wave Lithotripsy

The ACTN3 genotype in soccer players in response to acute eccentric training

Genetic factors can interfere with sporting performance. The identification of genetic predisposition of soccer players brings important information to trainers and coaches for individual training loads adjustment. Different responses to eccentric training could be observed by the genotype referred to as α-actinin-3 (ACTN3) in biomarkers of muscle damage, hormones and inflammatory responses. The aim of this study was to compare acute inflammatory responses, muscle damage and hormonal variations according to the eccentric training in soccer professional athletes with different genetic profiles of ACTN3 (XX, RX and RR). 37 soccer professional athletes (9 XX, 13 RX, 15 RR) were randomly divided into five stations associated to eccentric muscle contraction and plyometrics. Blood samples were taken from athletes pre-eccentric training, immediately after (post), 2- and 4-h post-eccentric training to determine hormone responses (cortisol and testosterone), muscle damage (CK and α-actin), and inflammatory responses (IL-6). After eccentric training, athletes XX presented higher levels for CK (4-h post), α-actin (post and 2-h post) and cortisol (post) compared to RR and RX athletes. However, RR and RX athletes presented higher levels of testosterone (post) and IL-6 (2h post and 4h post) compared to athletes XX. The main conclusion of this study is that professional soccer athletes homozygous to ACTN3XX gene are more susceptible to eccentric damage and present a higher catabolic state, demonstrated by metabolic, hormonal and immune responses post an eccentric training, in comparison to ACTN3RR and ACTN3RX groups.