Search

Sustained and dysregulated inflammation, concurrent tumor-induced immune suppression, and oxidative stress are profoundly involved in cancer initiation, presentation, and perpetuation. Within this prospective study, we simultaneously analyzed the preoperative indices of systemic inflammatory response and the representative byproducts of oxidative DNA, protein, and lipid damage with the aim of evaluating their clinical relevance among patients diagnosed with testicular germ-cell tumors (GCT). In the analytical cohort (n = 88, median age 34 years), neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and C-reactive protein (CRP) were significantly altered in patients with a higher tumor stage (p < 0.05). Highly suggestive correlations were found between NLR, dNLR, and SII and modified nucleoside 8-OHdG. CRP and albumin-to-globulin ratio (AGR) significantly correlated with thiols group level and maximal tumor dimension (p < 0.05). Based on receiver operating characteristic (ROC) curve analyses, all the evaluated pre-orchiectomy inflammation markers demonstrated strong performance in predicting metastatic disease; optimal cut-off points were determined for each indicator. Although further large-scale studies are warranted, inflammatory and redox indices may both complement the established tumor markers and standard clinicopathological prognostic variables and contribute to enhanced personalized risk-assessment among testicular GCT patients.

Sustained and dysregulated inflammation, concurrent tumor-induced immune suppression, and oxidative stress are profoundly involved in cancer initiation, presentation, and perpetuation. Within this prospective study, we simultaneously analyzed the preoperative indices of systemic inflammatory response and the representative byproducts of oxidative DNA, protein, and lipid damage with the aim of evaluating their clinical relevance among patients diagnosed with testicular germ-cell tumors (GCT). In the analytical cohort (n = 88, median age 34 years), neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and C-reactive protein (CRP) were significantly altered in patients with a higher tumor stage (p < 0.05). Highly suggestive correlations were found between NLR, dNLR, and SII and modified nucleoside 8-OHdG. CRP and albumin-to-globulin ratio (AGR) significantly correlated with thiols group level and maximal tumor dimension (p < 0.05). Based on receiver operating characteristic (ROC) curve analyses, all the evaluated pre-orchiectomy inflammation markers demonstrated strong performance in predicting metastatic disease; optimal cut-off points were determined for each indicator. Although further large-scale studies are warranted, inflammatory and redox indices may both complement the established tumor markers and standard clinicopathological prognostic variables and contribute to enhanced personalized risk-assessment among testicular GCT patients.

Currently, a lot of attention of scientists all over the world is paid to the perioperative management strategy, taking into account the volume of surgical intervention, the presence of comorbidities and their possible complications. This makes it possible to reduce mortality, decrease the number of adverse events in the intra- and postoperative period, effectively cope with pain, advance recovery and rehabilitation, and also increase patients’ satisfaction with the quality of medical care. We studied indices of 58 adult patients who underwent septoplasty. Patients were divided into 2 groups. In group “D”, dexmedetomidine was infused, which began 10 minutes before the induction of anesthesia at a dose of 0.7 μg/kg/h and ended 10 minutes before the end of the surgical intervention. The clinical blood test (hemoglobin level, erythrocytes, leukocytes, rods count), body temperature of patients, coagulogram (INR, fibrinogen level, Dyuk bleeding time) were studied. When comparing the indicators of clinical analysis in the postoperative period in the control group leukocytosis and stab left shift (p <0.001) was observed. For patients undergoing dexmedetomidine infusion, leukocyte and bacillus levels were normal. In both postoperative follow-up groups, low-grade fever was detected (p <0.001). In the control group, 12 hours after surgery, body temperature rose to febrile values. During the operative intervention, the “D” group was characterized by the better indices of blood coagulation. In the group "K" on the second day of the postoperative period, there was a slight increase in coagulation. The level of intraoperative blood loss in the “D” group was significantly lower than in the control group (p<0.001). In the “D” group in the postoperative period, the minimum decrease in hemoglobin was determined in contrast to the control group (p<0.001). The use of dexmedetomidine infusion leads to a decrease in the manifestations of a systemic inflammatory response in su

Introduction: Anastomotic leakage is one of the most severe early complications after colorectal surgery, and it is associated with a high reoperation rate-, and increased in short-term morbidity and mortality rates. It remains unclear whether anastomotic leakage is associated with poor oncologic outcomes. The aim of this study was to determine the impacts of anastomotic leakage on long-term oncologic outcomes, disease-free survival and overall mortality in patients who underwent curative surgery for colorectal cancer.Methods: This single-centre, retrospective, observational cohort study included patients who underwent curative surgery for colorectal cancer between 2005 and 2015 and who had a primary anastomosis. Survival- and multivariate cox regression analyses were performed to adjust for confounding.Results: A total of 1984 patients had a primary anastomosis after surgery. The overall incidence of anastomotic leakage was 7.5%; 19 patients were excluded because they were lost to follow-up. Of the remaining 1965 patients, 41 (2.1%) developed local recurrence associated with anastomotic leakage [adjusted hazard ratio (HR) = 2.25; 95% confidence interval (CI) 1.14-5.29; P = 0.03]. Distant recurrence developed in 291(14.8%) patients with no association with anastomotic leakage [adjusted HR = 1.30 (95% CI: 0.85-1.97) P = 0.23]. Anastomotic leakage was associated with increased long-term mortality [adjusted HR = 1.69 (95% CI 1.32-2.18) P <0.01]. Five year disease-free survival was significantly decreased in patients with anastomotic leakage, (log rank test P <0.01).Conclusion: Anastomotic leakage was significantly associated with increased rates of local recurrence, disease free-survival and overall mortality. Associations of anastomotic leakage with distant recurrence was not found.

Introduction: Anastomotic leakage is one of the most severe early complications after colorectal surgery, and it is associated with a high reoperation rate-, and increased in short-term morbidity and mortality rates. It remains unclear whether anastomotic leakage is associated with poor oncologic outcomes. The aim of this study was to determine the impacts of anastomotic leakage on long-term oncologic outcomes, disease-free survival and overall mortality in patients who underwent curative surgery for colorectal cancer.Methods: This single-centre, retrospective, observational cohort study included patients who underwent curative surgery for colorectal cancer between 2005 and 2015 and who had a primary anastomosis. Survival- and multivariate cox regression analyses were performed to adjust for confounding.Results: A total of 1984 patients had a primary anastomosis after surgery. The overall incidence of anastomotic leakage was 7.5%; 19 patients were excluded because they were lost to follow-up. Of the remaining 1965 patients, 41 (2.1%) developed local recurrence associated with anastomotic leakage [adjusted hazard ratio (HR) = 2.25; 95% confidence interval (CI) 1.14-5.29; P = 0.03]. Distant recurrence developed in 291(14.8%) patients with no association with anastomotic leakage [adjusted HR = 1.30 (95% CI: 0.85-1.97) P = 0.23]. Anastomotic leakage was associated with increased long-term mortality [adjusted HR = 1.69 (95% CI 1.32-2.18) P <0.01]. Five year disease-free survival was significantly decreased in patients with anastomotic leakage, (log rank test P <0.01).Conclusion: Anastomotic leakage was significantly associated with increased rates of local recurrence, disease free-survival and overall mortality. Associations of anastomotic leakage with distant recurrence was not found.

BACKGROUND AND OBJECTIVES: Systemic inflammation has been associated with poor survival in several tumor types, but has been less extensively studied in resectable metastatic disease. The aim of the present study was to evaluate the prognostic role of CRP in colorectal cancer patients with liver metastases (CRLM) compared to conventional tumor- and patient-related clinicopathological features as well as other indicators of the systemic inflammatory response (SIR). METHODS: A multinational retrospective study of 492 CRLM patients undergoing potentially curative resection of liver metastases between 1999 and 2009. Clinicopathological findings and the SIR markers CRP, hypoalbuminemia, and their combined Glasgow Prognostic Score (GPS) were analyzed. RESULTS: Multivariate analysis showed that preoperative CRP >10 mg/L was a strong predictor of compromised survival (HR = 1.72, 95%CI 1.84-2.50, P < 0.01). Patients with CRP ≤10 mg/L had a median survival of 4.27 years compared to only 47 days in patients with CRP ≥30 mg/L (P < 0.01). Similarly, increased GPS was independently predictive of poor survival (HR 1.67, 95%CI 1.22-2.27, P < 0.01), but hypoalbuminemia alone did not have significant prognostic value. CONCLUSIONS: CRP alone is a strong prognostic factor, following curative resection of colorectal liver metastases and should be taken into consideration when selecting treatment strategies in CRLM patients.

Background: An intense systemic inflammatory response is observed following reperfusion after cardiac arrest. Heparin-binding protein (HBP) is a granule protein released by neutrophils that intervenes in endothelial permeability regulation. In the present study, we investigated plasma levels of HBP in a large population of patients resuscitated from out-of-hospital cardiac arrest. We hypothesized that high circulating levels of HBP are associated with severity of post-cardiac arrest syndrome and poor outcome. Methods: Plasma was obtained from 278 patients enrolled in a prospective multicenter observational study in 21 intensive care units (ICU) in Finland. HBP was assayed at ICU admission and 48 h later. Multiple organ dysfunction syndrome (MODS) was defined as the 24 h Sequential Organ Failure Assessment (SOFA) score >= 12. ICU death and 12-month Cerebral Performance Category (CPC) were evaluated. Multiple linear and logistic regression tests and receiver operating characteristic curves with area under the curve (AUC) were performed. Results: Eighty-two percent of patients (229 of 278) survived to ICU discharge and 48 % (133 of 276) to 1 year with a favorable neurological outcome (CPC 1 or 2). At ICU admission, median plasma levels of HBP were markedly elevated, 15.4 [9.6-31.3] ng/mL, and persisted high 48 h later, 14.8 [9.8-31.1] ng/mL. Admission levels of HBP were higher in patients who had higher 24 h SOFA and cardiovascular SOFA score (p <0.0001) and in those who developed MODS compared to those who did not (29.3 [13.7-60.1] ng/mL vs. 13.6 [9.1-26.2] ng/mL, p <0.0001; AUC = 0.70 +/- 0.04, p = 0.0001). Admission levels of HBP were also higher in patients who died in ICU (31.0 [17.7-78.2] ng/mL) compared to those who survived (13.5 [9.1-25.5] ng/mL, p <0.0001) and in those with an unfavorable 12-month neurological outcome compared to those with a favorable one (18.9 [11.3-44.3] ng/mL vs. 12.8 [8.6-30.4] ng/mL, p <0.0001). Admission levels of HBP predicted early I

An intestinal obstruction refers to blockage of intestinal, is a potentially serious condition in which the intestines are blocked. The blockage may be either partial (incomplete) or totally occluded (complete) without vascular compromise. In strangulated intestinal obstruction there is compromised vascular flow associated with necrosis and / or gangrene., Una obstrucción intestinal se refiere al bloqueo intestinal, es una afección potencialmente grave en la que los intestinos están bloqueados. El bloqueo puede ser parcial (incompleto) o totalmente ocluido (completo) sin compromiso vascular. En la obstrucción intestinal estrangulada existe un flujo vascular comprometido asociado con necrosis y / o gangrena.

OBJECTIVE AND DESIGN: A prospective, randomised, double-blinded, clinical trial was performed at a level 1 trauma centre to determine if a prostacyclin analogue, epoprostenol (Flolan®), could attenuate systemic inflammatory response in patients with severe traumatic brain injury (TBI). SUBJECTS: 46 patients with severe TBI, randomised to epoprostenol (n = 23) or placebo (n = 23). TREATMENT: Epoprostenol, 0.5 ng · kg(-1) · min(-1), or placebo (saline) was given intravenously for 72 hours and then tapered off over the next 24 hours. METHODS: Interleukin-6 (IL-6), interleukin-8 (IL-8), soluble intracellular adhesion molecule-1 (sICAM-1), C-reactive protein (CRP), and asymmetric dimethylarginine (ADMA) levels were measured over five days. Measurements were made at 24 h intervals ≤24 h after TBI to 97-120 h after TBI. RESULTS: A significantly lower CRP level was detected in the epoprostenol group compared to the placebo group within 73-96 h (p = 0.04) and within 97-120 h (p = 0.008) after trauma. IL-6 within 73-96 h after TBI was significantly lower in the epoprostenol group compared to the placebo group (p = 0.04). ADMA was significantly increased within 49-72 h and remained elevated, but there was no effect of epoprostenol on ADMA levels. No significant differences between the epoprostenol and placebo groups were detected for IL-8 or sICAM-1. CONCLUSIONS: Administration of the prostacyclin analogue epoprostenol significantly decreased CRP and, to some extent, IL-6 levels in patients with severe TBI compared to placebo. These findings indicate an interesting option for treatment of TBI and warrants future larger studies. TRIAL REGISTRATION: ClinicalTrials.gov Identifier, NCT01363583.

OBJECTIVE AND DESIGN: A prospective, randomised, double-blinded, clinical trial was performed at a level 1 trauma centre to determine if a prostacyclin analogue, epoprostenol (Flolan®), could attenuate systemic inflammatory response in patients with severe traumatic brain injury (TBI). SUBJECTS: 46 patients with severe TBI, randomised to epoprostenol (n = 23) or placebo (n = 23). TREATMENT: Epoprostenol, 0.5 ng · kg(-1) · min(-1), or placebo (saline) was given intravenously for 72 hours and then tapered off over the next 24 hours. METHODS: Interleukin-6 (IL-6), interleukin-8 (IL-8), soluble intracellular adhesion molecule-1 (sICAM-1), C-reactive protein (CRP), and asymmetric dimethylarginine (ADMA) levels were measured over five days. Measurements were made at 24 h intervals ≤24 h after TBI to 97-120 h after TBI. RESULTS: A significantly lower CRP level was detected in the epoprostenol group compared to the placebo group within 73-96 h (p = 0.04) and within 97-120 h (p = 0.008) after trauma. IL-6 within 73-96 h after TBI was significantly lower in the epoprostenol group compared to the placebo group (p = 0.04). ADMA was significantly increased within 49-72 h and remained elevated, but there was no effect of epoprostenol on ADMA levels. No significant differences between the epoprostenol and placebo groups were detected for IL-8 or sICAM-1. CONCLUSIONS: Administration of the prostacyclin analogue epoprostenol significantly decreased CRP and, to some extent, IL-6 levels in patients with severe TBI compared to placebo. These findings indicate an interesting option for treatment of TBI and warrants future larger studies. TRIAL REGISTRATION: ClinicalTrials.gov Identifier, NCT01363583.

OBJECTIVE AND DESIGN: A prospective, randomised, double-blinded, clinical trial was performed at a level 1 trauma centre to determine if a prostacyclin analogue, epoprostenol (Flolan®), could attenuate systemic inflammatory response in patients with severe traumatic brain injury (TBI). SUBJECTS: 46 patients with severe TBI, randomised to epoprostenol (n = 23) or placebo (n = 23). TREATMENT: Epoprostenol, 0.5 ng · kg(-1) · min(-1), or placebo (saline) was given intravenously for 72 hours and then tapered off over the next 24 hours. METHODS: Interleukin-6 (IL-6), interleukin-8 (IL-8), soluble intracellular adhesion molecule-1 (sICAM-1), C-reactive protein (CRP), and asymmetric dimethylarginine (ADMA) levels were measured over five days. Measurements were made at 24 h intervals ≤24 h after TBI to 97-120 h after TBI. RESULTS: A significantly lower CRP level was detected in the epoprostenol group compared to the placebo group within 73-96 h (p = 0.04) and within 97-120 h (p = 0.008) after trauma. IL-6 within 73-96 h after TBI was significantly lower in the epoprostenol group compared to the placebo group (p = 0.04). ADMA was significantly increased within 49-72 h and remained elevated, but there was no effect of epoprostenol on ADMA levels. No significant differences between the epoprostenol and placebo groups were detected for IL-8 or sICAM-1. CONCLUSIONS: Administration of the prostacyclin analogue epoprostenol significantly decreased CRP and, to some extent, IL-6 levels in patients with severe TBI compared to placebo. These findings indicate an interesting option for treatment of TBI and warrants future larger studies. TRIAL REGISTRATION: ClinicalTrials.gov Identifier, NCT01363583.

В данной статье представлены результаты исследования биохимических показателей системного воспалительного ответа у новорожденных, перенесших тяжелую асфиксию при рождении. Обследовано 34 новорожденных, у которых определялись показатели воспаления: интерлейкин-6, интерлейкин-1β, интерлейкин-4, фактор некроза опухоли α и уровень средних молекул. Исследование позволило установить, что течение системного воспалительного ответа у выздоровевших новорожденных обусловлено активацией противовоспалительного цитокина интерлейкина-4, что, возможно, предотвратило прогрессирование системного воспалительного ответа и развитие эндогенной интоксикации. Течение системного воспалительного ответа у больных с летальным исходом характеризуется активацией как противовоспалительных, так и провоспалительных цитокинов с параллельным развитием эндогенной интоксикации и резким угнетением синтеза цитокинов на фоне прогрессирования эндогенной интоксикации на 7-е сутки жизни., У даній статті наведені результати дослідження біохімічних показників системної запальної відповіді в новонароджених, які перенесли тяжку асфіксію при народженні. Обстежено 34 новонароджених, в яких визначались показники запалення: інтерлейкін-6, інтерлейкін-1β, інтерлейкін-4, фактор некрозу пухлини α та рівень середніх молекул. Дослідження дозволило встановити, що перебіг системної запальної відповіді в новонароджених, які одужали, зумовлений активацією протизапального цитокіну інтерлейкіну-4, що, можливо, запобігло прогресуванню системної запальної відповіді та розвитку ендогенної інтоксикації. Перебіг системної запальної відповіді у хворих з летальним кінцем характеризується активацією як протизапальних, так і прозапальних цитокінів із паралельним розвитком ендогенної інтоксикації та різким пригніченням синтезу цитокінів на тлі прогресування ендогенної інтоксикації на 7-му добу життя., This article presents the results of a study of biochemical indicators of systemic inflammatory response in infants after severe birth asphyxia. In a group of 34 newborns there were determined the indicators of inflammation: interleukin-6, interleukin-1β, interleukin-4, tumor necrosis factor α and the level of weighted average molecules. The study revealed that the course of systemic inflammatory response in recovered infants was caused by the activation of anti-inflammatory cytokine interleukin-4, which may have prevented the progression of systemic inflammatory response and the development of endogenous intoxication. The course of systemic inflammatory response in died neonates was characterized by activation of anti-inflammatory as well as pro-inflammatory cytokines with the simultaneous development of endogenous intoxication and abrupt inhibition of cytokine synthesis against the progression of endogenous intoxication on the 7th day of life.

Producción Científica, Evaluation of host immune response to infection at the molecular level is a promising avenue to obtain diagnostic and prognostic tools for the clinical management of patients with sepsis. A recent report from Cajander and colleagues [1] has shown the potential of HLA-DR mRNA quantification by real-time PCR as a biomarker of immunosuppression in these patients. IgM is the first immunoglobulin produced in response to infection. In a pilot study, we have employed a next generation quantitative PCR method (nanoliter-sized droplet technology paired with digital PCR (ddPCR)) for detecting the early transcriptomic response of IgM in blood from patients with sepsis. Approval for the study protocol for both scientific and ethical aspects was obtained from the Committee for Clinical Research of Hospital Clínico Universitario, Valladolid, Spain. Written informed consent was obtained directly from each patient or a legal surrogate. The target gene transcript was IGHM, which encodes the constant region of the mu heavy chain, which defines the IgM isotype [2]. In blood, the cells producing IgM transcripts are B lymphocytes expressing CD20 [3], which was employed as housekeeping gene., Instituto de Salud Carlos III (grant PI13/02110)

Producción Científica, Evaluation of host immune response to infection at the molecular level is a promising avenue to obtain diagnostic and prognostic tools for the clinical management of patients with sepsis. A recent report from Cajander and colleagues [1] has shown the potential of HLA-DR mRNA quantification by real-time PCR as a biomarker of immunosuppression in these patients. IgM is the first immunoglobulin produced in response to infection. In a pilot study, we have employed a next generation quantitative PCR method (nanoliter-sized droplet technology paired with digital PCR (ddPCR)) for detecting the early transcriptomic response of IgM in blood from patients with sepsis. Approval for the study protocol for both scientific and ethical aspects was obtained from the Committee for Clinical Research of Hospital Clínico Universitario, Valladolid, Spain. Written informed consent was obtained directly from each patient or a legal surrogate. The target gene transcript was IGHM, which encodes the constant region of the mu heavy chain, which defines the IgM isotype [2]. In blood, the cells producing IgM transcripts are B lymphocytes expressing CD20 [3], which was employed as housekeeping gene., Instituto de Salud Carlos III (grant PI13/02110)

Producción Científica, Evaluation of host immune response to infection at the molecular level is a promising avenue to obtain diagnostic and prognostic tools for the clinical management of patients with sepsis. A recent report from Cajander and colleagues [1] has shown the potential of HLA-DR mRNA quantification by real-time PCR as a biomarker of immunosuppression in these patients. IgM is the first immunoglobulin produced in response to infection. In a pilot study, we have employed a next generation quantitative PCR method (nanoliter-sized droplet technology paired with digital PCR (ddPCR)) for detecting the early transcriptomic response of IgM in blood from patients with sepsis. Approval for the study protocol for both scientific and ethical aspects was obtained from the Committee for Clinical Research of Hospital Clínico Universitario, Valladolid, Spain. Written informed consent was obtained directly from each patient or a legal surrogate. The target gene transcript was IGHM, which encodes the constant region of the mu heavy chain, which defines the IgM isotype [2]. In blood, the cells producing IgM transcripts are B lymphocytes expressing CD20 [3], which was employed as housekeeping gene., Instituto de Salud Carlos III (grant PI13/02110)

OBJECTIVE AND DESIGN: A prospective, randomised, double-blinded, clinical trial was performed at a level 1 trauma centre to determine if a prostacyclin analogue, epoprostenol (Flolan®), could attenuate systemic inflammatory response in patients with severe traumatic brain injury (TBI). SUBJECTS: 46 patients with severe TBI, randomised to epoprostenol (n = 23) or placebo (n = 23). TREATMENT: Epoprostenol, 0.5 ng · kg(-1) · min(-1), or placebo (saline) was given intravenously for 72 hours and then tapered off over the next 24 hours. METHODS: Interleukin-6 (IL-6), interleukin-8 (IL-8), soluble intracellular adhesion molecule-1 (sICAM-1), C-reactive protein (CRP), and asymmetric dimethylarginine (ADMA) levels were measured over five days. Measurements were made at 24 h intervals ≤24 h after TBI to 97-120 h after TBI. RESULTS: A significantly lower CRP level was detected in the epoprostenol group compared to the placebo group within 73-96 h (p = 0.04) and within 97-120 h (p = 0.008) after trauma. IL-6 within 73-96 h after TBI was significantly lower in the epoprostenol group compared to the placebo group (p = 0.04). ADMA was significantly increased within 49-72 h and remained elevated, but there was no effect of epoprostenol on ADMA levels. No significant differences between the epoprostenol and placebo groups were detected for IL-8 or sICAM-1. CONCLUSIONS: Administration of the prostacyclin analogue epoprostenol significantly decreased CRP and, to some extent, IL-6 levels in patients with severe TBI compared to placebo. These findings indicate an interesting option for treatment of TBI and warrants future larger studies. TRIAL REGISTRATION: ClinicalTrials.gov Identifier, NCT01363583.

OBJECTIVE AND DESIGN: A prospective, randomised, double-blinded, clinical trial was performed at a level 1 trauma centre to determine if a prostacyclin analogue, epoprostenol (Flolan®), could attenuate systemic inflammatory response in patients with severe traumatic brain injury (TBI). SUBJECTS: 46 patients with severe TBI, randomised to epoprostenol (n = 23) or placebo (n = 23). TREATMENT: Epoprostenol, 0.5 ng · kg(-1) · min(-1), or placebo (saline) was given intravenously for 72 hours and then tapered off over the next 24 hours. METHODS: Interleukin-6 (IL-6), interleukin-8 (IL-8), soluble intracellular adhesion molecule-1 (sICAM-1), C-reactive protein (CRP), and asymmetric dimethylarginine (ADMA) levels were measured over five days. Measurements were made at 24 h intervals ≤24 h after TBI to 97-120 h after TBI. RESULTS: A significantly lower CRP level was detected in the epoprostenol group compared to the placebo group within 73-96 h (p = 0.04) and within 97-120 h (p = 0.008) after trauma. IL-6 within 73-96 h after TBI was significantly lower in the epoprostenol group compared to the placebo group (p = 0.04). ADMA was significantly increased within 49-72 h and remained elevated, but there was no effect of epoprostenol on ADMA levels. No significant differences between the epoprostenol and placebo groups were detected for IL-8 or sICAM-1. CONCLUSIONS: Administration of the prostacyclin analogue epoprostenol significantly decreased CRP and, to some extent, IL-6 levels in patients with severe TBI compared to placebo. These findings indicate an interesting option for treatment of TBI and warrants future larger studies. TRIAL REGISTRATION: ClinicalTrials.gov Identifier, NCT01363583.

Heat stroke (HS) is a life-threatening illness induced by prolonged exposure to a hot environment that causes central nervous system abnormalities and severe hyperthermia. Current data suggest that the pathophysiological responses to heat stroke may not only be due to the immediate effects of heat exposure per se but also the result of a systemic inflammatory response syndrome (SIRS). The observation that pro- (e.g., IL-1) and anti-inflammatory (e.g., IL-10) cytokines are elevated concomitantly during recovery suggests a complex network of interactions involved in the manifestation of heat-induced SIRS. In this study, we measured a set of circulating cytokine/soluble cytokine receptor proteins and liver cytokine and receptor mRNA accumulation in wild-type and tumor necrosis factor (TNF) receptor knockout mice to assess the effect of neutralization of TNF signaling on the SIRS following HS. Using a systems approach, we developed a computational model describing dynamic changes (intra- and extracellular events) in the cytokine signaling pathways in response to HS that was fitted to novel genomic (liver mRNA accumulation) and proteomic (circulating cytokines and receptors) data using global optimization. The model allows integration of relevant biological knowledge and formulation of new hypotheses regarding the molecular mechanisms behind the complex etiology of HS that may serve as future therapeutic targets. Moreover, using our unique modeling framework, we explored cytokine signaling pathways with three in silico experiments (e.g. by simulating different heat insult scenarios and responses in cytokine knockout strains in silico)., Published in PLOS ONE, v8 n9 article ID e73393, 5 Sep 2013. Prepared in cooperation with the Institute for Collaborative Biotechnologies and the Department of Chemical Engineering, University of California Santa Barbara.

Neutrophils serve as an intriguing model for the study of innate immune cellular activity induced by physiological stress. We measured changes in the transcriptome of circulating neutrophils following an experimental exercise trial (EXTRI) consisting of 1 h of intense cycling immediately followed by 1 h of intense running. Blood samples were taken at baseline, 3 h, 48 h, and 96 h post-EXTRI from eight healthy, endurance-trained, male subjects. RNA was extracted from isolated neutrophils. Differential gene expression was evaluated using Illumina microarrays and validated with quantitative PCR. Gene set enrichment analysis identified enriched molecular signatures chosen from the Molecular Signatures Database. Blood concentrations of muscle damage indexes, neutrophils, interleukin (IL)-6 and IL-10 were increased (P < 0.05) 3 h post-EXTRI. Upregulated groups of functionally related genes 3 h post-EXTRI included gene sets associated with the recognition of tissue damage, the IL-1 receptor, and Toll-like receptor (TLR) pathways (familywise error rate, P value < 0.05). The core enrichment for these pathways included TLRs, low-affinity immunoglobulin receptors, S100 calcium binding protein A12, and negative regulators of innate immunity, e.g., IL-1 receptor antagonist, and IL-1 receptor associated kinase-3. Plasma myoglobin changes correlated with neutrophil TLR4 gene expression (r = 0.74; P < 0.05). Neutrophils had returned to their nonactivated state 48 h post-EXTRI, indicating that their initial proinflammatory response was transient and rapidly counterregulated. This study provides novel insight into the signaling mechanisms underlying the neutrophil responses to endurance exercise, suggesting that their transcriptional activity was particularly induced by damage-associated molecule patterns, hypothetically originating from the leakage of muscle components into the circulation.

Cardiac surgery with cardiopulmonary bypass (CPB) results in hemodilution, systemic inflammatory response, activation of coagulation and fibrinolysis, and microembolisation, which may all contribute to postoperative organ dysfunction. As an attempt to attenuate these side effects, the use of minimized cardiopulmonary bypass (MCPB) systems has increased. Compared to conventional CPB (CCPB), they are characterized with reduced artificial surface area and blood-air interface. The goal of these alterations has been to reduce systemic inflammation, preserve coagulation function and minimize the need for blood tranfusions. This study was aimed at determining whether or not MCPB attenuates the adverse effects of CPB. In study I, the safety, feasibility and effect on transfusion requirements of MCPB was investigated in unselected coronary artery bypass surgery (CABG) patients. In studies II and III, the incidence of retinal microembolism after CABG and aortic valve replacement (AVR) surgery with MCPB was compared to that of CCPB by means of fluorescein angiography. Furthermore, in studies II and III, the effect of MCPB on systemic inflammation, coagulation, endothelial activation and injury, as well as on platelet activity, was compared to those of CCPB. In study IV, the effect of MCPB on intestinal mucosal damage following CPB was compared to CCPB in a porcine model of prolonged CPB. MCPB appeared as safe and feasible as CCPB in unselected CABG patients (Study I). MCPB was associated with decreased retinal microembolism compared to CCPB in CABG patients (Study II). Conversely, the difference in retinal microembolism in AVR patients was not statistically significant (Study III). MCPB was associated with a decrease in neutrophil activation in CABG and AVR patients as compared to CCPB. However, there were no differences in coagulation, endothelial activation and injury, or in platelet activity (Studies II, III). There were no differences in markers of intestinal muco, Tiivistelmä Sydänkeuhkokoneen käyttö aiheuttaa elimistössä hemodiluution, yleistyneen tulehdusvasteen ja hyytymisjärjestelmän aktivoitumisen sekä mikroembolisaatiota. Ilmiöt ovat yleensä lieviä ja ohimeneviä, mutta voivat johtaa elintoimintahäiriöihin ja pitkittyneeseen toipumiseen sydänleikkauksen jälkeen. Haittojen lievittämiseksi sydänkeuhkokonetta on pyritty kehittämään fysiologisemmaksi. Miniperfuusiolaitteistoissa kiertävän veren kontakti pintamateriaalien ja ilman kanssa jää pienemmäksi ja veren laimenemista tapahtuu vähemmän. Tutkimuksen tavoitteena oli selvittää voidaanko miniperfuusiolla lievittää sydänkeuhkokoneen haittoja. Ensimmäisessä osatyössä selvitettiin miniperfuusion käyttökelpoisuutta ja vaikutusta verensiirtotarpeeseen ohitusleikkauspotilailla valikoimattomassa aineistossa. Toisessa ja kolmannessa osatyössä selvitettiin silmänpohjan mikroembolioiden ilmaantuvuutta miniperfuusion ja perinteisen sydänkeuhkokoneen käytön jälkeen ohitusleikkauspotilailla ja aorttaläppäleikkauspotilailla. Toisessa ja kolmannessa osatyössä selvitettiin lisäksi miniperfuusion vaikutuksia yleistyneen tulehdusvasteen voimakkuuteen, hyytymisjärjestelmään sekä endoteelin aktivaatioon perinteiseen sydänkeuhkokoneeseen verrattuna. Neljännessä osatyössä verrattiin kokeellisessa mallissa miniperfuusion ja perinteisen sydänkeuhkokoneen vaikutuksia suoliston limakalvon eheyteen. Miniperfuusio ilmeni yhtä käyttökelpoiseksi kuin perinteinen sydänkeuhkokone ohitusleikkauspotilaiden hoidossa. Ohitusleikkauspotilailla ilmeni vähemmän silmänpohjan mikroembolioita miniperfuusion jälkeen, mutta aorttaläppäleikkauspotilailla ero ei ollut tilastollisesti merkitsevä. Miniperfuusion käyttöön liittyi vähemmän neutrofiilien aktivaatiota. Tekniikoiden välillä ei ilmennyt eroa hyytymisjärjestelmän eikä endoteelin aktivaatiota osoittavissa merkkiaineissa. Sydänkeuhkokoneen käyttö aiheutti saman tasoisen suoliston limakalvon vaurion miniperfuusiolla ja perinteisellä sydänkeuhkokoneella. Tutkimuks

Ultra-endurance exercise, such as an Ironman triathlon, induces muscle damage and a systemic inflammatory response. As the resolution of recovery in these parameters is poorly documented, we investigated indices of muscle damage and systemic inflammation in response to an Ironman triathlon and monitored these parameters 19 days into recovery. Blood was sampled from 42 well-trained male triathletes 2 days before, immediately after, and 1, 5 and 19 days after an Ironman triathlon. Blood samples were analyzed for hematological profile, and plasma values of myeloperoxidase (MPO), polymorphonuclear (PMN) elastase, cortisol, testosterone, creatine kinase (CK) activity, myoglobin, interleukin (IL)-6, IL-10 and high-sensitive C-reactive protein (hs-CRP). Immediately post-race there were significant (P < 0.001) increases in total leukocyte counts, MPO, PMN elastase, cortisol, CK activity, myoglobin, IL-6, IL-10 and hs-CRP, while testosterone significantly (P < 0.001) decreased compared to prerace. With the exception of cortisol, which decreased below prerace values (P < 0.001), these alterations persisted 1 day post-race (P < 0.001; P < 0.01 for IL-10). Five days post-race CK activity, myoglobin, IL-6 and hs-CRP had decreased, but were still significantly (P < 0.001) elevated. Nineteen days post-race most parameters had returned to prerace values, except for MPO and PMN elastase, which had both significantly (P < 0.001) decreased below prerace concentrations, and myoglobin and hs-CRP, which were slightly, but significantly higher than prerace. Furthermore, significant relationships between leukocyte dynamics, cortisol, markers of muscle damage, cytokines and hs-CRP after the Ironman triathlon were noted. This study indicates that the pronounced initial systemic inflammatory response induced by an Ironman triathlon declines rapidly. However, a low-grade systemic inflammation persisted until at least 5 days post-race, possibly reflecting incomplete muscle recovery.

Both a systemic inflammatory response as well as DNA damage has been observed following exhaustive endurance exercise. Hypothetically, exercise-induced DNA damage might either be a consequence of inflammatory processes or causally involved in inflammation and immunological alterations after strenuous prolonged exercise (e.g. by inducing lymphocyte apoptosis and lymphocytopenia). Nevertheless, up to now only few studies have addressed this issue and there is hardly any evidence regarding a direct relationship between DNA or chromosomal damage and inflammatory responses in the context of exercise. The most conclusive picture that emerges from available data is that reactive oxygen and nitrogen species (RONS) appear to be the key effectors which link inflammation with DNA damage. Considering the time-courses of inflammatory and oxidative stress responses on the one hand and DNA effects on the other the lack of correlations between these responses might also be explained by too short observation periods. This review summarizes and discusses the recent findings on this topic. Furthermore, data from our own study are presented that aimed to verify potential associations between several endpoints of genome stability and inflammatory, immune-endocrine and muscle damage parameters in competitors of an Ironman triathlon until 19 days into recovery. The current results indicate that DNA effects in lymphocytes are not responsible for exercise-induced inflammatory responses. Furthermore, this investigation shows that inflammatory processes, vice versa, do not promote DNA damage, neither directly nor via an increased formation of RONS derived from inflammatory cells. Oxidative DNA damage might have been counteracted by training- and exercise-induced antioxidant responses. However, further studies are needed that combine advanced -omics based techniques (transcriptomics, proteomics) with state-of-the-art biochemical biomarkers to gain more insights into the underlying mechanisms.

Cardiac surgery with cardiopulmonary bypass induces the activation of systemic inflammatory response syndrome (SIRS) and results in at least some degree of global myocardial ischemia. Although these responses are usually short-lived, they may lead to serious complications and organ system failures. The present study evaluated the effects of high-dose glucose-insulin (1IU/kg/h) treatment (GIK) administered with the hyperinsulinemic normoglycemic clamp technique and a leukocyte-depleting filter on markers of systemic inflammatory response and myocardial ischemia-reperfusion injury in certain cardiac surgical risk groups. The study involved four prospective randomized controlled clinical trials and 119 patients. Cardioprotective effects were measured as myocardial enzyme release, recovery of contractile function and incidence of arrhythmias in all studies. The hemodynamic and metabolic effects of high-dose glucose-insulin treatment were evaluated in patients admitted for combined aortic valve (AS) and coronary surgery (40) and for urgent coronary surgery (39), and the latter study also involved proinflammatory cytokine and C-reactive protein analyses. The impacts of leukocyte filter on the expression of neutrophil adhesion molecules along with proinflammatory cytokines were evaluated in patients admitted for combined aortic valve (AS) and coronary surgery (20) and for solitary coronary surgery (20). The high-dose glucose-insulin treatment was associated with better preserved myocardial contractile function and less need for inotropic support after combined aortic valve and coronary surgery (I) and attenuation of postoperative CRP release after urgent coronary surgery (II). No effects on postoperative myocardial enzyme release (I, II) or on proinflammatory cytokine responses (II) were detected. The number of hypoglycemic events was low. The use of a leukocyte filter throughout the cardiopulmonary bypass period increased the neutrophil adhesion molecule CD11b ex

Целью работы явилось изучение возможности использования полифенольных продуктов переработки винограда (ПППВ) для лечения и реабилитации метаболического синдрома и его кардиоваскулярных осложнений. Применялись экспериментальные, клинические, биохимические, инструментальные методы. ПППВ вызвали достоверные положительные изменения в системе ПОЛ, воспалительных маркеров, а также в функционировании органов и систем. Таким образом, ПППВ, как продукты сельскохозяйственного производства, могут быть использованы для лечения и реабилитации больных с метаболическим синдромом и его осложнениями., The aim of this work was to study the possibility of using polyphenol-products of grapes processing (PPGP) for the treatment and rehabilitation of metabolic syndrome and its cardiovascular complications. Experimental, clinical, biochemical, instrumental methods were applied. PPGP caused significant positive changes in the PLO, inflammatory markers, as well as in the functioning of organs and systems. Thus, PPGP as products of agricultural production can be used for the treatment and rehabilitation of patients with metabolic syndrome and its complications.