Alterations of the arginine metabolome in asthma.

PubMed

Lara, Abigail; Khatri, Sumita B; Wang, Zeneng; Comhair, Suzy A A; Xu, Weiling; Dweik, Raed A; Bodine, Melanie; Levison, Bruce S; Hammel, Jeffrey; Bleecker, Eugene; Busse, William; Calhoun, William J; Castro, Mario; Chung, Kian Fan; Curran-Everett, Douglas; Gaston, Benjamin; Israel, Elliot; Jarjour, Nizar; Moore, Wendy; Peters, Stephen P; Teague, W Gerald; Wenzel, Sally; Hazen, Stanley L; Erzurum, Serpil C

2008-10-01

As the sole nitrogen donor in nitric oxide (NO) synthesis and key intermediate in the urea cycle, arginine and its metabolic pathways are integrally linked to cellular respiration, metabolism, and inflammation. We hypothesized that arginine (Arg) bioavailability would be associated with airflow abnormalities and inflammation in subjects with asthma, and would be informative for asthma severity. Arg bioavailability was assessed in subjects with severe and nonsevere asthma and healthy control subjects by determination of plasma Arg relative to its metabolic products, ornithine and citrulline, and relative to methylarginine inhibitors of NO synthases, and by serum arginase activity. Inflammatory parameters, including fraction of exhaled NO (Fe(NO)), IgE, skin test positivity to allergens, bronchoalveolar lavage, and blood eosinophils, were also evaluated. Subjects with asthma had greater Arg bioavailability, but also increased Arg catabolism compared with healthy control subjects, as evidenced by higher levels of Fe(NO) and serum arginase activity. However, Arg bioavailability was positively associated with Fe(NO) only in healthy control subjects; Arg bioavailability was unrelated to Fe(NO) or other inflammatory parameters in severe or nonsevere asthma. Inflammatory parameters were related to airflow obstruction and reactivity in nonsevere asthma, but not in severe asthma. Conversely, Arg bioavailability was related to airflow obstruction in severe asthma, but not in nonsevere asthma. Modeling confirmed that measures of Arg bioavailabilty predict airflow obstruction only in severe asthma. Unlike Fe(NO), Arg bioavailability is not a surrogate measure of inflammation; however, Arg bioavailability is strongly associated with airflow abnormalities in severe asthma.

Serum inflammatory markers in the elderly: are they useful in differentiating sepsis from SIRS?

PubMed

Talebi-Taher, Mahshid; Babazadeh, Shahin; Barati, Mitra; Latifnia, Maryam

2014-01-01

Differentiating sepsis from other noninfectious causes of systemic inflammation is often difficult in the elderly. The aim of this study was to evaluate the ability of C-reactive protein (CRP), Erythrocyte Sedimentation Rate (ESR), procalcitonin (PCT), and Interleukin-6 (IL-6) to identify elderly patients with sepsis. In this single center prospective observational study, we included all consecutive elderly patients admitted with suspected sepsis and systemic inflammatory response syndrome (SIRS) in an emergency department. Blood samples for measuring CRP, PCT, IL-6, ESR and white blood cells (WBC) count were taken at first day of admission. Sensitivity, specificity, positive and negative predictive values were calculated for each inflammatory markers being studied. A total of 150 elderly patients aged 65 and older, 50 with sepsis and 50 with SIRS, and fifty individuals in a normal health status were included. CRP exhibited the greatest sensitivity (98%) and negative predictive value (98.6%) and performed best in differentiating patients with sepsis from those with SIRS. In a receiver operating characteristic curve analysis, IL-6 performed best in distinguishing between SIRS and the control group (AUC 0.75, 95% CI). On the other hand, both CRP and ESR appeared to be a more accurate diagnostic parameter for differentiating sepsis from SIRS among elderly patients.

Impact of processing parameters on the haemocompatibility of Bombyx mori silk films.

PubMed

Seib, F Philipp; Maitz, Manfred F; Hu, Xiao; Werner, Carsten; Kaplan, David L

2012-02-01

Silk has traditionally been used for surgical sutures due to its lasting strength and durability; however, the use of purified silk proteins as a scaffold material for vascular tissue engineering goes beyond traditional use and requires application-orientated biocompatibility testing. For this study, a library of Bombyx mori silk films was generated and exposed to various solvents and treatment conditions to reflect current silk processing techniques. The films, along with clinically relevant reference materials, were exposed to human whole blood to determine silk blood compatibility. All substrates showed an initial inflammatory response comparable to polylactide-co-glycolide (PLGA), and a low to moderate haemostasis response similar to polytetrafluoroethylene (PTFE) substrates. In particular, samples that were water annealed at 25 °C for 6 h demonstrated the best blood compatibility based on haemostasis parameters (e.g. platelet decay, thrombin-antithrombin complex, platelet factor 4, granulocytes-platelet conjugates) and inflammatory parameters (e.g. C3b, C5a, CD11b, surface-associated leukocytes). Multiple factors such as treatment temperature and solvent influenced the biological response, though no single physical parameter such as β-sheet content, isoelectric point or contact angle accurately predicted blood compatibility. These findings, when combined with prior in vivo data on silk, support a viable future for silk-based vascular grafts. Copyright © 2011 Elsevier Ltd. All rights reserved.

Laser flare photometry: a noninvasive, objective, and quantitative method to measure intraocular inflammation.

PubMed

Tugal-Tutkun, Ilknur; Herbort, Carl P

2010-10-01

Aqueous flare and cells are the two inflammatory parameters of anterior chamber inflammation resulting from disruption of the blood-ocular barriers. When examined with the slit lamp, measurement of intraocular inflammation remains subjective with considerable intra- and interobserver variations. Laser flare cell photometry is an objective quantitative method that enables accurate measurement of these parameters with very high reproducibility. Laser flare photometry allows detection of subclinical alterations in the blood-ocular barriers, identifying subtle pathological changes that could not have been recorded otherwise. With the use of this method, it has been possible to compare the effect of different surgical techniques, surgical adjuncts, and anti-inflammatory medications on intraocular inflammation. Clinical studies of uveitis patients have shown that flare measurements by laser flare photometry allowed precise monitoring of well-defined uveitic entities and prediction of disease relapse. Relationships of laser flare photometry values with complications of uveitis and visual loss further indicate that flare measurement by laser flare photometry should be included in the routine follow-up of patients with uveitis.

Prediction of inflammatory responses induced by biomaterials in contact with human blood using protein fingerprint from plasma.

PubMed

Engberg, Anna E; Nilsson, Per H; Huang, Shan; Fromell, Karin; Hamad, Osama A; Mollnes, Tom Eirik; Rosengren-Holmberg, Jenny P; Sandholm, Kerstin; Teramura, Yuji; Nicholls, Ian A; Nilsson, Bo; Ekdahl, Kristina N

2015-01-01

Inappropriate complement activation is often responsible for incompatibility reactions that occur when biomaterials are used. Complement activation is therefore a criterion included in legislation regarding biomaterials testing. However, no consensus is yet available regarding appropriate complement-activation-related test parameters. We examined protein adsorption in plasma and complement activation/cytokine release in whole blood incubated with well-characterized polymers. Strong correlations were found between the ratio of C4 to its inhibitor C4BP and generation of 10 (mainly pro-inflammatory) cytokines, including IL-17, IFN-γ, and IL-6. The levels of complement activation products correlated weakly (C3a) or not at all (C5a, sC5b-9), confirming their poor predictive values. We have demonstrated a direct correlation between downstream biological effects and the proteins initially adhering to an artificial surface after contact with blood. Consequently, we propose the C4/C4BP ratio as a robust, predictor of biocompatibility with superior specificity and sensitivity over the current gold standard. Copyright © 2014 Elsevier Ltd. All rights reserved.

Elevated serum adipsin may predict unsuccessful treatment for cows' milk allergy but other biomarkers do not.

PubMed

Salmivesi, Susanna; Paassilta, Marita; Huhtala, Heini; Nieminen, Riina; Moilanen, Eeva; Korppi, Matti

2018-02-01

This study evaluated whether 15 allergy, immunology or inflammatory markers predicted the long-term use of cows' milk or milk products seven years after the start of oral immunotherapy (OIT) for cows' milk allergy in children. The following laboratory parameters were measured before the OIT at Tampere University Hospital, Finland, and after the six-month escalation phase: serum total immunoglobulin (Ig) E, milk-specific IgG and IgG4, eosinophil cationic protein, eosinophil-derived neurotoxin, interleukins 4, 5, 6, 10 and 12p70 and serum adipokines adiponectin, adipsin, leptin and resistin. Follow-up data from a seven-year phone questionnaire in 2015 were available for 24 children: 14 successful and 10 unsuccessful milk users. There were no significant differences in any of the 15 markers measured at the start of the study between the subjects who later formed the successful and unsuccessful groups. At the end of the six-month escalation phase of OIT, serum adipsin was higher in the group who were unsuccessful milk users at the seven-year follow-up study. None of the 15 allergy, immunology or inflammatory markers were useful in predicting the outcome of OIT. Preliminary evidence was found that high serum adipsin after the six-month escalation phase of OIT might predict unsuccessful outcome. ©2017 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Anti-inflammatory drugs and prediction of new structures by comparative analysis.

PubMed

Bartzatt, Ronald

2012-01-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) are a group of agents important for their analgesic, anti-inflammatory, and antipyretic properties. This study presents several approaches to predict and elucidate new molecular structures of NSAIDs based on 36 known and proven anti-inflammatory compounds. Based on 36 known NSAIDs the mean value of Log P is found to be 3.338 (standard deviation= 1.237), mean value of polar surface area is 63.176 Angstroms2 (standard deviation = 20.951 A2), and the mean value of molecular weight is 292.665 (standard deviation = 55.627). Nine molecular properties are determined for these 36 NSAID agents, including Log P, number of -OH and -NHn, violations of Rule of 5, number of rotatable bonds, and number of oxygens and nitrogens. Statistical analysis of these nine molecular properties provides numerical parameters to conform to in the design of novel NSAID drug candidates. Multiple regression analysis is accomplished using these properties of 36 agents followed with examples of predicted molecular weight based on minimum and maximum property values. Hierarchical cluster analysis indicated that licofelone, tolfenamic acid, meclofenamic acid, droxicam, and aspirin are substantially distinct from all remaining NSAIDs. Analysis of similarity (ANOSIM) produced R = 0.4947, which indicates low to moderate level of dissimilarity between these 36 NSAIDs. Non-hierarchical K-means cluster analysis separated the 36 NSAIDs into four groups having members of greatest similarity. Likewise, discriminant analysis divided the 36 agents into two groups indicating the greatest level of distinction (discrimination) based on nine properties. These two multivariate methods together provide investigators a means to compare and elucidate novel drug designs to 36 proven compounds and ascertain to which of those are most analogous in pharmacodynamics. In addition, artificial neural network modeling is demonstrated as an approach to predict numerous molecular properties of new drug designs that is based on neural training from 36 proven NSAIDs. Comprehensive and effective approaches are presented in this study for the design of new NSAID type agents which are so very important for inhibition of COX-2 and COX-1 isoenzymes.

Predicting and explaining inflammation in Crohn's disease patients using predictive analytics methods and electronic medical record data.

PubMed

Reddy, Bhargava K; Delen, Dursun; Agrawal, Rupesh K

2018-01-01

Crohn's disease is among the chronic inflammatory bowel diseases that impact the gastrointestinal tract. Understanding and predicting the severity of inflammation in real-time settings is critical to disease management. Extant literature has primarily focused on studies that are conducted in clinical trial settings to investigate the impact of a drug treatment on the remission status of the disease. This research proposes an analytics methodology where three different types of prediction models are developed to predict and to explain the severity of inflammation in patients diagnosed with Crohn's disease. The results show that machine-learning-based analytic methods such as gradient boosting machines can predict the inflammation severity with a very high accuracy (area under the curve = 92.82%), followed by regularized regression and logistic regression. According to the findings, a combination of baseline laboratory parameters, patient demographic characteristics, and disease location are among the strongest predictors of inflammation severity in Crohn's disease patients.

Trends in white blood cell and platelet indices in a comparison of patients with papillary thyroid carcinoma and multinodular goiter do not permit differentiation between the conditions.

PubMed

Machairas, Nikolaos; Kostakis, Ioannis D; Prodromidou, Anastasia; Stamopoulos, Paraskevas; Feretis, Themistoklis; Garoufalia, Zoe; Damaskos, Christos; Tsourouflis, Gerasimos; Kouraklis, Gregory

2017-11-01

Carcinogenesis has been related to systematic inflammatory response. Our aim was to study white blood cell and platelet indices as markers of this inflammatory response in thyroid cancer and to associate them with various clinicopathological parameters. We included 228 patients who underwent thyroidectomy within a period of 54 months, 89 with papillary thyroid carcinoma and 139 with multinodular hyperplasia. We examined potential links between white blood cell and platelet indices on the one hand and the type thyroid pathology and various clinicopathological parameters on the other. No significant differences were detected between thyroid cancer and multinodular hyperplasia and no significant associations were detected with regard to lymphovascular invasion and tumor size. However, the mean platelet volume was higher in multifocal tumors, while the platelet count, plateletcrit, and platelet-to-lymphocyte ratio were increased in cases with extrathyroidal extension and in T3 tumors. Additionally, T3 tumors had lower platelet distribution width. These associations demonstrated low accuracy in predicting these pathological features, but they were found to provide a satisfying negative predictive value, with the exception of the mean platelet volume. White blood cell and platelet indices cannot assist in distinguishing benign goiter from thyroid cancer. However, they can provide information about tumor multifocality, extrathyroidal extension, and presence of a T3 tumor, and they may be used as a means to exclude these pathological characteristics, especially the last two, in papillary thyroid carcinoma.

Proteomics to predict the response to tumour necrosis factor-α inhibitors in rheumatoid arthritis using a supervised cluster-analysis based protein score.

PubMed

Cuppen, Bvj; Fritsch-Stork, Rde; Eekhout, I; de Jager, W; Marijnissen, A C; Bijlsma, Jwj; Custers, M; van Laar, J M; Lafeber, Fpjg; Welsing, Pmj

2018-01-01

In rheumatoid arthritis (RA), it is of major importance to identify non-responders to tumour necrosis factor-α inhibitors (TNFi) before starting treatment, to prevent a delay in effective treatment. We developed a protein score for the response to TNFi treatment in RA and investigated its predictive value. In RA patients eligible for biological treatment included in the BiOCURA registry, 53 inflammatory proteins were measured using xMAP® technology. A supervised cluster analysis method, partial least squares (PLS), was used to select the best combination of proteins. Using logistic regression, a predictive model containing readily available clinical parameters was developed and the potential of this model with and without the protein score to predict European League Against Rheumatism (EULAR) response was assessed using the area under the receiving operating characteristics curve (AUC-ROC) and the net reclassification index (NRI). For the development step (n = 65 patient), PLS revealed 12 important proteins: CCL3 (macrophage inflammatory protein, MIP1a), CCL17 (thymus and activation-regulated chemokine), CCL19 (MIP3b), CCL22 (macrophage-derived chemokine), interleukin-4 (IL-4), IL-6, IL-7, IL-15, soluble cluster of differentiation 14 (sCD14), sCD74 (macrophage migration inhibitory factor), soluble IL-1 receptor I, and soluble tumour necrosis factor receptor II. The protein score scarcely improved the AUC-ROC (0.72 to 0.77) and the ability to improve classification and reclassification (NRI = 0.05). In validation (n = 185), the model including protein score did not improve the AUC-ROC (0.71 to 0.67) or the reclassification (NRI = -0.11). No proteomic predictors were identified that were more suitable than clinical parameters in distinguishing TNFi non-responders from responders before the start of treatment. As the results of previous studies and this study are disparate, we currently have no proteomic predictors for the response to TNFi.

Body mass index and other anthropometric parameters in patients with diffuse large B-cell lymphoma: physiopathological significance and predictive value in the immunochemotherapy era.

PubMed

Sarkozy, Clémentine; Camus, Vincent; Tilly, Hervé; Salles, Gilles; Jardin, Fabrice

2015-07-01

Diffuse large B-cell lymphoma (DLBCL) is the most common form of aggressive non-Hodgkin lymphoma, accounting for 30-40% of newly diagnosed cases. Obesity is a well-defined risk factor for DLBCL. However, the impact of body mass index (BMI) on DLBCL prognosis is controversial. Recent studies suggest that skeletal muscle wasting (sarcopenia) or loss of fat mass can be detected by computed tomography (CT) images and is useful for predicting the clinical outcome in several types of cancer including DLBCL. Several hypotheses have been proposed to explain the differences in DLBCL outcome according to BMI or weight that include tolerance to treatment, inflammatory background and chemotherapy or rituximab metabolism. In this review, we summarize the available literature, addressing the impact and physiopathological relevance of simple anthropometric tools including BMI and tissue distribution measurements. We also discuss their relationship with other nutritional parameters and their potential role in the management of patients with DLBCL.

A Biomathematical Model of Pneumococcal Lung Infection and Antibiotic Treatment in Mice.

PubMed

Schirm, Sibylle; Ahnert, Peter; Wienhold, Sandra; Mueller-Redetzky, Holger; Nouailles-Kursar, Geraldine; Loeffler, Markus; Witzenrath, Martin; Scholz, Markus

2016-01-01

Pneumonia is considered to be one of the leading causes of death worldwide. The outcome depends on both, proper antibiotic treatment and the effectivity of the immune response of the host. However, due to the complexity of the immunologic cascade initiated during infection, the latter cannot be predicted easily. We construct a biomathematical model of the murine immune response during infection with pneumococcus aiming at predicting the outcome of antibiotic treatment. The model consists of a number of non-linear ordinary differential equations describing dynamics of pneumococcal population, the inflammatory cytokine IL-6, neutrophils and macrophages fighting the infection and destruction of alveolar tissue due to pneumococcus. Equations were derived by translating known biological mechanisms and assuming certain response kinetics. Antibiotic therapy is modelled by a transient depletion of bacteria. Unknown model parameters were determined by fitting the predictions of the model to data sets derived from mice experiments of pneumococcal lung infection with and without antibiotic treatment. Time series of pneumococcal population, debris, neutrophils, activated epithelial cells, macrophages, monocytes and IL-6 serum concentrations were available for this purpose. The antibiotics Ampicillin and Moxifloxacin were considered. Parameter fittings resulted in a good agreement of model and data for all experimental scenarios. Identifiability of parameters is also estimated. The model can be used to predict the performance of alternative schedules of antibiotic treatment. We conclude that we established a biomathematical model of pneumococcal lung infection in mice allowing predictions regarding the outcome of different schedules of antibiotic treatment. We aim at translating the model to the human situation in the near future.

Colorectal tumors: the histology report.

PubMed

Lanza, Giovanni; Messerini, Luca; Gafà, Roberta; Risio, Mauro

2011-03-01

Epithelial colorectal tumors are common pathologic entities. Their histology report should be comprehensive of a series of pathologic parameters essential for the correct clinical management of the patients. Diagnostic histologic criteria of adenomatous, serrated, inflammatory, and hamartomatous polyps and of polyposis syndromes are discussed. In addition, the pathologic features of early and advanced colorectal cancer are described and a checklist is given. Finally, molecular prognostic and predictive factors currently employed in the treatment of colorectal cancer are discussed. Copyright © 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd.. All rights reserved.

Modulation of inflammation by low and high doses of ionizing radiation: Implications for benign and malign diseases.

PubMed

Frey, Benjamin; Hehlgans, Stephanie; Rödel, Franz; Gaipl, Udo S

2015-11-28

Inflammation is a homeostatic mechanism aiming to maintain tissue integrity. The underlying immunological mechanisms and the interrelationship between ionizing radiation and inflammation are complex and multifactorial on cellular and chemical levels. On the one hand, radiation with single doses exceeding 1 Gy might initiate inflammatory reactions and thereby impact on tumor development. On the other hand, radiation is capable of attenuating an established inflammatory process, which is clinically used for the treatment of inflammatory and degenerative diseases with low-dose radiotherapy (single dose <1 Gy). At higher doses, ionizing radiation, especially in combination with additional immune stimulation, fosters the induction of immunogenic forms of tumor cell death and shifts the tumor microenvironment as well as the infiltration of immune cells from an anti- to a pro-inflammatory state. Distinct tumor infiltrating immune cells predict the response to radiochemotherapy in a multitude of tumor entities. While a high tumor infiltration of these adaptive immune cells mostly predicts a favorable disease outcome, a high infiltration of tumor-associated macrophages predicts an unfavorable response. Pro-inflammatory events should dominate over anti-inflammatory ones in this scenario. This review focuses on how ionizing radiation modulates inflammatory events in benign inflammatory and in malign diseases. A special focus is set on the role of tumor infiltrating lymphocytes and macrophages as biomarkers to predict treatment response and anti-tumor immunity and on mechanisms implicated in the anti-inflammatory effects of low-dose radiation therapy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The clinical utility of health-related quality of life screening in a pediatric inflammatory bowel disease clinic.

PubMed

Ryan, Jamie L; Mellon, Michael W; Junger, Katherine W F; Hente, Elizabeth A; Denson, Lee A; Saeed, Shehzad A; Hommel, Kevin A

2013-11-01

Adjusting to symptom flares, treatment regimens, and side effects places youth with inflammatory bowel disease (IBD) at increased risk for emotional and behavioral problems and adverse disease outcomes. Implementation of psychosocial screening into clinical practice remains a challenge. This study examines the clinical utility of health-related quality of life (HRQOL) screening in predicting disease outcome and healthcare utilization. One hundred twelve youth of 7 to 18 years diagnosed with IBD and their parents. Youth completed standardized measures of HRQOL and depression. Parents completed a proxy report of HRQOL. Pediatric gastroenterologists provided the Physician Global Assessment. Families were recruited from a pediatric gastroenterology clinic. Retrospective chart reviews examined disease outcome and healthcare utilization for 12 months after baseline measurement. Linear regressions, controlling for demographic and disease parameters, revealed that baseline measurement of youth and parent proxy-reported HRQOL predicted the number of IBD-related hospital admissions, gastroenterology clinic visits, emergency department visits, psychology clinic visits, telephone contacts, and pain management referrals over the next 12 months. Disease outcome was not significant. Lower HRQOL was predictive of increased healthcare utilization among youth with IBD. Regular HRQOL screening may be the impetus to providing better case management and allocating resources based on ongoing care needs and costs. Proactive interventions focused on patients with poor HRQOL may be an efficient approach to saving on healthcare costs and resource utilization.

Nature is the best source of anti-inflammatory drugs: indexing natural products for their anti-inflammatory bioactivity.

PubMed

Aswad, Miran; Rayan, Mahmoud; Abu-Lafi, Saleh; Falah, Mizied; Raiyn, Jamal; Abdallah, Ziyad; Rayan, Anwar

2018-01-01

The aim was to index natural products for less expensive preventive or curative anti-inflammatory therapeutic drugs. A set of 441 anti-inflammatory drugs representing the active domain and 2892 natural products representing the inactive domain was used to construct a predictive model for bioactivity-indexing purposes. The model for indexing the natural products for potential anti-inflammatory activity was constructed using the iterative stochastic elimination algorithm (ISE). ISE is capable of differentiating between active and inactive anti-inflammatory molecules. By applying the prediction model to a mix set of (active/inactive) substances, we managed to capture 38% of the anti-inflammatory drugs in the top 1% of the screened set of chemicals, yielding enrichment factor of 38. Ten natural products that scored highly as potential anti-inflammatory drug candidates are disclosed. Searching the PubMed revealed that only three molecules (Moupinamide, Capsaicin, and Hypaphorine) out of the ten were tested and reported as anti-inflammatory. The other seven phytochemicals await evaluation for their anti-inflammatory activity in wet lab. The proposed anti-inflammatory model can be utilized for the virtual screening of large chemical databases and for indexing natural products for potential anti-inflammatory activity.

The Onset of Type 2 Diabetes: Proposal for a Multi-Scale Model

PubMed Central

Tieri, Paolo; De Graaf, Albert; Franceschi, Claudio; Liò, Pietro; Van Ommen, Ben; Mazzà, Claudia; Tuchel, Alexander; Bernaschi, Massimo; Samson, Clare; Colombo, Teresa; Castellani, Gastone C; Capri, Miriam; Garagnani, Paolo; Salvioli, Stefano; Nguyen, Viet Anh; Bobeldijk-Pastorova, Ivana; Krishnan, Shaji; Cappozzo, Aurelio; Sacchetti, Massimo; Morettini, Micaela; Ernst, Marc

2013-01-01

Background Type 2 diabetes mellitus (T2D) is a common age-related disease, and is a major health concern, particularly in developed countries where the population is aging, including Europe. The multi-scale immune system simulator for the onset of type 2 diabetes (MISSION-T2D) is a European Union-funded project that aims to develop and validate an integrated, multilevel, and patient-specific model, incorporating genetic, metabolic, and nutritional data for the simulation and prediction of metabolic and inflammatory processes in the onset and progression of T2D. The project will ultimately provide a tool for diagnosis and clinical decision making that can estimate the risk of developing T2D and predict its progression in response to possible therapies. Recent data showed that T2D and its complications, specifically in the heart, kidney, retina, and feet, should be considered a systemic disease that is sustained by a pervasive, metabolically-driven state of inflammation. Accordingly, there is an urgent need (1) to understand the complex mechanisms underpinning the onset of this disease, and (2) to identify early patient-specific diagnostic parameters and related inflammatory indicators. Objective We aim to accomplish this mission by setting up a multi-scale model to study the systemic interactions of the biological mechanisms involved in response to a variety of nutritional and metabolic stimuli and stressors. Methods Specifically, we will be studying the biological mechanisms of immunological/inflammatory processes, energy intake/expenditure ratio, and cell cycle rate. The overall architecture of the model will exploit an already established immune system simulator as well as several discrete and continuous mathematical methods for modeling of the processes critically involved in the onset and progression of T2D. We aim to validate the predictions of our models using actual biological and clinical data. Results This study was initiated in March 2013 and is expected to be completed by February 2016. Conclusions MISSION-T2D aims to pave the way for translating validated multilevel immune-metabolic models into the clinical setting of T2D. This approach will eventually generate predictive biomarkers for this disease from the integration of clinical data with metabolic, nutritional, immune/inflammatory, genetic, and gut microbiota profiles. Eventually, it should prove possible to translate these into cost-effective and mobile-based diagnostic tools. PMID:24176906

Inflammatory bowel disease registries for collection of patient iron parameters in Europe

PubMed Central

Halfvarson, Jonas; Cummings, Fraser; Grip, Olof; Savoye, Guillaume

2018-01-01

Iron deficiency without anemia and iron deficiency anemia are common and frequently overlooked complications of inflammatory bowel disease. Despite the frequency and impact of iron deficiency in inflammatory bowel disease, there are gaps in our understanding about its incidence, prevalence and natural history and, consequently, patients may be undertreated. Medical registries have a key role in collecting data on the disease’s natural history, the safety and effectiveness of drugs in routine clinical practice, and the quality of care delivered by healthcare services. Even though iron deficiency impacts inflammatory bowel disease patients and healthcare systems substantially, none of the established European inflammatory bowel disease registries systematically collects information on iron parameters and related outcomes. Collection of robust iron parameter data from patient registries is one way to heighten awareness about the importance of iron deficiency in this disease and to generate data to improve the quality of patient care, patient outcomes, and thus quality of life. This objective could be achieved through collection of specific laboratory, clinical, and patient-reported measurements that could be incorporated into existing registries. This review describes the status of current European inflammatory bowel disease registries and the data they generate, in order to highlight their potential role in collecting iron data, to discuss how such information gathering could contribute to our understanding of iron deficiency anemia, and to provide practical information in regard to the incorporation of accumulated iron parameter data into registries. PMID:29563751

Bottom-up modeling approach for the quantitative estimation of parameters in pathogen-host interactions

PubMed Central

Lehnert, Teresa; Timme, Sandra; Pollmächer, Johannes; Hünniger, Kerstin; Kurzai, Oliver; Figge, Marc Thilo

2015-01-01

Opportunistic fungal pathogens can cause bloodstream infection and severe sepsis upon entering the blood stream of the host. The early immune response in human blood comprises the elimination of pathogens by antimicrobial peptides and innate immune cells, such as neutrophils or monocytes. Mathematical modeling is a predictive method to examine these complex processes and to quantify the dynamics of pathogen-host interactions. Since model parameters are often not directly accessible from experiment, their estimation is required by calibrating model predictions with experimental data. Depending on the complexity of the mathematical model, parameter estimation can be associated with excessively high computational costs in terms of run time and memory. We apply a strategy for reliable parameter estimation where different modeling approaches with increasing complexity are used that build on one another. This bottom-up modeling approach is applied to an experimental human whole-blood infection assay for Candida albicans. Aiming for the quantification of the relative impact of different routes of the immune response against this human-pathogenic fungus, we start from a non-spatial state-based model (SBM), because this level of model complexity allows estimating a priori unknown transition rates between various system states by the global optimization method simulated annealing. Building on the non-spatial SBM, an agent-based model (ABM) is implemented that incorporates the migration of interacting cells in three-dimensional space. The ABM takes advantage of estimated parameters from the non-spatial SBM, leading to a decreased dimensionality of the parameter space. This space can be scanned using a local optimization approach, i.e., least-squares error estimation based on an adaptive regular grid search, to predict cell migration parameters that are not accessible in experiment. In the future, spatio-temporal simulations of whole-blood samples may enable timely stratification of sepsis patients by distinguishing hyper-inflammatory from paralytic phases in immune dysregulation. PMID:26150807

Bottom-up modeling approach for the quantitative estimation of parameters in pathogen-host interactions.

PubMed

Lehnert, Teresa; Timme, Sandra; Pollmächer, Johannes; Hünniger, Kerstin; Kurzai, Oliver; Figge, Marc Thilo

2015-01-01

Opportunistic fungal pathogens can cause bloodstream infection and severe sepsis upon entering the blood stream of the host. The early immune response in human blood comprises the elimination of pathogens by antimicrobial peptides and innate immune cells, such as neutrophils or monocytes. Mathematical modeling is a predictive method to examine these complex processes and to quantify the dynamics of pathogen-host interactions. Since model parameters are often not directly accessible from experiment, their estimation is required by calibrating model predictions with experimental data. Depending on the complexity of the mathematical model, parameter estimation can be associated with excessively high computational costs in terms of run time and memory. We apply a strategy for reliable parameter estimation where different modeling approaches with increasing complexity are used that build on one another. This bottom-up modeling approach is applied to an experimental human whole-blood infection assay for Candida albicans. Aiming for the quantification of the relative impact of different routes of the immune response against this human-pathogenic fungus, we start from a non-spatial state-based model (SBM), because this level of model complexity allows estimating a priori unknown transition rates between various system states by the global optimization method simulated annealing. Building on the non-spatial SBM, an agent-based model (ABM) is implemented that incorporates the migration of interacting cells in three-dimensional space. The ABM takes advantage of estimated parameters from the non-spatial SBM, leading to a decreased dimensionality of the parameter space. This space can be scanned using a local optimization approach, i.e., least-squares error estimation based on an adaptive regular grid search, to predict cell migration parameters that are not accessible in experiment. In the future, spatio-temporal simulations of whole-blood samples may enable timely stratification of sepsis patients by distinguishing hyper-inflammatory from paralytic phases in immune dysregulation.

Coffee consumption modulates inflammatory processes in an individual fashion.

PubMed

Muqaku, Besnik; Tahir, Ammar; Klepeisz, Philip; Bileck, Andrea; Kreutz, Dominique; Mayer, Rupert L; Meier, Samuel M; Gerner, Marlene; Schmetterer, Klaus; Gerner, Christopher

2016-12-01

Anti-inflammatory effects of coffee consumption have been reported to be caused by caffeine and adenosine receptor signaling. However, contradictory effects have been observed. Many kinds of chronic diseases are linked to inflammation; therefore a profound understanding of potential effects of coffee consumption is desirable. We performed ex vivo experiments with eight individuals investigating peripheral blood mononuclear cells isolated from venous blood before and after coffee consumption, as well as in vitro experiments applying caffeine on isolated cells. After in vitro inflammatory stimulation of the cells, released cytokines, chemokines, and eicosanoids were determined and quantified using targeted mass spectrometric methods. Remarkably, the release of inflammation mediators IL6, IL8, GROA, CXCL2, CXCL5 as well as PGA2, PGD2, prostaglandin E2 (PGE2), LTC4, LTE4, and 15S-HETE was significantly affected after coffee consumption. While in several individuals coffee consumption or caffeine treatment caused significant downregulation of most inflammation mediators, in other healthy individuals exactly the opposite effects were observed. Ruling out age, sex, coffee consumption habits, the metabolic kinetics of caffeine in blood and the individual amount of regulatory T cells or CD39 expression as predictive parameters, we demonstrated here that coffee consumption may have significant pro- or anti-inflammatory effects in an individual fashion. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Rapid screening for inflammatory neuropathies by standardized clinical criteria

PubMed Central

Tramontozzi, Louis A.

2016-01-01

Abstract Background: Delay in recognition and treatment of inflammatory neuropathies increases morbidity and mortality. We have developed and standardized 3 clinical screening criteria that rapidly detect inflammatory neuropathies. Methods: We reviewed all patients with definite large fiber neuropathy in 2 different patient populations: 1 from a private neurology clinic and the other from a tertiary care center. Patients were divided into 2 groups: those with an inflammatory neuropathy and those with a noninflammatory neuropathy. We specifically noted the 3 key neuropathy characteristics: onset, distribution, and associated systemic features (ODS). We studied the sensitivity and specificity of ODS in differentiating between inflammatory and noninflammatory neuropathies. Results: A total of 206 patients were included: 51 from the private clinic and 155 from the tertiary care center. The sensitivity of using ODS in detecting an inflammatory neuropathy was 96% and the specificity was 85%. The positive predictive value of ODS was 0.8 and negative predictive value was 0.97. Conclusions: Rapid screening for inflammatory neuropathies by ODS clinical criteria is highly sensitive and has a high negative predictive value for noninflammatory neuropathies. ODS uses simple clinical criteria to rapidly screen for patients with a potentially treatable form of neuropathy and accelerate their diagnostic evaluation. Classification of evidence: This study provides Class IV evidence that 3 neuropathy characteristics—onset, distribution, and associated systemic features—accurately identify patients with inflammatory neuropathies. PMID:29443273

Nutritional status in patients with active inflammatory bowel disease: prevalence of malnutrition and methods for routine nutritional assessment.

PubMed

Mijac, Dragana D; Janković, Goran L J; Jorga, Jagoda; Krstić, Miodrag N

2010-08-01

Malnutrition is a common feature of inflammatory bowel disease (IBD). There are numerous methods for the assessment of nutritional status, but the gold standard has not yet been established. The aims of the study were to estimate the prevalence of undernutrition and to evaluate methods for routine nutritional assessment of active IBD patients. Twenty-three patients with active Crohn disease, 53 patients with active ulcerative colitis and 30 controls were included in the study. The nutritional status was assessed by extensive anthropometric measurements, percentage of weight loss in the past 1-6 months and biochemical markers of nutrition. All investigated nutritional parameters were significantly different in IBD patients compared to control subjects, except MCV, tryglicerides and serum total protein level. Serum albumin level and body mass index (BMI) were the most predictive parameters of malnutrition. According to different assessment methods the prevalence of undernutrition and severe undernutrition in patients with active IBD were 25.0%-69.7% and 1.3%-31.6%, respectively, while in the control subjects no abnormalities have been detected. There was no statistically significant difference of nutritional parameters between UC and CD patients except lower mid-arm muscle circumference in UC group. Malnutrition is common in IBD patients. BMI and serum albumin are simple and convenient methods for the assessment of the nutritional status in IBD patients. Further studies with larger group of patients are necessary to elucidate the prevalence of malnutrition and the most accurate assessment methods in IBD patients.

Bidirectional Prospective Associations Between Cardiac Autonomic Activity and Inflammatory Markers.

PubMed

Hu, Mandy Xian; Lamers, Femke; Neijts, Melanie; Willemsen, Gonneke; de Geus, Eco J C; Penninx, Brenda W J H

2018-06-01

Autonomic nervous system (ANS) imbalance has been cross-sectionally associated with inflammatory processes. Longitudinal studies are needed to shed light on the nature of this relationship. We examined cross-sectional and bidirectional prospective associations between cardiac autonomic measures and inflammatory markers. Analyses were conducted with baseline (n = 2823), 2-year (n = 2099), and 6-year (n = 1774) data from the Netherlands Study of Depression and Anxiety. To compare the pattern of results, prospective analyses with ANS (during sleep, leisure time, and work) and inflammation were conducted in two data sets from the Netherlands Twin Register measured for 4.9 years (n = 356) and 5.4 years (n = 472). Autonomic nervous system measures were heart rate (HR) and respiratory sinus arrhythmia (RSA). Inflammatory markers were C-reactive protein (CRP) and interleukin (IL)-6. The Netherlands Study of Depression and Anxiety results showed that higher HR and lower RSA were cross-sectionally significantly associated with higher inflammatory levels. Higher HR predicted higher levels of CRP (B = .065, p < .001) and IL-6 (B = .036, p = .014) at follow-up. Higher CRP levels predicted lower RSA (B = -.024, p = .048) at follow-up. The Netherlands Twin Register results confirmed that higher HR was associated with higher CRP and IL-6 levels 4.9 years later. Higher IL-6 levels predicted higher HR and lower RSA at follow-up. Autonomic imbalance is associated with higher levels of inflammation. Independent data from two studies converge in evidence that higher HR predicts subsequent higher levels of CRP and IL-6. Inflammatory markers may also predict future ANS activity, but evidence for this was less consistent.

Effect of Supragingival Irrigation with Aerosolized 0.5% Hydrogen Peroxide on Clinical Periodontal Parameters, Markers of Systemic Inflammation, and Morphology of Gingival Tissues in Patients with Periodontitis

PubMed Central

Žekonis, Gediminas; Žekonis, Jonas; Gleiznys, Alvydas; Noreikienė, Viktorija; Balnytė, Ingrida; Šadzevičienė, Renata; Narbutaitė, Julija

2016-01-01

Background Various studies have shown that non-surgical periodontal treatment is correlated with reduction in clinical parameters and plasma levels of inflammatory markers. The aim of this study was to evaluate the effect of long-term weekly supragingival irrigations with aerosolized 0.5% hydrogen peroxide as maintenance therapy followed by non-surgical periodontal treatment on clinical parameters, plasma levels of inflammatory markers, and morphological changes in gingival tissues of patients with periodontitis. Material/Methods In total, 43 patients with chronic periodontitis were randomly allocated to long-term maintenance therapy. The patients’ periodontal status was assessed using clinical parameters of approximal plaque index, modified gingival index, bleeding index, pocket probing depth, and plasma levels of inflammatory markers (high-sensitivity C-reactive protein and white blood cell count) at baseline and after 1, 2, and 3 years. The morphological status of gingival tissues (immediately after supragingival irrigation) was assessed microscopically. Results Complete data were obtained on 34 patients. A highly statistically significant and consistent reduction was observed in all long-term clinical parameters and plasma levels of inflammatory markers. Morphological data showed abundant spherical bubbles in gingival tissues. Conclusions 1. The present study showed that non-surgical periodontal treatment with long-term weekly supragingival irrigations with aerosolized 0.5% hydrogen peroxide improved clinical periodontal status and plasma levels of inflammatory markers and may be a promising method in periodontology. 2. We found that supragingival irrigation with aerosolized 0.5% hydrogen peroxide created large numbers of spherical bubbles in gingival tissues. PMID:27743448

Significant role of serum CRP in differentiating inflammatory from non-inflammatory causes of thyrotoxicosis

PubMed Central

Baruah, Manash P.; Bhattacharya, Bhaskar

2012-01-01

Background: C-reactive protein (CRP), which is a marker of inflammation, has not been widely studied in inflammatory thyroid disorders particularly in sub-acute thyroiditis (SAT). Aim: This study was aimed to find the significance of CRP level rise in patients with SAT and compare that to the rise in erythrocyte sedimentation rate (ESR), a gold standard laboratory parameter in establishing the diagnosis of SAT. Materials and Methods: Serum CRP levels were measured at initial presentation in 28 subjects with SAT(12 male, 16 female, age (Mean +SD) 37.96 ±8.5 years),and 19 patients with Graves’ disease (2 male, 17 female, age [Mean +SD] 36.8 ±16.5 years) as controls. Erythrocyte sedimentation rate (ESR) was measured in all 28 patients with SAT by Westergrens’ method. Either Tc99 nucleotide thyroid scan or high resolution ultrasonography (HR-USG) was performed to differentiate SAT from Graves’ disease.Fine needle aspiration cytology (FNAC) of thyroid was performed selected patients. Results: Serum CRP level was high in 61% of SAT patients but in none of the Graves′patients. Mean (SEM) (90%CI) serum CRP level (mg/L) was also significantly higher (P <0.0004) in the SAT group [27.55 (5.76) (15.72-39.38)], than in the Graves’ group [4.09 (0.12) (3.81-4.36)]. The sensitivity of serum CRP was 73.33%, specificity 53.85%, positive predictive value (PPV) 64.71%, and negative predictive value (NPV) 63.64% as compared to the sensitivity (53.57%), specificity (15.38%), PPV (57.69 %), and NPV (13.33%) of ESR. Conclusion: There is significantly higher rise in serum CRP level in patients with SAT is compared to patients with Graves’ disease. It correlates well with the rise in ESR. Such findings of this pilot study highlight the scope of using serum CRP as a diagnostic marker of SAT specially in situations when it may be confused with Graves’ disease, another common cause of thyrotoxicosis. It is logical to carry out studies to find a particular cut-off for serum CRP which can serve as an objective parameter for grading the inflammation in patients with SAT. PMID:23226645

Significant role of serum CRP in differentiating inflammatory from non-inflammatory causes of thyrotoxicosis.

PubMed

Baruah, Manash P; Bhattacharya, Bhaskar

2012-11-01

C-reactive protein (CRP), which is a marker of inflammation, has not been widely studied in inflammatory thyroid disorders particularly in sub-acute thyroiditis (SAT). This study was aimed to find the significance of CRP level rise in patients with SAT and compare that to the rise in erythrocyte sedimentation rate (ESR), a gold standard laboratory parameter in establishing the diagnosis of SAT. Serum CRP levels were measured at initial presentation in 28 subjects with SAT(12 male, 16 female, age (Mean +SD) 37.96 ±8.5 years),and 19 patients with Graves' disease (2 male, 17 female, age [Mean +SD] 36.8 ±16.5 years) as controls. Erythrocyte sedimentation rate (ESR) was measured in all 28 patients with SAT by Westergrens' method. Either Tc(99) nucleotide thyroid scan or high resolution ultrasonography (HR-USG) was performed to differentiate SAT from Graves' disease.Fine needle aspiration cytology (FNAC) of thyroid was performed selected patients. Serum CRP level was high in 61% of SAT patients but in none of the Graves'patients. Mean (SEM) (90%CI) serum CRP level (mg/L) was also significantly higher (P <0.0004) in the SAT group [27.55 (5.76) (15.72-39.38)], than in the Graves' group [4.09 (0.12) (3.81-4.36)]. The sensitivity of serum CRP was 73.33%, specificity 53.85%, positive predictive value (PPV) 64.71%, and negative predictive value (NPV) 63.64% as compared to the sensitivity (53.57%), specificity (15.38%), PPV (57.69 %), and NPV (13.33%) of ESR. There is significantly higher rise in serum CRP level in patients with SAT is compared to patients with Graves' disease. It correlates well with the rise in ESR. Such findings of this pilot study highlight the scope of using serum CRP as a diagnostic marker of SAT specially in situations when it may be confused with Graves' disease, another common cause of thyrotoxicosis. It is logical to carry out studies to find a particular cut-off for serum CRP which can serve as an objective parameter for grading the inflammation in patients with SAT.

Use of diffusion-weighted magnetic resonance imaging to distinguish between lung cancer and focal inflammatory lesions: a comparison of intravoxel incoherent motion derived parameters and apparent diffusion coefficient.

PubMed

Deng, Yu; Li, Xinchun; Lei, Yongxia; Liang, Changhong; Liu, Zaiyi

2016-11-01

Background Using imaging techniques to diagnose malignant and inflammatory lesions in the lung can be challenging. Purpose To compare intravoxel incoherent motion (IVIM) and apparent diffusion coefficient (ADC) magnetic resonance imaging (MRI) analysis in their ability to discriminate lung cancer from focal inflammatory lung lesions. Material and Methods Thirty-eight patients with lung masses were included: 30 lung cancers and eight inflammatory lesions. Patients were imaged with 3.0T MRI diffusion weighted imaging (DWI) using 10 b values (range, 0-1000 s/mm 2 ). Tissue diffusivity ( D), pseudo-diffusion coefficient ( D*), and perfusion fraction ( f) were calculated using segmented biexponential analysis. ADC (total) was calculated with monoexponential fitting of the DWI data. D, D*, f, and ADC were compared between lung cancer and inflammatory lung lesions. Receiver operating characteristic analysis was performed for all DWI parameters. Results The ADC was significantly higher for inflammatory lesions than for lung cancer ([1.21 ± 0.20] × 10 -3 mm 2 /s vs. [0.97 ± 0.15] × 10 -3 mm 2 /s; P = 0.004). By IVIM, f was found to be significantly higher in inflammatory lesions than lung cancer ([46.10 ± 12.92] % vs. [29.29 ± 10.89] %; P = 0.005). There was no difference in D and D* between lung cancer and inflammatory lesions ( P = 0.747 and 0.124, respectively). f showed comparable diagnostic performance with ADC in differentiating lung cancer from inflammatory lung lesions, with areas under the curve of 0.833 and 0.826, sensitivity 80.0% and 73.3%, and specificity 75.0% and 87.5%, respectively. Conclusion The IVIM parameter f value provides comparable diagnostic performance with ADC and could be used as a surrogate marker for differentiating lung cancer from inflammatory lesions.

Predictors of response to anti-tumor necrosis factor therapy in ulcerative colitis.

PubMed

Zampeli, Evanthia; Gizis, Michalis; Siakavellas, Spyros I; Bamias, Giorgos

2014-08-15

Ulcerative colitis (UC) is an immune-mediated, chronic inflammatory disease of the large intestine. Its course is characterized by flares of acute inflammation and periods of low-grade chronic inflammatory activity or remission. Monoclonal antibodies against tumor necrosis factor (anti-TNF) are part of the therapeutic armamentarium and are used in cases of moderate to severe UC that is refractory to conventional treatment with corticosteroids and/or immunosuppressants. Therapeutic response to these agents is not uniform and a large percentage of patients either fail to improve (primary non-response) or lose response after a period of improvement (secondary non-response/loss of response). In addition, the use of anti-TNF agents has been related to uncommon but potentially serious adverse effects that preclude their administration or lead to their discontinuation. Finally, use of these medications is associated with a considerable cost for the health system. The identification of parameters that may predict response to anti-TNF drugs in UC would help to better select for patients with a high probability to respond and minimize risk and costs for those who will not respond. Analysis of the major clinical trials and the accumulated experience with the use of anti-TNF drugs in UC has resulted to the report of such prognostic factors. Included are clinical and epidemiological characteristics, laboratory markers, endoscopic indicators and molecular (immunological/genetic) signatures. Such predictive parameters of long-term outcomes may either be present at the commencement of treatment or determined during the early period of therapy. Validation of these prognostic markers in large cohorts of patients with variable characteristics will facilitate their introduction into clinical practice and the best selection of UC patients who will benefit from anti-TNF therapy.

Design and synthesis of some new 2,3'-bipyridine-5-carbonitriles as potential anti-inflammatory/antimicrobial agents.

PubMed

Elzahhar, Perihan A; Elkazaz, Salwa; Soliman, Raafat; El-Tombary, Alaa A; Shaltout, Hossam A; El-Ashmawy, Ibrahim M; Abdel Wahab, Abeer E; El-Hawash, Soad A

2017-08-01

Inflammation may cause accumulation of fluid in the injured area, which may promote bacterial growth. Other reports disclosed that non-steroidal anti-inflammatory drugs may enhance progression of bacterial infection. This work describes synthesis of new series of 2,3'-bipyridine-5-carbonitriles as structural analogs of etoricoxib, linked at position-6 to variously substituted thio or oxo moieties. Biological screening results revealed that compounds 2b, 4b, 7e and 8 showed significant acute and chronic AI activities and broad spectrum of antimicrobial activity. In addition, similarity ensemble approach was applied to predict potential biological targets of the tested compounds. Then, pharmacophore modeling study was employed to determine the most important structural parameters controlling bioactivity. Moreover, title compounds showed physicochemical properties within those considered adequate for drug candidates. This study explored the potential of such series of compounds as structural leads for further modification to develop a new class of dual AI-antimicrobial agents.

Fear and C-reactive protein cosynergize annual pulse increases in healthy adults

PubMed Central

Shenhar-Tsarfaty, Shani; Yayon, Nadav; Waiskopf, Nir; Shapira, Itzhak; Toker, Sharon; Zaltser, David; Berliner, Shlomo; Ritov, Ya'acov; Soreq, Hermona

2015-01-01

Recent international terror outbreaks notably involve long-term mental health risks to the exposed population, but whether physical health risks are also anticipated has remained unknown. Here, we report fear of terror-induced annual increases in resting heart rate (pulse), a notable risk factor of all-cause mortality. Partial least squares analysis based on 325 measured parameters successfully predicted annual pulse increases, inverse to the expected age-related pulse decline, in approximately 4.1% of a cohort of 17,380 apparently healthy active Israeli adults. Nonbiased hierarchical regression analysis among 27 of those parameters identified pertinent fear of terror combined with the inflammatory biomarker C-reactive protein as prominent coregulators of the observed annual pulse increases. In comparison, basal pulse primarily depended on general physiological parameters and reduced cholinergic control over anxiety and inflammation, together indicating that consistent exposure to terror threats ignites fear-induced exacerbation of preexisting neuro-immune risks of all-cause mortality. PMID:25535364

Early identification of ‘acute-onset’ chronic inflammatory demyelinating polyneuropathy

PubMed Central

Sung, Jia-Ying; Tani, Jowy; Park, Susanna B.; Kiernan, Matthew C.

2014-01-01

Distinguishing patients with acute-onset chronic inflammatory demyelinating polyneuropathy from acute inflammatory demyelinating polyneuropathy prior to relapse is often challenging at the onset of their clinical presentation. In the present study, nerve excitability tests were used in conjunction with the clinical phenotype and disease staging, to differentiate between patients with acute-onset chronic inflammatory demyelinating polyneuropathy and patients with acute inflammatory demyelinating polyneuropathy at an early stage, with the aim to better guide treatment. Clinical assessment, staging and nerve excitability tests were undertaken on patients initially fulfilling the diagnostic criteria of acute inflammatory demyelinating polyneuropathy soon after symptom onset and their initial presentation. Patients were subsequently followed up for minimum of 12 months to determine if their clinical presentations were more consistent with acute-onset chronic inflammatory demyelinating polyneuropathy. Clinical severity as evaluated by Medical Research Council sum score and Hughes functional grading scale were not significantly different between the two cohorts. There was no difference between the time of onset of initial symptoms and nerve excitability test assessment between the two cohorts nor were there significant differences in conventional nerve conduction study parameters. However, nerve excitability test profiles obtained from patients with acute inflammatory demyelinating polyneuropathy demonstrated abnormalities in the recovery cycle of excitability, including significantly reduced superexcitability (P < 0.001) and prolonged relative refractory period (P < 0.01), without changes in threshold electrotonus. In contrast, in patients with acute-onset chronic inflammatory demyelinating polyneuropathy, a different pattern occurred with the recovery cycle shifted downward (increased superexcitability, P < 0.05; decreased subexcitability, P < 0.05) and increased threshold change in threshold electrotonus in both hyperpolarizing and depolarizing directions [depolarizing threshold electrotonus (90–100 ms) P < 0.005, hyperpolarizing threshold electrotonus (10–20 ms), P < 0.01, hyperpolarizing threshold electrotonus (90–100 ms), P < 0.05], perhaps suggesting early hyperpolarization. In addition, using excitability parameters superexcitability, subexcitability and hyperpolarizing threshold electrotonus (10–20 ms), the patients with acute inflammatory demyelinating polyneuropathy and acute-onset chronic inflammatory demyelinating polyneuropathy could be clearly separated into two non-overlapping groups. Studies of nerve excitability may be able to differentiate acute from acute-onset chronic inflammatory demyelinating polyneuropathy at an early stage. Characteristic nerve excitability parameter changes occur in early acute-onset chronic inflammatory demyelinating polyneuropathy, to match the clinical phenotype. Importantly, this pattern of change was strikingly different to that shown by patients with acute inflammatory demyelinating polyneuropathy, suggesting that nerve excitability techniques may be useful in distinguishing acute-onset chronic inflammatory demyelinating polyneuropathy from acute inflammatory demyelinating polyneuropathy at the initial stage. PMID:24983276

Anti-Inflammatory and Anti-Fibrotic Profile of Fish Oil Emulsions Used in Parenteral Nutrition-Associated Liver Disease

PubMed Central

Pastor-Clerigues, Alfonso; Marti-Bonmati, Ezequiel; Milara, Javier; Almudever, Patricia; Cortijo, Julio

2014-01-01

Home parenteral nutrition (PN) is associated with many complications including severe hepatobiliary dysfunction. Commercial ω-6 fatty acid-soybean based-lipid emulsions in PN may mediate long term PN associate liver disease (PNALD) whereas ω-3-fish oil parenteral emulsions have shown to reverse PNALD in children. However, its clinical effectiveness in adults has been scarcely reported. In this work, we study the role of soybean and fish oil lipid commercial emulsions on inflammatory and profibrotic liver markers in adults with long term PNALD and in in vitro cellular models. Inflammatory and profibrotic markers were measured in serum of ten adults with long term PNALD and in culture supernatants of monocytes. Liver epithelial to mesenchymal transition (EMT) was induced by transforming growth factor beta 1 (TGFβ1) to evaluate in vitro liver fibrosis. Omegaven®, a 100% fish oil commercial emulsion, was infused during four months in two patients with severe long term PNALD reversing, at the first month, the inflammatory, profibrotic and clinical parameters of PNALD. The effect was maintained during the treatment course but impaired when conventional lipid emulsions were reintroduced. The other patients under chronic soybean oil-based PN showed elevated inflammatory and profibrotic parameters. In vitro human monocytes stimulated with lipopolysaccharide induced a strong inflammatory response that was suppressed by Omegaven®, but increased by soybean emulsions. In other experiments, TGFβ1 induced EMT that was suppressed by Omegaven® and enhanced by soybean oil lipid emulsions. Omegaven® improves clinical, anti-inflammatory and anti-fibrotic parameters in adults with long-term home PNALD. PMID:25502575

Model Based Targeting of IL-6-Induced Inflammatory Responses in Cultured Primary Hepatocytes to Improve Application of the JAK Inhibitor Ruxolitinib

PubMed Central

Sobotta, Svantje; Raue, Andreas; Huang, Xiaoyun; Vanlier, Joep; Jünger, Anja; Bohl, Sebastian; Albrecht, Ute; Hahnel, Maximilian J.; Wolf, Stephanie; Mueller, Nikola S.; D'Alessandro, Lorenza A.; Mueller-Bohl, Stephanie; Boehm, Martin E.; Lucarelli, Philippe; Bonefas, Sandra; Damm, Georg; Seehofer, Daniel; Lehmann, Wolf D.; Rose-John, Stefan; van der Hoeven, Frank; Gretz, Norbert; Theis, Fabian J.; Ehlting, Christian; Bode, Johannes G.; Timmer, Jens; Schilling, Marcel; Klingmüller, Ursula

2017-01-01

IL-6 is a central mediator of the immediate induction of hepatic acute phase proteins (APP) in the liver during infection and after injury, but increased IL-6 activity has been associated with multiple pathological conditions. In hepatocytes, IL-6 activates JAK1-STAT3 signaling that induces the negative feedback regulator SOCS3 and expression of APPs. While different inhibitors of IL-6-induced JAK1-STAT3-signaling have been developed, understanding their precise impact on signaling dynamics requires a systems biology approach. Here we present a mathematical model of IL-6-induced JAK1-STAT3 signaling that quantitatively links physiological IL-6 concentrations to the dynamics of IL-6-induced signal transduction and expression of target genes in hepatocytes. The mathematical model consists of coupled ordinary differential equations (ODE) and the model parameters were estimated by a maximum likelihood approach, whereas identifiability of the dynamic model parameters was ensured by the Profile Likelihood. Using model simulations coupled with experimental validation we could optimize the long-term impact of the JAK-inhibitor Ruxolitinib, a therapeutic compound that is quickly metabolized. Model-predicted doses and timing of treatments helps to improve the reduction of inflammatory APP gene expression in primary mouse hepatocytes close to levels observed during regenerative conditions. The concept of improved efficacy of the inhibitor through multiple treatments at optimized time intervals was confirmed in primary human hepatocytes. Thus, combining quantitative data generation with mathematical modeling suggests that repetitive treatment with Ruxolitinib is required to effectively target excessive inflammatory responses without exceeding doses recommended by the clinical guidelines. PMID:29062282

Clinical and atopic parameters and airway inflammatory markers in childhood asthma: a factor analysis

PubMed Central

Leung, T; Wong, G; Ko, F; Lam, C; Fok, T

2005-01-01

Background: Recent studies have repeatedly shown weak correlations among lung function parameters, atopy, exhaled nitric oxide level (FeNO), and airway inflammatory markers, suggesting that they are non-overlapping characteristics of asthma in adults. A study was undertaken to determine, using factor analysis, whether the above features represent separate dimensions of childhood asthma. Methods: Clinically stable asthmatic patients aged 7–18 years underwent spirometric testing, methacholine bronchial challenge, blood sampling for atopy markers and chemokine levels (macrophage derived chemokine (MDC), thymus and activation regulated chemokine (TARC), and eotaxin), FeNO, and chemokines (MDC and eotaxin) and leukotriene B4 measurements in exhaled breath condensate (EBC). Results: The mean (SD) forced expiratory volume in 1 second (FEV1) and FeNO of 92 patients were 92.1 (15.9)% predicted and 87.3 (65.7) ppb, respectively. 59% of patients received inhaled corticosteroids. Factor analysis selected four different factors, explaining 55.5% of total variance. The Kaiser-Meyer-Olkin measure of sampling adequacy was 0.587. Plasma total and specific IgE levels, peripheral blood eosinophil percentage, and FeNO loaded on factor 1; plasma TARC and MDC concentrations on factor 2; MDC, eotaxin and leukotriene B4 concentrations in EBC on factor 3; and plasma eotaxin concentration together with clinical indices including body mass index and disease severity score loaded on factor 4. Post hoc factor analyses revealed similar results when outliers were excluded. Conclusions: The results suggest that atopy related indices and airway inflammation are separate dimensions in the assessment of childhood asthma, and inflammatory markers in peripheral blood and EBC are non-overlapping factors of asthma. PMID:16055623

Model Based Targeting of IL-6-Induced Inflammatory Responses in Cultured Primary Hepatocytes to Improve Application of the JAK Inhibitor Ruxolitinib.

PubMed

Sobotta, Svantje; Raue, Andreas; Huang, Xiaoyun; Vanlier, Joep; Jünger, Anja; Bohl, Sebastian; Albrecht, Ute; Hahnel, Maximilian J; Wolf, Stephanie; Mueller, Nikola S; D'Alessandro, Lorenza A; Mueller-Bohl, Stephanie; Boehm, Martin E; Lucarelli, Philippe; Bonefas, Sandra; Damm, Georg; Seehofer, Daniel; Lehmann, Wolf D; Rose-John, Stefan; van der Hoeven, Frank; Gretz, Norbert; Theis, Fabian J; Ehlting, Christian; Bode, Johannes G; Timmer, Jens; Schilling, Marcel; Klingmüller, Ursula

2017-01-01

IL-6 is a central mediator of the immediate induction of hepatic acute phase proteins (APP) in the liver during infection and after injury, but increased IL-6 activity has been associated with multiple pathological conditions. In hepatocytes, IL-6 activates JAK1-STAT3 signaling that induces the negative feedback regulator SOCS3 and expression of APPs. While different inhibitors of IL-6-induced JAK1-STAT3-signaling have been developed, understanding their precise impact on signaling dynamics requires a systems biology approach. Here we present a mathematical model of IL-6-induced JAK1-STAT3 signaling that quantitatively links physiological IL-6 concentrations to the dynamics of IL-6-induced signal transduction and expression of target genes in hepatocytes. The mathematical model consists of coupled ordinary differential equations (ODE) and the model parameters were estimated by a maximum likelihood approach, whereas identifiability of the dynamic model parameters was ensured by the Profile Likelihood. Using model simulations coupled with experimental validation we could optimize the long-term impact of the JAK-inhibitor Ruxolitinib, a therapeutic compound that is quickly metabolized. Model-predicted doses and timing of treatments helps to improve the reduction of inflammatory APP gene expression in primary mouse hepatocytes close to levels observed during regenerative conditions. The concept of improved efficacy of the inhibitor through multiple treatments at optimized time intervals was confirmed in primary human hepatocytes. Thus, combining quantitative data generation with mathematical modeling suggests that repetitive treatment with Ruxolitinib is required to effectively target excessive inflammatory responses without exceeding doses recommended by the clinical guidelines.

Outcome Prediction in Pneumonia Induced ALI/ARDS by Clinical Features and Peptide Patterns of BALF Determined by Mass Spectrometry

PubMed Central

Frenzel, Jochen; Gessner, Christian; Sandvoss, Torsten; Hammerschmidt, Stefan; Schellenberger, Wolfgang; Sack, Ulrich; Eschrich, Klaus; Wirtz, Hubert

2011-01-01

Background Peptide patterns of bronchoalveolar lavage fluid (BALF) were assumed to reflect the complex pathology of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) better than clinical and inflammatory parameters and may be superior for outcome prediction. Methodology/Principal Findings A training group of patients suffering from ALI/ARDS was compiled from equal numbers of survivors and nonsurvivors. Clinical history, ventilation parameters, Murray's lung injury severity score (Murray's LISS) and interleukins in BALF were gathered. In addition, samples of bronchoalveolar lavage fluid were analyzed by means of hydrophobic chromatography and MALDI-ToF mass spectrometry (MALDI-ToF MS). Receiver operating characteristic (ROC) analysis for each clinical and cytokine parameter revealed interleukin-6>interleukin-8>diabetes mellitus>Murray's LISS as the best outcome predictors. Outcome predicted on the basis of BALF levels of interleukin-6 resulted in 79.4% accuracy, 82.7% sensitivity and 76.1% specificity (area under the ROC curve, AUC, 0.853). Both clinical parameters and cytokines as well as peptide patterns determined by MALDI-ToF MS were analyzed by classification and regression tree (CART) analysis and support vector machine (SVM) algorithms. CART analysis including Murray's LISS, interleukin-6 and interleukin-8 in combination was correct in 78.0%. MALDI-ToF MS of BALF peptides did not reveal a single identifiable biomarker for ARDS. However, classification of patients was successfully achieved based on the entire peptide pattern analyzed using SVM. This method resulted in 90% accuracy, 93.3% sensitivity and 86.7% specificity following a 10-fold cross validation (AUC = 0.953). Subsequent validation of the optimized SVM algorithm with a test group of patients with unknown prognosis yielded 87.5% accuracy, 83.3% sensitivity and 90.0% specificity. Conclusions/Significance MALDI-ToF MS peptide patterns of BALF, evaluated by appropriate mathematical methods can be of value in predicting outcome in pneumonia induced ALI/ARDS. PMID:21991318

Outcome prediction in pneumonia induced ALI/ARDS by clinical features and peptide patterns of BALF determined by mass spectrometry.

PubMed

Frenzel, Jochen; Gessner, Christian; Sandvoss, Torsten; Hammerschmidt, Stefan; Schellenberger, Wolfgang; Sack, Ulrich; Eschrich, Klaus; Wirtz, Hubert

2011-01-01

Peptide patterns of bronchoalveolar lavage fluid (BALF) were assumed to reflect the complex pathology of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) better than clinical and inflammatory parameters and may be superior for outcome prediction. A training group of patients suffering from ALI/ARDS was compiled from equal numbers of survivors and nonsurvivors. Clinical history, ventilation parameters, Murray's lung injury severity score (Murray's LISS) and interleukins in BALF were gathered. In addition, samples of bronchoalveolar lavage fluid were analyzed by means of hydrophobic chromatography and MALDI-ToF mass spectrometry (MALDI-ToF MS). Receiver operating characteristic (ROC) analysis for each clinical and cytokine parameter revealed interleukin-6>interleukin-8>diabetes mellitus>Murray's LISS as the best outcome predictors. Outcome predicted on the basis of BALF levels of interleukin-6 resulted in 79.4% accuracy, 82.7% sensitivity and 76.1% specificity (area under the ROC curve, AUC, 0.853). Both clinical parameters and cytokines as well as peptide patterns determined by MALDI-ToF MS were analyzed by classification and regression tree (CART) analysis and support vector machine (SVM) algorithms. CART analysis including Murray's LISS, interleukin-6 and interleukin-8 in combination was correct in 78.0%. MALDI-ToF MS of BALF peptides did not reveal a single identifiable biomarker for ARDS. However, classification of patients was successfully achieved based on the entire peptide pattern analyzed using SVM. This method resulted in 90% accuracy, 93.3% sensitivity and 86.7% specificity following a 10-fold cross validation (AUC = 0.953). Subsequent validation of the optimized SVM algorithm with a test group of patients with unknown prognosis yielded 87.5% accuracy, 83.3% sensitivity and 90.0% specificity. MALDI-ToF MS peptide patterns of BALF, evaluated by appropriate mathematical methods can be of value in predicting outcome in pneumonia induced ALI/ARDS.

Changes in spatiotemporal gait parameters following intravenous immunoglobulin treatment for chronic inflammatory demyelinating polyneuropathy.

PubMed

Vo, Mary L; Chin, Russell L; Miranda, Caroline; Latov, Norman

2017-10-01

Gait impairment is a common presenting symptom in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). However, gait parameters have not previously been evaluated in detail as potential independent outcome measures. We prospectively measured changes in spatiotemporal gait parameters of 20 patients with CIDP at baseline and following treatment with intravenous immunoglobulin (IVIG), using GAITRite® a computerized walkway system with embedded sensors. Overall, study patients showed significant improvements in gait velocity, cadence, stride length, double support time, stance phase, and swing phase following IVIG treatment. Mean changes in velocity, stance phase, and swing phase, exhibited the greatest statistical significance among the subgroup that exhibited clinically meaningful improvement in Inflammatory Neuropathy Cause and Treatment disability score, Medical Research Council sum score, and grip strength. Assessment of gait parameters, in particular velocity, step phase and swing phase, is a potentially sensitive outcome measure for evaluating treatment response in CIDP. Muscle Nerve 56: 732-736, 2017. © 2017 Wiley Periodicals, Inc.

Prediction of Individual Serum Infliximab Concentrations in Inflammatory Bowel Disease by a Bayesian Dashboard System.

PubMed

Eser, Alexander; Primas, Christian; Reinisch, Sieglinde; Vogelsang, Harald; Novacek, Gottfried; Mould, Diane R; Reinisch, Walter

2018-01-30

Despite a robust exposure-response relationship of infliximab in inflammatory bowel disease (IBD), attempts to adjust dosing to individually predicted serum concentrations of infliximab (SICs) are lacking. Compared with labor-intensive conventional software for pharmacokinetic (PK) modeling (eg, NONMEM) dashboards are easy-to-use programs incorporating complex Bayesian statistics to determine individual pharmacokinetics. We evaluated various infliximab detection assays and the number of samples needed to precisely forecast individual SICs using a Bayesian dashboard. We assessed long-term infliximab retention in patients being dosed concordantly versus discordantly with Bayesian dashboard recommendations. Three hundred eighty-two serum samples from 117 adult IBD patients on infliximab maintenance therapy were analyzed by 3 commercially available assays. Data from each assay was modeled using NONMEM and a Bayesian dashboard. PK parameter precision and residual variability were assessed. Forecast concentrations from both systems were compared with observed concentrations. Infliximab retention was assessed by prediction for dose intensification via Bayesian dashboard versus real-life practice. Forecast precision of SICs varied between detection assays. At least 3 SICs from a reliable assay are needed for an accurate forecast. The Bayesian dashboard performed similarly to NONMEM to predict SICs. Patients dosed concordantly with Bayesian dashboard recommendations had a significantly longer median drug survival than those dosed discordantly (51.5 versus 4.6 months, P < .0001). The Bayesian dashboard helps to assess the diagnostic performance of infliximab detection assays. Three, not single, SICs provide sufficient information for individualized dose adjustment when incorporated into the Bayesian dashboard. Treatment adjusted to forecasted SICs is associated with longer drug retention of infliximab. © 2018, The American College of Clinical Pharmacology.

Is the disease course predictable in inflammatory bowel diseases?

PubMed Central

Lakatos, Peter Laszlo; Kiss, Lajos S

2010-01-01

During the course of the disease, most patients with Crohn’s disease (CD) may eventually develop a stricturing or a perforating complication, and a significant number of patients with both CD and ulcerative colitis will undergo surgery. In recent years, research has focused on the determination of factors important in the prediction of disease course in inflammatory bowel diseases to improve stratification of patients, identify individual patient profiles, including clinical, laboratory and molecular markers, which hopefully will allow physicians to choose the most appropriate management in terms of therapy and intensity of follow-up. This review summarizes the available evidence on clinical, endoscopic variables and biomarkers in the prediction of short and long-term outcome in patients with inflammatory bowel diseases. PMID:20518079

Derivation and Validation of a Biomarker-Based Clinical Algorithm to Rule Out Sepsis From Noninfectious Systemic Inflammatory Response Syndrome at Emergency Department Admission: A Multicenter Prospective Study.

PubMed

Mearelli, Filippo; Fiotti, Nicola; Giansante, Carlo; Casarsa, Chiara; Orso, Daniele; De Helmersen, Marco; Altamura, Nicola; Ruscio, Maurizio; Castello, Luigi Mario; Colonetti, Efrem; Marino, Rossella; Barbati, Giulia; Bregnocchi, Andrea; Ronco, Claudio; Lupia, Enrico; Montrucchio, Giuseppe; Muiesan, Maria Lorenza; Di Somma, Salvatore; Avanzi, Gian Carlo; Biolo, Gianni

2018-05-07

To derive and validate a predictive algorithm integrating a nomogram-based prediction of the pretest probability of infection with a panel of serum biomarkers, which could robustly differentiate sepsis/septic shock from noninfectious systemic inflammatory response syndrome. Multicenter prospective study. At emergency department admission in five University hospitals. Nine-hundred forty-seven adults in inception cohort and 185 adults in validation cohort. None. A nomogram, including age, Sequential Organ Failure Assessment score, recent antimicrobial therapy, hyperthermia, leukocytosis, and high C-reactive protein values, was built in order to take data from 716 infected patients and 120 patients with noninfectious systemic inflammatory response syndrome to predict pretest probability of infection. Then, the best combination of procalcitonin, soluble phospholypase A2 group IIA, presepsin, soluble interleukin-2 receptor α, and soluble triggering receptor expressed on myeloid cell-1 was applied in order to categorize patients as "likely" or "unlikely" to be infected. The predictive algorithm required only procalcitonin backed up with soluble phospholypase A2 group IIA determined in 29% of the patients to rule out sepsis/septic shock with a negative predictive value of 93%. In a validation cohort of 158 patients, predictive algorithm reached 100% of negative predictive value requiring biomarker measurements in 18% of the population. We have developed and validated a high-performing, reproducible, and parsimonious algorithm to assist emergency department physicians in distinguishing sepsis/septic shock from noninfectious systemic inflammatory response syndrome.

In vitro and in vivo evaluation of the inflammatory potential of various nanoporous hydroxyapatite biomaterials.

PubMed

Velard, Frédéric; Schlaubitz, Silke; Fricain, Jean-Christophe; Guillaume, Christine; Laurent-Maquin, Dominique; Möller-Siegert, Janina; Vidal, Loïc; Jallot, Edouard; Sayen, Stéphanie; Raissle, Olivier; Nedelec, Jean-Marie; Vix-Guterl, Cathie; Anselme, Karine; Amédée, Joëlle; Laquerrière, Patrice

2015-01-01

To discriminate the most important physicochemical parameters for bone reconstruction, the inflammatory potential of seven nanoporous hydroxyapatite powders synthesized by hard or soft templating was evaluated both in vitro and in vivo. After physical and chemical characterization of the powders, we studied the production of inflammatory mediators by human primary monocytes after 4 and 24 h in contact with powders, and the host response after 2 weeks implantation in a mouse critical size defect model. In vitro results highlighted increases in the secretion of TNF-α, IL-1, -8, -10 and proMMP-2 and -9 and decreases in the secretion of IL-6 only for powders prepared by hard templating. In vivo observations confirmed an extensive inflammatory tissue reaction and a strong resorption for the most inflammatory powder in vitro. These findings highlight that the most critical physicochemical parameters for these nanoporous hydroxyapatite are, the crystallinity that controls dissolution potential, the specific surface area and the size and shape of crystallites.

Hyperammonemia and Systemic Inflammatory Response Syndrome Predicts Presence of Hepatic Encephalopathy in Dogs with Congenital Portosystemic Shunts

PubMed Central

Tivers, Mickey S.; Handel, Ian; Gow, Adam G.; Lipscomb, Vicky J.; Jalan, Rajiv; Mellanby, Richard J.

2014-01-01

Hepatic encephalopathy (HE) is an important cause of morbidity and mortality in patients with liver disease. The pathogenesis of he is incompletely understood although ammonia and inflammatory cytokines have been implicated as key mediators. To facilitate further mechanistic understanding of the pathogenesis of HE, a large number of animal models have been developed which often involve the surgical creation of an anastomosis between the hepatic portal vein and the caudal vena cava. One of the most common congenital abnormalities in dogs is a congenital portosystemic shunt (cpss), which closely mimics these surgical experimental models of HE. Dogs with a cPSS often have clinical signs which mimic clinical signs observed in humans with HE. Our hypothesis is that the pathogenesis of HE in dogs with a cPSS is similar to humans with HE. The aim of the study was to measure a range of clinical, haematological and biochemical parameters, which have been linked to the development of HE in humans, in dogs with a cPSS and a known HE grade. One hundred and twenty dogs with a cPSS were included in the study and multiple regression analysis of clinical, haematological and biochemical variables revealed that plasma ammonia concentrations and systemic inflammatory response syndrome scores predicted the presence of HE. Our findings further support the notion that the pathogenesis of canine and human HE share many similarities and indicate that dogs with cPSS may be an informative spontaneous model of human HE. Further investigations on dogs with cPSS may allow studies on HE to be undertaken without creating surgical models of HE thereby allowing the number of large animals used in animal experimentation to be reduced. PMID:24392080

Hyperammonemia and systemic inflammatory response syndrome predicts presence of hepatic encephalopathy in dogs with congenital portosystemic shunts.

PubMed

Tivers, Mickey S; Handel, Ian; Gow, Adam G; Lipscomb, Vicky J; Jalan, Rajiv; Mellanby, Richard J

2014-01-01

Hepatic encephalopathy (HE) is an important cause of morbidity and mortality in patients with liver disease. The pathogenesis of he is incompletely understood although ammonia and inflammatory cytokines have been implicated as key mediators. To facilitate further mechanistic understanding of the pathogenesis of HE, a large number of animal models have been developed which often involve the surgical creation of an anastomosis between the hepatic portal vein and the caudal vena cava. One of the most common congenital abnormalities in dogs is a congenital portosystemic shunt (cpss), which closely mimics these surgical experimental models of HE. Dogs with a cPSS often have clinical signs which mimic clinical signs observed in humans with HE. Our hypothesis is that the pathogenesis of HE in dogs with a cPSS is similar to humans with HE. The aim of the study was to measure a range of clinical, haematological and biochemical parameters, which have been linked to the development of HE in humans, in dogs with a cPSS and a known HE grade. One hundred and twenty dogs with a cPSS were included in the study and multiple regression analysis of clinical, haematological and biochemical variables revealed that plasma ammonia concentrations and systemic inflammatory response syndrome scores predicted the presence of HE. Our findings further support the notion that the pathogenesis of canine and human HE share many similarities and indicate that dogs with cPSS may be an informative spontaneous model of human HE. Further investigations on dogs with cPSS may allow studies on HE to be undertaken without creating surgical models of HE thereby allowing the number of large animals used in animal experimentation to be reduced.

The significance and predictive value of free light chains in the urine of patients with chronic inflammatory rheumatic disease.

PubMed

Bramlage, Carsten Paul; Froelich, Britta; Wallbach, Manuel; Minguet, Joan; Grupp, Clemens; Deutsch, Cornelia; Bramlage, Peter; Koziolek, Michael; Müller, Gerhard Anton

2016-12-01

In patients with rheumatic diseases, reliable markers for determining disease activity are scarce. One potential parameter is the level of immunoglobulin free light chains (FLCs), which is known to be elevated in the blood of patients with certain rheumatic diseases. Few studies have quantified FLCs in urine, a convenient source of test sample, in patients with different rheumatic diseases. We carried out a retrospective analysis of patients with rheumatic disease attending the University hospital of Goettingen, Germany. Subjects were included if they had urine levels of both κ and λ FLCs available and did not have myeloma. Data regarding systemic inflammation and kidney function were recorded, and FLC levels were correlated with inflammatory markers. Of the 382 patients with rheumatic disease, 40.1 % had chronic polyarthritis, 21.2 % connective tissue disease, 18.6 % spondyloarthritis and 15.7 % vasculitis. Elevated levels of κ FLCs were found for 84 % of patients and elevated λ for 52.7 %. For the patients with rheumatoid arthritis, FLCs correlated with C-reactive protein (κ, r = 0.368, p < 0.001; λ, r = 0.398, p < 0.001) and erythrocyte sedimentation rate (κ, r = 0.692, p < 0.001; λ, r = 0.612, p < 0.001). Patients being treated with rituximab displayed FLC levels similar to those of the reference group. There were clear elevations in both κ and λ FLCs in patients with rheumatic disease, but not in κ/λ ratio. The correlation between FLCs and inflammatory markers in patients with rheumatoid arthritis demonstrates their potential for predicting disease activity.

Inflammatory parameters in Caco-2 cells: effect of stimuli nature, concentration, combination and cell differentiation.

PubMed

Van De Walle, Jacqueline; Hendrickx, Aurélie; Romier, Béatrice; Larondelle, Yvan; Schneider, Yves-Jacques

2010-08-01

Enterocytes regulate gut maintenance and defence by secreting and responding to inflammatory mediators and by modulating the intestinal epithelial permeability. In order to develop an in vitro model of the acute phase of intestinal inflammation, Caco-2 cells were exposed to the inflammatory mediators IL-1beta, TNF-alpha, IFN-gamma and LPS, and the importance of several experimental parameters, i.e. cell differentiation, stimulus nature, concentration and combination on the inflammatory response was assessed by measuring the production of IL-6, IL-8, PGE-2 and NO and by evaluating the monolayer permeability. A maximal increase in IL-8, IL-6 and PGE-2 production and monolayer permeability was observed when using the cytokines simultaneously at their highest level, but this relied mainly on IL-1beta. The effects of TNF-alpha on IL-8 and IL-6 or NO production were stronger upon combination with IL-1beta or IFN-gamma, respectively, whereas cells were unaffected by the presence of LPS. Although NO production, induced by IFN-gamma-containing combinations, was observed only in differentiated cells, general inflammatory response was higher in proliferating cells. The use of a mixture of IL-1beta, TNF-alpha and IFN-gamma thus accurately mimics intestinal inflammatory processes, but cell differentiation and stimuli combination are important parameters to take into account for in vitro studies on intestinal inflammation. Copyright (c) 2010. Published by Elsevier Ltd.

[Combined forecasting system of peritonitis outcome].

PubMed

Lebedev, N V; Klimov, A E; Agrba, S B; Gaidukevich, E K

To create a reliable system for assessing of severity and prediction of the outcome of peritonitis. Critical analysis of the systems for peritonitis severity assessment is presented. The study included outcomes of 347 patients who admitted at the Department of Faculty Surgery of Peoples' Friendship University of Russia in 2015-2016. The cause of peritonitis were destructive forms of acute appendicitis, cholecystitis, perforated gastroduodenal ulcer, various perforation of small and large intestines (including tumor). Combined forecasting system for peritonitis severity assessment is created. The system includes clinical, laboratory data, assessment of systemic inflammatory response (SIRS) and severity of organ failure (qSOFA). The authors focused on easily identifiable parameters which are available in virtually any surgical hospital. Threshold value (lethal outcome probability over 50%) is 8 scores in this system. Sensitivity, specificity and accuracy were 93.3, 99.7 and 98.9%, respectively according to ROC-curve that exceeds those parameters of MPI and APACHE II.

Efficacy of combined orthodontic-periodontic treatment for patients with periodontitis and its effect on inflammatory cytokines: A comparative study.

PubMed

Zhang, Jin; Zhang, Ai-Min; Zhang, Zong-Mei; Jia, Jin-Lin; Sui, Xin-Xin; Yu, Lu-Rui; Liu, Hai-Tao

2017-10-01

In this study, we aimed to investigate the efficacy of combined orthodontic-periodontic treatment in the treatment of patients with periodontitis and its effects on the levels of inflammatory cytokines. A total of 117 patients with periodontitis were randomly assigned to the basic group (receiving basic periodontic treatment, n = 58) and the combined group (receiving combined orthodontic-periodontic treatment, n = 59). In addition, 52 healthy people without periodontal disease were selected as the normal group. Probing depth, tooth mobility, plaque index, clinical attachment level, and sulcus bleeding index were recorded. ELISA was applied to detect gingival crevicular fluid (GCF) and serum levels of inflammatory cytokines. A 2-year clinical follow-up was conducted. Before treatment, the periodontal parameters (probing depth, tooth mobility, plaque index, clinical attachement level, and sulcus bleeding index) and GCF and serum levels of inflammatory cytokines (high-sensitivity C-reactive protein, interleukin-1β, interleukin-5, interleukin-6, interleukin-8, tumor necrosis factor-α, and prostaglandin E2) in the combined and basic groups were higher than those in the normal group. After 6 and 18 months of treatment, the periodontal parameters and GCF and serum levels of inflammatory cytokines decreased in the combined and basic groups. The periodontal parameters and the GCF and serum levels of inflammatory cytokines in the combined group were significantly lower than those in the basic group after 18 months of treatment. The combined group had a lower recurrence rate compared with the basic group. Combined orthodontic-periodontic treatment had good clinical efficacy in the treatment of periodontitis and could effectively decrease the levels of inflammatory cytokines. Copyright © 2017 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

Education, income and ethnic differences in cumulative biological risk profiles in a national sample of US adults: NHANES III (1988-1994).

PubMed

Seeman, Teresa; Merkin, Sharon S; Crimmins, Eileen; Koretz, Brandon; Charette, Susan; Karlamangla, Arun

2008-01-01

Data from the nationally representative US National Health and Nutrition Examination Survey (NHANES) III cohort were used to examine the hypothesis that socio-economic status is consistently and negatively associated with levels of biological risk, as measured by nine biological parameters known to predict health risks (diastolic and systolic blood pressure, pulse, HDL and total cholesterol, glycosylated hemoglobin, c-reactive protein, albumin and waist-hip ratio), resulting in greater cumulative burdens of biological risk among those of lower education and/or income. As hypothesized, consistent education and income gradients were seen for biological parameters reflecting cardiovascular, metabolic and inflammatory risk: those with lower education and income exhibiting greater prevalence of high-risk values for each of nine individual biological risk factors. Significant education and income gradients were also seen for summary indices reflecting cumulative burdens of cardiovascular, metabolic and inflammatory risks as well as overall total biological risks. Multivariable cumulative logistic regression models revealed that the education and income effects were each independently and negatively associated with cumulative biological risks, and that these effects remained significant independent of age, gender, ethnicity and lifestyle factors such as smoking and physical activity. There were no significant ethnic differences in the patterns of association between socio-economic status and biological risks, but older age was associated with significantly weaker education and income gradients.

The degree of mutual anisotropy of biological liquids polycrystalline nets as a parameter in diagnostics and differentiations of hominal inflammatory processes

NASA Astrophysics Data System (ADS)

Angelsky, O. V.; Ushenko, Yu. A.; Balanetska, V. O.

2011-09-01

To characterize the degree of consistency of parameters of the optically uniaxial birefringent protein nets of blood plasma a new parameter - complex degree of mutual anisotropy is suggested. The technique of polarization measuring the coordinate distributions of the complex degree of mutual anisotropy of blood plasma is developed. It is shown that statistic approach to the analysis of the complex degree of mutual anisotropy distributions of blood plasma is effective during the diagnostics and differentiation of an acute inflammatory processes as well as acute and gangrenous appendicitis.

Early identification of 'acute-onset' chronic inflammatory demyelinating polyneuropathy.

PubMed

Sung, Jia-Ying; Tani, Jowy; Park, Susanna B; Kiernan, Matthew C; Lin, Cindy Shin-Yi

2014-08-01

Distinguishing patients with acute-onset chronic inflammatory demyelinating polyneuropathy from acute inflammatory demyelinating polyneuropathy prior to relapse is often challenging at the onset of their clinical presentation. In the present study, nerve excitability tests were used in conjunction with the clinical phenotype and disease staging, to differentiate between patients with acute-onset chronic inflammatory demyelinating polyneuropathy and patients with acute inflammatory demyelinating polyneuropathy at an early stage, with the aim to better guide treatment. Clinical assessment, staging and nerve excitability tests were undertaken on patients initially fulfilling the diagnostic criteria of acute inflammatory demyelinating polyneuropathy soon after symptom onset and their initial presentation. Patients were subsequently followed up for minimum of 12 months to determine if their clinical presentations were more consistent with acute-onset chronic inflammatory demyelinating polyneuropathy. Clinical severity as evaluated by Medical Research Council sum score and Hughes functional grading scale were not significantly different between the two cohorts. There was no difference between the time of onset of initial symptoms and nerve excitability test assessment between the two cohorts nor were there significant differences in conventional nerve conduction study parameters. However, nerve excitability test profiles obtained from patients with acute inflammatory demyelinating polyneuropathy demonstrated abnormalities in the recovery cycle of excitability, including significantly reduced superexcitability (P < 0.001) and prolonged relative refractory period (P < 0.01), without changes in threshold electrotonus. In contrast, in patients with acute-onset chronic inflammatory demyelinating polyneuropathy, a different pattern occurred with the recovery cycle shifted downward (increased superexcitability, P < 0.05; decreased subexcitability, P < 0.05) and increased threshold change in threshold electrotonus in both hyperpolarizing and depolarizing directions [depolarizing threshold electrotonus (90-100 ms) P < 0.005, hyperpolarizing threshold electrotonus (10-20 ms), P < 0.01, hyperpolarizing threshold electrotonus (90-100 ms), P < 0.05], perhaps suggesting early hyperpolarization. In addition, using excitability parameters superexcitability, subexcitability and hyperpolarizing threshold electrotonus (10-20 ms), the patients with acute inflammatory demyelinating polyneuropathy and acute-onset chronic inflammatory demyelinating polyneuropathy could be clearly separated into two non-overlapping groups. Studies of nerve excitability may be able to differentiate acute from acute-onset chronic inflammatory demyelinating polyneuropathy at an early stage. Characteristic nerve excitability parameter changes occur in early acute-onset chronic inflammatory demyelinating polyneuropathy, to match the clinical phenotype. Importantly, this pattern of change was strikingly different to that shown by patients with acute inflammatory demyelinating polyneuropathy, suggesting that nerve excitability techniques may be useful in distinguishing acute-onset chronic inflammatory demyelinating polyneuropathy from acute inflammatory demyelinating polyneuropathy at the initial stage. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Inflamm-aging does not simply reflect increases in pro-inflammatory markers.

PubMed

Morrisette-Thomas, Vincent; Cohen, Alan A; Fülöp, Tamàs; Riesco, Éléonor; Legault, Véronique; Li, Qing; Milot, Emmanuel; Dusseault-Bélanger, Françis; Ferrucci, Luigi

2014-07-01

Many biodemographic studies use biomarkers of inflammation to understand or predict chronic disease and aging. Inflamm-aging, i.e. chronic low-grade inflammation during aging, is commonly characterized by pro-inflammatory biomarkers. However, most studies use just one marker at a time, sometimes leading to conflicting results due to complex interactions among the markers. A multidimensional approach allows a more robust interpretation of the various relationships between the markers. We applied principal component analysis (PCA) to 19 inflammatory biomarkers from the InCHIANTI study. We identified a clear, stable structure among the markers, with the first axis explaining inflammatory activation (both pro- and anti-inflammatory markers loaded strongly and positively) and the second axis innate immune response. The first but not the second axis was strongly correlated with age (r=0.56, p<0.0001, r=0.08 p=0.053), and both were strongly predictive of mortality (hazard ratios per PCA unit (95% CI): 1.33 (1.16-1.53) and 0.87 (0.76-0.98) respectively) and multiple chronic diseases, but in opposite directions. Both axes were more predictive than any individual markers for baseline chronic diseases and mortality. These results show that PCA can uncover a novel biological structure in the relationships among inflammatory markers, and that key axes of this structure play important roles in chronic disease. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Influence of phenotype at diagnosis and of other potential prognostic factors on the course of inflammatory bowel disease.

PubMed

Romberg-Camps, M J L; Dagnelie, P C; Kester, A D M; Hesselink-van de Kruijs, M A M; Cilissen, M; Engels, L G J B; Van Deursen, C; Hameeteman, W H A; Wolters, F L; Russel, M G V M; Stockbrügger, R W

2009-02-01

Disease course in inflammatory bowel disease (IBD) is variable and difficult to predict. To optimize prognosis, it is of interest to identify phenotypic characteristics at disease onset and other prognostic factors that predict disease course. The aim of this study was to evaluate such factors in a population-based IBD group. IBD patients diagnosed between 1 January 1991 and 1 January 2003 were included. A follow-up questionnaire was developed and medical records were reviewed. Patients were classified according to phenotype at diagnosis and risk factors were registered. Disease severity, cumulative medication use, and "surgical" and "nonsurgical" recurrence rates were calculated as outcome parameters. In total, 476 Crohn's disease (CD), 630 ulcerative colitis (UC), and 81 indeterminate colitis (IC) patients were diagnosed. In CD (mean follow-up 7.6 years), 50% had undergone resective surgery. In UC (mean follow-up 7 years), colectomy rate was 8.3%. First year cumulative recurrence rates per 100 patient-years for CD, UC, and IC were 53, 44, and 42%, respectively. In CD, small bowel localization and stricturing disease were negative prognostic factors for surgery, as was young age. Overall recurrence rate was increased by young age and current smoking. In UC, extensive colitis increased surgical risk. In UC, older age at diagnosis initially increased recurrence risk but was subsequently protective. This population-based IBD study showed high recurrence rates in the first year. In CD, small bowel localization, stricturing disease, and young age were predictive for disease recurrence. In UC, extensive colitis and older age at diagnosis were negative prognostic predictors.

Exploring Black-White Differences in the Relationship Between Inflammation and Timing of Menopause.

PubMed

Nowakowski, Alexandra C H; Graves, Katelyn Y

2017-06-01

Understanding the biosocial context of menopausal timing offers insight into social and health inequalities. Prior research on inflammatory chronic conditions suggests that inflammation may predict how early women experience menopause. We explore the ability of black race to moderate the overall relationship between chronic inflammation and timing of menopause. We use data from the National Social Life, Health, and Aging Project on inflammation, age of last menstruation, and race as well as relevant social and medical covariates. We conduct event history modeling to predict age at menopause by inflammatory biomarker levels. Using interaction analysis, we investigate whether being black may shape the overall relationship between inflammation status and menopause timing. Our analyses find no significant statistical interactions between black race and inflammation in predicting menopausal onset. However, we do identify independent correlational relationships between inflammation and black race (r = 0.136) and between menopausal timing and black race (r = -0.129) as well as inflammation (r = -0.138) that emerge as significant in corresponding regression models. We conclude that race probably does not moderate associations between inflammation and menopause. Yet, we also note that the original parameter estimate for black race's impact on menopausal onset (HR = 1.29, p < 0.05) becomes non-significant in a model that includes inflammation (HR = 1.06, p < 0.01). To translate our findings into policy and practice implications, we present alternate conceptualizations of black-white disparity in the inflammation-menopause relationship and recommend future research using mediation modeling.

Inflammatory and Metabolic Dysregulation and the 2-Year Course of Depressive Disorders in Antidepressant Users

PubMed Central

Vogelzangs, Nicole; Beekman, Aartjan TF; van Reedt Dortland, Arianne KB; Schoevers, Robert A; Giltay, Erik J; de Jonge, Peter; Penninx, Brenda WJH

2014-01-01

Scarce evidence suggests that inflammatory and metabolic dysregulation predicts poor response to antidepressants, which could result in worse depression outcome. This study prospectively examined whether inflammatory and metabolic dysregulation predicted the 2-year course of depressive disorders among antidepressant users. Data were from the Netherlands Study of Depression and Anxiety, including 315 persons (18–65 years) with a current depressive disorder (major depressive disorder, dysthymia) at baseline according to the DSM-IV criteria and using antidepressants. Inflammatory (C-reactive protein, interleukin-6 (IL-6), tumor-necrosis factor-α) and metabolic (waist circumference, triglycerides, high-density lipoprotein (HDL) cholesterol, blood pressure, fasting glucose) factors were measured at baseline. Primary outcome for course of depression was indicated by whether or not a DSM-IV depressive disorder diagnosis was still/again present at 2-year follow-up, indicating chronicity of depression. Elevated IL-6, low HDL cholesterol, hypertriglyceridemia, and hyperglycemia were associated with chronicity of depression in antidepressant users. Persons showing ⩾4 inflammatory or metabolic dysregulations had a 1.90 increased odds of depression chronicity (95% CI=1.12–3.23). Among persons who recently (ie, at most 3 months) started antidepressant medication (N=103), having ⩾4 dysregulations was associated with a 6.85 increased odds of depression chronicity (95% CI=1.95–24.06). In conclusion, inflammatory and metabolic dysregulations were found to predict a more chronic course of depressive disorders among patients using antidepressants. This could suggest that inflammatory and metabolic dysregulation worsens depression course owing to reduced antidepressant treatment response and that alternative intervention treatments may be needed for depressed persons with inflammatory and metabolic dysregulation. PMID:24442097

Can Rheumatologists Predict Eventual Need for Orthopaedic Intervention in Patients with Rheumatoid Arthritis? Results of a Systematic Review and Analysis of Two UK Inception Cohorts.

PubMed

Nikiphorou, Elena; Carpenter, Lewis; Norton, Sam; Morris, Stephen; MacGregor, Alex; Dixey, Josh; Williams, Peter; Kiely, Patrick; Walsh, David Andrew; Young, Adam

2017-03-01

The structural damage caused by rheumatoid arthritis (RA) can often be mitigated by orthopaedic surgery in late disease. This study evaluates the value of predictive factors for orthopaedic intervention. A systematic review of literature was undertaken to identify papers describing predictive factors for orthopaedic surgery in RA. Manuscripts were selected if they met inclusion criteria of cohort study design, diagnosis of RA, follow-up duration/disease duration ≥3 years, any orthopaedic surgical interventions recorded, and then summarised for predictive factors. A separate predictive analysis was performed on two consecutive UK Early RA cohorts, linked to national datasets. The literature search identified 15 reports examining predictive factors for orthopaedic intervention, 4 inception, 5 prospective and 6 retrospective. Despite considerable variation, acute phase, x-ray scores, women and genotyping were the most commonly reported prognostic markers. The current predictive analysis included 1602 procedures performed in 711 patients (25-year cumulative incidence 26%). Earlier recruitment year, erosions and lower haemoglobin predicted both intermediate and major surgery (P<0.05). Studies report variations in type of and predictive power of clinical and laboratory parameters for different surgical interventions suggesting specific contributions from different pathological and/or patient-level factors. Our current analysis suggests that attention to non-inflammatory factors in addition to suppression of inflammation is needed to minimise the burden of orthopaedic surgery.

Waist circumference shows the highest predictive value for metabolic syndrome, and waist-to-hip ratio for its components, in Spanish adolescents.

PubMed

Perona, Javier S; Schmidt-RioValle, Jacqueline; Rueda-Medina, Blanca; Correa-Rodríguez, María; González-Jiménez, Emilio

2017-09-01

Both waist circumference (WC) and waist-to-hip ratio (WHR) have been proposed as predictors of metabolic syndrome (MetS) in adolescents, but no consensus has been reached to date. This study hypothesizes that WC provides a greater predictive value for MetS in Spanish adolescents than WHR. A cross-sectional study was performed on 1001 adolescents (13.2 ± 1.2 years) randomly recruited from schools in southeast Spain. Anthropometric measures were correlated with the components of MetS (triglycerides, glucose, blood pressure, and high-density lipoprotein cholesterol) as well as inflammation markers (interleukin-6 and tumor necrosis factor-alpha , C-reactive protein, and ceruloplasmin). Receiver-operator curves were created to determine the predictive value of these variables for MetS. Boys had higher values of all anthropometric parameters compared with girls, but the prevalence of MetS was significantly higher in girls. WHR was the only parameter that correlated significantly with all biochemical and inflammatory variables in boys. In girls, WHR, body mass index, waist-to-height ratio, WC, and body fat percentage correlated only with plasma insulin levels, systolic and diastolic pressures, and ceruloplasmin. In both groups, all anthropometric measures were able to predict MetS (area under the curve > 0.94). In particular, WC was able to predict MetS with area under the curve = 1.00. However, WHR was able to predict a higher number of components of MetS. WHR was the anthropometric index that showed the highest predictive value for MetS components, whereas WC was the one that best predicted the MetS among the population of adolescents studied. These findings justify the need to incorporate WHR and WC determinations into daily clinical practice to predict the MetS. Copyright © 2017 Elsevier Inc. All rights reserved.

Systemic inflammatory mediators in post-traumatic complex regional pain syndrome (CRPS I) - longitudinal investigations and differences to control groups.

PubMed

Schinkel, Christian; Scherens, A; Köller, M; Roellecke, G; Muhr, G; Maier, C

2009-03-17

The Complex Regional Pain Syndrome I (CRPS I) is a disease that might affect an extremity after trauma or operation. The pathogenesis remains yet unclear. It has clinical signs of severe local inflammation as a result of an exaggerated inflammatory response but neurogenic dysregulation also contributes to it. Some studies investigated the role inflammatory mediators and cytokines; however, few longitudinal studies exist and control groups except healthy controls were not investigated yet. To get further insights into the role of systemic inflammatory mediators in CRPS I, we investigated a variety of pro-, anti-, or neuro-inflammatory mediators such as C-Reactive Protein (CRP), White Blood Cell Count (WBC), Interleukins 4, 6, 8, 10, 11, 12 (p70), Interferon gamma, Tumor-Necrosis-Factor alpha (TNF-a) and its soluble Receptors I/II, soluble Selectins (E,L,P), Substance-P (SP), and Calcitonin Gene-Related Peptide (CGRP) at different time points in venous blood from patients with acute (AC) and chronic (CC) CRPS I, patients with forearm fractures (FR), with neuralgia (NE), and from healthy volunteers (C). No significant changes for serum parameters investigated in CRPS compared to control groups were found except for CC/C (CGRP p = 0.007), FR/C (CGRP p = 0.048) and AC/CC (IL-12 p = 0.02; TNFRI/II p = 0.01; SP p = 0.049). High interindividual variations were observed. No intra- or interindividual correlation of parameters with clinical course (e.g. chronification) or outcome was detectable. Although clinically appearing as inflammation in acute stages, local rather than systemic inflammatory responses seem to be relevant in CRPS. Variable results from different studies might be explained by unpredictable intermittent release of mediators from local inflammatory processes into the blood combined with high interindividual variabilities. A clinically relevant difference to various control groups was not notable in this pilot study. Determination of systemic inflammatory parameters is not yet helpful in diagnostic and follow-up of CRPS I.

Physicians' approaches to the use of gastroprotective strategies in low-risk non-steroidal anti-inflammatory drug users.

PubMed

Murthy, S K; Kauldher, S; Targownik, L E

2006-05-01

Many doctors unnecessarily prescribe gastroprotective strategies to non-steroidal anti-inflammatory drugs users at low risk of non-steroidal anti-inflammatory drug-related gastrointestinal complications. To identify factors that predict the overuse of gastroprotective strategies in low-risk non-steroidal anti-inflammatory drug users. We distributed a questionnaire to family doctors and general internists consisting of a clinical vignette describing a low-risk hypothetical patient with osteoarthritis who was a candidate for non-steroidal anti-inflammatory drug therapy. Respondents were asked whether they would prescribe this patient a gastroprotective strategy and to estimate the annual risk of that patient developing a gastrointestinal complication with non-steroidal anti-inflammatory drug use. Respondents inappropriately recommending a gastroprotective strategy were compared with respondents who opted not to use gastroprotection. We received 340 responses (response rate of 28.3%), of which 278 supplied analysable data. Thirty-five percent of respondents inappropriately recommended a gastroprotective strategy for the low-risk subject. Inappropriate prescribers were significantly more likely to overestimate the risk of gastrointestinal complications with traditional non-steroidal anti-inflammatory drugs and this was strongly predictive of gastroprotective strategy recommendation in logistic regression. Many doctors inappropriately recommend gastroprotective strategies in low-risk non-steroidal anti-inflammatory drug users. Improving doctors' awareness of non-steroidal anti-inflammatory drug-associated gastrointestinal risks may lead to a decrease in inappropriate utilization of gastroprotective strategies in low-risk patients.

Predictive value of preoperative inflammatory response biomarkers for metabolic syndrome and post-PCNL systemic inflammatory response syndrome in patients with nephrolithiasis.

PubMed

Tang, Kun; Liu, Haoran; Jiang, Kehua; Ye, Tao; Yan, Libin; Liu, Peijun; Xia, Ding; Chen, Zhiqiang; Xu, Hua; Ye, Zhangqun

2017-10-17

Neutrophil to lymphocyte ratio (NLR), derived neutrophil to lymphocyte ratio (dNLR), platelet to lymphocyte ratio (PLR) and lymphocyte to monocyte ratio (LMR) were promising biomarkers used to predict diagnosis and prognosis in various inflammatory responses diseases and cancers. However, there have been no reports regarding these biomarkers in kidney stone patients. This study aimed to evaluate the predictive value of inflammatory biomarkers for metabolic syndrome (MetS) and post-PCNL SIRS in nephrolithiasis patients. We retrospectively enrolled 513 patients with nephrolithiasis and 204 healthy controls. NLR, dNLR, LMR and PLR in nephrolithiasis patients were significantly higher than control group. Patients with renal stone have higher NLR, dNLR, LMR and PLR than those without. ROC curve analysis indicated NLR, dNLR, LMR and PLR for predicting patients with nephrolithiasis and MetS, displayed AUC of 0.730, 0.717, 0.627 and 0.606. Additionally, ROC curves, using post-PCNL SIRS as the end-point for NLR, dNLR, LMR and PLR with AUC of 0.831, 0.813, 0.723 and 0.685. Multivariate analysis revealed that NLR, dNLR represented independent factors for predicting post-PCNL SIRS. While LMR independently associated with MetS. These resluts demonstrate preoperative NLR, dNLR and LMR appears to be effective predictors of post-PCNL SIRS and LMR of MetS in nephrolithiasis patients.

Metabolite Profiling and Pharmacokinetic Evaluation of Hydrocortisone in a Perfused Three-Dimensional Human Liver Bioreactor

PubMed Central

Sarkar, Ujjal; Rivera-Burgos, Dinelia; Large, Emma M.; Hughes, David J.; Ravindra, Kodihalli C.; Dyer, Rachel L.; Ebrahimkhani, Mohammad R.; Griffith, Linda G.

2015-01-01

Endotoxin lipopolysaccharide (LPS) is known to cause liver injury primarily involving inflammatory cells such as Kupffer cells, but few in vitro culture models are applicable for investigation of inflammatory effects on drug metabolism. We have developed a three-dimensional human microphysiological hepatocyte–Kupffer cell coculture system and evaluated the anti-inflammatory effect of glucocorticoids on liver cultures. LPS was introduced to the cultures to elicit an inflammatory response and was assessed by the release of proinflammatory cytokines, interleukin 6 and tumor necrosis factor α. A sensitive and specific reversed-phase–ultra high-performance liquid chromatography–quadrupole time of flight–mass spectrometry method was used to evaluate hydrocortisone disappearance and metabolism at near physiologic levels. For this, the systems were dosed with 100 nM hydrocortisone and circulated for 2 days; hydrocortisone was depleted to approximately 30 nM, with first-order kinetics. Phase I metabolites, including tetrahydrocortisone and dihydrocortisol, accounted for 8–10% of the loss, and 45–52% consisted of phase II metabolites, including glucuronides of tetrahydrocortisol and tetrahydrocortisone. Pharmacokinetic parameters, i.e., half-life, rate of elimination, clearance, and area under the curve, were 23.03 hours, 0.03 hour−1, 6.6 × 10−5 l⋅hour−1, and 1.03 (mg/l)*h, respectively. The ability of the bioreactor to predict the in vivo clearance of hydrocortisone was characterized, and the obtained intrinsic clearance values correlated with human data. This system offers a physiologically relevant tool for investigating hepatic function in an inflamed liver. PMID:25926431

Metabolite profiling and pharmacokinetic evaluation of hydrocortisone in a perfused three-dimensional human liver bioreactor.

PubMed

Sarkar, Ujjal; Rivera-Burgos, Dinelia; Large, Emma M; Hughes, David J; Ravindra, Kodihalli C; Dyer, Rachel L; Ebrahimkhani, Mohammad R; Wishnok, John S; Griffith, Linda G; Tannenbaum, Steven R

2015-07-01

Endotoxin lipopolysaccharide (LPS) is known to cause liver injury primarily involving inflammatory cells such as Kupffer cells, but few in vitro culture models are applicable for investigation of inflammatory effects on drug metabolism. We have developed a three-dimensional human microphysiological hepatocyte-Kupffer cell coculture system and evaluated the anti-inflammatory effect of glucocorticoids on liver cultures. LPS was introduced to the cultures to elicit an inflammatory response and was assessed by the release of proinflammatory cytokines, interleukin 6 and tumor necrosis factor α. A sensitive and specific reversed-phase-ultra high-performance liquid chromatography-quadrupole time of flight-mass spectrometry method was used to evaluate hydrocortisone disappearance and metabolism at near physiologic levels. For this, the systems were dosed with 100 nM hydrocortisone and circulated for 2 days; hydrocortisone was depleted to approximately 30 nM, with first-order kinetics. Phase I metabolites, including tetrahydrocortisone and dihydrocortisol, accounted for 8-10% of the loss, and 45-52% consisted of phase II metabolites, including glucuronides of tetrahydrocortisol and tetrahydrocortisone. Pharmacokinetic parameters, i.e., half-life, rate of elimination, clearance, and area under the curve, were 23.03 hours, 0.03 hour(-1), 6.6 × 10(-5) l⋅hour(-1), and 1.03 (mg/l)*h, respectively. The ability of the bioreactor to predict the in vivo clearance of hydrocortisone was characterized, and the obtained intrinsic clearance values correlated with human data. This system offers a physiologically relevant tool for investigating hepatic function in an inflamed liver. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

Effect of omega-3 supplementation on inflammatory parameters in patients on chronic ambulatory peritoneal dialysis

PubMed Central

Naini, Afsoon Emami; Asiabi, Reza Ebrahimi Kord; Keivandarian, Noushin; Moeinzadeh, Firouzeh

2015-01-01

Background: End stage renal disease (ESRD) is a state of micro inflammation that attenuates patient's life span and quality of life. Inflammatory markers like interlukin 6 (IL-6) and C- reactive protein (CRP) can predict inflammatory state in ESRD patients. Dietary limitations are risk factors for omega-3 deficiency in these patients. Omega-3 supplementation is an attractive material that proposed in inflammation modulation. The aim of this study is evaluation of effect of omega-3 supplementation on IL-6 and CRP level in chronic ambulatory peritoneal dialysis (CAPD) patients. Materials and Methods: This randomized controlled double-blind clinical trial is performed in 40 CAPD patients in two academic hospitals in Isfahan, Iran. One group received 1000 mg omega-3 capsule (each capsule contains 180 mg Eicosapentanoic and 120 mg Dosahexanoic acid) three times a day orally for 8 weeks (n = 20) and the other matched group by placebo (n = 20). Serum level of IL-6 and quantitative CRP (Q-CRP) were measured in beginning and the end of the study. Finally all data were analyzed by SPSS version 18. Results: Mean age of patients was 53 years old in omega-3 group patients and 54 years old in placebo group. There were not any differences in CRP and IL-6 level in the beginning and the end of study between two groups (P: 0.81 and 0.10 for CRP and 0.26 and 0.23 for IL-6, respectively). Conclusion: Omega-3 supplementation did not effect on inflammatory markers (Q-CRP and IL-6) in CAPD patients after 8 weeks. PMID:26436081

High Intensity Interval Training Reduces the Levels of Serum Inflammatory Cytokine on Women with Metabolic Syndrome.

PubMed

Steckling, F M; Farinha, J B; Santos, D L D; Bresciani, G; Mortari, J A; Stefanello, S T; Courtes, A A; Duarte, T; Duarte, M M M F; Moresco, R N; Cardoso, M S; Soares, F A A

2016-11-01

Objectives: This study investigate the effects of a high intensity interval training (HIIT) and 2 weeks of detraining in functional and body composition parameters, lipoproteins, glucose metabolismand inflammation markers in postmenopausal women with metabolic syndrome (MS). Design: 17 untrained women with MS underwent a HIIT program for 12 weeks. Methods: The training was performed in treadmills, 3 days per week, with intensity ranging from 70-90% of the maximum heart rate (HR max ) and 2 weeks untrained (inactive). Functional and body composition parameters were evaluated before and after the training, while maximal oxygen uptake, lipoprotein and inflammation markers were analyzed before, after training and also in detraining. Results: The HITT program resulted in changesparameters as glucose, HbA1cand NOx after training. In addition, a reduction in pro-inflammatory interleukins and an increase in IL-10 after the HIIT program were found. However, an increase in plasma levels of lipoprotein was found and body composition parameters remain unaltered.Besides, only 2 weeks of detraining are able to revert the effects on inflammatory parameters afforded by the HIIT program. Conclusions: The HIIT program used here positively affected inflammatory profile and other parameters, as glucose, HbA1cand NOx, on postmenopausal women with MS. Moreover, 2 weeks of detraining can reverse the beneficial effects of HIIT program. Our results point out the necessity to aply acontinuous HITT program, in order maintain the benefits detected, to post menopausal women with MS. © Georg Thieme Verlag KG Stuttgart · New York.

Time-courses of plasma IL-6 and HMGB-1 reflect initial severity of clinical presentation but do not predict poor neurologic outcome following subarachnoid hemorrhage.

PubMed

Kiiski, Heikki; Långsjö, Jaakko; Tenhunen, Jyrki; Ala-Peijari, Marika; Huhtala, Heini; Hämäläinen, Mari; Moilanen, Eeva; Öhman, Juha; Peltola, Jukka

2017-03-01

Patients with aneurysmal subarachnoid hemorrhage (aSAH) experience high mortality and morbidity. Neuroinflammation causes brain damage expansion after aSAH. Due to the complexity of the inflammatory response multiple biomarkers are needed to evaluate its' progression. We studied inflammatory process after aSAH by measuring two inflammatory biomarkers, interleukin-6 (IL-6) and high-mobility group box 1 (HMGB1) at simultaneous time-points after aSAH. In this prospective population-based study, IL-6 and HMGB1 were measured in aSAH patients (n = 47) for up to five days. Plasma concentrations of IL-6 and HMGB1 were measured at 0, 12 and 24 h after hospital admission, and thereafter daily for up to five days or until the patient was transferred from the intensive care unit (ICU). The patients' neurological outcomes were evaluated with the modified Rankin Scale at six months after aSAH. A high IL-6 level during the first day after aSAH was associated with a severe initial clinical presentation (p = 0.002) and infection during follow-up (p = 0.031). The HMGB1 level did not associate with these parameters. There was no correlation between IL-6 and HMGB1 levels at any time point during the follow-up. The concentrations of IL-6 and HMGB1 were not associated with neurological outcome. High initial IL-6 values seem to reflect the intensity of the inflammatory response but not the brain damage per se. An early inflammatory response might even be beneficial since although elevated IL-6 levels were observed in patients with a more severe initial clinical presentation, they were not associated with neurological outcome. The lack of correlation between IL-6 and HMGB1 questions the role of macrophages in the process of the secretion of these inflammatory markers after aSAH, instead pointing to the activation of alternative pro-inflammatory pathways.

Sample size considerations using mathematical models: an example with Chlamydia trachomatis infection and its sequelae pelvic inflammatory disease.

PubMed

Herzog, Sereina A; Low, Nicola; Berghold, Andrea

2015-06-19

The success of an intervention to prevent the complications of an infection is influenced by the natural history of the infection. Assumptions about the temporal relationship between infection and the development of sequelae can affect the predicted effect size of an intervention and the sample size calculation. This study investigates how a mathematical model can be used to inform sample size calculations for a randomised controlled trial (RCT) using the example of Chlamydia trachomatis infection and pelvic inflammatory disease (PID). We used a compartmental model to imitate the structure of a published RCT. We considered three different processes for the timing of PID development, in relation to the initial C. trachomatis infection: immediate, constant throughout, or at the end of the infectious period. For each process we assumed that, of all women infected, the same fraction would develop PID in the absence of an intervention. We examined two sets of assumptions used to calculate the sample size in a published RCT that investigated the effect of chlamydia screening on PID incidence. We also investigated the influence of the natural history parameters of chlamydia on the required sample size. The assumed event rates and effect sizes used for the sample size calculation implicitly determined the temporal relationship between chlamydia infection and PID in the model. Even small changes in the assumed PID incidence and relative risk (RR) led to considerable differences in the hypothesised mechanism of PID development. The RR and the sample size needed per group also depend on the natural history parameters of chlamydia. Mathematical modelling helps to understand the temporal relationship between an infection and its sequelae and can show how uncertainties about natural history parameters affect sample size calculations when planning a RCT.

Application of Box-Behnken design for ultrasonic-assisted extraction of polysaccharides from Paeonia emodi.

PubMed

Ahmad, Ajaz; Alkharfy, Khalid M; Wani, Tanveer A; Raish, Mohammad

2015-01-01

The objective of the present work was to study the ultrasonic assisted extraction and optimization of polysaccharides from Paeonia emodi and evaluation of its anti-inflammatory response. Specifically, the optimization of polysaccharides was carried out using Box-Behnken statistical experimental design. Response surface methodology (RSM) of three factors (extraction temperature, extraction time and liquid solid ratio) was employed to optimize the percentage yield of the polysaccharides. The experimental data were fitted to quadratic response surface models using multiple regression analysis with high coefficient of determination value (R) of 0.9906. The highest polysaccharide yield (8.69%) as per the Derringer's desirability prediction tool was obtained under the optimal extraction condition (extraction temperature 47.03 °C, extraction time 15.68 min, and liquid solid ratio 1.29 ml/g) with a desirability value of 0.98. These optimized values of tested parameters were validated under similar conditions (n = 6), an average of 8.13 ± 2.08% of polysaccharide yield was obtained in an optimized extraction conditions with 93.55% validity. The anti-inflammatory effect of polysaccharides of P. emodi were studied on carrageenan induced paw edema. In vivo results showed that the P. emodi 200mg/kg of polysaccharide extract exhibited strong potential against inflammatory response induced by 1% suspension of carrageenean in normal saline. Copyright © 2014 Elsevier B.V. All rights reserved.

Association Between Nutritional Status, Inflammatory Condition, and Prognostic Indexes with Postoperative Complications and Clinical Outcome of Patients with Gastrointestinal Neoplasia.

PubMed

Costa, Milena Damasceno de Souza; Vieira de Melo, Camila Yandara Sousa; Amorim, Ana Carolina Ribeiro de; Cipriano Torres, Dilênia de Oliveira; Dos Santos, Ana Célia Oliveira

2016-10-01

The aim of this study is to describe and relate nutritional and inflammatory status and prognostic indexes with postoperative complications and clinical outcome of patients with gastrointestinal malignancies. Twenty-nine patients were evaluated; nutritional assessment was carried out by subjective and objective parameters; albumin, pre-albumin, C-reactive protein (CRP), and alpha-1-acid glycoprotein (AGP) were determined. To assess prognosis, the Glasgow scale, the Prognostic Inflammatory Nutritional Index (PINI), and CRP/albumin ratio were used; the clinical outcomes considered were hospital discharge and death. A high Subjective Global Assessment (SGA) score was associated with the occurrence of postoperative complications: 73% of the patients with postoperative complications had the highest SGA score, but only 6% of those without postoperative complications had the highest SGA score (P < 0.001). Greater occurrence of death was observed in patients with a high SGA score, low serum albumin, increased CRP, PINI > 1, and Glasgow score 2. There was a positive correlation between weight loss percentage with serum CRP levels (P = 0.002), CRP/albumin (P = 0.002), PINI (P = 0.002), and Glasgow score (P = 0.000). This study provides evidence that the assessment of the nutritional status and the use of prognostic indexes are good tools for predicting postoperative complications and clinical outcome in patients with gastrointestinal neoplasia.

Inflammatory markers in SIRS, sepsis and septic shock.

PubMed

Herzum, I; Renz, H

2008-01-01

Despite great advancement in the understanding of the pathophysiology and in the development of novel therapeutic approaches, mortality of sepsis still remains unacceptably high. Adequate laboratory diagnostics represents a major requirement for the improvement of this situation. For a better understanding of the immunological dysregulation in this disease, several markers are now available for routine diagnostics in the clinical laboratory. They include the cytokines interleukin (IL) -6, IL-8, procalcitonin and the LPS-binding protein (LBP). These novel markers will be compared to the conventional procedure of diagnosing inflammatory and infectious disease, such as measurements of C-reactive protein (CRP) as a major acute phase protein and differential blood counting. Important questions addressed in this review are the usefulness of these markers for early diagnosis, their role as prognostic markers and in the risk assessment of patients. Furthermore, we will discuss whether these parameters are to differentiate between systemic inflammatory response syndrome (SIRS) and sepsis at its different degrees. In the case of an infectious nature of the disease, it is important to differentiate between viral or bacterial origin and to monitor the responsiveness of antibiotic therapies. The literature was analysed with focus on the evidence for diagnostic and analytical performance. For this purpose international definition and staging criteria were used in context of criteria for assay performance including sensitivity, specificity, negative and positive predictive values, ROC analysis and other analytical criteria.

Progression of chronic periodontitis can be predicted by the levels of Porphyromonas gingivalis and Treponema denticola in subgingival plaque.

PubMed

Byrne, S J; Dashper, S G; Darby, I B; Adams, G G; Hoffmann, B; Reynolds, E C

2009-12-01

Chronic periodontitis is an inflammatory disease of the supporting tissues of the teeth associated with bacteria. Diagnosis is achieved retrospectively by clinical observation of attachment loss. Predicting disease progression would allow for targeted preventive therapy. The aim of this study was to monitor disease progression in patients on a maintenance program and determine the levels of specific bacteria in subgingival plaque samples and then examine the ability of the clinical parameters of disease and levels of specific bacteria in the plaque samples to predict disease progression. During a 12-month longitudinal study of 41 subjects, 25 sites in 21 subjects experienced disease progression indicated by at least 2 mm of clinical attachment loss. Real-time polymerase chain reaction was used to determine the levels of Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, Fusobacterium nucleatum, and Prevotella intermedia in subgingival plaque samples. No clinical parameters were able to predict periodontal disease progression. In sites undergoing imminent periodontal disease progression within the next 3 months, significant partial correlations were found between P. gingivalis and T. forsythia (r = 0.55, P < 0.001) and T. denticola and T. forsythia (r = 0.43, P = 0.04). The odds of a site undergoing imminent periodontal disease progression increased with increasing levels of P. gingivalis and T. denticola. Monitoring the proportions of P. gingivalis and T. denticola in subgingival plaque has the potential to help identify sites at significant risk for progression of periodontitis, which would assist in the targeted treatment of disease.

Time Courses of Inflammatory Markers after Aneurysmal Subarachnoid Hemorrhage and Their Possible Relevance for Future Studies.

PubMed

Höllig, Anke; Stoffel-Wagner, Birgit; Clusmann, Hans; Veldeman, Michael; Schubert, Gerrit A; Coburn, Mark

2017-01-01

Aneurysmal subarachnoid hemorrhage triggers an intense inflammatory response, which is suspected to increase the risk for secondary complications such as delayed cerebral ischemia (DCI). However, to date, the monitoring of the inflammatory response to detect secondary complications such as DCI has not become part of the clinical routine diagnostic. Here, we aim to illustrate the time courses of inflammatory parameters after aneurysmal subarachnoid hemorrhage (aSAH) and discuss the problems of inflammatory parameters as biomarkers but also their possible relevance for deeper understanding of the pathophysiology after aSAH and sophisticated planning of future studies. In this prospective cohort study, 109 patients with aSAH were initially included, n  = 28 patients had to be excluded. Serum and-if possible-cerebral spinal fluid samples ( n  = 48) were retrieved at days 1, 4, 7, 10, and 14 after aSAH. Samples were analyzed for leukocyte count and C-reactive protein (CRP) (serum samples only) as well as matrix metallopeptidase 9 (MMP9), intercellular adhesion molecule 1 (ICAM1), and leukemia inhibitory factor (LIF) [both serum and cerebrospinal fluid (CSF) samples]. Time courses of the inflammatory parameters were displayed and related to the occurrence of DCI. We illustrate the time courses of leukocyte count, CRP, MMP9, ICAM1, and LIF in patients' serum samples from the first until the 14th day after aSAH. Time courses of MMP9, ICAM1, and LIF in CSF samples are demonstrated. Furthermore, no significant difference was shown relating the time courses to the occurrence of DCI. We estimate that the wide range of the measured values hampers their interpretation and usage as a biomarker. However, understanding the inflammatory response after aSAH and generating a multicenter database may facilitate further studies: realistic sample size calculations on the basis of a multicenter database will increase the quality and clinical relevance of the acquired results.

Predictive relevance of clinical scores and inflammatory parameters in secondary peritonitis.

PubMed

Zügel, Nikolaus P; Kox, Martin; Lichtwark-Aschoff, Michael; Gippner-Steppert, Cornelia; Jochum, Marianne

2011-01-01

To measure and evaluate clinical scores and various inflammation parameters for providing a better outcome assessment of patients with secondary peritonitis. Prospective study. ICU of a university and a university affiliated hospital. Fifty-six patients with severe secondary peritonitis were enrolled in this study executed within 4 years. Blood samples were taken preoperatively and 2, 6, 8, 12, 18, 24, 30, 36, 42 and 48 hours post operation, thereafter every 12th hour until day 5 respectively once daily until day 14. Etiology of peritonitis, clinical score systems (APACHE II, MOF and SOFA), and 27 mainly with activity tests or enzyme-immunoassays measurable inflammation parameters were simultaneously analyzed and stratified into lethal outcome (n = 11) or survival (n = 45), respectively. The etiological distribution of peritonitis was identical among both groups. Proportion of intraperitoneal fungi, E. coli, and bacteroids was substantially higher during the primary operation in the group with lethal outcome. With increasing significance initial and follow-up APACHE II, MOF and SOFA scores provided higher values in this group. Various plasma/serum parameters of hemostasis, leukocyte proteolytic system, acute phase reaction, cytokine system, cell adhesion, opsonization, and main organ functions showed significantly different values between both groups at the preoperative stage and/or during observation period I (day 0-4). Logistic regression analysis revealed the SOFA score and neopterin concentration as the combination with the best sensitivity (63.6%) and specificity (93.2%) for predicting the patients' survival even at the preoperative stage. For the observation period I, the combination of SOFA score and TNF receptor II showed the highest predictive sensitivity (72.7%) and specificity (95.6%). Evaluation of the severity of secondary peritonitis using a scoring system with high prognostic relevance could conceivably result in an earlier and adequate application of intensive care such as hemofiltration, administration of immunoglobulins and serial abdominal lavage to improve successful outcome.

Dietary inflammatory index, bone health and body composition in a population of young adults: a cross-sectional study.

PubMed

Correa-Rodríguez, María; Rueda-Medina, Blanca; González-Jiménez, Emilio; Correa-Bautista, Jorge Enrique; Ramírez-Vélez, Robinson; Schmidt-RioValle, Jacqueline

2018-03-07

Diet quality has been postulated as a relevant factor in disorders like obesity and osteoporosis as it modulates inflammatory biomarkers. The aim of this study was to investigate whether the dietary inflammatory index (DII) is associated with bone health status and body composition parameters in a population of young adults. The study population consisted of 599 young adults (aged 20.41 ± 2.72). Linear regression analysis revealed that weight and fat-free mass (FFM) were significantly associated with the DII after adjustments for age, sex and total energy (β = -0.91, 95% CI -1.782, -0.213, p = .013 and β = -0.059, 95% CI -0.842, -0.107, p = .011, respectively). Our results suggest that the inflammatory potential of diet, measured using the DII, is associated with obesity-related parameters such as FFM and weight, although it may not contribute to osteoporosis in early adulthood.

Erythrocyte sedimentation rate as baseline predictor for the development of uveitis in children with juvenile idiopathic arthritis.

PubMed

Haasnoot, Arenda J W; van Tent-Hoeve, Maretta; Wulffraat, Nico M; Schalij-Delfos, Nicoline E; Los, Leonoor I; Armbrust, Wineke; Zuithoff, Nicolaas P A; de Boer, Joke H

2015-02-01

To analyze inflammatory parameters as possible predictors for the development of uveitis in juvenile idiopathic arthritis (JIA) patients. Further, to analyze the predictive value of demographic and clinical factors at the onset of arthritis. Retrospective cohort study. In 358 children with oligoarthritis and rheumatoid factor-negative polyarthritis, erythrocyte sedimentation rate (ESR), C-reactive protein, leukocyte count, presence of antinuclear antibodies (ANA), presence of human leukocyte antigen (HLA-)B27, age of onset of JIA, and sex were analyzed for their predictive value for the onset of uveitis. One hundred forty-seven patients (41%) were diagnosed with chronic anterior uveitis. Young age of onset, presence of ANA, and elevated ESR appeared to be predictive factors according to univariate analyses (P = .029, P = .007, and P = 5E(-4), respectively). According to multivariate analysis, young age of onset and elevated ESR appeared to be predictive after adjusting for the other relevant factors (P = .004 and P = .001, respectively). A prediction model was developed. Elevated ESR appears to be a predictor for the occurrence of uveitis in patients with JIA. Since ESR is already routinely tested in patients with recently diagnosed arthritis, its use as a biomarker can easily be implemented in daily practice. Copyright © 2015 Elsevier Inc. All rights reserved.

Body mass index influences infliximab post-infusion levels and correlates with prospective loss of response to the drug in a cohort of inflammatory bowel disease patients under maintenance therapy with Infliximab.

PubMed

Scaldaferri, Franco; D'Ambrosio, Daria; Holleran, Grainne; Poscia, Andrea; Petito, Valentina; Lopetuso, Loris; Graziani, Cristina; Laterza, Lucrezia; Pistone, Maria Teresa; Pecere, Silvia; Currò, Diego; Gaetani, Eleonora; Armuzzi, Alessandro; Papa, Alfredo; Cammarota, Giovanni; Gasbarrini, Antonio

2017-01-01

Infliximab is an effective treatment for inflammatory bowel disease (IBD). Studies differ regarding the influence of body mass index (BMI) on the response to infliximab, with the majority of studies indicating that increased BMI may be associated with a poorer response to Infliximab. However, the pharmacokinetic mechanisms causing this have not yet been reported. Examine the correlation between BMI/immunosuppressant use with clinical response, trough and post-infusion levels of infliximab, tumour necrosis factor-α(TNF-α) and anti-drug antibodies(ATI), and determine if these factors can predict future response. We collected serum from 24 patients receiving Infliximab before and 30 minutes following infusion. Clinical parameters were collected retrospectively and prospectively. ELISA measurements of infliximab, TNF-α and ATI were performed. We confirmed that patients with higher infliximab trough levels have a better response rate and that patients with an elevated BMI display a higher rate of loss of response (20%). Patients with a higher BMI had elevated post-infusion levels of infliximab. Additionally, the ratio of IFX/TNF-α trough levels correlated with clinical response to the following infusion. This study confirms that an elevated BMI is associated with a poorer response to infliximab. For the first time, we describe that a higher BMI correlates with higher post-infusion levels, however this does not correlate with a higher rate of response to the drug, suggesting that circulating drug levels do not correlate with tissue levels. Furthermore, in our small cohort of patients, we identified a possible predictive marker of future response to treatment which may be used to guide dose escalation and predict non-response to infliximab.

Sepsis biomarkers in neutropaenic systemic inflammatory response syndrome patients on standard care wards.

PubMed

Ratzinger, Franz; Haslacher, Helmuth; Perkmann, Thomas; Schmetterer, Klaus G; Poeppl, Wolfgang; Mitteregger, Dieter; Dorffner, Georg; Burgmann, Heinz

2015-08-01

Neutropaenic patients are at a high risk of contracting severe infections. In particular, in these patients, parameters with a high negative predictive value are desirable for excluding infection or bacteraemia. This study evaluated sepsis biomarkers in neutropaenic patients suffering from systemic inflammatory response syndrome (SIRS). Further, the predictive capacities of evaluated biomarkers in neutropaenic SIRS patients were compared to non-neutropaenic SIRS patients. In this prospective observational cohort study, patients with clinically suspected sepsis were screened. The predictive capacities of procalcitonin (PCT), C-reactive protein and lipopolysaccharide-binding protein (LBP) in neutropaenic SIRS patients were evaluated in terms of their potential to identify infection or bacteraemia and were compared to results for non-neutropaenic SIRS patients. To select an appropriate control cohort, propensity score matching was applied, balancing confounding factors between neutropaenic and non-neutropaenic SIRS patients. Of 3370 prospectively screened patients with suspected infection, 51 patients suffered from neutropaenic SIRS. For the identification of infection, none of the assessed biomarkers presented a clinically relevant discriminatory potency. Lipopolysaccharide-binding protein and PCT demonstrated discriminatory capacity to discriminate between nonbacteraemic and bacteraemic SIRS in patients with neutropaenia [receiver-operating characteristics-area under the curves (ROC-AUCs): 0.860, 0.818]. In neutropaenic SIRS patients, LBP had a significantly better ROC-AUC than in a comparable non-neutropaenic patient cohort for identifying bacteraemia (P = 0.01). In neutropaenic SIRS patients, none of the evaluated biomarkers was able to adequately identify infection. LBP and PCT presented a good performance in identifying bacteraemia. Therefore, these markers could be used for screening purposes to increase the pretest probability of blood culture analysis. © 2015 Stichting European Society for Clinical Investigation Journal Foundation.

Association between cardiac autonomic function, oxidative stress and inflammatory response in impaired fasting glucose subjects: cross-sectional study.

PubMed

Thiyagarajan, Ramkumar; Subramanian, Senthil Kumar; Sampath, Nishanth; Madanmohan Trakroo; Pal, Pravati; Bobby, Zachariah; Paneerselvam, Sankar; Das, Ashok Kumar

2012-01-01

The worldwide burden of diabetes in 2030 is projected around 552 million. Diabetes leads to higher risk for cardiovascular diseases (CVD). Altered cardiac autonomic function (CAF) measured by heart rate variability (HRV) is observed in early stages of diabetes but the relationship between impaired fasting glucose (IFG) and HRV is still debatable. The aim of the study was to evaluate the association between CAF, oxidative stress, insulin resistance (IR), and inflammatory response in IFG subjects. Cross-sectional blinded study. Volunteers recruited from health awareness camps underwent CAF and biochemical tests. Based on fasting plasma glucose (FPG) participants (n = 123) were divided into two groups, normal fasting glucose (n = 76) and IFG (n = 47). The comparison of parameters between the groups was carried out using student t test and Mann-Whitney U test for parametric and non-parametric data respectively. The correlation between the parameters was analyzed by Spearman's rank correlation using SPSS 13.0. The resting cardiovagal modulation parameters, heart rate response to forced timed breathing, and orthostatic stress were reduced in IFG subjects. Fasting plasma lipid profile, coronary atherogenic lipid risk factors, IR, thiobarbituric acid reactive substance (TBARS), high sensitive C-reactive protein, and tumor necrosis factor alpha were increased and total antioxidant capacity (TAC) was decreased significantly in IFG group but no significant alteration was observed in high-density lipoprotein (HDL-c). Cardiovagal modulation parameters were negatively correlated with triglycerides, FPG, insulin, IR, TBARS, and inflammatory markers and positively with TAC. There is a continuous interplay between the altered CAF, hyperinsulinemia, IR, oxidative stress parameters, inflammatory response, and IFG in which one factor perpetuates another leading to the progression of disease.

Effect of steroids on inflammatory markers and clinical parameters in congenital open heart surgery: a randomised controlled trial.

PubMed

Amanullah, Muhammad M; Hamid, Mohammad; Hanif, Hashim M; Muzaffar, Marium; Siddiqui, Maria T; Adhi, Fatima; Ahmad, Khabir; Khan, Shahjahan; Hasan, Zahra

2016-03-01

Cardiopulmonary bypass is associated with systemic inflammatory response. Steroids suppress this response, although the therapeutic evidence remains controversial. We hypothesised that intravenous steroids in children undergoing open-heart surgery would decrease inflammation leading to better early post-operative outcomes. We conducted a randomised controlled trial to evaluate the trends in the levels of immunomodulators and their effects on clinical parameters. To assess the effects of intravenous steroids on early post-operative inflammatory markers and clinical parameters in children undergoing open-heart surgery. A randomised controlled trial involving 152 patients, from one month up to 18 years of age, who underwent open-heart surgery for congenital heart disease from April 2010-2012 was carried out. Patients were randomised and administered either three scheduled intravenous pulse doses of dexamethasone (1 mg/kg) or placebo. Blood samples were drawn at four time intervals and serum levels of inflammatory cytokines - Interleukin-6, 8, 10, 18, and tumour necrosis factor-alpha - were measured. Clinical parameters were also assessed. Blood cytokine levels were compared between the dexamethasone (n=65) and placebo (n=64) groups. Interleukin-6 levels were lower at 6 and 24 hours post-operatively (p<0.001), and Interleukin-10 levels were higher 6 hours post-operatively (p<0.001) in the steroid group. Interleukin-8, 18, and tumour necrosis factor-alpha levels did not differ between the groups at any time intervals. The clinical parameters were similar in both the groups. Dexamethasone caused quantitative suppression of Interleukin-6 and increased Interleukin-10 activation, contributing to reduced immunopathology, but it did not translate into clinical benefit in the short term.

Hemostatic, inflammatory, and oxidative markers in pesticide user farmers.

PubMed

Madani, Fatima Zohra; Hafida, Merzouk; Merzouk, Sid Ahmed; Loukidi, Bouchra; Taouli, Katia; Narce, Michel

2016-01-01

The aim of this work was to investigate inflammatory, oxidative, and thrombotic parameters as biomarkers in farmers exposed to pesticides. Fifty farmers using chemical pesticides and 60 unexposed control men participated in this study. The Mediterranean diet compliance, the duration of pesticide use, and personal protection for pesticides handling were recorded using self-administered questionnaires. Serum biochemical parameters, oxidant/antioxidant, inflammatory, and thrombosis markers were determined. Our findings showed oxidative stress reflected by an increase in malondialdehyde, carbonyl proteins and superoxide anion levels and a decrease in vitamins C and E, glutathione, catalase, and superoxide dismutase activities in farmers. Serum C-reactive protein, prothrombin, and fibrinogen levels were enhanced in these farmers. In conclusion, inflammation, oxidative stress, and metabolic perturbations reflected the possibility of the effects of pesticides to farmers.

Development of anti-inflammatory drugs - the research and development process.

PubMed

Knowles, Richard Graham

2014-01-01

The research and development process for novel drugs to treat inflammatory diseases is described, and several current issues and debates relevant to this are raised: the decline in productivity, attrition, challenges and trends in developing anti-inflammatory drugs, the poor clinical predictivity of experimental models of inflammatory diseases, heterogeneity within inflammatory diseases, 'improving on the Beatles' in treating inflammation, and the relationships between big pharma and biotechs. The pharmaceutical research and development community is responding to these challenges in multiple ways which it is hoped will lead to the discovery and development of a new generation of anti-inflammatory medicines. © 2013 Nordic Pharmacological Society. Published by John Wiley & Sons Ltd.

Raman spectroscopy detects deterioration in biomechanical properties of bone in a glucocorticoid-treated mouse model of rheumatoid arthritis

NASA Astrophysics Data System (ADS)

Maher, Jason R.; Takahata, Masahiko; Awad, Hani A.; Berger, Andrew J.

2011-08-01

Although glucocorticoids are frequently prescribed for the symptomatic management of inflammatory disorders such as rheumatoid arthritis, extended glucocorticoid exposure is the leading cause of physician-induced osteoporosis and leaves patients at a high risk of fracture. To study the biochemical effects of glucocorticoid exposure and how they might affect biomechanical properties of the bone, Raman spectra were acquired from ex vivo tibiae of glucocorticoid- and placebo-treated wild-type mice and a transgenic mouse model of rheumatoid arthritis. Statistically significant spectral differences were observed due to both treatment regimen and mouse genotype. These differences are attributed to changes in the overall bone mineral composition, as well as the degree of phosphate mineralization in tibial cortical bone. In addition, partial least squares regression was used to generate a Raman-based prediction of each tibia's biomechanical strength as quantified by a torsion test. The Raman-based predictions were as accurate as those produced by microcomputed tomography derived parameters, and more accurate than the clinically-used parameter of bone mineral density. These results suggest that Raman spectroscopy could be a valuable tool for monitoring bone biochemistry in studies of bone diseases such as osteoporosis, including tests of drugs being developed to combat these diseases.

Designing a Pediatric Severe Sepsis Screening Tool

PubMed Central

Sepanski, Robert J.; Godambe, Sandip A.; Mangum, Christopher D.; Bovat, Christine S.; Zaritsky, Arno L.; Shah, Samir H.

2014-01-01

We sought to create a screening tool with improved predictive value for pediatric severe sepsis (SS) and septic shock that can be incorporated into the electronic medical record and actively screen all patients arriving at a pediatric emergency department (ED). “Gold standard” SS cases were identified using a combination of coded discharge diagnosis and physician chart review from 7,402 children who visited a pediatric ED over 2 months. The tool’s identification of SS was initially based on International Consensus Conference on Pediatric Sepsis (ICCPS) parameters that were refined by an iterative, virtual process that allowed us to propose successive changes in sepsis detection parameters in order to optimize the tool’s predictive value based on receiver operating characteristics (ROC). Age-specific normal and abnormal values for heart rate (HR) and respiratory rate (RR) were empirically derived from 143,603 children seen in a second pediatric ED over 3 years. Univariate analyses were performed for each measure in the tool to assess its association with SS and to characterize it as an “early” or “late” indicator of SS. A split-sample was used to validate the final, optimized tool. The final tool incorporated age-specific thresholds for abnormal HR and RR and employed a linear temperature correction for each category. The final tool’s positive predictive value was 48.7%, a significant, nearly threefold improvement over the original ICCPS tool. False positive systemic inflammatory response syndrome identifications were nearly sixfold lower. PMID:24982852

The utility of fecal calprotectin in predicting the need for escalation of therapy in inflammatory bowel disease.

PubMed

Kwapisz, Lukasz; Gregor, Jamie; Chande, Nilesh; Yan, Brian; Ponich, Terry; Mosli, Mahmoud

2017-08-01

Fecal calprotectin is an important biomarker used in the evaluation of inflammatory bowel disease. It has proven to be an effective tool in initial screening as well monitoring response to therapy. The aim of this study is to examine the utility of fecal calprotectin both as a predictor for the escalation of therapy in established inflammatory bowel disease and as a predictor of de novo diagnosis. Patients with signs and symptoms concerning for inflammatory bowel disease presenting to outpatient clinics were recruited to provide fecal calprotectin stool samples prior to endoscopic evaluation. Patients were followed up for at least one year and monitored clinically for any change in symptomatology, escalation of therapy or development of IBD, confirmed endoscopically. A total of 126 patients, of whom 72 were known to have underlying inflammatory bowel disease, were included in the final analysis. Among the patients with elevated fecal calprotectin levels and known inflammatory bowel disease, 66% (33/50) went on to have escalation of therapy within 12 months compared to 18% (4/22) if the fecal calprotectin levels were in the normal range (p < .0001). For the remaining patients who at baseline did not have inflammatory bowel disease and a normal endoscopic evaluation, elevated fecal calprotectin resulted in no cases (0/17) of a new diagnosis in the next 12 months. Fecal calprotectin is a useful test for predicting escalation of therapy in established inflammatory bowel disease.

Prevalence and risk factors of Clostridium difficile infection in patients hospitalized for flare of inflammatory bowel disease: a retrospective assessment.

PubMed

Regnault, Helene; Bourrier, Anne; Lalande, Valerie; Nion-Larmurier, Isabelle; Sokol, Harry; Seksik, Philippe; Barbut, Frederic; Cosnes, Jacques; Beaugerie, Laurent

2014-12-01

Recent studies have identified a high frequency of Clostridium difficile infections in patients with active inflammatory bowel disease. To retrospectively assess the determinants and results of Clostridium difficile testing upon the admission of patients hospitalized with active inflammatory bowel disease in a tertiary care centre and to determine the predicting factors of Clostridium difficile infections. We reviewed all admissions from January 2008 and December 2010 for inflammatory bowel disease flare-ups. A toxigenic culture and a stool cytotoxicity assay were performed for all patients tested for Clostridium difficile. Out of 813 consecutive stays, Clostridium difficile diagnostic assays have been performed in 59% of inpatients. The independent predictive factors for the testing were IBD (ulcerative colitis: OR 2.0, 95% CI 1.5-2.9; p<0.0001) and colonic involvement at admission (OR 2.2, 95% CI 1.5-3.1, p<0.0001). Clostridium difficile infection was present in 7.0% of the inpatients who underwent testing. In a multivariate analysis, the only independent predictor was the intake of nonsteroidal anti-inflammatory drugs within the two months before admission (OR 3.8, 95% CI 1.2-12.3; p=0.02). Clostridium difficile infection is frequently associated with active inflammatory bowel disease. Our study suggests that a recent intake of nonsteroidal anti-inflammatory drugs is a risk factor for inflammatory bowel disease -associated Clostridium difficile infection. Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Maternal immune status in pregnancy is related to offspring's immune responses and atopy risk.

PubMed

Herberth, G; Hinz, D; Röder, S; Schlink, U; Sack, U; Diez, U; Borte, M; Lehmann, I

2011-08-01

The influence of maternal immune responses in pregnancy on children's immune competence and the development of atopic diseases later in life are poorly understood. To determine potential maternal effects on the maturation of children's immune system and resulting disease risks, we analysed immune responses in mother-child pairs in a prospective birth cohort study. Within the Lifestyle and Environmental factors and their Influence on Newborns Allergy risk (LINA) study, concentrations of Th1/Th2/Th17 and inflammatory cytokines/chemokines as well as IgE were measured in phytohemagglutinin and lipopolysaccharide stimulated maternal blood in the 34th week of gestation and in corresponding children's blood at birth and 1 year after (n = 353 mother-child pairs). Information on atopic outcomes during the first year of life was obtained from questionnaires. Concentrations of inflammatory markers, excepting TNF-α, were manifold higher in cord blood samples compared with maternal blood. Th1/Th2 cytokines were lower in children's blood with a Th2 bias at birth. Maternal inflammatory parameters (MCP-1, IL-10, TNF-α) in pregnancy showed an association with corresponding cytokines blood levels in children at the age of one. High maternal IgE concentrations in pregnancy were associated with increased children's IgE at birth and at the age of one, whereas children's atopic dermatitis (AD) was determined by maternal AD. Maternal inflammatory cytokines during pregnancy correlate with children's corresponding cytokines at the age of one but are not related to IgE or AD. While maternal IgE predicts children's IgE, AD in children is only associated with maternal disease. © 2011 John Wiley & Sons A/S.

Baseline and postoperative levels of C-reactive protein and interleukins as inflammatory predictors of atrial fibrillation following cardiac surgery: a systematic review and meta-analysis.

PubMed

Weymann, Alexander; Popov, Aron-Frederik; Sabashnikov, Anton; Ali-Hasan-Al-Saegh, Sadeq; Ryazanov, Mikhail; Tse, Gary; Mirhosseini, Seyed Jalil; Liu, Tong; Lotfaliani, Mohammadreza; Sedaghat, Meghdad; Baker, William L; Ghanei, Azam; Yavuz, Senol; Zeriouh, Mohamed; Izadpanah, Payman; Dehghan, Hamidreza; Testa, Luca; Nikfard, Maryam; Sá, Michel Pompeu Barros de Oliveira; Mashhour, Ahmed; Nombela-Franco, Luis; Rezaeisadrabadi, Mohammad; D'Ascenzo, Fabrizio; Zhigalov, Konstantin; Benedetto, Umberto; Aminolsharieh Najafi, Soroosh; Szczechowicz, Marcin; Roever, Leonardo; Meng, Lei; Gong, Mengqi; Deshmukh, Abhishek J; Palmerini, Tullio; Linde, Cecilia; Filipiak, Krzysztof J; Stone, Gregg W; Biondi-Zoccai, Giuseppe; Calkins, Hugh

2018-01-01

Postoperative atrial fibrillation (POAF) is a leading arrhythmia with high incidence and serious clinical implications after cardiac surgery. Cardiac surgery is associated with systemic inflammatory response including increase in cytokines and activation of endothelial and leukocyte responses. This systematic review and meta-analysis aimed to determine the strength of evidence for evaluating the association of inflammatory markers, such as C-reactive protein (CRP) and interleukins (IL), with POAF following isolated coronary artery bypass grafting (CABG), isolated valvular surgery, or a combination of these procedures. We conducted a meta-analysis of studies evaluating measured baseline (from one week before surgical procedures) and postoperative levels (until one week after surgical procedures) of inflammatory markers in patients with POAF. A compre-hensive search was performed in electronic medical databases (Medline/PubMed, Web of Science, Embase, Science Direct, and Google Scholar) from their inception through May 2017 to identify relevant studies. A comprehensive subgroup analysis was performed to explore potential sources of heterogeneity. A literature search of all major databases retrieved 1014 studies. After screening, 42 studies were analysed including a total of 8398 patients. Pooled analysis showed baseline levels of CRP (standard mean difference [SMD] 0.457 mg/L, p < 0.001), baseline levels of IL-6 (SMD 0.398 pg/mL, p < 0.001), postoperative levels of CRP (SMD 0.576 mg/L, p < 0.001), postoperative levels of IL-6 (SMD 1.66 pg/mL, p < 0.001), postoperative levels of IL-8 (SMD 0.839 pg/mL, p < 0.001), and postoperative levels of IL-10 (SMD 0.590 pg/mL, p < 0.001) to be relevant inflammatory parameters significantly associated with POAF. Perioperative inflammation is proposed to be involved in the pathogenesis of POAF. Therefore, perioperative assessment of CRP, IL-6, IL-8, and IL-10 can help clinicians in terms of predicting and monitoring for POAF.

Diagnostic value of inflammatory cell infiltrates, tumor stroma percentage and disease-free survival in patients with colorectal cancer

PubMed Central

Jakubowska, Katarzyna; Kisielewski, Wojciech; Kańczuga-Koda, Luiza; Koda, Mariusz; Famulski, Waldemar

2017-01-01

The anticancer immune defense mechanism involves humoral and cellular responses. The main effector mechanisms of antitumor responses involve the following: the activity of cytotoxic T cells; the activation of macrophages and neutrophils; the activity of cytokines secreted by T cells; and natural killer cell activity. Selected cell populations are responsible for the stimulation or suppression of the immune system against tumor cells. Therefore, the aim of the present study was to evaluate the location, extent and composition of the cellular inflammatory infiltration of tumors in patients with colorectal cancer (CRC). In addition, the correlation between cellular inflammatory infiltration, and anatomoclinical and histopathological features of patients was evaluated. The study involved 160 patients diagnosed with primary operable CRC. The local inflammatory infiltrate was assessed in the invasive front and center of the tumor using light microscopy with hematoxylin and eosin (H&E) staining, according to the Klintrup-Makinen criteria, tumor stroma percentage, and Glasgow microenvironment score. The inflammatory infiltrate in the invasive front of the tumor was correlated with gender (P=0.018), the invasion of blood vessels (P=0.020) and lymph vessels (P=0.038), the presence of tumor-infiltrating lymphocytes in the invasive front (P=0.033) and center (P<0.001) of the tumor, fibrosis (P<0.001), and the degree of desmoplasmic stroma (P=0.004). In contrast, inflammatory infiltration in the center of the tumor was associated with the tumor node metastasis stage (P=0.012), Dukes' stage (P=0.009), primary tumor stage (P=0.036), lymph node status (P=0.005), number of lymph nodes (P=0.006), invasion of lymph node pouches (P=0.021), size of lymph node metastasis (P=0.025) and the degree of desmoplasmic stroma (P=0.002). The low-group, who demonstrated an absent or weak inflammatory cell infiltrate in the invasive front of the tumor, had a statistically significant shorter disease-free survival (DFS) time (P=0.004). Inflammatory cell infiltrate in the invasive front was identified as an independent predictive factor in CRC (P=0.041). In conclusion, the degree of inflammatory cell infiltration in the invasive front of the primary tumor significantly affects various variables that determine disease progression and DFS rates of patients with CRC. Furthermore, the routine histopathological assessment of this parameter in tissue stained with H&E may have potential prognostic value. PMID:28927159

Dietary Inflammatory Index and Cardiometabolic Risk Parameters in Overweight and Sedentary Subjects.

PubMed

Camargo-Ramos, Claudia Marcela; Correa-Bautista, Jorge Enrique; Correa-Rodríguez, María; Ramírez-Vélez, Robinson

2017-10-06

Nutrition has been established as a relevant factor in the development of cardiovascular disease (CVD). We aimed to investigate the relationship between the dietary inflammatory index (DII) and cardiometabolic risk parameters in a cohort of 90 overweight and sedentary adults from Bogotá, Colombia. A 24-h dietary record was used to calculate the DII. Body composition variables, flow-mediated dilation (FMD), pulse wave velocity (PWV), lipid profile, glucose, glycosylated hemoglobin (Hb1Ac), and blood pressure were measured and a cardiometabolic risk score (MetScore) was calculated. A lower DII score (anti-inflammatory diet) was significantly associated with higher high-density lipoprotein-cholesterol (HDL-C) and FMD, and lower Hb1Ac and MetScore ( p < 0.05). A lower DII score was inversely correlated with plasma triglyceride levels ( r = -0.354, p < 0.05), glucose ( r = -0.422, p < 0.05), MetScore ( r = -0.228, p < 0.05), and PWV ( r = -0.437, p < 0.05), and positively with FMD ( r = 0.261, p < 0.05). In contrast, a higher DII score (pro-inflammatory diet) showed a positive relationship with MetScore ( r = 0.410, p < 0.05) and a negative relationship with FMD ( r = -0.233, p < 0.05). An increased inflammatory potential of diet was inversely associated with an improved cardiometabolic profile, suggesting the importance of promoting anti-inflammatory diets as an effective strategy for preventing CVD.

Anti-oxidant and anti-inflammatory effects of apigenin in a rat model of sepsis: an immunological, biochemical, and histopathological study.

PubMed

Karamese, Murat; Erol, Huseyin Serkan; Albayrak, Mevlut; Findik Guvendi, Gulname; Aydin, Emsal; Aksak Karamese, Selina

2016-06-01

We hypothesize that apigenin may inhibit some cellular process of sepsis-induced spleen injury and simultaneously improve inflammation and oxidative stress. Therefore, the aim of this study was to investigate the potential protective effects of apigenin in a polymicrobial sepsis rat model of by cecal ligation and puncture. 64 female Wistar albino rats were divided into 8 groups. The pro-inflammatory (tumor necrosis factor-alpha, interleukin-6, and interleukin-1-beta) and anti-inflammatory (tumor growth factor-beta and interleukin-10) cytokine levels were measured by enzyme-linked immunosorbent assay. CD3, CD68, and nuclear factor kappa B (NF-κB) positivity rates were detected by immunohistochemical methods. Oxidative stress parameters were measured by tissue biochemistry. Sepsis caused a significant increase in TNF-alpha, IL-1-beta, IL-6, and TGF-beta levels whereas it reduced IL-10 level. Additionally, it led to an increase in CD3, CD68, and NF-κB positivity rates as well as oxidative stress parameters levels. However, apigenin inhibited the inflammation process, increased the IL-10 level and normalized the oxidative stress parameters. Pretreatment with apigenin results in a significant reduction in the amount of inflammatory cells. The beneficial effect of apigenin on spleen injury also involved inhibition of NF-κB pathway, suppression of proinflammatory cytokines, and induction of anti-inflammatory cytokine production. Additionally, it led to a decrease in oxidative stress in spleen tissue. Taking everything into account, apigenin may be an alternative therapeutic option for prevention of sepsis-induced organ.

Inflammatory and Other Biomarkers: Role in Pathophysiology and Prediction of Gestational Diabetes Mellitus

PubMed Central

Abell, Sally K.; De Courten, Barbora; Boyle, Jacqueline A.; Teede, Helena J.

2015-01-01

Understanding pathophysiology and identifying mothers at risk of major pregnancy complications is vital to effective prevention and optimal management. However, in current antenatal care, understanding of pathophysiology of complications is limited. In gestational diabetes mellitus (GDM), risk prediction is mostly based on maternal history and clinical risk factors and may not optimally identify high risk pregnancies. Hence, universal screening is widely recommended. Here, we will explore the literature on GDM and biomarkers including inflammatory markers, adipokines, endothelial function and lipids to advance understanding of pathophysiology and explore risk prediction, with a goal to guide prevention and treatment of GDM. PMID:26110385

Resveratrol supplementation decreases blood glucose without changing the circulating CD14+CD16+ monocytes and inflammatory cytokines in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled study.

PubMed

Khodabandehloo, Hadi; Seyyedebrahimi, ShadiSadat; Esfahani, Ensieh Nasli; Razi, Farideh; Meshkani, Reza

2018-06-01

Chronic low-grade inflammation is the hallmark of type 2 diabetes (T2D). Although in vitro and animal studies have shown that resveratrol exerts anti-inflammatory effects, clinical trials addressing these effects in patients with T2D are limited. Therefore, in the present study, we hypothesized that supplementation of resveratrol might improve inflammatory markers in patients with T2D in a randomized, double-blind, placebo-controlled clinical trial. A total of 45 T2D patients were supplemented with either of 800 mg/d resveratrol or placebo capsules for 8 weeks. Percentage of CD14 + CD16 + monocytes, plasma levels of inflammatory cytokines (tumor necrosis factor α, interleukin [IL] 1β, IL-6, and monocyte chemoattractant protein-1), the expression levels of genes involved in the inflammatory responses (toll-like receptor 2, toll-like receptor 4, and nuclear factor κB), lipopolysaccharide-stimulated cytokine (tumor necrosis factor α, IL-1β, and IL-6) secretion from peripheral blood mononuclear cells, and metabolic and anthropometric parameters were assessed at both the baseline level and the end of the study. Compared with the placebo group, we could not detect any significant difference in the percentage of CD14 + CD16 + monocytes, lipopolysaccharide-induced cytokine secretion, plasma levels of inflammatory cytokines, and the expression of inflammatory genes in resveratrol group. Moreover, we did not find any significant change in the metabolic and anthropometric parameters except for a significant reduction in fasting blood glucose and blood pressure. In conclusion, 8-week supplementation of resveratrol reduces blood glucose level in patients with T2D without improving their inflammatory markers. Copyright © 2018 Elsevier Inc. All rights reserved.

Anti-inflammatory intestinal activity of Combretum duarteanum Cambess. in trinitrobenzene sulfonic acid colitis model

PubMed Central

de Morais Lima, Gedson Rodrigues; Machado, Flavia Danniele Frota; Périco, Larissa Lucena; de Faria, Felipe Meira; Luiz-Ferreira, Anderson; Souza Brito, Alba Regina Monteiro; Pellizzon, Cláudia Helena; Hiruma-Lima, Clélia Akiko; Tavares, Josean Fechine; Barbosa Filho, José Maria; Batista, Leônia Maria

2017-01-01

AIM To evaluate the anti-inflammatory intestinal effect of the ethanolic extract (EtOHE) and hexane phase (HexP) obtained from the leaves of Combretum duarteanum (Cd). METHODS Inflammatory bowel disease was induced using trinitrobenzenesulfonic acid in acute and relapsed ulcerative colitis in rat models. Damage scores, and biochemical, histological and immunohistochemical parameters were evaluated. RESULTS Both Cd-EtOHE and Cd-HexP caused significant reductions in macroscopic lesion scores and ulcerative lesion areas. The vegetable samples inhibited myeloperoxidase increase, as well as pro-inflammatory cytokines TNF-α and IL-1β. Anti-inflammatory cytokine IL-10 also increased in animals treated with the tested plant samples. The anti-inflammatory intestinal effect is related to decreased expression of cyclooxygenase-2, proliferating cell nuclear antigen, and an increase in superoxide dismutase. CONCLUSION The data indicate anti-inflammatory intestinal activity. The effects may also involve participation of the antioxidant system and principal cytokines relating to inflammatory bowel disease. PMID:28293082

Atrial Electromechanical Properties in Inflammatory Bowel Disease.

PubMed

Efe, Tolga Han; Cimen, Tolga; Ertem, Ahmet Goktug; Coskun, Yusuf; Bilgin, Murat; Sahan, Haluk Furkan; Pamukcu, Hilal Erken; Yayla, Cagri; Sunman, Hamza; Yuksel, Ilhami; Yeter, Ekrem

2016-09-01

There is much evidence linking inflammation to the initiation and continuation of atrial fibrillation (AF). Inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), are chronic systemic inflammatory disorders. Atrial electromechanical delay (EMD) has been known as an early marker of AF. The objectives of this study were to evaluate the atrial electromechanical properties in patients with IBD. Fifty-two patients with IBD and 26 healthy controls were recruited in the study. Twenty-five of patients with IBD were on active period, and the remaining 27 were on remission period. Atrial electromechanical properties were measured by using transthoracic echocardiography and tissue Doppler imaging and simultaneous surface ECG recording. Interatrial EMD, left intraatrial EMD, and right intraatrial EMD were calculated. Patients on activation with IBD had significantly prolonged left and right intraatrial EMDs and interatrial EMD compared to patients on remission (P = 0.048, P = 0.036, P < 0.001, respectively) and healthy controls (P < 0.001, for all comparisons). Left and right intraatrial EMDs and interatrial EMD were also found to be higher when patients on remission with IBD compared with healthy controls. No statistical difference was observed between UC and CD in terms of inter- and intraatrial EMDs. Atrial electromechanical conduction is prolonged in IBD, and exposure to chronic inflammation may lead to structural and electrophysiological changes in the atrial tissue that causes slow conduction. Measurement of atrial EMD parameters might be used to predict the risk for the development of AF in patients with IBD. © 2016, Wiley Periodicals, Inc.

Inflammatory and oxidative stress-related effects associated with neurotoxicity are maintained after exclusively prenatal trichloroethylene exposure

PubMed Central

Blossom, Sarah J.; Melnyk, Stepan B.; Li, Ming; Wessinger, William D.; Cooney, Craig A.

2016-01-01

Trichloroethylene (TCE) is a widespread environmental toxicant with immunotoxic and neurotoxic potential. Previous studies have shown that continuous developmental exposure to TCE encompassing gestation and early life as well as postnatal only exposure in the drinking water of MRL+/+ mice promoted CD4+ T cell immunotoxicity, glutathione depletion and oxidative stress in the cerebellum, as well increased locomotor activity in male offspring. The purpose of this study was to characterize the effects of exclusively prenatal exposure on these parameters. Another goal was to investigate potential plasma oxidative stress/inflammatory biomarkers to possibly be used as predictors of TCE-mediated neurotoxicity. In the current study, 6 week old male offspring of dams exposed gestationally to 0, 0.01, and 0.1 mg/ml TCE in the drinking water were evaluated. Our results confirmed that the oxidized phenotype in plasma and cerebellum was maintained after exclusively prenatal exposure. A Phenotypic analysis by flow cytometry revealed that TCE exposure expanded the effector/memory subset of peripheral CD4+ T cells in association with increased production of pro-inflammatory cytokines IFN-γ and IL-17. Serum biomarkers of oxidative stress and inflammation were also elevated in plasma suggesting that systemic effects are important and may be used to predict neurotoxicity in our model. These results suggested that the prenatal period is a critical stage of life by which the developing CNS and immune system are susceptible to long-lasting changes mediated by TCE. PMID:26812193

Inflammatory Bowel Disease.

PubMed

2016-01-01

Inflammation response plays an important role in host survival, and it also leads to acute and chronic inflammatory diseases such as rheumatoid arthritis, bowel diseases, allergic rhinitis, asthma, atopic dermatitis and various neurodegenerative diseases. During the course of inflammation, the ROS level increases. In addition to ROS, several inflammatory mediators produced at the site lead to numerous cell-mediated damages. Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is a chronic intestinal disorder resulting from a dysfunctional epithelial, innate and adaptive immune response to intestinal microorganisms. The methods involving indomethacin-induced enterocolitis in rats with macroscopic changes of IBD, myeloperoxidase assay, microscopic (histologic) characters and biochemical parameters are discussed.

[Dependence of anti-inflammatory effects of high peak-power pulsed electromagnetic radiation of extremely high frequency on exposure parameters].

PubMed

Gapeev, A B; Mikhaĭlik, E N; Rubanik, A V; Cheremis, N K

2007-01-01

A pronounced anti-inflammatory effect of high peak-power pulsed electromagnetic radiation of extremely high frequency was shown for the first time in a model of zymosan-induced footpad edema in mice. Exposure to radiation of specific parameters (35, 27 GHz, peak power 20 kW, pulse widths 400-600 ns, pulse repetition frequency 5-500 Hz) decreased the exudative edema and local hyperthermia by 20% compared to the control. The kinetics and the magnitude of the anti-inflammatory effect were comparable with those induced by sodium diclofenac at a dose of 3 mg/kg. It was found that the anti-inflammatory effect linearly increased with increasing pulse width at a fixed pulse repetition frequency and had threshold dependence on the average incident power density of the radiation at a fixed pulse width. When animals were whole-body exposed in the far-field zone of radiator, the optimal exposure duration was 20 min. Increasing the average incident power density upon local exposure of the inflamed paw accelerated both the development of the anti-inflammatory effect and the reactivation time. The results obtained will undoubtedly be of great importance in the hygienic standardization of pulsed electromagnetic radiation and in further studies of the mechanisms of its biological action.

Pro-inflammatory cytokines and oxidative stress/antioxidant parameters characterize the bio-humoral profile of early cachexia in lung cancer patients.

PubMed

Fortunati, Nicoletta; Manti, Roberta; Birocco, Nadia; Pugliese, Mariateresa; Brignardello, Enrico; Ciuffreda, Libero; Catalano, Maria G; Aragno, Manuela; Boccuzzi, Giuseppe

2007-12-01

Cancer-related cachexia, that is present in about 50% of cancer patients and accounts for 20% of all cancer deaths, is clinically characterized by progressive weight loss, anorexia, metabolic alterations, asthenia, depletion of lipid stores and severe loss of skeletal muscle proteins. The main biochemical and molecular alterations that are responsible for the syndrome are prematurely present in the progress of the disease and the identification of the early stages of cachexia can be useful in targetting patients who will benefit from early treatment. The aim of the present study was to delineate the bio-humoral profile of a group of lung cancer patients either non-cachectic or cachectic by evaluating serum pro-inflammatory cytokines and oxidative stress/antioxidant parameters (both recognized to be involved in cachexia pathogenesis) and pro-inflammatory cytokine gene expression in PBMC (Peripheral blood mononuclear cells) of cancer patients. All serum pro-inflammatory cytokines and oxidative stress/antioxidant parameters significantly increased in neoplastic patients, but only TNF-alpha, ROS, GSH and vitamin E showed a significantly greater increase in cachectic patients. Pro-inflammatory cytokine gene expression mirrored serum level behaviour except for IL-6 that was increased in serum but not as gene expression, suggesting its provenience from tumour tissue. Our data support that the simultaneous determination of ROS, GSH, vitamin E, together with TNF-alpha allows the identification of a lung cancer patient developing cancer-related cachexia. This bio-humoral profile should be used for the early diagnosis and follow-up of the syndrome. Moreover, the evaluation of gene expression in patient PBMC was helpful in differentiating tumour vs host factors, therefore being useful in the study of pathogenetic mechanisms in neoplastic cachectic patients.

Effects of tylosin, tilmicosin and tulathromycin on inflammatory mediators in bronchoalveolar lavage fluid of lipopolysaccharide-induced lung injury.

PubMed

Er, Ayse; Yazar, Enver

2012-12-01

The aim of this study was to determine the anti-inflammatory effects of macrolides through kinetic parameters in bronchoalveolar lavage fluid (BALF) of lipopolysaccharide-induced lung injury. Rats were divided into four groups: lipopolysaccharide (LPS), LPS + tylosin, LPS + tilmicosin and LPS + tulathromycin. BALF samples were collected at sampling times. TNF, IL-1β, IL-6, IL-10 and 13,14-dihydro-15-keto-prostaglandin F2α (PGM) and C-reactive protein (CRP) were analysed. Area under the curve (AUC) and maximum plasma concentration (Cmax) values of inflammatory mediators were determined by a pharmacokinetic computer programme. When inflammatory mediator concentrations were compared between the LPS group and other groups for each sampling time, the three macrolides had no pronounced depressor effect on cytokine levels, but they depressed PGM and CRP levels. In addition, tylosin and tilmicosin decreased the AUC0-24 level of TNF, while tilmicosin decreased the AUC0-24 level of IL-10. Tylosin and tulathromycin decreased the AUC0-24 of PGM, and all three macrolides decreased the AUC0-24 of CRP. Especially tylosin and tulathromycin may have more expressed anti-inflammatory effects than tilmicosin, via depressing the production of inflammatory mediators in the lung. The AUC may be used for determining the effects of drugs on inflammation. In this study, the antiinflammatory effects of these antibiotics were evaluated with kinetic parameters as a new and different approach.

Dietary Inflammatory Index and Cardiometabolic Risk Parameters in Overweight and Sedentary Subjects

PubMed Central

Camargo-Ramos, Claudia Marcela

2017-01-01

Nutrition has been established as a relevant factor in the development of cardiovascular disease (CVD). We aimed to investigate the relationship between the dietary inflammatory index (DII) and cardiometabolic risk parameters in a cohort of 90 overweight and sedentary adults from Bogotá, Colombia. A 24-h dietary record was used to calculate the DII. Body composition variables, flow-mediated dilation (FMD), pulse wave velocity (PWV), lipid profile, glucose, glycosylated hemoglobin (Hb1Ac), and blood pressure were measured and a cardiometabolic risk score (MetScore) was calculated. A lower DII score (anti-inflammatory diet) was significantly associated with higher high-density lipoprotein-cholesterol (HDL-C) and FMD, and lower Hb1Ac and MetScore (p < 0.05). A lower DII score was inversely correlated with plasma triglyceride levels (r = −0.354, p < 0.05), glucose (r = −0.422, p < 0.05), MetScore (r = −0.228, p < 0.05), and PWV (r = −0.437, p < 0.05), and positively with FMD (r = 0.261, p < 0.05). In contrast, a higher DII score (pro-inflammatory diet) showed a positive relationship with MetScore (r = 0.410, p < 0.05) and a negative relationship with FMD (r = −0.233, p < 0.05). An increased inflammatory potential of diet was inversely associated with an improved cardiometabolic profile, suggesting the importance of promoting anti-inflammatory diets as an effective strategy for preventing CVD. PMID:28984835

Faecal calprotectin assay after induction with anti-Tumour Necrosis Factor α agents in inflammatory bowel disease: Prediction of clinical response and mucosal healing at one year.

PubMed

Guidi, Luisa; Marzo, Manuela; Andrisani, Gianluca; Felice, Carla; Pugliese, Daniela; Mocci, Giammarco; Nardone, Olga; De Vitis, Italo; Papa, Alfredo; Rapaccini, Gianlodovico; Forni, Franca; Armuzzi, Alessandro

2014-11-01

Faecal calprotectin levels correlate with inflammation in inflammatory bowel disease. We evaluated the role of faecal calprotectin after anti-Tumour Necrosis Factor α induction in inflammatory bowel disease patients to predict therapeutic effect at one year. Faecal calprotectin levels were measured in stools of 63 patients before and after induction of anti-Tumour Necrosis Factor α therapy. Clinical activity, measured by clinical indices, was assessed before and after biologic treatment. Clinical responders after induction were included in the study and colonoscopy was performed before and after one year of treatment to assess mucosal healing. 63 patients (44 Crohn's disease, 19 ulcerative colitis) were prospectively included (41.2% males, mean age at diagnosis 33 years). A sustained clinical response during the first year was observed in 57% of patients; median faecal calprotectin was 106 μg/g after induction versus 308 μg/g pre-induction (p<0.0001). Post-induction faecal calprotectin was significantly lower in responders versus non-responders (p=0.0002). Post-induction faecal calprotectin had 83% sensitivity and 74% specificity (cut-off ≤ 168 μg/g) for predicting a sustained clinical response at one year (p=0.0001); also, sensitivity was 79% and specificity 57% (cut-off ≤ 121 μg/g) for predicting mucosal healing (p=0.0001). In inflammatory bowel disease faecal calprotectin assay after anti-Tumour Necrosis Factor α induction can be used as a marker to predict sustained clinical response and mucosal healing at one year. Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

The dynamics of acute inflammation

NASA Astrophysics Data System (ADS)

Kumar, Rukmini

The acute inflammatory response is the non-specific and immediate reaction of the body to pathogenic organisms, tissue trauma and unregulated cell growth. An imbalance in this response could lead to a condition commonly known as "shock" or "sepsis". This thesis is an attempt to elucidate the dynamics of acute inflammatory response to infection and contribute to its systemic understanding through mathematical modeling and analysis. The models of immunity discussed use Ordinary Differential Equations (ODEs) to model the variation of concentration in time of the various interacting species. Chapter 2 discusses three such models of increasing complexity. Sections 2.1 and 2.2 discuss smaller models that capture the core features of inflammation and offer general predictions concerning the design of the system. Phase-space and bifurcation analyses have been used to examine the behavior at various parameter regimes. Section 2.3 discusses a global physiological model that includes several equations modeling the concentration (or numbers) of cells, cytokines and other mediators. The conclusions drawn from the reduced and detailed models about the qualitative effects of the parameters are very similar and these similarities have also been discussed. In Chapter 3, the specific applications of the biologically detailed model are discussed in greater detail. These include a simulation of anthrax infection and an in silico simulation of a clinical trial. Such simulations are very useful to biologists and could prove to be invaluable tools in drug design. Finally, Chapter 4 discusses the general problem of extinction of populations modeled as continuous variables in ODES is discussed. The average time to extinction and threshold are estimated based on analyzing the equivalent stochastic processes.

A score for the differential diagnosis of bradykinin- and histamine-induced head and neck swellings.

PubMed

Lenschow, M; Bas, M; Johnson, F; Wirth, M; Strassen, U

2018-05-02

Acute edema of the head and neck region may lead to life-threatening dyspnea and require quick and targeted treatment. They can be subdivided in bradykinin- and histamine-mediated swellings, which require treatment with different classes of pharmaceuticals. Clinical pathways for differential diagnoses do not exist so far, although it is known that early treatment is decisive for faster symptom relief and reduced expression of the swellings. Aim of the study was the creation of a clinical algorithm for identification of bradykinin-mediated angioedema. 188 patients that presented to our outpatient department between 2010 and 2016 with an acute, non-inflammatory swelling of the head and neck region were included in our retrospective study. All available anamnestic and clinical parameters were obtained from patient files. Parameters showing significant differences between the two groups were included in our score. Utilization of the Youden's index allowed determination of an optimal cut-off value. 76 patients could be assigned to the histamine and 112 patients to bradykinin group. The following parameters were included in our score: age, dyspnea, itching or erythema, glucocorticoid response and intake of ACEi/AT-II blockers. The cut-off value is set at three points. The proposed score yielded a sensitivity for identification of bradykinin-mediated angioedema of 96%, a specificity of 84%, a positive predictive value of 91% and a negative predictive value of 93%. Utilization of the proposed score allows quick and reliable assignment of patients to the correct subgroup and thereby reduces time for treatment.

Comparison of periodontal and peri-implant inflammatory parameters among patients with prediabetes, type 2 diabetes mellitus and non-diabetic controls.

PubMed

Abduljabbar, Tariq; Al-Sahaly, Faisal; Al-Kathami, Mohammed; Afzal, Sibtain; Vohra, Fahim

2017-07-01

The aim was to compare periodontal and periimplant inflammatory parameters (plaque index [PI], bleeding on probing [BOP], probing depth [PD] and marginal bone loss [MBL]) among patients with prediabetes, type-2 diabetes mellitus (T2DM) and non-diabetic controls. Forty-five patients with prediabetes (Group-1), 43 patients with T2DM (Group-2) and 42 controls (Group-3) were included. Demographic data was recorded using a questionnaire. Full mouth and periimplant clinical (PI, BOP and PD) were assessed and the radiographic MBL were measured on digital radiographs. In all groups, haemoglobin A1c (HbA1c) levels were also measured. p values less than .05 were considered statistically significant. The mean HbA1c levels of participants in groups 1, 2 and 3 were 6.1%, 8.4% and 4.8%, respectively. The mean duration of prediabetes and T2DM among patients in groups 1 and 2 were 1.9 ± 0.3 and 3.1 ± 0.5 years, respectively. Periodontal and periimplant PI, BOP, PD and MBL were higher in groups 1 (p < .05) and 2 (p < .05) than group 3. There was no difference in these parameters in groups 1 and 2. Periodontal and periimplant inflammatory parameters were worse among patients with prediabetes and T2DM compared with controls; however, these parameters were comparable among patients with prediabetes and T2DM.

Dehydroepiandrosterone in relation to other adrenal hormones during an acute inflammatory stressful disease state compared with chronic inflammatory disease: role of interleukin-6 and tumour necrosis factor.

PubMed

Straub, Rainer H; Lehle, Karin; Herfarth, Hans; Weber, Markus; Falk, Werner; Preuner, Jurgen; Scholmerich, Jurgen

2002-03-01

Serum levels of dehydroepiandrosterone (DHEA) and DHEA sulphate (DHEAS) are low in chronic inflammatory diseases, although the reasons are unexplained. Furthermore, the behaviour of serum levels of these hormones during an acute inflammatory stressful disease state is not well known. In this study in patients with an acute inflammatory stressful disease state (13 patients undergoing cardiothoracic surgery) and patients with chronic inflammation (61 patients with inflammatory bowel diseases (IBD)) vs. 120 controls, we aimed to investigate adrenal hormone shifts looking at serum levels of DHEA in relation to other adrenal hormones. Furthermore, we tested the predictive role of serum tumour necrosis factor (TNF) and interleukin-6 (IL-6) for a change of serum levels of DHEA in relation to other adrenal hormones. The molar ratio of serum levels of DHEA/androstenedione (ASD) was increased in patients with an acute inflammatory stressful disease state and was decreased in patients with chronic inflammation. The molar ratio of serum levels of DHEAS/DHEA was reduced during an acute inflammatory stressful disease state and was increased in patients with chronic inflammation. A multiple linear regression analysis revealed that elevated serum levels of TNF were associated with a high ratio of serum levels of DHEA/ASD in all groups (for IL-6 in patients with an acute inflammatory stressful disease state only), and, similarly, elevated serum levels of TNF were associated with a high ratio of serum levels of DHEAS/DHEA only in IBD (for IL-6 only in healthy subjects). This study indicates that changes of serum levels of DHEA in relation to serum levels of other adrenal hormones are completely different in patients with an acute inflammatory stressful disease state compared with patients with chronic inflammation. The decrease of serum levels of DHEAS and DHEA is typical for chronic inflammation and TNF and IL-6 play a predictive role for these changes.

Inflammatory role and prognostic value of platelet chemokines in acute coronary syndrome.

PubMed

Blanchet, X; Cesarek, K; Brandt, J; Herwald, H; Teupser, D; Küchenhoff, H; Karshovska, E; Mause, S F; Siess, W; Wasmuth, H; Soehnlein, O; Koenen, R R; Weber, C; von Hundelshausen, P

2014-12-01

Activated platelets and neutrophils exacerbate atherosclerosis. Platelets release the chemokines CXCL4, CXCL4L1 and CCL5, whereas myeloperoxidase (MPO) and azurocidin are neutrophil-derived. We investigated whether plasma levels of these platelet and neutrophil mediators are affected by the acute coronary syndrome (ACS), its medical treatment, concomitant clinical or laboratory parameters, and predictive for the progression of coronary artery disease (CAD). In an observational study, the association of various factors with plasma concentrations of platelet chemokines and neutrophil mediators in 204 patients, either upon admission with ACS and 6 hours later or without ACS or CAD, was determined by multiple linear regression. Mediator release was further analysed after activation of blood with ACS-associated triggers such as plaque material. CXCL4, CXCL4L1, CCL5, MPO and azurocidin levels were elevated in ACS. CXCL4 and CCL5 but not CXCL4L1 or MPO were associated with platelet counts and CRP. CXCL4 (in association with heparin treatment) and MPO declined over 6 hours during ACS. Elevated CCL5 was associated with a progression of CAD. Incubating blood with plaque material, PAR1 and PAR4 activation induced a marked release of CXCL4 and CCL5, whereas CXCL4L1 and MPO were hardly or not altered. Platelet chemokines and neutrophil products are concomitantly elevated in ACS and differentially modulated by heparin treatment. CCL5 levels during ACS predict a progression of preexisting CAD. Platelet-derived products appear to dominate the inflammatory response during ACS, adding to the emerging evidence that ACS per se may promote vascular inflammation.

Association of peripheral inflammation with body mass index and depressive relapse in bipolar disorder.

PubMed

Bond, David J; Andreazza, Ana C; Hughes, John; Dhanoa, Taj; Torres, Ivan J; Kozicky, Jan-Marie; Young, L Trevor; Lam, Raymond W; Yatham, Lakshmi N

2016-03-01

Bipolar I disorder (BD) is associated with increased inflammation, which is believed to be central to disease etiology and progression. However, BD patients also have high rates of obesity, itself an inflammatory condition, and the relative contributions of mood illness and obesity to inflammation are unknown. Moreover, the impact of inflammation on clinical illness course has not been well studied. The objectives of this analysis were therefore: (1) to determine if inflammation in BD is mood illness-related or secondary to elevated body mass index (BMI), and (2) to investigate the impact of inflammation on prospectively-ascertained relapse into depression and mania. We measured the serum levels of 7 inflammatory cytokines (TNF-α, γ-interferon, monocyte chemoattractant protein-1 [MCP-1], IL-1α, IL-2, IL-6, and IL-8) and 2 anti-inflammatory cytokines (IL-4 and IL-10) in 52 early-stage BD patients and 22 healthy subjects. In patients, a multivariate multiple regression model that controlled for psychotropic medications found that higher BMI, but not recent (past-6-month) mood episodes, predicted greater inflammatory cytokines (p=.05). Healthy subjects also had a BMI-related increase in inflammatory cytokines (p<.01), but it was counter-balanced by a compensatory increase in anti-inflammatory cytokines (p=.02), reducing their total inflammatory burden from higher BMI. In patients, linear regression showed that two inflammatory cytokines predicted depressive relapse in the 12 months after cytokine measurement: IL-1α (p<.01) and MCP-1 (p<.01). These results suggest that elevated BMI is a significant contributor to inflammation in BD, more so even than recent mood illness severity. They also point to inflammation as an important predictor of illness course, particularly depressive relapse. Copyright © 2015 Elsevier Ltd. All rights reserved.

A consideration of biomarkers to be used for evaluation of inflammation in human nutritional studies.

PubMed

Calder, P C; Ahluwalia, N; Albers, R; Bosco, N; Bourdet-Sicard, R; Haller, D; Holgate, S T; Jönsson, L S; Latulippe, M E; Marcos, A; Moreines, J; M'Rini, C; Müller, M; Pawelec, G; van Neerven, R J J; Watzl, B; Zhao, J

2013-01-01

To monitor inflammation in a meaningful way, the markers used must be valid: they must reflect the inflammatory process under study and they must be predictive of future health status. In 2009, the Nutrition and Immunity Task Force of the International Life Sciences Institute, European Branch, organized an expert group to attempt to identify robust and predictive markers, or patterns or clusters of markers, which can be used to assess inflammation in human nutrition studies in the general population. Inflammation is a normal process and there are a number of cells and mediators involved. These markers are involved in, or are produced as a result of, the inflammatory process irrespective of its trigger and its location and are common to all inflammatory situations. Currently, there is no consensus as to which markers of inflammation best represent low-grade inflammation or differentiate between acute and chronic inflammation or between the various phases of inflammatory responses. There are a number of modifying factors that affect the concentration of an inflammatory marker at a given time, including age, diet and body fatness, among others. Measuring the concentration of inflammatory markers in the bloodstream under basal conditions is probably less informative compared with data related to the concentration change in response to a challenge. A number of inflammatory challenges have been described. However, many of these challenges are poorly standardised. Patterns and clusters may be important as robust biomarkers of inflammation. Therefore, it is likely that a combination of multiple inflammatory markers and integrated readouts based upon kinetic analysis following defined challenges will be the most informative biomarker of inflammation.

A gene expression inflammatory signature specifically predicts multiple myeloma evolution and patients survival.

PubMed

Botta, C; Di Martino, M T; Ciliberto, D; Cucè, M; Correale, P; Rossi, M; Tagliaferri, P; Tassone, P

2016-12-16

Multiple myeloma (MM) is closely dependent on cross-talk between malignant plasma cells and cellular components of the inflammatory/immunosuppressive bone marrow milieu, which promotes disease progression, drug resistance, neo-angiogenesis, bone destruction and immune-impairment. We investigated the relevance of inflammatory genes in predicting disease evolution and patient survival. A bioinformatics study by Ingenuity Pathway Analysis on gene expression profiling dataset of monoclonal gammopathy of undetermined significance, smoldering and symptomatic-MM, identified inflammatory and cytokine/chemokine pathways as the most progressively affected during disease evolution. We then selected 20 candidate genes involved in B-cell inflammation and we investigated their role in predicting clinical outcome, through univariate and multivariate analyses (log-rank test, logistic regression and Cox-regression model). We defined an 8-genes signature (IL8, IL10, IL17A, CCL3, CCL5, VEGFA, EBI3 and NOS2) identifying each condition (MGUS/smoldering/symptomatic-MM) with 84% accuracy. Moreover, six genes (IFNG, IL2, LTA, CCL2, VEGFA, CCL3) were found independently correlated with patients' survival. Patients whose MM cells expressed high levels of Th1 cytokines (IFNG/LTA/IL2/CCL2) and low levels of CCL3 and VEGFA, experienced the longest survival. On these six genes, we built a prognostic risk score that was validated in three additional independent datasets. In this study, we provide proof-of-concept that inflammation has a critical role in MM patient progression and survival. The inflammatory-gene prognostic signature validated in different datasets clearly indicates novel opportunities for personalized anti-MM treatment.

Predictive Blood Chemistry Parameters for Pansteatitis-Affected Mozambique Tilapia (Oreochromis mossambicus)

PubMed Central

Chapman, Robert W.; Somerville, Stephen E.; Guillette, Matthew P.; Botha, Hannes; Hoffman, Andre; Luus-Powell, Wilmien J.; Smit, Willem J.; Lebepe, Jeffrey; Myburgh, Jan; Govender, Danny; Tucker, Jonathan; Boggs, Ashley S. P.

2016-01-01

One of the largest river systems in South Africa, the Olifants River, has experienced significant changes in water quality due to anthropogenic activities. Since 2005, there have been various “outbreaks” of the inflammatory disease pansteatitis in several vertebrate species. Large-scale pansteatitis-related mortality events have decimated the crocodile population at Lake Loskop and decreased the population at Kruger National Park. Most pansteatitis-related diagnoses within the region are conducted post-mortem by either gross pathology or histology. The application of a non-lethal approach to assess the prevalence and pervasiveness of pansteatitis in the Olifants River region would be of great importance for the development of a management plan for this disease. In this study, several plasma-based biomarkers accurately classified pansteatitis in Mozambique tilapia (Oreochromis mossambicus) collected from Lake Loskop using a commercially available benchtop blood chemistry analyzer combined with data interpretation via artificial neural network analysis. According to the model, four blood chemistry parameters (calcium, sodium, total protein and albumin), in combination with total length, diagnose pansteatitis to a predictive accuracy of 92 percent. In addition, several morphometric traits (total length, age, weight) were also associated with pansteatitis. On-going research will focus on further evaluating the use of blood chemistry to classify pansteatitis across different species, trophic levels, and within different sites along the Olifants River. PMID:27115488

Proposal for a recovery prediction method for patients affected by acute mediastinitis

PubMed Central

2012-01-01

Background An attempt to find a prediction method of death risk in patients affected by acute mediastinitis. There is not such a tool described in available literature for that serious disease. Methods The study comprised 44 consecutive cases of acute mediastinitis. General anamnesis and biochemical data were included. Factor analysis was used to extract the risk characteristic for the patients. The most valuable results were obtained for 8 parameters which were selected for further statistical analysis (all collected during few hours after admission). Three factors reached Eigenvalue >1. Clinical explanations of these combined statistical factors are: Factor1 - proteinic status (serum total protein, albumin, and hemoglobin level), Factor2 - inflammatory status (white blood cells, CRP, procalcitonin), and Factor3 - general risk (age, number of coexisting diseases). Threshold values of prediction factors were estimated by means of statistical analysis (factor analysis, Statgraphics Centurion XVI). Results The final prediction result for the patients is constructed as simultaneous evaluation of all factor scores. High probability of death should be predicted if factor 1 value decreases with simultaneous increase of factors 2 and 3. The diagnostic power of the proposed method was revealed to be high [sensitivity =90%, specificity =64%], for Factor1 [SNC = 87%, SPC = 79%]; for Factor2 [SNC = 87%, SPC = 50%] and for Factor3 [SNC = 73%, SPC = 71%]. Conclusion The proposed prediction method seems a useful emergency signal during acute mediastinitis control in affected patients. PMID:22574625

A model combining age, equivalent uniform dose and IL-8 may predict radiation esophagitis in patients with non-small cell lung cancer.

PubMed

Wang, Shulian; Campbell, Jeff; Stenmark, Matthew H; Stanton, Paul; Zhao, Jing; Matuszak, Martha M; Ten Haken, Randall K; Kong, Feng-Ming

2018-03-01

To study whether cytokine markers may improve predictive accuracy of radiation esophagitis (RE) in non-small cell lung cancer (NSCLC) patients. A total of 129 patients with stage I-III NSCLC treated with radiotherapy (RT) from prospective studies were included. Thirty inflammatory cytokines were measured in platelet-poor plasma samples. Logistic regression was performed to evaluate the risk factors of RE. Stepwise Akaike information criterion (AIC) and likelihood ratio test were used to assess model predictions. Forty-nine of 129 patients (38.0%) developed grade ≥2 RE. Univariate analysis showed that age, stage, concurrent chemotherapy, and eight dosimetric parameters were significantly associated with grade ≥2 RE (p < 0.05). IL-4, IL-5, IL-8, IL-13, IL-15, IL-1α, TGFα and eotaxin were also associated with grade ≥2 RE (p < 0.1). Age, esophagus generalized equivalent uniform dose (EUD), and baseline IL-8 were independently associated grade ≥2 RE. The combination of these three factors had significantly higher predictive power than any single factor alone. Addition of IL-8 to toxicity model significantly improves RE predictive accuracy (p = 0.019). Combining baseline level of IL-8, age and esophagus EUD may predict RE more accurately. Refinement of this model with larger sample sizes and validation from multicenter database are warranted. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Clinical effects of diet supplementation with DHA in pediatric patients suffering from cystic fibrosis.

PubMed

Leggieri, E; De Biase, R V; Savi, D; Zullo, S; Halili, I; Quattrucci, S

2013-08-01

Cystic fibrosis (CF) patients present an altered fatty acid (FA) metabolism characterized by imbalance in the arachidonic/docosohexasenoic acid (AA/DHA) ratio in favour of the former which can contribute to the increase in pulmonary inflammation. The present study aims to assess respiratory, nutritional, clinical and laboratory parameters, and inflammatory markers after six months of DHA supplementation in paediatric patients suffering from CF. A dose of 1 g/10 kg/die was administered to ten CF patients of paediatric age for the first month and 250 mg/10 kg/die for the remaining 5 months. We carried out follow-ups at T0 (baseline), T6 (after six months of the diet) and T12 (six months after supplementation was interrupted) during which respiratory, nutritional, clinical and laboratory parameters were assessed. After six months of DHA supplementation inflammatory marker levels had diminished: interleukin 8 (IL-8) and Tumour Necrosis Factor Alfa (TNF-α) in serum, and calprotectin in stools. In addition, auxometric parameters were improved as was the clinical condition of patients, who tolerated DHA well. Dietetic integration with DHA seems to improve clinical condition and the inflammatory pulmonary and intestinal state of pediatric patients suffering from CF.

[Level of sIgA, IgG, IgA in vaginal secretion in women with chronic inflammatory disease of small pelvis organs].

PubMed

Shibina, L V; Krasnoproshina, L I; Ordiiants, I M; Slatinova, O V; Skhodova, S A

2013-01-01

Determine levels of sIgA, IgG, IgA in vaginal secretion and saliva of women of reproductive age with chronic inflammatory diseases of small pelvis organs (IDSPO) at exacerbation stage and remission period. Clinical-laboratory and gynecological examination of 105 women was carried out. Based on the results obtained 3 groups were formed: patients with IDSPO at exacerbation stage; patients at remission stage; clinically healthy women. sIgA, IgG, IgA parameters were studied in vaginal secretion and saliva in women with IDSPO at exacerbation stage and remission period by radial immune diffusion in gel by Manchini method. An increase of immunoglobulin level in vaginal secretion of women with IDSPO at remission period and a sharper increase of these parameters during exacerbation of the disease compared with women of the control group were detected. During analysis of sIgA, IgG, IgA levels in saliva in the same groups of women the results were obtained that give evidence that the presence of IDSPO and local immune reaction do not lead to the changes of these parameters. The obtained parameters on the dependence of an increase of immunoglobulin levels in vaginal secretions and the degree of intensity of the inflammatory process give basis to use them with the aim of additional diagnostics.

Leukotriene A4 Hydrolase Genotype and HIV Infection Influence Intracerebral Inflammation and Survival From Tuberculous Meningitis.

PubMed

Thuong, Nguyen T T; Heemskerk, Dorothee; Tram, Trinh T B; Thao, Le T P; Ramakrishnan, Lalita; Ha, Vu T N; Bang, Nguyen D; Chau, Tran T H; Lan, Nguyen H; Caws, Maxine; Dunstan, Sarah J; Chau, Nguyen V V; Wolbers, Marcel; Mai, Nguyen T H; Thwaites, Guy E

2017-04-01

Tuberculous meningitis (TBM) is the most devastating form of tuberculosis, yet very little is known about the pathophysiology. We hypothesized that the genotype of leukotriene A4 hydrolase (encoded by LTA4H), which determines inflammatory eicosanoid expression, influences intracerebral inflammation, and predicts survival from TBM. We characterized the pretreatment clinical and intracerebral inflammatory phenotype and 9-month survival of 764 adults with TBM. All were genotyped for single-nucleotide polymorphism rs17525495, and inflammatory phenotype was defined by cerebrospinal fluid (CSF) leukocyte and cytokine concentrations. LTA4H genotype predicted survival of human immunodeficiency virus (HIV)-uninfected patients, with TT-genotype patients significantly more likely to survive TBM than CC-genotype patients, according to Cox regression analysis (univariate P = .040 and multivariable P = .037). HIV-uninfected, TT-genotype patients had high CSF proinflammatory cytokine concentrations, with intermediate and lower concentrations in those with CT and CC genotypes. Increased CSF cytokine concentrations correlated with more-severe disease, but patients with low CSF leukocytes and cytokine concentrations were more likely to die from TBM. HIV infection independently predicted death due to TBM (hazard ratio, 3.94; 95% confidence interval, 2.79-5.56) and was associated with globally increased CSF cytokine concentrations, independent of LTA4H genotype. LTA4H genotype and HIV infection influence pretreatment inflammatory phenotype and survival from TBM. LTA4H genotype may predict adjunctive corticosteroid responsiveness in HIV-uninfected individuals. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Sleep and biological parameters in professional burnout: A psychophysiological characterization

PubMed Central

Sauvet, Fabien; Gomez-Merino, Danielle; Boucher, Thierry; Elbaz, Maxime; Delafosse, Jean Yves; Leger, Damien; Chennaoui, Mounir

2018-01-01

Professional burnout syndrome has been described in association with insomnia and metabolic, inflammatory and immune correlates. We investigated the interest of exploring biological parameters and sleep disturbances in relation to burnout symptoms among white-collar workers. Fifty-four participants with burnout were compared to 86 healthy control participants in terms of professional rank level, sleep, job strain (Karasek questionnaire), social support, anxiety and depression (HAD scale). Fasting concentrations of glycaemia, glycosylated hemoglobin (HbA1C), total-cholesterol, triglycerides, C-reactive protein (CRP), thyroid stimulating hormone (TSH), 25-hydroxyvitamin D (25[OH]D), and white blood cell (WBC) counts were assessed. Analysis of variance and a forward Stepwise Multiple Logistic Regression were made to identify predictive factors of burnout. Besides reporting more job strain (in particular job control p = 0.02), higher levels of anxiety (p<0.001), and sleep disorders related to insomnia (OR = 21.5, 95%CI = 8.8–52.3), participants with burnout presented higher levels of HbA1C, glycaemia, CRP, lower levels of 25(OH)D, higher number of leukocytes, neutrophils and monocytes (P<0.001 for all) and higher total-cholesterol (P = 0.01). In particular, when HbA1c is > 3.5%, the prevalence of burnout increases from 16.6% to 60.0% (OR = 4.3, 95%CI = 2.8–6.9). Strong significant positive correlation existed between HbA1C and the two dimensions (emotional exhaustion and depersonalization (r = 0.79 and r = 0.71, p<0.01)) of burnout. Models including job strain, job satisfaction, anxiety and insomnia did not predict burnout (p = 0.30 and p = 0.50). However, when HbA1C levels is included, the prediction of burnout became significant (P = 0.03). Our findings demonstrated the interest of sleep and biological parameters, in particular HbA1C levels, in the characterization of professional burnout. PMID:29385150

Sleep and biological parameters in professional burnout: A psychophysiological characterization.

PubMed

Metlaine, Arnaud; Sauvet, Fabien; Gomez-Merino, Danielle; Boucher, Thierry; Elbaz, Maxime; Delafosse, Jean Yves; Leger, Damien; Chennaoui, Mounir

2018-01-01

Professional burnout syndrome has been described in association with insomnia and metabolic, inflammatory and immune correlates. We investigated the interest of exploring biological parameters and sleep disturbances in relation to burnout symptoms among white-collar workers. Fifty-four participants with burnout were compared to 86 healthy control participants in terms of professional rank level, sleep, job strain (Karasek questionnaire), social support, anxiety and depression (HAD scale). Fasting concentrations of glycaemia, glycosylated hemoglobin (HbA1C), total-cholesterol, triglycerides, C-reactive protein (CRP), thyroid stimulating hormone (TSH), 25-hydroxyvitamin D (25[OH]D), and white blood cell (WBC) counts were assessed. Analysis of variance and a forward Stepwise Multiple Logistic Regression were made to identify predictive factors of burnout. Besides reporting more job strain (in particular job control p = 0.02), higher levels of anxiety (p<0.001), and sleep disorders related to insomnia (OR = 21.5, 95%CI = 8.8-52.3), participants with burnout presented higher levels of HbA1C, glycaemia, CRP, lower levels of 25(OH)D, higher number of leukocytes, neutrophils and monocytes (P<0.001 for all) and higher total-cholesterol (P = 0.01). In particular, when HbA1c is > 3.5%, the prevalence of burnout increases from 16.6% to 60.0% (OR = 4.3, 95%CI = 2.8-6.9). Strong significant positive correlation existed between HbA1C and the two dimensions (emotional exhaustion and depersonalization (r = 0.79 and r = 0.71, p<0.01)) of burnout. Models including job strain, job satisfaction, anxiety and insomnia did not predict burnout (p = 0.30 and p = 0.50). However, when HbA1C levels is included, the prediction of burnout became significant (P = 0.03). Our findings demonstrated the interest of sleep and biological parameters, in particular HbA1C levels, in the characterization of professional burnout.

Circulating levels of FAS/APO-1 in patients with the systemic inflammatory response syndrome.

PubMed

Torre, Donato; Tambini, Roberto; Manfredi, Mariangela; Mangani, Valerio; Livi, Paola; Maldifassi, Viviana; Campi, Paolo; Speranza, Filippo

2003-04-01

Resolution of inflammation/infection involves removal of neutrophils and other inflammatory cells by the induction of apoptosis. Fas/Apo-1 is a widely occurring apoptotic signal receptor molecule expressed by almost any type of cell, which is also released in a soluble circulating form. In this study we investigated the role of circulating Fas/Apo-1 in patients with systemic inflammatory response syndrome (SIRS). We evaluated 57 critically ill patients, 34 with infectious SIRS (sepsis and septic shock), and 23 patients with noninfectious SIRS. Circulating Fas/Apo-1 was determined by a commercially available immunoassay. Our results clearly show that levels of Fas/Apo-1 were significantly elevated in patients with infectious and noninfectious SIRS (10.4 +/- 8.1 pg/mL, controls: 5.0 +/- 0.7 pg/mL; p < 0.0001). In addition, Fas/Apo-1 levels were not able in predicting in predicting poor outcome of patients with SIRS. In conclusion, these results show that increased levels of Fas/Apo-1 from patients with SIRS is a mechanism which contribute to inflammatory response through accumulation of neutrophils at sites of inflammation/infection.

Circulating interleukin-6 and high-sensitivity C-reactive protein decrease after periodontal therapy in otherwise healthy subjects.

PubMed

Marcaccini, Andrea M; Meschiari, César A; Sorgi, Carlos A; Saraiva, Maria C P; de Souza, Ana M; Faccioli, Lúcia H; Tanus-Santos, José E; Novaes, Arthur B; Gerlach, Raquel F

2009-04-01

Periodontal disease has been associated with many chronic inflammatory systemic diseases, and a common chronic inflammation pathway has been suggested for these conditions. However, few studies have evaluated whether periodontal disease, in the absence of other known inflammatory conditions and smoking, affects circulating markers of chronic inflammation. This study compared chronic inflammation markers in control individuals and patients with periodontal disease and observed whether non-surgical periodontal therapy affected inflammatory disease markers after 3 months. Plasma and serum of 20 controls and 25 patients with periodontal disease were obtained prior to and 3 months after non-surgical periodontal therapy. All patients were non-smokers, they did not use any medication, and they had no history or detectable signs and symptoms of systemic diseases. Periodontal and systemic parameters included probing depth, bleeding on probing, clinical attachment level, hematologic parameters, as well as the following inflammatory markers: interleukin (IL)-6, high-sensitivity C-reactive protein (hs-CRP), CD40 ligand, monocyte chemoattractant protein (MCP)-1, soluble P-selectin (sP-selectin), soluble vascular adhesion molecule (sVCAM)-1, and soluble intercellular adhesion molecule (sICAM)-1. There were no differences in the hematologic parameters of the patients in the control and periodontal disease groups. Among the tested inflammatory markers, IL-6 concentrations were higher in the periodontal disease group at baseline compared to the controls (P = 0.006). Therapy was highly effective (P <0.001 for all the analyzed clinical parameters), and a decrease in circulating IL-6 and hs-CRP concentrations was observed 3 months after therapy (P = 0.001 and P = 0.006, respectively). Our results also suggest that the CD40 ligand marker may have been different in the control and periodontal disease groups prior to the therapy (P = 0.009). In apparently otherwise healthy patients, periodontal disease is associated with increased circulating concentrations of IL-6 and hs-CRP, which decreased 3 months after non-surgical periodontal therapy. With regard to the CD40 ligand, MCP-1, sP-selectin, sVCAM-1, and sICAM-1, no changes were seen in the periodontal disease group between baseline and 3 months after therapy.

CFD: computational fluid dynamics or confounding factor dissemination? The role of hemodynamics in intracranial aneurysm rupture risk assessment.

PubMed

Xiang, J; Tutino, V M; Snyder, K V; Meng, H

2014-10-01

Image-based computational fluid dynamics holds a prominent position in the evaluation of intracranial aneurysms, especially as a promising tool to stratify rupture risk. Current computational fluid dynamics findings correlating both high and low wall shear stress with intracranial aneurysm growth and rupture puzzle researchers and clinicians alike. These conflicting findings may stem from inconsistent parameter definitions, small datasets, and intrinsic complexities in intracranial aneurysm growth and rupture. In Part 1 of this 2-part review, we proposed a unifying hypothesis: both high and low wall shear stress drive intracranial aneurysm growth and rupture through mural cell-mediated and inflammatory cell-mediated destructive remodeling pathways, respectively. In the present report, Part 2, we delineate different wall shear stress parameter definitions and survey recent computational fluid dynamics studies, in light of this mechanistic heterogeneity. In the future, we expect that larger datasets, better analyses, and increased understanding of hemodynamic-biologic mechanisms will lead to more accurate predictive models for intracranial aneurysm risk assessment from computational fluid dynamics. © 2014 by American Journal of Neuroradiology.

Bochum ultrasound score versus clinical and electrophysiological parameters in distinguishing acute-onset chronic from acute inflammatory demyelinating polyneuropathy.

PubMed

Kerasnoudis, Antonios; Pitarokoili, Kallia; Behrendt, Volker; Gold, Ralf; Yoon, Min-Suk

2015-06-01

The aim of this study was to evaluate whether a nerve ultrasound score (Bochum ultrasound score, BUS), clinical, and electrophysiological parameters could distinguish subacute chronic (CIDP) from acute inflammatory demyelinating polyneuropathy (AIDP). Phase 1: The charts of 35 patients with polyradiculoneuropathy were evaluated retrospectively regarding BUS, clinical, and electrophysiological parameters (A-waves, sural nerve sparing pattern, sensory ratio>1). Phase 2: All parameters were evaluated prospectively in 10 patients with subacute polyradiculoneuropathy. Phase 1: A sum score of ≥2 points in BUS and the presence of sensory symptoms were significantly more frequent in the subacute CIDP group than in the AIDP group (P<0.001).The electrophysiological parameters showed no significant changes between the 2 groups. Phase 2: BUS (83.3%; 100%;), sensory symptoms (100%; 75%), absence of autonomic nervous system dysfunction (83.3%; 75%), or bulbar palsy (83.3%; 50%) showed the best sensitivity and specificity in distinguishing subacute CIDP from AIDP. BUS is a useful diagnostic tool for distinguishing subacute CIDP from AIDP. © 2014 Wiley Periodicals, Inc.

Evaluation of the association of sleep apnea-related systemic inflammation with CRP, ESR, and neutrophil-to-lymphocyte ratio.

PubMed

Korkmaz, Mukadder; Korkmaz, Hakan; Küçüker, Fatma; Ayyıldız, Sema Nur; Çankaya, Soner

2015-02-13

Obstructive sleep apnea syndrome (OSAS) is characterized by cyclic episodes of hypoxemia and reoxygenation. It has been suggested that OSAS is associated with chronic inflammation within the microvasculature. This low-grade inflammation may play a role in the pathophysiology of OSAS-related comorbidities. Evaluation of the inflammatory markers may predict the degree of the systemic inflammation and this may be a prognostic factor for future adverse events such as cardiovascular risks. Proinflammatory cytokines have been extensively studied in sleep-disordered breathing. Neutrophil-to-lymphocyte ratio is a recently described indicator of systemic inflammation, but it has not been studied in OSAS patients. In this study we aimed to evaluate the easily measurable parameters of systemic inflammation in these patients. We conducted this study to examine the association among OSAS and C- reactive protein, erythrocyte sedimentation rate, and neutrophil-to-lymphocyte ratio. OSAS patients who underwent overnight polysomnography were studied retrospectively. They were divided into 4 groups: control, mild, moderate, and severe OSAS patients. Blood test results and inflammatory markers were compared between the groups. One-way ANOVA and Kruskall-Wallis H test were used for statistical analysis. A total of 147 patients were included in the study. No differences in evaluated inflammatory markers were observed among the 4 groups. Evaluation of the OSAS-related systemic inflammation is not likely to be possible by CRP, ESR, or neutrophil-to-lymphocyte ratio measurements. These markers do not seem to be associated with the degree of the upper airway obstruction.

Inflammatory and oxidative stress-related effects associated with neurotoxicity are maintained after exclusively prenatal trichloroethylene exposure.

PubMed

Blossom, Sarah J; Melnyk, Stepan B; Li, Ming; Wessinger, William D; Cooney, Craig A

2017-03-01

Trichloroethylene (TCE) is a widespread environmental toxicant with immunotoxic and neurotoxic potential. Previous studies have shown that continuous developmental exposure to TCE encompassing gestation and early life as well as postnatal only exposure in the drinking water of MRL+/+ mice promoted CD4 + T cell immunotoxicity, glutathione depletion and oxidative stress in the cerebellum, as well increased locomotor activity in male offspring. The purpose of this study was to characterize the effects of exclusively prenatal exposure on these parameters. Another goal was to investigate potential plasma oxidative stress/inflammatory biomarkers to possibly be used as predictors of TCE-mediated neurotoxicity. In the current study, 6 week old male offspring of dams exposed gestationally to 0, 0.01, and 0.1mg/ml TCE in the drinking water were evaluated. Our results confirmed that the oxidized phenotype in plasma and cerebellum was maintained after exclusively prenatal exposure. A Phenotypic analysis by flow cytometry revealed that TCE exposure expanded the effector/memory subset of peripheral CD4 + T cells in association with increased production of pro-inflammatory cytokines IFN-γ and IL-17. Serum biomarkers of oxidative stress and inflammation were also elevated in plasma suggesting that systemic effects are important and may be used to predict neurotoxicity in our model. These results suggested that the prenatal period is a critical stage of life by which the developing CNS and immune system are susceptible to long-lasting changes mediated by TCE. Copyright © 2016 Elsevier B.V. All rights reserved.

High-intensity interval training improves inflammatory and adipokine profiles in postmenopausal women with metabolic syndrome.

PubMed

Steckling, Flávia Mariel; Farinha, Juliano Boufleur; Figueiredo, Felipe da Cunha; Santos, Daniela Lopes Dos; Bresciani, Guilherme; Kretzmann, Nélson Alexandre; Stefanello, Sílvio Terra; Courtes, Aline Alves; Beck, Maristela de Oliveira; Sangoi Cardoso, Manuela; Duarte, Marta Maria Medeiros Frescura; Moresco, Rafael Noal; Soares, Félix Alexandre Antunes

2018-02-12

This study investigate the effects of high-intensity interval training (HIIT) on systemic levels of inflammatory and hormonal markers in postmenopausal women with metabolic syndrome (MS). Fifteen postmenopausal women with MS completed the training on treadmills. Functional, body composition parameters, maximal oxygen uptake (VO 2 max), and lipid profile were assessed before and after HIIT. Serum or plasma levels of cytokines and hormonal markers were measured along the intervention. The analysis of messenger RNA (mRNA) expression of these cytokines was performed in peripheral blood mononuclear cells (PBMC). VO 2 max and some anthropometric parameters were improved after HIIT, while decreased levels of proinflammatory markers and increased levels of interleukin-10 (IL-10) were also found. Adipokines were also modulated after 12 weeks or training. The mRNA expression of the studied genes was unchanged after HIIT. In conclusion, HIIT benefits inflammatory and hormonal axis on serum or plasma samples, without changes on PBMC of postmenopausal MS patients.

Diphenyl diselenide attenuates oxidative stress and inflammatory parameters in ulcerative colitis: A comparison with ebselen.

PubMed

Petronilho, Fabricia; Michels, Monique; Danielski, Lucinéia G; Goldim, Mariana Pereira; Florentino, Drielly; Vieira, Andriele; Mendonça, Mariana G; Tournier, Moema; Piacentini, Bárbara; Giustina, Amanda Della; Leffa, Daniela D; Pereira, Gregório W; Pereira, Volnei D; Rocha, João Batista Teixeira Da

2016-09-01

The aim of this study was to evaluate the effects of diphenyl diselenide (PhSe)2 and ebselen (EB) in ulcerative colitis (UC) induced by dextran sulfate sodium (DSS) in rats. The effects of (PhSe)2 and EB in rats submitted to DSS-induced colitis were determined by measurement of oxidative stress parameters, inflammatory response and bowel histopathological alterations. Animals developed moderate to severe neutrophil infiltration in histopathology assay in DSS rats and (PhSe)2 improved this response. Moreover, the treatment with (PhSe)2 decreased the oxidative damage in lipids and proteins, as well as reversed the superoxide dismutase (SOD) and catalase (CAT) levels in rats treated with DSS. EB was able only to reverse damage in lipids and the low levels of SOD in this animal model. The organoselenium compounds tested demonstrated an anti-inflammatory and antioxidant activity reducing the colon damage, being (PhSe)2 more effective than EB. Copyright © 2016 Elsevier GmbH. All rights reserved.

Warfarin affects acute inflammatory response induced by subcutaneous polyvinyl sponge implantation in rats.

PubMed

Mirkov, Ivana; Popov Aleksandrov, Aleksandra; Demenesku, Jelena; Ninkov, Marina; Mileusnic, Dina; Kataranovski, Dragan; Kataranovski, Milena

2017-09-01

Warfarin (WF) is an anticoagulant which also affects physiological processes other than hemostasis. Our previous investigations showed the effect of WF which gained access to the organism via skin on resting peripheral blood granulocytes. Based on these data, the aim of the present study was to examine whether WF could modulate the inflammatory processes as well. To this aim the effect of WF on the inflammatory response induced by subcutaneous sponge implantation in rats was examined. Warfarin-soaked polyvinyl sponges (WF-sponges) were implanted subcutaneously and cell infiltration into sponges, the levels of nitric oxide (NO) and inflammatory cytokines tumor necrosis factor (TNF) and interleukin-6 (IL-6) production by sponge cells were measured as parameters of inflammation. T cell infiltration and cytokine interferon-γ (IFN-γ), interleukin-17 (IL-17) and interleukin-10 (IL-10) were measured at day 7 post implantation. Warfarin exerted both stimulatory and suppressive effects depending on the parameter examined. Flow cytometry of cells recovered from sponges showed higher numbers of granulocytes (HIS48 + cells) at days 1 and 3 post implantation and CD11b + cells at day 1 compared to control sponges. Cells from WF-sponges had an increased NO production (Griess reaction) at days 1 and 7. In contrast, lower levels of TNF (measured by ELISA) production by cells recovered from WF-soaked sponges were found in the early (day one) phase of reaction with unchanged levels at other time points. While IL-6 production by cells recovered from WF-soaked sponges was decreased at day 1, it was increased at day 7. Higher T cell numbers were noted in WF sponges at day 7 post implantation, and recovered cells produced more IFN-γ and IL-17, while IL-10 production remained unchanged. Warfarin affects some of the parameters of inflammatory reaction induced by subcutaneous polyvinyl sponge implantation. Differential (both stimulatory as well as inhibitory) effects of WF on inflammatory response to sponge implants might affect the course and/or duration of this reaction.

Severe Alcoholic Pancreatitis-Associated Acute Lung Injury in Veterans: Risks, Mechanisms, Prediction, and Therapeutic Relevance

DTIC Science & Technology

2017-10-01

discovered that one of the controls, who is morbidly obese , diabetic, had a very high number of dead inflammatory cells in circulation. While this is a...very interesting finding, it is more likely that the dead inflammatory cells are coming from the obesity and severe diabetes. Because of this severe

Risk factors and frequency of tuberculosis-associated immune reconstitution inflammatory syndrome among HIV/Tuberculosis co-infected patients in Southern India.

PubMed

Vignesh, Ramachandran; Swathirajan, Chinnambedu R; Solomon, Sunil S; Shankar, Esaki Muthu; Murugavel, Kailapuri G

2017-01-01

Immune reconstitution inflammatory syndrome (IRIS) continues to be a complication in HIV/tuberculosis (TB) co-infected patients initiating highly active antiretroviral therapy (HAART). The aim of this study was to evaluate the risk factors associated with developing IRIS to identify a possible biomarker to predict or diagnose IRIS in patients initiating HAART. A total of 175 HIV/TB co-infected patients initiating HAART were followed up longitudinally during September 2010 to May 2013 attending a HIV care clinic in Chennai. Patients were followed up longitudinally after HAART initiation and baseline demographic, laboratory parameters and treatment characteristics between patients with IRIS events and those without IRIS events were compared. Chi-square or Fisher's exact test for categorical variables and a Wilcoxon rank-sum test for continuous variables were performed using SPSS, version 12.0 software. Patients with IRIS had a significantly lower median baseline CD4+ T-cell count (P = 0.0039). There were no differences in terms of sex, CD4 T-cell %, plasma viral load, time interval between initiating ATT and HAART between the IRIS and non-IRIS patients. Low CD4+ T-cell count (<100 cells/μL) could be used as a marker to screen and monitor patients initiating HAART.

Peritumoral eosinophils predict recurrence in colorectal cancer.

PubMed

Harbaum, Lars; Pollheimer, Marion J; Kornprat, Peter; Lindtner, Richard A; Bokemeyer, Carsten; Langner, Cord

2015-03-01

In colorectal cancer, the presence and extent of eosinophil granulocyte infiltration may render important prognostic information. However, it remains unclear whether an increasing number of eosinophils might simply be linked to the overall inflammatory cell reaction or represent a self-contained, antitumoral mechanism that needs to be documented and promoted therapeutically. Peri- and intratumoral eosinophil counts were retrospectively assessed in 381 primary colorectal cancers from randomly selected patients. Tumors were diagnosed in American Joint Committee on Cancer (AJCC)/Union Internationale Contre le Cancer (UICC) stage I in 21%, stage II in 32%, stage III in 33%, and stage IV in 14%. Presence and extent of eosinophils was related to various histopathological parameters as well as patients' outcome. Overall, peri- and intratumoral eosinophils were observed in 86 and 75% cancer specimens. The peritumoral eosinophil count correlated strongly with the intratumoral eosinophil count (R=0.69; P<0.001) and with the intensity of the overall inflammatory cell reaction (R=0.318; P<0.001). Both increasing peri- and intratumoral eosinophil counts were significantly associated with lower T and N classification, better tumor differentiation, absence of vascular invasion, as well as improved progression-free and cancer-specific survival. However, only peritumoral eosinophils, but not intratumoral, were an independent prognosticator of favorable progression-free (hazard ratio 0.75; 95% confidence interval 0.58-0.98; P=0.04) and cancer-specific survival (hazard ratio 0.7; 95% confidence interval 0.52-0.93; P=0.01)-independent of the intensity of overall inflammatory cell reaction. This was also found for patients with AJCC/UICC stage II disease, wherein the presence of peritumoral eosinophils was significantly associated with favorable outcome. In conclusion, the number of peritumoral eosinophils had a significant favorable impact on prognosis of colorectal cancer patients independent of the overall tumor-associated inflammatory response. Evaluation of peritumoral eosinophils represents a promising readily assessable tool and should therefore routinely be commented on in the pathology report.

Predictors of Aggressive Inflammatory Bowel Disease

PubMed Central

Yarur, Andres J.; Strobel, Sebastian G.; Deshpande, Amar R.

2011-01-01

Inflammatory bowel disease comprises a group of conditions characterized by idiopathic inflammation of the gastrointestinal tract. The natural course of disease can range from an indolent course with prolonged periods of remission to aggressive, incapacitating disease. Predicting which patients are more susceptible to developing severe disease is important, especially when choosing therapeutic agents and treatment strategies. This paper reviews current evidence on the main demographic, clinical, endoscopic, histologic, serologic, and genetic markers that predict aggressive inflammatory bowel disease. In ulcerative colitis, we considered disease to be aggressive when patients had a high relapse rate, need for admission and/or surgery, development of colon cancer, or extraintestinal manifestations. We defined aggressive Crohn's disease as having a high relapse rate, development of penetrating disease, need for repeat surgery, or multiple admissions for flares. In Crohn's disease, involvement of the upper gastrointestinal tract and ileum, penetrating disease, early age at diagnosis, smoking, extensive ulceration of the mucosa, high titers of serum antibodies, and mutations of the NOD2 gene are markers of aggressive disease. In ulcerative colitis, patients with more extensive involvement of the colon (pancolitis) have more symptomatology and are at higher risk for needing a colectomy and developing colon cancer. Also, plasmocytic infiltration of the colonic mucosa and crypt atrophy predict treatment failure. As with diagnosis, no single method can predict disease aggressiveness. Multiple serologic and genetic tests are being developed to refine the accuracy of prediction. Endoscopic findings can also predict the future course of disease. At present, clinical manifestations are the most useful way to make therapeutic decisions. PMID:22298958

Transferrin Level Before Treatment and Genetic Polymorphism in HFE Gene as Predictive Markers for Response to Adalimumab in Crohn's Disease Patients.

PubMed

Repnik, Katja; Koder, Silvo; Skok, Pavel; Ferkolj, Ivan; Potočnik, Uroš

2016-08-01

Tumor necrosis factor α inhibitors (anti-TNF) have improved treatment of several complex diseases, including Crohn's disease (CD). However, the effect varies and approximately one-third of the patients do not respond. Since blood parameters as well as genetic factors have shown a great potential to predict response during treatment, the aim of the study was to evaluate response to anti-TNF treatment with adalimumab (ADA) between genes HFE and TF and haematological parameters in Slovenian refractory CD patients. Single nucleotide polymorphisms (SNPs) rs1799852 in gene TF and rs2071303 in gene HFE were genotyped in 68 refractory CD patients for which response has been measured using inflammatory bowel disease questionnaire (IBDQ) index. Haematological parameters and IBDQ index were determined before therapy and after 4, 12, 20 and 30 weeks. We found novel strong association between SNP rs2071303 in gene HFE and response to ADA treatment, particularly patients with G allele comparing to A allele had better response after 20 weeks (p = 0.008). Further, we found strong association between transferrin level at baseline and treatment response after 12, 20 and 30 weeks, where average transferrin level before therapy was lower in responders (2.38 g/L) compared to non-responders (2.89 g/L, p = 0.005). Association was found between transferrin level in week 30 and SNP rs1799852 (p = 0.023), and between MCHC level before treatment and SNP rs2071303 (p = 0.007). Our results suggest that SNP in gene HFE as well as haematological markers serve as promising prognostic markers of response to anti-TNF treatment in CD patients.

Is the bronchodilator test an useful tool to measure asthma control?

PubMed

Ferrer Galván, Marta; Javier Alvarez Gutiérrez, Francisco; Romero Falcón, Auxiliadora; Romero Romero, Beatriz; Sáez, Antonia; Medina Gallardo, Juan Francisco

2017-05-01

Asthma control includes the control of symptoms and future risk. We sought to evaluate the usefulness of the degree of spirometric reversibility of the forced expiratory volume in one second (FEV 1 ) as the target parameter of control. Patients with bronchial asthma were followed up for one year. The clinical, functional, inflammatory and control parameters of the asthma were collected. The area under the curve (AUC) was estimated to establish the cutoff point of the post-bronchodilator FEV 1 reversibility in relation to non-control asthma. In the univariate analysis, the differences between groups were studied based on the degree of estimated reversibility. Factors with a significance <0.1 were included in the multivariate analysis by binary logistic regression. A total of 407 patients with a mean age of 38.1 ± 16.7 years were included. When the patients were grouped into controlled and non-controlled groups, compared with post-bronchodilator FEV 1 reversibility, the cutoff point obtained for the non-controlled group was ≥10% (sensitivity: 65.8%, specificity: 48.4%, positive predictive value: 69.5%, and AUC: 0.619 [0.533-0.700], p < 0.01). In the year-long follow-up of this group (post-bronchodilator FEV 1 ≥10), an increased use of relief medication was observed, along with a significantly progressive drop in post-bronchodilator FEV 1 and post-bronchodilator FEV 1 /FVC (forced expiratory volume in one second/forced vital capacity). Spirometric reversibility can be useful in assessing control in asthmatic patients and can predict future risk parameters. The cutoff point related to the non-control of asthma found in our work was ≥10%. Copyright © 2017 Elsevier Ltd. All rights reserved.

Steatosis influences the clinical profiles and long-term outcomes of interferon-treated chronic hepatitis C and liver cirrhosis patients.

PubMed

Nirei, Kazushige; Matsumura, Hiroshi; Kumakawa, Mariko; Matsumoto, Naoki; Nakamura, Hitomi; Yamagami, Hiroaki; Matsuoka, Shunichi; Moriyama, Mitsuhiko

2017-01-01

Objective: This study aimed to assess the relationship between steatosis and long-term outcomes of patients with chronic hepatitis C (CH) and liver cirrhosis (LC). Patients and methods: The study population included 282 subjects with CH or LC who underwent liver biopsy at our institute. All patients achieved a sustained virological response (SVR) to interferon (IFN). Clinical characteristics, including age, gender and body mass index (BMI), were compared. The liver biopsy specimens of all patients were examined and scores were assigned to indicate the severity of each of the following features: inflammatory cell infiltration in the periportal, parenchymal and portal areas; F (fibrosis) stage; portal sclerotic change; perivenular fibrosis; pericellular fibrosis; bile duct damage; hepatic steatosis. Results: Of the 282 patients, 112 (39.7%) were free of steatosis. The other 170 patients (60.3%) had steatosis. The blood biochemical parameters of the patients with hepatic steatosis were significantly poorer than those of patients free of steatosis. Inflammatory cell infiltration and F stage were both significantly more severe in patients with than in those without steatosis. The incidences of hepatocellular carcinoma differed significantly between the two groups. However, the incidences of hepatocellular carcinoma did not differ significantly between the groups with BMI above and below 25. Conclusion: We consider hepatic steatosis to potentially affect the blood biochemical parameters and clinical profiles of Japanese patients with CH due to hepatitis virus type C. Patients with this form of CH showed favorable clinical responses to IFN. Furthermore, fibrosis and steatosis appear to affect the long-term outcomes of these patients. However, BMI alone cannot be used to predict HCC development.

Spine Conditions: Mechanical and Inflammatory Low Back Pain.

PubMed

Ledford, Christopher

2017-10-01

Mechanical low back pain (LBP) is an injury or derangement of an anatomic structure in the low back. When evaluating patients with LBP, clinicians should maintain clinical suspicion for vertebral fracture, cancer, and cauda equina syndrome. Management includes patient education focused on exercise, massage, and behavioral approaches such as cognitive behavioral therapy. Acupuncture can be an effective alternative and specific herbal supplements may provide short-term pain relief. The prognosis for patients with mechanical LBP is good. Inflammatory LBP is pain resulting from a systemic inflammatory condition, often referred to as axial spondyloarthritis. Ankylosing spondylitis is chronic inflammatory LBP characterized by early onset (mean age 24 years), with a higher prevalence in men. Five clinical parameters can help identify inflammatory LBP: improvement with exercise, pain at night, insidious onset, onset at younger than 40 years, and no improvement with rest. Management of inflammatory LBP typically includes nonsteroidal anti-inflammatory drugs and structured exercise programs, with emphasis on the involvement of a rheumatology subspecialist. Spondyloarthritis is associated with other rheumatic or autoimmune conditions, including rheumatoid arthritis, inflammatory bowel disease, and psoriasis. These should be considered when evaluating patients with inflammatory LBP. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.

Model-Based Individualized Treatment of Chemotherapeutics: Bayesian Population Modeling and Dose Optimization

PubMed Central

Jayachandran, Devaraj; Laínez-Aguirre, José; Rundell, Ann; Vik, Terry; Hannemann, Robert; Reklaitis, Gintaras; Ramkrishna, Doraiswami

2015-01-01

6-Mercaptopurine (6-MP) is one of the key drugs in the treatment of many pediatric cancers, auto immune diseases and inflammatory bowel disease. 6-MP is a prodrug, converted to an active metabolite 6-thioguanine nucleotide (6-TGN) through enzymatic reaction involving thiopurine methyltransferase (TPMT). Pharmacogenomic variation observed in the TPMT enzyme produces a significant variation in drug response among the patient population. Despite 6-MP’s widespread use and observed variation in treatment response, efforts at quantitative optimization of dose regimens for individual patients are limited. In addition, research efforts devoted on pharmacogenomics to predict clinical responses are proving far from ideal. In this work, we present a Bayesian population modeling approach to develop a pharmacological model for 6-MP metabolism in humans. In the face of scarcity of data in clinical settings, a global sensitivity analysis based model reduction approach is used to minimize the parameter space. For accurate estimation of sensitive parameters, robust optimal experimental design based on D-optimality criteria was exploited. With the patient-specific model, a model predictive control algorithm is used to optimize the dose scheduling with the objective of maintaining the 6-TGN concentration within its therapeutic window. More importantly, for the first time, we show how the incorporation of information from different levels of biological chain-of response (i.e. gene expression-enzyme phenotype-drug phenotype) plays a critical role in determining the uncertainty in predicting therapeutic target. The model and the control approach can be utilized in the clinical setting to individualize 6-MP dosing based on the patient’s ability to metabolize the drug instead of the traditional standard-dose-for-all approach. PMID:26226448

Defining the neurotoxin derived illness chronic ciguatera using markers of chronic systemic inflammatory disturbances: a case/control study.

PubMed

Shoemaker, Ritchie C; House, Dennis; Ryan, James C

2010-01-01

Ciguatoxins are extremely potent neurotoxins, produced by tropical marine dinoflagellates, that persistently enter into our food web. Over 100,000 people annually experience acute ciguatera poisoning from consuming toxic fish. Roughly 5% of these victims will develop chronic ciguatera (CC), a widespread, multisymptom, multisystem, chronic illness that can last tens of years. CC is marked by disproportionate disability and non-specific refractory symptoms such as fatigue, cognitive deficits and pain, and is suggestive of other illnesses. Its unknown pathophysiology makes both diagnosis and treatment difficult. We wanted to compare objective parameters of visual contrast sensitivity testing, measures of innate immune response and genetic markers in cases to controls to assess the potential for the presence of persistent inflammatory parameters that are demonstrated in other biotoxin associated illnesses at a single specialty clinic. Using 59 CC cases and 59 controls we present in retrospective review, in all cases, abnormalities in immune responses paralleling the chronic systemic inflammatory response syndrome seen in several other chronic diseases. This study defines a preliminary case definition using medical history, total symptoms, visual contrast sensitivity, HLA DR genotype analysis, reduction of regulatory neuropeptides VIP and MSH, and multiple measures of inflammatory immune response, especially C4a and TGFβ1, thereby providing a basis for identification and targeted therapy. CC provides a model for chronic human illness associated with initiation of inflammatory responses by biologically produced neurotoxins. Copyright © 2010 Elsevier Inc. All rights reserved.

Therapeutic efficacy of osthole against dinitrobenzene sulphonic acid induced-colitis in rats.

PubMed

Khairy, Hanan; Saleh, Hanan; Badr, Abeer M; Marie, Mohamed-Assem S

2018-04-01

Several mediators were associated with the pathogenesis of inflammatory bowel disease such as oxidative stress through the production of reactive oxygen metabolites, neutrophils infiltration and release of pro-inflammatory cytokines. This study was designed to investigate the therapeutic efficacy of osthole against dinitrobenzene sulfonic acid (DNBS) induced-colitis in rats through its anti-oxidant and anti-inflammatory properties. Colitis was induced in rats by single intracolonic instillation of (250 μl DNBS-25 mg/rat). Then 4 days later, rats were received oral administration of either (osthole 50 mg/kg), (sulfasalazine 500 mg/kg) or both in combination for 7 consecutive days. Body weight, some hematological parameters, colonic malondialdehyde (MDA) and myeloperoxidase activity (MPO), antioxidant parameters, colon injury and mucosa architectures were assessed. T helper (Th1)-related cytokines [Tumor necrosis factor alpha (TNF-α) and interferon-gamma (INF-γ)], Th2-relarted cytokines (interleukin-4 [IL-4 and IL-10], and Th-17 related cytokines [IL-17] were determined by ELISA. Osthole significantly improved the loss in body weight. That was accompanied with a remarkable amelioration of the disruption of the colonic architecture as well as a significant improvement in the antioxidant defense system. A reduction in MPO and MDA was observed in flamed colon. Treatment with either osthole or combination therapy showed suppressive activities on pro-inflammatory Th2-related cytokines and upregulation of anti-inflammatory Th2-related cytokines The results of this study suggest that osthole exert beneficial therapeutic effect in experimental colitis and improved the efficacy of the synthetized drugs such as sulfasalazine. Therefore, osthole may have a valuable sound in the treatment of inflammatory bowel disease. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Transcranial direct current stimulation improves long-term memory deficits in an animal model of attention-deficit/hyperactivity disorder and modulates oxidative and inflammatory parameters.

PubMed

Leffa, Douglas Teixeira; Bellaver, Bruna; Salvi, Artur Alban; de Oliveira, Carla; Caumo, Wolnei; Grevet, Eugenio Horacio; Fregni, Felipe; Quincozes-Santos, André; Rohde, Luis Augusto; Torres, Iraci L S

2018-04-05

Transcranial direct current stimulation (tDCS) is a technique that modulates neuronal activity and has been proposed as a potential therapeutic tool for attention-deficit/hyperactivity disorder (ADHD) symptoms. Although pilot studies have shown evidence of efficacy, its mechanism of action remains unclear. We evaluated the effects of tDCS on behavioral (working and long-term memory) and neurochemical (oxidative and inflammatory parameters) outcomes related to ADHD pathophysiology. We used the most widely accepted animal model of ADHD: spontaneously hypertensive rats (SHR). The selected behavioral outcomes have been shown to be altered in both ADHD patients and animal models, and were chosen for their relation to the proposed mechanistic action of tDCS. Adult male SHR and their control, the Wistar Kyoto rats (WKY), were subjected to 20 min of bicephalic tDCS or sham stimulation for 8 consecutive days. Working memory, long-term memory, and neurochemical outcomes were evaluated. TDCS improved long-term memory deficits presented by the SHR. No change in working memory performance was observed. In the hippocampus, tDCS increased both the production of reactive oxygen species in SHR and the levels of the antioxidant molecule glutathione in both strains. TDCS also modulated inflammatory response in the brains of WKY by downregulating pro-inflammatory cytokines. TDCS had significant effects that were specific for strain, type of behavioral and neurochemical outcomes. The long-term memory improvement in the SHR may point to a possible therapeutic role of tDCS in ADHD that does not seem to be mediated by inflammatory markers. Additionally, the anti-inflammatory effects observed in the brain of WKY after tDCS needs to be further explored. Copyright © 2018 Elsevier Inc. All rights reserved.

Pulmonary exposure to carbonaceous nanomaterials and sperm quality.

PubMed

Skovmand, Astrid; Jacobsen Lauvås, Anna; Christensen, Preben; Vogel, Ulla; Sørig Hougaard, Karin; Goericke-Pesch, Sandra

2018-01-31

Semen quality parameters are potentially affected by nanomaterials in several ways: Inhaled nanosized particles are potent inducers of pulmonary inflammation, leading to the release of inflammatory mediators. Small amounts of particles may translocate from the lungs into the lung capillaries, enter the systemic circulation and ultimately reach the testes. Both the inflammatory response and the particles may induce oxidative stress which can directly affect spermatogenesis. Furthermore, spermatogenesis may be indirectly affected by changes in the hormonal milieu as systemic inflammation is a potential modulator of endocrine function. The aim of this study was to investigate the effects of pulmonary exposure to carbonaceous nanomaterials on sperm quality parameters in an experimental mouse model. Effects on sperm quality after pulmonary inflammation induced by carbonaceous nanomaterials were investigated by intratracheally instilling sexually mature male NMRI mice with four different carbonaceous nanomaterials dispersed in nanopure water: graphene oxide (18 μg/mouse/i.t.), Flammruss 101, Printex 90 and SRM1650b (0.1 mg/mouse/i.t. each) weekly for seven consecutive weeks. Pulmonary inflammation was determined by differential cell count in bronchoalveolar lavage fluid. Epididymal sperm concentration and motility were measured by computer-assisted sperm analysis. Epididymal sperm viability and morphological abnormalities were assessed manually using Hoechst 33,342/PI flourescent and Spermac staining, respectively. Epididymal sperm were assessed with regard to sperm DNA integrity (damage). Daily sperm production was measured in the testis, and testosterone levels were measured in blood plasma by ELISA. Neutrophil numbers in the bronchoalveolar fluid showed sustained inflammatory response in the nanoparticle-exposed groups one week after the last instillation. No significant changes in epididymal sperm parameters, daily sperm production or plasma testosterone levels were found. Despite the sustained pulmonary inflammatory response, an eight week exposure to graphene oxide, Flammruss 101, Printex 90 and the diesel particle SRM1650b in the present study did not appear to affect semen parameters, daily sperm production or testosterone concentration in male NMRI mice.

Analysis of Cytokine Levels in Tears and Clinical Correlations After Intense Pulsed Light Treating Meibomian Gland Dysfunction.

PubMed

Liu, Ruixing; Rong, Bei; Tu, Ping; Tang, Yun; Song, Wenjing; Toyos, Rolando; Toyos, Melissa; Yan, Xiaoming

2017-11-01

To investigate the change from baseline of inflammatory markers in tears of dry eye disease (DED) subjects owing to meibomian gland dysfunction (MGD) after intense pulsed light (IPL) treatment and meibomian gland expression (MGE) compared to sham treatment, and the correlations with ocular surface parameters. Randomized, double-masked, controlled study. Those randomized into the active treatment arm received 3 consecutive treatments (14∼16 J/cm 2 ) approximately 4 weeks apart in the periocular region. Control eyes received 3 treatments in the same intervals of 0 J/cm 2 . Tear samples in all eyes were collected and analyzed at baseline, week 12, and/or week 4 for interleukin (IL)-17A, IL-6, and prostaglandin E2 (PGE2). The correlations between cytokines and ocular surface parameters were analyzed before and after IPL treatment. All of the inflammatory markers declined in value compared to baselines. IL-17A and IL-6 showed statistically significant decreases compared to sham treatment at each measured time point. PGE2 showed statistically significant decreases compared to sham at week 12. Results showed that the expressions of IL-17A and IL-6 correlated well with ocular surface parameters of the lower eyelid before IPL. The changed values of IL-6 and PGE2 in tears correlated with the changed values of partial ocular surface parameters after IPL treatment in study eyes, respectively. The study results suggest that IPL can significantly reduce inflammatory markers in tears of patients suffering with DED owing to MGD after IPL treatment. These findings indicate that IL-17A and IL-6 play roles in the pathogenesis of DED owing to MGD, and the reduction of the inflammatory factors is consistent with the improvement of partial clinical symptoms and signs. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Inhaled corticosteroids do not influence the early inflammatory response and clinical presentation of hospitalized subjects with COPD exacerbation.

PubMed

Crisafulli, Ernesto; Guerrero, Mónica; Menéndez, Rosario; Huerta, Arturo; Martinez, Raquel; Gimeno, Alexandra; Soler, Néstor; Torres, Antoni

2014-10-01

Inhaled corticosteroids are anti-inflammatory medications that can down-regulate the immunologic response in patients with COPD; however, their role at onset of COPD exacerbation is still not understood. The aim of this study was to assess the early inflammatory response and clinical presentation of patients with COPD exacerbation mediated by inhaled corticosteroids. Prospective data were collected on 123 hospitalized subjects with COPD exacerbation over a 30-month period at 2 Spanish university hospitals. Based on domiciliary use, comparative analyses were performed between subjects who did not use inhaled corticosteroids (n = 58) and subjects who did (n = 65). Measurements of serum biomarkers were recorded on admission to the hospital (day 1) and on day 3; clinical, physiological, microbiological, and severity data and mortality/readmission rates were also recorded. At days 1 and 3, both groups showed a similar inflammatory response; fluticasone produced lower levels of interleukin-8 compared with budesonide (P < .01). All clinical features considered were similar in the 2 groups; multivariate analysis predicting clinical complications on hospitalization showed air-flow obstruction severity as the only predictive factor (odds ratio 3.13, 95% CI 1.13-8.63, P = .02). Our study demonstrates a lack of inhaled corticosteroid influence in the early systemic inflammatory response to and clinical presentation of COPD exacerbation. Copyright © 2014 by Daedalus Enterprises.

Inflammatory Markers and Preeclampsia: A Systematic Review.

PubMed

Black, Kathleen Darrah; Horowitz, June Andrews

Preeclampsia (PE), a serious and variable pregnancy complication affecting 5%-10% of the obstetric population, has an undetermined etiology, yet inflammation is concomitant with its development, particularly in relation to endothelial dysfunction. The purpose of this systematic review was to examine the published evidence concerning an association between PE and inflammatory markers for their usefulness in the prediction or early identification of women with PE in antepartum clinical settings. In this systematic review, we used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The Cumulative Index for Nursing and Allied Health and MEDLINE/OVID were the electronic databases used for identifying published articles. We placed no time limit on the publication year. The search generated 798 articles. After removing duplicates, screening abstracts, and conducting full-text reviews, we retained 73 articles and examined 57 unique markers. This review shows that C-reactive protein and the cytokines, specifically the proinflammatory markers IL-6, IL-8, and tumor necrosis factor alpha, garner the most support as potential inflammatory markers for clinical surveillance of PE, particularly during the second and third trimesters. Based on this review, we cannot recommend any single inflammatory marker for routine clinical use to predict/identify PE onset or progression. Research is recommended to examine a combination panel of these four inflammatory markers both with and without clinical risk factors toward the goal of translation to practice.

Anti-Inflammatory and Antioxidative Stress Effects of Oryzanol in Glaucomatous Rabbits.

PubMed

Panchal, Shital S; Patidar, Rajesh K; Jha, Abhishek B; Allam, Ahmed A; Ajarem, Jamaan; Butani, Shital B

2017-01-01

Purpose . γ -Oryzanol works by anti-inflammatory and radical scavenging activity as a neuroprotective, anticancer, antiulcer, and immunosuppressive agent. The present study was conducted to investigate effect of oryzanol in acute and chronic experimental glaucoma in rabbits. Methods . Effect of oryzanol was evaluated in 5% dextrose induced acute model of ocular hypertension in rabbit eye. Chronic model of glaucoma was induced with subconjunctival injection of 5% of 0.3 ml phenol. Treatment with oryzanol was given for next two weeks after induction of glaucoma. From anterior chamber of rabbit eye aqueous humor was collected to assess various oxidative stress parameters like malondialdehyde, superoxide dismutase, glutathione peroxidase, catalase, nitric oxide, and inflammatory parameters like TNF- α and IL-6. Structural damage in eye was examined by histopathological studies. Results . In acute model of ocular hypertension oryzanol did not alter raised intraocular pressure. In chronic model of glaucoma oryzanol exhibited significant reduction in oxidative stress followed by reduction in intraocular pressure. Oryzanol treatment reduced level of TNF- α and IL-6. Histopathological studies revealed decreased structural damage of trabecular meshwork, lamina cribrosa, and retina with oryzanol treatment. Conclusions . Oryzanol showed protective effect against glaucoma by its antioxidative stress and anti-inflammatory property. Treatment with oryzanol can reduce optic nerve damage.

Alarmin S100A8/S100A9 as a biomarker for molecular imaging of local inflammatory activity.

PubMed

Vogl, Thomas; Eisenblätter, Michel; Völler, Tom; Zenker, Stefanie; Hermann, Sven; van Lent, Peter; Faust, Andreas; Geyer, Christiane; Petersen, Beatrix; Roebrock, Kirsten; Schäfers, Michael; Bremer, Christoph; Roth, Johannes

2014-08-06

Inflammation has a key role in the pathogenesis of various human diseases. The early detection, localization and monitoring of inflammation are crucial for tailoring individual therapies. However, reliable biomarkers to detect local inflammatory activities and to predict disease outcome are still missing. Alarmins, which are locally released during cellular stress, are early amplifiers of inflammation. Here, using optical molecular imaging, we demonstrate that the alarmin S100A8/S100A9 serves as a sensitive local and systemic marker for the detection of even sub-clinical disease activity in inflammatory and immunological processes like irritative and allergic contact dermatitis. In a model of collagen-induced arthritis, we use S100A8/S100A9 imaging to predict the development of disease activity. Furthermore, S100A8/S100A9 can act as a very early and sensitive biomarker in experimental leishmaniasis for phagocyte activation linked to an effective Th1-response. In conclusion, the alarmin S100A8/S100A9 is a valuable and sensitive molecular target for novel imaging approaches to monitor clinically relevant inflammatory disorders on a molecular level.

Interaction between cytokine gene polymorphisms and the effect of physical exercise on clinical and inflammatory parameters in older women: study protocol for a randomized controlled trial.

PubMed

Pereira, Daniele S; Queiroz, Bárbara Z; Mateo, Elvis C C; Assumpção, Alexandra M; Felício, Diogo C; Miranda, Aline S; Anjos, Daniela M C; Jesus-Moraleida, Fabianna; Dias, Rosângela C; Pereira, Danielle A G; Teixeira, Antônio L; Pereira, Leani S M

2012-08-08

Aging is associated with chronic low-grade inflammatory activity with an elevation of cytokine levels. An association between regular physical activity and reduction of blood levels of anti-inflammatory cytokines is demonstrated in the literature pointing to an anti-inflammatory effect related to exercise. However, there is no consensus regarding which type of exercise and which parameters are the most appropriate to influence inflammatory markers. Evidence indicates that the single nucleotide polymorphism (SNP) can influence the synthesis of those cytokines affecting their production. The design of this study is a randomized controlled trial. The aim of this study is to investigate the interaction between the cytokine genes SNP and the effect of physical activity on older women. The main outcomes are: serum levels of sTNFR-1, sTNFR-2, interleukin (IL)-6, IL-10, measured by the ELISA method; genotyping of tumor necrosis factor- (TNF)-alpha (rs1800629), IL6 (rs1800795), IL10 (rs1800896) by the TaqMan Method (Applied Biosystems, Foster City, CA, USA); and physical performance assessed by Timed Up and Go and 10-Meter Walk Tests. Secondary outcomes include: Geriatric Depression Scale, Perceived Stress Scaleand aerobic capacity, assessed by the six-minute walk; and lower limb muscle strength, using an isokinetic dinamometer (Biodex Medical Systems, Inc., Shirley, NY,USA). Both exercise protocols will be performed three times a week for 10 weeks, 30 sessions in total. Investigating the interaction between genetic factors and exercise effects of both protocols of exercise on the levels of inflammatory cytokine levels can contribute to guide clinical practice related to treatment and prevention of functional changes due to chronic inflammatory activity in older adults. This approach could develop new perspectives on preventive and treatment proposals in physical therapy and in the management of the older patient. (ReBEC) RBR9v9cwf.

A Peptide Targeting Inflammatory CNS Lesions in the EAE Rat Model of Multiple Sclerosis.

PubMed

Boiziau, Claudine; Nikolski, Macha; Mordelet, Elodie; Aussudre, Justine; Vargas-Sanchez, Karina; Petry, Klaus G

2018-06-01

Multiple sclerosis is characterized by inflammatory lesions dispersed throughout the central nervous system (CNS) leading to severe neurological handicap. Demyelination, axonal damage, and blood brain barrier alterations are hallmarks of this pathology, whose precise processes are not fully understood. In the experimental autoimmune encephalomyelitis (EAE) rat model that mimics many features of human multiple sclerosis, the phage display strategy was applied to select peptide ligands targeting inflammatory sites in CNS. Due to the large diversity of sequences after phage display selection, a bioinformatics procedure called "PepTeam" designed to identify peptides mimicking naturally occurring proteins was used, with the goal to predict peptides that were not background noise. We identified a circular peptide CLSTASNSC called "Ph48" as an efficient binder of inflammatory regions of EAE CNS sections including small inflammatory lesions of both white and gray matter. Tested on human brain endothelial cells hCMEC/D3, Ph48 was able to bind efficiently when these cells were activated with IL1β to mimic inflammatory conditions. The peptide is therefore a candidate for further analyses of the molecular alterations in inflammatory lesions.

Two-dimensional grayscale ultrasound and spectral Doppler waveform evaluation of dogs with chronic enteropathies.

PubMed

Gaschen, Lorrie; Kircher, Patrick

2007-08-01

Sonography is an important diagnostic tool to examine the gastrointestinal tract of dogs with chronic diarrhea. Two-dimensional grayscale ultrasound parameters to assess for various enteropathies primarily focus on wall thickness and layering. Mild, generalized thickening of the intestinal wall with maintenance of the wall layering is common in inflammatory bowel disease. Quantitative and semi-quantitative spectral Doppler arterial waveform analysis can be utilized for various enteropathies, including inflammatory bowel disease and food allergies. Dogs with inflammatory bowel disease have inadequate hemodynamic responses during digestion of food. Dogs with food allergies have prolonged vasodilation and lower resistive and pulsatility indices after eating allergen-inducing foods.

Predictive factors for moderate or severe exacerbations in asthma patients receiving outpatient care.

PubMed

Gutiérrez, Francisco Javier Álvarez; Galván, Marta Ferrer; Gallardo, Juan Francisco Medina; Mancera, Marta Barrera; Romero, Beatriz Romero; Falcón, Auxiliadora Romero

2017-05-02

Asthma exacerbations are important events that affect disease control, but predictive factors for severe or moderate exacerbations are not known. The objective was to study the predictive factors for moderate (ME) and severe (SE) exacerbations in asthma patients receiving outpatient care. Patients aged > 12 years with asthma were included in the study and followed-up at 4-monthly intervals over a 12-month period. Clinical (severity, level of control, asthma control test [ACT]), atopic, functional, inflammatory, SE and ME parameters were recorded. Univariate analysis was used to compare data from patients presenting at least 1 SE or ME during the follow-up period vs no exacerbations. Statistically significant (p <0.1) factors were then subjected to multiple analysis by binary logistic regression. A total of 330 patients completed the study, most of whom were atopic (76%), women (nearly 70%), with moderate and mild persistent asthma (>80%). Twenty-seven patients (8%) had a SE and 183 had a ME (58.5%) during follow-up. In the case of SEs, the only predictive factor identified in the multiple analysis was previous SE (baseline visit OR 4.218 95% CI 1.53-11.58, 4-month follow-up OR 6.88 95% CI 2.018-23.51) and inhalation technique (OR 3.572 95% CI 1.324-9.638). In the case of MEs, the only predictive factor found in the multiple analysis were previous ME (baseline visit OR 2.90 95% CI 1.54-5.48, 4-month follow- up OR 1.702 95% CI 1.146-2.529). The primary predictive factor for SE or ME is prior SE or ME, respectively. SEs seem to constitute a specific patient "phenotype", in which the sole predictive factor is prior SEs.

C-Reactive Protein and Prediction of 1-Year Mortality in Prevalent Hemodialysis Patients

PubMed Central

Bazeley, Jonathan; Bieber, Brian; Li, Yun; Morgenstern, Hal; de Sequera, Patricia; Combe, Christian; Yamamoto, Hiroyasu; Gallagher, Martin; Port, Friedrich K.

2011-01-01

Summary Background and objectives Measurement of C-reactive protein (CRP) levels remains uncommon in North America, although it is now routine in many countries. Using Dialysis Outcomes and Practice Patterns Study data, our primary aim was to evaluate the value of CRP for predicting mortality when measured along with other common inflammatory biomarkers. Design, setting, participants, & measurements We studied 5061 prevalent hemodialysis patients from 2005 to 2008 in 140 facilities routinely measuring CRP in 10 countries. The association of CRP with mortality was evaluated using Cox regression. Prediction of 1-year mortality was assessed in logistic regression models with differing adjustment variables. Results Median baseline CRP was lower in Japan (1.0 mg/L) than other countries (6.0 mg/L). CRP was positively, monotonically associated with mortality. No threshold below which mortality rate leveled off was identified. In prediction models, CRP performance was comparable with albumin and exceeded ferritin and white blood cell (WBC) count based on measures of model discrimination (c-statistics, net reclassification improvement [NRI]) and global model fit (generalized R2). The primary analysis included age, gender, diabetes, catheter use, and the four inflammatory markers (omitting one at a time). Specifying NRI ≥5% as appropriate reclassification of predicted mortality risk, NRI for CRP was 12.8% compared with 10.3% for albumin, 0.8% for ferritin, and <0.1% for WBC. Conclusions These findings demonstrate the value of measuring CRP in addition to standard inflammatory biomarkers to improve mortality prediction in hemodialysis patients. Future studies are indicated to identify interventions that lower CRP and to identify whether they improve clinical outcomes. PMID:21868617

Choosing the appropriate forecasting model for predictive parameter control.

PubMed

Aleti, Aldeida; Moser, Irene; Meedeniya, Indika; Grunske, Lars

2014-01-01

All commonly used stochastic optimisation algorithms have to be parameterised to perform effectively. Adaptive parameter control (APC) is an effective method used for this purpose. APC repeatedly adjusts parameter values during the optimisation process for optimal algorithm performance. The assignment of parameter values for a given iteration is based on previously measured performance. In recent research, time series prediction has been proposed as a method of projecting the probabilities to use for parameter value selection. In this work, we examine the suitability of a variety of prediction methods for the projection of future parameter performance based on previous data. All considered prediction methods have assumptions the time series data has to conform to for the prediction method to provide accurate projections. Looking specifically at parameters of evolutionary algorithms (EAs), we find that all standard EA parameters with the exception of population size conform largely to the assumptions made by the considered prediction methods. Evaluating the performance of these prediction methods, we find that linear regression provides the best results by a very small and statistically insignificant margin. Regardless of the prediction method, predictive parameter control outperforms state of the art parameter control methods when the performance data adheres to the assumptions made by the prediction method. When a parameter's performance data does not adhere to the assumptions made by the forecasting method, the use of prediction does not have a notable adverse impact on the algorithm's performance.

Electroconvulsive seizures (ECS) do not prevent LPS-induced behavioral alterations and microglial activation.

PubMed

van Buel, E M; Bosker, F J; van Drunen, J; Strijker, J; Douwenga, W; Klein, H C; Eisel, U L M

2015-12-12

Long-term neuroimmune activation is a common finding in major depressive disorder (MDD). Literature suggests a dual effect of electroconvulsive therapy (ECT), a highly effective treatment strategy for MDD, on neuroimmune parameters: while ECT acutely increases inflammatory parameters, such as serum levels of pro-inflammatory cytokines, there is evidence to suggest that repeated ECT sessions eventually result in downregulation of the inflammatory response. We hypothesized that this might be due to ECT-induced attenuation of microglial activity upon inflammatory stimuli in the brain. Adult male C57Bl/6J mice received a series of ten electroconvulsive seizures (ECS) or sham shocks, followed by an intracerebroventricular (i.c.v.) lipopolysaccharide (LPS) or phosphate-buffered saline (PBS) injection. Brains were extracted and immunohistochemically stained for the microglial marker ionized calcium-binding adaptor molecule 1 (Iba1). In addition, a sucrose preference test and an open-field test were performed to quantify behavioral alterations. LPS induced a short-term reduction in sucrose preference, which normalized within 3 days. In addition, LPS reduced the distance walked in the open field and induced alterations in grooming and rearing behavior. ECS did not affect any of these parameters. Phenotypical analysis of microglia demonstrated an LPS-induced increase in microglial activity ranging from 84 to 213 % in different hippocampal regions (CA3 213 %; CA1 84 %; dentate gyrus 131 %; and hilus 123 %). ECS-induced alterations in microglial activity were insignificant, ranging from -2.6 to 14.3 % in PBS-injected mice and from -20.2 to 6.6 % in LPS-injected mice. We were unable to demonstrate an effect of ECS on LPS-induced microglial activity or behavioral alterations.

Perioperative supplementation with bifidobacteria improves postoperative nutritional recovery, inflammatory response, and fecal microbiota in patients undergoing colorectal surgery: a prospective, randomized clinical trial

PubMed Central

MIZUTA, Minoru; ENDO, Izuru; YAMAMOTO, Sumiharu; INOKAWA, Hidetoshi; KUBO, Masatoshi; UDAKA, Tetsunobu; SOGABE, Osanori; MAEDA, Hiroya; SHIRAKAWA, Kazutoyo; OKAZAKI, Eriko; ODAMAKI, Toshitaka; ABE, Fumiaki; XIAO, Jin-zhong

2015-01-01

The use of probiotics has been widely documented to benefit human health, but their clinical value in surgical patients remains unclear. The present study investigated the effect of perioperative oral administration of probiotic bifidobacteria to patients undergoing colorectal surgery. Sixty patients undergoing colorectal resection were randomized to two groups prior to resection. One group (n=31) received a probiotic supplement, Bifidobacterium longum BB536, preoperatively for 7–14 days and postoperatively for 14 days, while the other group (n=29) received no intervention as a control. The occurrences of postoperative infectious complications were recorded. Blood and fecal samples were collected before and after surgery. No significant difference was found in the incidence of postoperative infectious complications and duration of hospital stay between the two groups. In comparison to the control group, the probiotic group tended to have higher postoperative levels of erythrocytes, hemoglobin, lymphocytes, total protein, and albumin and lower levels of high sensitive C-reactive proteins. Postoperatively, the proportions of fecal bacteria changed significantly; Actinobacteria increased in the probiotic group, Bacteroidetes and Proteobacteria increased in the control group, and Firmicutes decreased in both groups. Significant correlations were found between the proportions of fecal bacteria and blood parameters; Actinobacteria correlated negatively with blood inflammatory parameters, while Bacteroidetes and Proteobacteria correlated positively with blood inflammatory parameters. In the subgroup of patients who received preoperative chemoradiotherapy treatment, the duration of hospital stay was significantly shortened upon probiotic intervention. These results suggest that perioperative oral administration of bifidobacteria may contribute to a balanced intestinal microbiota and attenuated postoperative inflammatory responses, which may subsequently promote a healthy recovery after colorectal resection. PMID:27200261

Evidence for gastroprotective, anti-inflammatory and antioxidant potential of methanolic extract of Cordia dichotoma leaves on indomethacin and stress induced gastric lesions in Wistar rats.

PubMed

Hatware, Ketan Vinayakrao; Sharma, Sanjay; Patil, Kiran; Shete, Meghanath; Karri, Sravani; Gupta, Gaurav

2018-07-01

The Cordia dichotoma (CD) is having anticancer and other pharmacological effects as it contains mainly flavonoids. The present study was aimed to demonstrate the gastroprotective effect of methanolic extract of CD leaves (MECD) obtained using Soxhlet extractor. In this study the qualitative phytochemical analysis of MECD revealed the presence of bioflavonoids and determination of quercetin was confirmed by HPLC analysis. The MECD was administered orally at doses 50 mg/kg, 100 mg/kg and 200 mg/kg against indomethacin induced gastric ulceration and stress-induced gastric ulceration in Wistar rats. Omeprazole at 10 mg/kg orally was used as the reference standard. The various parameters like gastric volume, gastric pH, total acidity, ulcer index, percent protection were estimated for assessment of anti-secretory and gastroprotective effects of MECD. At the same time antioxidant parameters like superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) in addition to that inflammatory parameters such as tumor necrosis factor-α (TNF-α), interleukin-6 and interleukin-10 were also estimated according to their respective method of estimation using analyzing kit. The MECD have reduced gastric volume, total acidity and gastric mucosal damage in both the experimental models significantly and dose dependently as compared with control group. Similarly the antioxidant enzymes like SOD and CAT were increased while MDA levels were decreased significantly, at the same time TNF-α and IL-6 levels were decreased and anti-inflammatory IL-10 levels were increased significantly in MECD treated groups. Thus the pretreatment with MECD has shown significant gastroprotective potential probably due to its antioxidant and anti-inflammatory properties. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Fat-free mass depletion and inflammation in patients with bronchiectasis.

PubMed

Olveira, Gabriel; Olveira, Casilda; Gaspar, Inmaculada; Porras, Nuria; Martín-Núñez, Gracia; Rubio, Elehazara; Colomo, Natalia; Rojo-Martínez, Gemma; Soriguer, Federico

2012-12-01

Fat-free mass depletion has been related to increased inflammatory activity and to increased morbidity and mortality in chronic respiratory diseases. The aims of our study were to determine the nutritional status and serum levels of adipocytokines and inflammatory cytokines in patients with bronchiectasis of any etiology and their relation with respiratory parameters. A cross-sectional study was designed that included patients aged >14 years with diagnostic criteria for bronchiectasis. Anthropometric parameters; a diet questionnaire; hand grip dynamometry; levels of leptin, adiponectin, interleukin-6 (IL-6), tumor necrosis factor-α, and ultrasensitive C-reactive protein; as well as respiratory parameters (ie, clinical, radiologic, and spirometric values) were assessed. Ninety-three clinically stable patients were recruited, 43 with cystic fibrosis, 31 with noncystic fibrosis bronchiectasis, and 19 with cystic fibrosis transmembrane conductance regulator-related bronchiectasis. Fat-free mass depletion was present in 31% of patients, with no differences according to the etiology of the bronchiectasis. Correlations were found between inflammatory cytokines (ie, IL-6) and exacerbations, bronchorrea, forced expiratory volume in 1 second, and Bhalla score. Patients with worse respiratory disease severity, malnutrition, and diabetes had significantly higher levels of IL-6. Adiponectin correlated significantly and positively with fat mass and fat mass index and negatively with fat-free mass, fat-free mass index, and hand dynamometry. Leptin correlated positively with body mass index, fat mass and fat mass index, and negatively with fat-free mass, fat-free mass index, and dynamometry. Patients with bronchiectasis present a high percentage of fat-free mass depletion, independent of the etiology of the disease. The levels of inflammatory cytokines (especially IL-6) may be useful markers of disease severity. Adiponectin levels were higher in patients with fat-free mass depletion. Copyright © 2012 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

Role of docosahexaenoic acid treatment in improving liver histology in pediatric nonalcoholic fatty liver disease.

PubMed

Nobili, Valerio; Carpino, Guido; Alisi, Anna; De Vito, Rita; Franchitto, Antonio; Alpini, Gianfranco; Onori, Paolo; Gaudio, Eugenio

2014-01-01

Nonalcoholic fatty liver disease (NAFLD) is one of the most important causes of liver-related morbidity and mortality in children. Recently, we have reported the effects of docosahexaenoic acid (DHA), the major dietary long-chain polyunsaturated fatty acids, in children with NAFLD. DHA exerts a potent anti-inflammatory activity through the G protein-coupled receptor (GPR)120. Our aim was to investigate in pediatric NAFLD the mechanisms underlying the effects of DHA administration on histo-pathological aspects, GPR120 expression, hepatic progenitor cell activation and macrophage pool. 20 children with untreated NAFLD were included. Children were treated with DHA for 18 months. Liver biopsies before and after the treatment were analyzed. Hepatic progenitor cell activation, macrophage pool and GPR120 expression were evaluated and correlated with clinical and histo-pathological parameters. GPR120 was expressed by hepatocytes, liver macrophages, and hepatic progenitor cells. After DHA treatment, the following modifications were present: i) the improvement of histo-pathological parameters such as NAFLD activity score, ballooning, and steatosis; ii) the reduction of hepatic progenitor cell activation in correlation with histo-pathological parameters; iii) the reduction of the number of inflammatory macrophages; iv) the increase of GPR120 expression in hepatocytes; v) the reduction of serine-311-phosphorylated nuclear factor kappa B (NF-κB) nuclear translocation in hepatocytes and macrophages in correlation with serum inflammatory cytokines. DHA could modulate hepatic progenitor cell activation, hepatocyte survival and macrophage polarization through the interaction with GPR120 and NF-κB repression. In this scenario, the modulation of GPR120 exploits a novel crucial role in the regulation of the cell-to-cell cross-talk that drives inflammatory response, hepatic progenitor cell activation and hepatocyte survival.

[Evaluation of inflammatory cells (tumor infiltrating lymphocytes - TIL) in malignant melanoma].

PubMed

Dundr, Pavel; Němejcová, Kristýna; Bártů, Michaela; Tichá, Ivana; Jakša, Radek

2018-01-01

The evaluation of inflammatory infiltrate (tumor infiltrating lymphocytes - TIL) should be a standard part of biopsy examination for malignant melanoma. Currently, the most commonly used assessment method according to Clark is not optimal and there have been attempts to find an alternative system. Here we present an overview of possible approaches involving five different evaluation methods based on hematoxylin-eosin staining, including the recent suggestion of unified TIL evaluation method for all solid tumors. The issue of methodology, prognostic and predictive significance of TIL determination as well as the importance of immunohistochemical subtyping of inflammatory infiltrate is discussed.

An inflammation-related nomogram for predicting the survival of patients with non-small cell lung cancer after pulmonary lobectomy.

PubMed

Wang, Ying; Qu, Xiao; Kam, Ngar-Woon; Wang, Kai; Shen, Hongchang; Liu, Qi; Du, Jiajun

2018-06-26

Emerging inflammatory response biomarkers are developed to predict the survival of patients with cancer, the aim of our study is to establish an inflammation-related nomogram based on the classical predictive biomarkers to predict the survivals of patients with non-small cell lung cancer (NSCLC). Nine hundred and fifty-two NSCLC patients with lung cancer surgery performed were enrolled into this study. The cutoffs of inflammatory response biomarkers were determined by Receiver operating curve (ROC). Univariate and multivariate analysis were conducted to select independent prognostic factors to develop the nomogram. The median follow-up time was 40.0 months (range, 1 to 92 months). The neutrophil to lymphocyte ratio (cut-off: 3.10, HR:1.648, P = 0.045) was selected to establish the nomogram which could predict the 5-year OS probability. The C-index of nomogram was 0.72 and the 5-year OS calibration curve displayed an optimal agreement between the actual observed outcomes and the predictive results. Neutrophil to lymphocyte ratio was shown to be a valuable biomarker for predicting survival of patients with NSCLC. The addition of neutrophil to lymphocyte ratio could improve the accuracy and predictability of the nomogram in order to provide reference for clinicians to assess patient outcomes.

Pathogenesis and Prediction of Future Rheumatoid Arthritis

DTIC Science & Technology

2014-10-01

characterized by abnormalities of the immune system prior to the onset of the clinically apparent inflammatory joint disease that currently defines RA. The...the clinically apparent inflammatory joint disease that currently defines RA. The primary goal of this project is to investigate this preclinical...environmental exposures such as smoking, periodontal disease were ascertained. Goal 2. Local and governmental IRB approvals, and HRPO approval, were obtained

How to predict clinical relapse in inflammatory bowel disease patients

PubMed Central

Liverani, Elisa; Scaioli, Eleonora; Digby, Richard John; Bellanova, Matteo; Belluzzi, Andrea

2016-01-01

Inflammatory bowel diseases have a natural course characterized by alternating periods of remission and relapse. Disease flares occur in a random way and are currently unpredictable for the most part. Predictors of benign or unfavourable clinical course are required to facilitate treatment decisions and to avoid overtreatment. The present article provides a literature review of the current evidence on the main clinical, genetic, endoscopic, histologic, serologic and fecal markers to predict aggressiveness of inflammatory bowel disease and discuss their prognostic role, both in Crohn’s disease and ulcerative colitis. No single marker seems to be reliable alone as a flare predictor, even in light of promising evidence regarding the role of fecal markers, in particular fecal calprotectin, which has reported good results recently. In order to improve our daily clinical practice, validated prognostic scores should be elaborated, integrating clinical and biological markers of prognosis. Finally, we propose an algorithm considering clinical history and biological markers to intercept patients with high risk of clinical relapse. PMID:26811644

Effect of a trans fatty acid-enriched diet on biochemical and inflammatory parameters in Wistar rats.

PubMed

Longhi, Rafael; Almeida, Roberto Farina; Machado, Letiane; Duarte, Maria Marta Medeiros Frescura; Souza, Débora Guerini; Machado, Priscila; de Assis, Adriano Martimbianco; Quincozes-Santos, André; Souza, Diogo Onofre

2017-04-01

Recent data regarding trans fatty acids (TFAs) have implicated these lipids as particularly deleterious to human health, causing systemic inflammation, endothelial dysfunction and possibly inflammation in the central nervous system (CNS). We aimed to clarify the impact of partially hydrogenated soybean oil (PHSO) with different TFA concentrations on cerebrospinal fluid (CSF), serum and hepatic parameters in adult Wistar rats. Wistar rats (n = 15/group) were fed either a normolipidic diet or a hyperlipidic diet for 90 days. The normolipidic and hyperlipidic diets had the same ingredients except for fat compositions, concentrations and calories. We used lard in the cis fatty acid group and PHSO in the trans fatty acid group. The intervention groups were as follows: (1) low lard (LL), (2) high lard (HL), (3) low partially hydrogenated soybean oil (LPHSO) and (4) high partially hydrogenated soybean oil (HPHSO). Body weight, lipid profiles and the inflammatory responses in the CSF, serum and liver tissue were analyzed. Surprisingly, with the PHSO diet we observed a worse metabolic response that was associated with oxidative stress in hepatic tissue as well as impaired serum and CSF fluid parameters at both PHSO concentrations. In many analyses, there were no significant differences between the LPHSO and HPHSO diets. Dietary supplementation with PHSO impaired inflammatory parameters in CSF and blood, induced insulin resistance, altered lipid profiles and caused hepatic damage. Overall, these findings suggest that fat composition is more important than the quantity of fat consumed in terms of cis and trans fatty acid diets.

Methods for using groundwater model predictions to guide hydrogeologic data collection, with application to the Death Valley regional groundwater flow system

USGS Publications Warehouse

Tiedeman, C.R.; Hill, M.C.; D'Agnese, F. A.; Faunt, C.C.

2003-01-01

Calibrated models of groundwater systems can provide substantial information for guiding data collection. This work considers using such models to guide hydrogeologic data collection for improving model predictions by identifying model parameters that are most important to the predictions. Identification of these important parameters can help guide collection of field data about parameter values and associated flow system features and can lead to improved predictions. Methods for identifying parameters important to predictions include prediction scaled sensitivities (PSS), which account for uncertainty on individual parameters as well as prediction sensitivity to parameters, and a new "value of improved information" (VOII) method presented here, which includes the effects of parameter correlation in addition to individual parameter uncertainty and prediction sensitivity. In this work, the PSS and VOII methods are demonstrated and evaluated using a model of the Death Valley regional groundwater flow system. The predictions of interest are advective transport paths originating at sites of past underground nuclear testing. Results show that for two paths evaluated the most important parameters include a subset of five or six of the 23 defined model parameters. Some of the parameters identified as most important are associated with flow system attributes that do not lie in the immediate vicinity of the paths. Results also indicate that the PSS and VOII methods can identify different important parameters. Because the methods emphasize somewhat different criteria for parameter importance, it is suggested that parameters identified by both methods be carefully considered in subsequent data collection efforts aimed at improving model predictions.

The Impact of Meal Timing on Cardiometabolic Syndrome Indicators in Shift Workers

PubMed Central

Molzof, Hylton E.; Wirth, Michael D.; Burch, James B.; Shivappa, Nitin; Hébert, James R.; Johnson, Russell L.; Gamble, Karen L.

2017-01-01

The aims of this study were to 1) compare the inflammatory potential of night- and day-shift nurses’ diets in regard to time-of-day and work status, and 2) explore how the timing of food intake during work and off-work is associated with cardiometabolic syndrome (CMS) risk factors between these two groups. Female nurses (N = 17; 8 day-shift and 9 night-shift) reported food intake over 9 days. On a middle day off of work, metabolic parameters were measured after an overnight fast. Energy/macronutrient intake and inflammatory potential of dietary intake (as assessed via the Dietary Inflammatory IndexTM) were calculated for nurses’ workdays, work nights, off-work days, and off-work nights. Work-night total food intake (grams) accounted for a significant amount of variance in CMS risk factors for night-shift nurses only. Increased total gram consumption during night-shift nurses’ work nights was associated with increased lipid levels – independent of the macronutrient composition of the food consumed. Alternatively, for night-shift nurses, work-day intake of several food parameters accounted for a significant proportion of variance in HDL cholesterol levels, with higher intake associated with higher HDL levels. For both day- and night-shift nurses, food intake during the day was more pro-inflammatory regardless of shift-type or work status. Our novel approach of combining time-of-day-specific and work-day-specific analyses of dietary inflammatory factors and macronutrient composition with measurement of CMS risk factors suggests a link between meal timing and cardiometabolic health for shift-working nurses. PMID:28107043

Efficient temporal and interlayer parameter prediction for weighted prediction in scalable high efficiency video coding

NASA Astrophysics Data System (ADS)

Tsang, Sik-Ho; Chan, Yui-Lam; Siu, Wan-Chi

2017-01-01

Weighted prediction (WP) is an efficient video coding tool that was introduced since the establishment of the H.264/AVC video coding standard, for compensating the temporal illumination change in motion estimation and compensation. WP parameters, including a multiplicative weight and an additive offset for each reference frame, are required to be estimated and transmitted to the decoder by slice header. These parameters cause extra bits in the coded video bitstream. High efficiency video coding (HEVC) provides WP parameter prediction to reduce the overhead. Therefore, WP parameter prediction is crucial to research works or applications, which are related to WP. Prior art has been suggested to further improve the WP parameter prediction by implicit prediction of image characteristics and derivation of parameters. By exploiting both temporal and interlayer redundancies, we propose three WP parameter prediction algorithms, enhanced implicit WP parameter, enhanced direct WP parameter derivation, and interlayer WP parameter, to further improve the coding efficiency of HEVC. Results show that our proposed algorithms can achieve up to 5.83% and 5.23% bitrate reduction compared to the conventional scalable HEVC in the base layer for SNR scalability and 2× spatial scalability, respectively.

Diagnosis of edema and inflammation in human intestines using ultrawideband radar

NASA Astrophysics Data System (ADS)

Smith, Sonny; Narayanan, Ram M.; Messaris, Evangelos

2015-05-01

Human intestines are vital organs, which are often subjected to chronic issues. In particular, Crohn's disease is a bowel aliment resulting in inflammation along the lining of one's digestive tract. Moreover, such an inflammatory condition causes changes in the thickness of the intestines; and we posit induce changes in the dielectric properties detectable by radar. This detection hinges on the increase in fluid content in the afflicted area, which is described by effective medium approximations (EMA). In this paper, we consider one of the constitutive parameters (i.e. relative permittivity) of different human tissues and introduce a simple numerical, electromagnetic multilayer model. We observe how the increase in water content in one layer can be approximated to predict the effective permittivity of that layer. Moreover, we note trends in how such an accumulation can influence the total effective reflection coefficient of the multiple layers.

Markers of Oxidative Stress and Neuroprogression in Depression Disorder

PubMed Central

Vaváková, Magdaléna; Trebatická, Jana

2015-01-01

Major depression is multifactorial disorder with high prevalence and alarming prognostic in the nearest 15 years. Several mechanisms of depression are known. Neurotransmitters imbalance and imbalance between neuroprogressive and neuroprotective factors are observed in major depression. Depression is accompanied by inflammatory responses of the organism and consequent elevation of proinflammatory cytokines and increased lipid peroxidation are described in literature. Neuropsychiatric disorders including major depression are also associated with telomerase shortening, oxidative changes in nucleotides, and polymorphisms in several genes connected to metabolism of reactive oxygen species. Mitochondrion dysfunction is directly associated with increasing levels of oxidative stress. Oxidative stress plays significant role in pathophysiology of major depression via actions of free radicals, nonradical molecules, and reactive oxygen and nitrogen species. Products of oxidative stress represent important parameters for measuring and predicting of depression status as well as for determining effectiveness of administrated antidepressants. Positive effect of micronutrients, vitamins, and antioxidants in depression treatment is also reviewed. PMID:26078821

Post-Exercise Heart Rate Recovery Independently Predicts Clinical Outcome in Patients with Acute Decompensated Heart Failure.

PubMed

Youn, Jong-Chan; Lee, Hye Sun; Choi, Suk-Won; Han, Seong-Woo; Ryu, Kyu-Hyung; Shin, Eui-Cheol; Kang, Seok-Min

2016-01-01

Post-exercise heart rate recovery (HRR) is an index of parasympathetic function associated with clinical outcome in patients with chronic heart failure. However, its relationship with the pro-inflammatory response and prognostic value in consecutive patients with acute decompensated heart failure (ADHF) has not been investigated. We measured HRR and pro-inflammatory markers in 107 prospectively and consecutively enrolled, recovered ADHF patients (71 male, 59 ± 15 years, mean ejection fraction 28.9 ± 14.2%) during the pre-discharge period. The primary endpoint included cardiovascular (CV) events defined as CV mortality, cardiac transplantation, or rehospitalization due to HF aggravation. The CV events occurred in 30 (28.0%) patients (5 cardiovascular deaths and 7 cardiac transplantations) during the follow-up period (median 214 days, 11-812 days). When the patients with ADHF were grouped by HRR according to the Contal and O'Quigley's method, low HRR was shown to be associated with significantly higher levels of serum monokine-induced by gamma interferon (MIG) and poor clinical outcome. Multivariate Cox regression analysis revealed that low HRR was an independent predictor of CV events in both enter method and stepwise method. The addition of HRR to a model significantly increased predictability for CV events across the entire follow-up period. Impaired post-exercise HRR is associated with a pro-inflammatory response and independently predicts clinical outcome in patients with ADHF. These findings may explain the relationship between autonomic dysfunction and clinical outcome in terms of the inflammatory response in these patients.

Prediction of disease course in inflammatory bowel diseases.

PubMed

Lakatos, Peter Laszlo

2010-06-07

Clinical presentation at diagnosis and disease course of both Crohn's disease (CD) and ulcerative colitis are heterogeneous and variable over time. Since most patients have a relapsing course and most CD patients develop complications (e.g. stricture and/or perforation), much emphasis has been placed in the recent years on the determination of important predictive factors. The identification of these factors may eventually lead to a more personalized, tailored therapy. In this TOPIC HIGHLIGHT series, we provide an update on the available literature regarding important clinical, endoscopic, fecal, serological/routine laboratory and genetic factors. Our aim is to assist clinicians in the everyday practical decision-making when choosing the treatment strategy for their patients suffering from inflammatory bowel diseases.

The Effects of Ramadan Fasting on Body Composition, Blood Pressure, Glucose Metabolism, and Markers of Inflammation in NAFLD Patients: An Observational Trial.

PubMed

Aliasghari, Fereshteh; Izadi, Azimeh; Gargari, Bahram Pourghassem; Ebrahimi, Sara

2017-01-01

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease and is a serious global health problem. Regarding the increasing prevalence of NAFLD, finding various strategies to prevent and manage the disease is of great importance. The aim of this study was to determine the effects of caloric restriction during Ramadan fasting on anthropometric indices, fasting glucose, plasma insulin, insulin resistance, and inflammatory cytokines (C-reactive protein and interleukin 6) in patients with NAFLD. We conducted this study with 83 patients with NAFLD, 42 of whom decided to fast and 41 controls who decided not to fast for Ramadan, between June 18 and July 17, 2015. Anthropometric parameters were measured and a sample of venous blood was obtained for biochemical assays before and after Ramadan. There was a significant decrease in all anthropometric parameters as well as fasting glucose, plasma insulin, and insulin resistance. Relative to the nonfasting group, fasting significantly reduced circulating inflammatory, but changes in blood pressure after Ramadan were not significant. This study shows significant effects on parameters during Ramadan fasting such as anthropometric indices, fasting glucose, plasma insulin, and inflammatory cytokines in patients with NAFLD. The results of this study suggest that Ramadan fasting may be useful to improve NAFLD, so further studies are needed in this area.

Plasma B-type natriuretic peptide and anti-inflammatory cytokine interleukin-10 levels predict adverse clinical outcome in chronic heart failure patients with depressive symptoms: a 1-year follow-up study.

PubMed

Parissis, John T; Farmakis, Dimitrios; Nikolaou, Maria; Birmpa, Dionysia; Bistola, Vassiliki; Paraskevaidis, Ioannis; Ikonomidis, Ignatios; Gaitani, Stavroula; Venetsanou, Koula; Filippatos, Gerasimos; Kremastinos, Dimitrios Th

2009-10-01

To assess the prognostic value of a wide spectrum of neurohormonal and inflammatory markers along with functional status and exercise capacity, in hospitalized chronic heart failure (CHF) patients with depressive symptoms. A total of 300 consecutive hospitalized CHF patients were screened for depressive symptomatology using the Zung self-rated depression scale (SDS). Patients with depressive symptoms (Zung SDS > or = 40) underwent a 6 min walking test, and evaluation of left ventricular ejection fraction, B-type natriuretic peptide (BNP), and plasma inflammatory/anti-inflammatory factors [interleukin (IL)-6, IL-10, tumour necrosis factor-alpha, soluble intercellular adhesion molecule-1, and vascular cell adhesion molecule-1]. Patients were subsequently followed for up to 1 year for major adverse cardiovascular events (MACE, death or hospitalization due to cardiovascular causes). One hundred and fourteen patients (38%) had a Zung SDS > or = 40. One-year event-free survival of these patients was 19% (mean +/- SE, 150 +/- 12 days). In multivariate analysis, only BNP (HR = 1.001, P = 0.002) and IL-10 (HR = 0.864, P = 0.049) were independent predictors of MACE. Using receiver operator characteristics analysis-derived cut-offs, a BNP value of 290 pg/mL predicted MACE with 86% sensitivity and 69% specificity, whereas an IL-10 value of 5 pg/mL predicted MACE with 61% sensitivity and 78% specificity. Event-free survival differed significantly between patients with BNP < 290 pg/mL and IL-10 > 5 pg/mL (261 +/- 44 days) and those with BNP > 290 pg/mL and IL-10 < 5 pg/mL (79 +/- 11 days, P = 0.0001). Neurohormonal activation and defective anti-inflammatory properties are independent predictors of long-term outcome in hospitalized CHF patients with depressive symptoms.

A novel collaborative representation and SCAD based classification method for fibrosis and inflammatory activity analysis of chronic hepatitis C

NASA Astrophysics Data System (ADS)

Cai, Jiaxin; Chen, Tingting; Li, Yan; Zhu, Nenghui; Qiu, Xuan

2018-03-01

In order to analysis the fibrosis stage and inflammatory activity grade of chronic hepatitis C, a novel classification method based on collaborative representation (CR) with smoothly clipped absolute deviation penalty (SCAD) penalty term, called CR-SCAD classifier, is proposed for pattern recognition. After that, an auto-grading system based on CR-SCAD classifier is introduced for the prediction of fibrosis stage and inflammatory activity grade of chronic hepatitis C. The proposed method has been tested on 123 clinical cases of chronic hepatitis C based on serological indexes. Experimental results show that the performance of the proposed method outperforms the state-of-the-art baselines for the classification of fibrosis stage and inflammatory activity grade of chronic hepatitis C.

Development of Prediction Model and Experimental Validation in Predicting the Curcumin Content of Turmeric (Curcuma longa L.).

PubMed

Akbar, Abdul; Kuanar, Ananya; Joshi, Raj K; Sandeep, I S; Mohanty, Sujata; Naik, Pradeep K; Mishra, Antaryami; Nayak, Sanghamitra

2016-01-01

The drug yielding potential of turmeric ( Curcuma longa L.) is largely due to the presence of phyto-constituent 'curcumin.' Curcumin has been found to possess a myriad of therapeutic activities ranging from anti-inflammatory to neuroprotective. Lack of requisite high curcumin containing genotypes and variation in the curcumin content of turmeric at different agro climatic regions are the major stumbling blocks in commercial production of turmeric. Curcumin content of turmeric is greatly influenced by environmental factors. Hence, a prediction model based on artificial neural network (ANN) was developed to map genome environment interaction basing on curcumin content, soli and climatic factors from different agroclimatic regions for prediction of maximum curcumin content at various sites to facilitate the selection of suitable region for commercial cultivation of turmeric. The ANN model was developed and tested using a data set of 119 generated by collecting samples from 8 different agroclimatic regions of Odisha. The curcumin content from these samples was measured that varied from 7.2% to 0.4%. The ANN model was trained with 11 parameters of soil and climatic factors as input and curcumin content as output. The results showed that feed-forward ANN model with 8 nodes (MLFN-8) was the most suitable one with R 2 value of 0.91. Sensitivity analysis revealed that minimum relative humidity, altitude, soil nitrogen content and soil pH had greater effect on curcumin content. This ANN model has shown proven efficiency for predicting and optimizing the curcumin content at a specific site.

Development of Prediction Model and Experimental Validation in Predicting the Curcumin Content of Turmeric (Curcuma longa L.)

PubMed Central

Akbar, Abdul; Kuanar, Ananya; Joshi, Raj K.; Sandeep, I. S.; Mohanty, Sujata; Naik, Pradeep K.; Mishra, Antaryami; Nayak, Sanghamitra

2016-01-01

The drug yielding potential of turmeric (Curcuma longa L.) is largely due to the presence of phyto-constituent ‘curcumin.’ Curcumin has been found to possess a myriad of therapeutic activities ranging from anti-inflammatory to neuroprotective. Lack of requisite high curcumin containing genotypes and variation in the curcumin content of turmeric at different agro climatic regions are the major stumbling blocks in commercial production of turmeric. Curcumin content of turmeric is greatly influenced by environmental factors. Hence, a prediction model based on artificial neural network (ANN) was developed to map genome environment interaction basing on curcumin content, soli and climatic factors from different agroclimatic regions for prediction of maximum curcumin content at various sites to facilitate the selection of suitable region for commercial cultivation of turmeric. The ANN model was developed and tested using a data set of 119 generated by collecting samples from 8 different agroclimatic regions of Odisha. The curcumin content from these samples was measured that varied from 7.2% to 0.4%. The ANN model was trained with 11 parameters of soil and climatic factors as input and curcumin content as output. The results showed that feed-forward ANN model with 8 nodes (MLFN-8) was the most suitable one with R2 value of 0.91. Sensitivity analysis revealed that minimum relative humidity, altitude, soil nitrogen content and soil pH had greater effect on curcumin content. This ANN model has shown proven efficiency for predicting and optimizing the curcumin content at a specific site. PMID:27766103

The electrophysiological response to immunoglobulin therapy in chronic inflammatory demyelinating polyneuropathy.

PubMed

Otto, M; Markvardsen, L; Tankisi, H; Jakobsen, J; Fuglsang-Frederiksen, A

2017-06-01

To characterize changes in motor nerve conduction studies (MNCS) and motor unit number index (MUNIX) following treatment with subcutaneous immunoglobulin and to assess whether these changes are related to muscle strength. Data from 23 patients participating in a randomized, controlled trial were analyzed. MNCS and MUNIX were performed before and after 12 weeks of treatment. Isokinetic strength (IMS) was measured in various muscles together with grip strength (GS). Proximally evoked compound muscle action potential (CMAP) amplitudes and MUNIX tended to be better preserved in treated patients (P=.049 and .045). Changes in other parameters did not differ between groups. There was no correlation between changes in electrophysiological parameters and IMS. Changes in GS were related to median nerve motor conduction velocity, distal motor latency, CMAP amplitudes, and distally evoked CMAP duration (P=.013-.035). Proximally evoked CMAP amplitudes appear to be the best MNCS parameter to assess treatment outcome in chronic inflammatory demyelinating polyneuropathy. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effects of JP-8 on Molecular and Histological Parameters Related to Acute Skin Irritation

DTIC Science & Technology

2000-06-01

in irritant dermatitis are understood. Cytokines are cell signaling molecules that are involved in the inflammatory response. These include the...are involved in inflammatory responses in contact dermatitis (Figure 2, Ormerod et al., 1997). The analysis of iNOS mRNA or protein, as well as the...placed into a Bessman steel tissue pulverizer (Fisher Scientific, Cat # 08-418-2) that was pre-chilled in liquid nitrogen. Using a lead hammer

A Trypsin Inhibitor from Tamarind Reduces Food Intake and Improves Inflammatory Status in Rats with Metabolic Syndrome Regardless of Weight Loss.

PubMed

Carvalho, Fabiana M C; Lima, Vanessa C O; Costa, Izael S; Medeiros, Amanda F; Serquiz, Alexandre C; Lima, Maíra C J S; Serquiz, Raphael P; Maciel, Bruna L L; Uchôa, Adriana F; Santos, Elizeu A; Morais, Ana H A

2016-09-27

Trypsin inhibitors are studied in a variety of models for their anti-obesity and anti-inflammatory bioactive properties. Our group has previously demonstrated the satietogenic effect of tamarind seed trypsin inhibitors (TTI) in eutrophic mouse models and anti-inflammatory effects of other trypsin inhibitors. In this study, we evaluated TTI effect upon satiety, biochemical and inflammatory parameters in an experimental model of metabolic syndrome (MetS). Three groups of n = 5 male Wistar rats with obesity-based MetS received for 10 days one of the following: (1) Cafeteria diet; (2) Cafeteria diet + TTI (25 mg/kg); and (3) Standard diet. TTI reduced food intake in animals with MetS. Nevertheless, weight gain was not different between studied groups. Dyslipidemia parameters were not different with the use of TTI, only the group receiving standard diet showed lower very low density lipoprotein (VLDL) and triglycerides (TG) (Kruskal-Wallis, p < 0.05). Interleukin-6 (IL-6) production did not differ between groups. Interestingly, tumor necrosis factor-alpha (TNF-α) was lower in animals receiving TTI. Our results corroborate the satietogenic effect of TTI in a MetS model. Furthermore, we showed that TTI added to a cafeteria diet may decrease inflammation regardless of weight loss. This puts TTI as a candidate for studies to test its effectiveness as an adjuvant in MetS treatment.

A Trypsin Inhibitor from Tamarind Reduces Food Intake and Improves Inflammatory Status in Rats with Metabolic Syndrome Regardless of Weight Loss

PubMed Central

Carvalho, Fabiana M. C.; Lima, Vanessa C. O.; Costa, Izael S.; Medeiros, Amanda F.; Serquiz, Alexandre C.; Lima, Maíra C. J. S.; Serquiz, Raphael P.; Maciel, Bruna L. L.; Uchôa, Adriana F.; Santos, Elizeu A.; Morais, Ana H. A.

2016-01-01

Trypsin inhibitors are studied in a variety of models for their anti-obesity and anti-inflammatory bioactive properties. Our group has previously demonstrated the satietogenic effect of tamarind seed trypsin inhibitors (TTI) in eutrophic mouse models and anti-inflammatory effects of other trypsin inhibitors. In this study, we evaluated TTI effect upon satiety, biochemical and inflammatory parameters in an experimental model of metabolic syndrome (MetS). Three groups of n = 5 male Wistar rats with obesity-based MetS received for 10 days one of the following: (1) Cafeteria diet; (2) Cafeteria diet + TTI (25 mg/kg); and (3) Standard diet. TTI reduced food intake in animals with MetS. Nevertheless, weight gain was not different between studied groups. Dyslipidemia parameters were not different with the use of TTI, only the group receiving standard diet showed lower very low density lipoprotein (VLDL) and triglycerides (TG) (Kruskal–Wallis, p < 0.05). Interleukin-6 (IL-6) production did not differ between groups. Interestingly, tumor necrosis factor-alpha (TNF-α) was lower in animals receiving TTI. Our results corroborate the satietogenic effect of TTI in a MetS model. Furthermore, we showed that TTI added to a cafeteria diet may decrease inflammation regardless of weight loss. This puts TTI as a candidate for studies to test its effectiveness as an adjuvant in MetS treatment. PMID:27690087

N-Acetylcysteine and deferoxamine reduce pulmonary oxidative stress and inflammation in rats after coal dust exposure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pinho, R.A.; Silveira, P.C.L.; Silva, L.A.

2005-11-01

Coal dust inhalation induces oxidative damage and inflammatory infiltration on lung parenchyma. Thus, the aim of this study was to determine whether N-acetylcysteine (NAC) administered alone or in combination with deferoxamine (DFX), significantly reduced the inflammatory infiltration and oxidative damage in the lungs of rats exposed to coal dust. Forty-two male Wistar rats (200-250 g) were exposed to the coal dust (3 mg/0.5 mL saline, 3 days/week, for 3 weeks) by intratracheal instillation. The animals were randomly divided into three groups: saline 0.9% (n = 8), supplemented with NAC (20 mg/kg of body weight/day, intraperitoneal injection (i.p.)) (n = 8),more » and supplemented with NAC (20 mg/kg of body weight/day, i.p.) plus DFX (20 mg/kg of body weight/week) (n = 8). Control animals received only saline solution (0.5 mL). Lactate dehydrogenase activity and total cell number were determined in the bronchoalveolar lavage fluid. We determined lipid peroxidation and oxidative protein damage parameters and catalase and superoxide dismutase activities in the lungs of animals. Intratracheal instillation of coal dust in the lungs of rats led to an inflammatory response and induced significant oxidative damage. The administration of NAC alone or in association with DFX reduced the inflammatory response and the oxidative stress parameters in rats exposed to coal dust.« less

Characteristics of Perimenstrual Asthma and Its Relation to Asthma Severity and Control

PubMed Central

Rao, Chitra K.; Moore, Charity G.; Bleecker, Eugene; Busse, William W.; Calhoun, William; Castro, Mario; Chung, Kian Fan; Erzurum, Serpil C.; Israel, Elliot; Curran-Everett, Douglas

2013-01-01

Background: Although perimenstrual asthma (PMA) has been associated with severe and difficult-to-control asthma, it remains poorly characterized and understood. The objectives of this study were to identify clinical, demographic, and inflammatory factors associated with PMA and to assess the association of PMA with asthma severity and control. Methods: Women with asthma recruited to the National Heart, Lung, and Blood Institute Severe Asthma Research Program who reported PMA symptoms on a screening questionnaire were analyzed in relation to basic demographics, clinical questionnaire data, immunoinflammatory markers, and physiologic parameters. Univariate comparisons between PMA and non-PMA groups were performed. A severity-adjusted model predicting PMA was created. Additional models addressed the role of PMA in asthma control. Results: Self-identified PMA was reported in 17% of the subjects (n = 92) and associated with higher BMI, lower FVC % predicted, and higher gastroesophageal reflux disease rates. Fifty-two percent of the PMA group met criteria for severe asthma compared with 30% of the non-PMA group. In multivariable analyses controlling for severity, aspirin sensitivity and lower FVC % predicted were associated with the presence of PMA. Furthermore, after controlling for severity and confounders, PMA remained associated with more asthma symptoms and urgent health-care utilization. Conclusions: PMA is common in women with severe asthma and associated with poorly controlled disease. Aspirin sensitivity and lower FVC % predicted are associated with PMA after adjusting for multiple factors, suggesting that alterations in prostaglandins may contribute to this phenotype. PMID:23632943

Quantitative Contrast-Enhanced Ultrasound Parameters in Crohn Disease: Their Role in Disease Activity Determination With Ultrasound.

PubMed

Medellin-Kowalewski, Alexandra; Wilkens, Rune; Wilson, Alexandra; Ruan, Ji; Wilson, Stephanie R

2016-01-01

The primary objective of our study was to examine the association between contrast-enhanced ultrasound (CEUS) parameters and established gray-scale ultrasound with color Doppler imaging (CDI) for the determination of disease activity in patients with Crohn disease. Our secondary objective was to develop quantitative time-signal intensity curve thresholds for disease activity. One hundred twenty-seven patients with Crohn disease underwent ultrasound with CDI and CEUS. Reviewers graded wall thickness, inflammatory fat, and mural blood flow as showing remission or inflammation (mild, moderate, or severe). If both gray-scale ultrasound and CDI predicted equal levels of disease activity, the studies were considered concordant. If ultrasound images suggested active disease not supported by CDI findings, the ultrasound results for disease activity were indeterminate. Time-signal intensity curves from CEUS were acquired with calculation of peak enhancement (PE), and AUCs. Interobserver variation and associations between PE and ultrasound parameters were examined. Multiclass ROC analysis was used to develop CEUS thresholds for activity. Ninety-six (76%) studies were concordant, 19 of which showed severe disease, and 31 (24%) studies were indeterminate. Kappa analyses revealed good interobserver agreement on grades for CDI (κ = 0.76) and ultrasound (κ = 0.80) assessments. PE values on CEUS and wall thickness showed good association with the Spearman rank correlation coefficient for the entire population (ρ = 0.62, p < 0.01) and for the concordant group (ρ = 0.70, p < 0.01). Multiclass ROC analyses of the concordant group using wall thickness alone as the reference standard showed cutoff points of 18.2 dB for differentiating mild versus moderate activity (sensitivity, 89.0% and specificity, 87.0%) and 23.0 dB for differentiating moderate versus severe (sensitivity, 90% and specificity, 86.8%). Almost identical cutoff points were observed when using ultrasound global assessment as the reference standard: using 18.2 dB to differentiate mild versus moderate activity yielded sensitivity of 89.2% and specificity of 90.9% and using 22.9 dB to differentiate moderate versus severe activity yielded sensitivity of 89.5% and specificity of 83.1%. Quantitative CEUS parameters integrated into inflammatory assessments with ultrasound reduce indeterminate results and improve disease activity level determinations.

[Using dynamic magnetotherapy and transdermal electroneurostimulation in the combined treatment of patients with mandibular fractures and concomitant periodontal inflammatory diseases].

PubMed

Lepilin, A V; Erokina, N L; Rogatina, T V; Khlusov, I Iu

2009-01-01

The objective of this study was to compare results of dynamic magnetotherapy (DMT), transdermal electroneurostimulation (TDENS), and traditional ultrahigh frequency (UHF) therapy in 473 patients with mandibular fractures and concomitant inflammatory diseases of paradontium. The parameters measured in the study included hygienic and paradontal indices, microcirculation patterns (using laser Doppler flowmetry), and the degree of mandibular fragment consolidation. It was shown that combined treatment with DMT and TDENS using an AMO-ATOS-E apparatus permits to eliminate clinical symptoms of paradontal inflammatory diseases twice as fast as traditional ultrahigh frequency therapy and ensures a two-fold reduction in the frequency of complications.

Inflammatory response in mixed viral-bacterial community-acquired pneumonia.

PubMed

Bello, Salvador; Mincholé, Elisa; Fandos, Sergio; Lasierra, Ana B; Ruiz, María A; Simon, Ana L; Panadero, Carolina; Lapresta, Carlos; Menendez, Rosario; Torres, Antoni

2014-07-29

The role of mixed pneumonia (virus+bacteria) in community-acquired pneumonia (CAP) has been described in recent years. However, it is not known whether the systemic inflammatory profile is different compared to monomicrobial CAP. We wanted to investigate this profile of mixed viral-bacterial infection and to compare it to monomicrobial bacterial or viral CAP. We measured baseline serum procalcitonin (PCT), C reactive protein (CRP), and white blood cell (WBC) count in 171 patients with CAP with definite etiology admitted to a tertiary hospital: 59 (34.5%) bacterial, 66 (39.%) viral and 46 (27%) mixed (viral-bacterial). Serum PCT levels were higher in mixed and bacterial CAP compared to viral CAP. CRP levels were higher in mixed CAP compared to the other groups. CRP was independently associated with mixed CAP. CRP levels below 26 mg/dL were indicative of an etiology other than mixed in 83% of cases, but the positive predictive value was 45%. PCT levels over 2.10 ng/mL had a positive predictive value for bacterial-involved CAP versus viral CAP of 78%, but the negative predictive value was 48%. Mixed CAP has a different inflammatory pattern compared to bacterial or viral CAP. High CRP levels may be useful for clinicians to suspect mixed CAP.

Commensal Gut-Derived Anaerobes as Novel Therapy for Inflammatory Autoimmune Diseases

DTIC Science & Technology

2012-05-01

Luckey D, Marietta EV, Miller ME, Murray JA, White BA and Taneja V. 2012. HLA-DR polymorphism, gut microbiome and sex may predict susceptibility or...Gomez A, Yoeman C, Luckey D, Marietta EV, Miller ME, Murray JA, White BA and Taneja V. 2012. HLA-DR polymorphism, gut microbiome and sex may... Gut -Derived Anaerobes as Novel Therapy for Inflammatory Autoimmune Diseases Veena Taneja Mayo Clinic Rochester, MN 55905

The value of negative Chlamydia trachomatis antibody in prediction of normal tubes in infertile women.

PubMed

Raoofi, Z; Barchinegad, M; Haghighi, L

2013-01-01

To evaluate the value of Chlamydia trachomatis antibody testing in prediction of at least one normal tube in infertile women. Eighty infertile women without any history of abdominal or pelvic surgery, pelvic inflammatory disease, and endometriosis were recruited in this cross-sectional study from 2009 to 2010. The patients underwent hysterosalpingography, laparoscopy, and anti Chlamydia trachomatis IgG antibody (CAT) testing. We compared laparoscopy findings and CAT regarding sensitivity, specificity, accuracy, and predicting value of tubal conditions. The CAT was positive in 50 patients (62.5%) and laparoscopy was positive in 32 patients (40%). The CAT was significantly higher in women with tubal disease (1.88 +/- 0.34) versus in women with normal tubes (1.21 +/- 0.28) (p = 0.003). Five out of 30 sero-negative women had unilateral tubal abnormality and none of them had bilateral tubal obstruction or severe pelvic adhesion. The sensitivity, specificity, positive and negative predictive value, and accuracy of the CAT in prediction of one normal tube were 100%, 42.25%, 18%, 100%, and 48.75%, respectively. The negative predictive value of CAT to predict at least one normal tube in infertile women without history of abdominal or pelvic surgery, pelvic inflammatory disease, and endometriosis was 100%.

Exercise capacity in pediatric patients with inflammatory bowel disease.

PubMed

Ploeger, Hilde E; Takken, Tim; Wilk, Boguslaw; Issenman, Robert M; Sears, Ryan; Suri, Soni; Timmons, Brian W

2011-05-01

To examine exercise capacity in youth with Crohn's disease (CD) and ulcerative colitis (UC). Eleven males and eight females with CD and six males and four females with UC participated. Patients performed standard exercise tests to assess peak power (PP) and mean power (MP) and peak aerobic mechanical power (W(peak)) and peak oxygen uptake (VO(2peak)). Fitness variables were compared with reference data and also correlated with relevant clinical outcomes. Pediatric patients with inflammatory bowel disease had lower PP (∼90% of predicted), MP (∼88% of predicted), W(peak) (∼91% of predicted), and VO(2peak) (∼75% of predicted) compared with reference values. When patients with CD or UC were compared separately to reference values, W(peak) was significantly lower only in the CD group. No statistically significant correlations were found between any exercise variables and disease duration (r = 0.01 to 0.14, P = .47 to .95) or disease activity (r = -0.19 to -0.31, P = .11 to .38), measured by pediatric CD activity index or pediatric ulcerative colitis activity index. After controlling for chronological age, recent hemoglobin levels were significantly correlated with PP (r = 0.45, P = .049), MP (r = 0.63, P = .003), VO(2peak) (r = 0.62, P = .004), and W(peak) (r = 0.70, P = .001). Pediatric patients with inflammatory bowel disease exhibit impaired aerobic and anaerobic exercise capacity compared with reference values. Copyright © 2011 Mosby, Inc. All rights reserved.

Peripheral Inflammatory Markers Contributing to Comorbidities in Autism

PubMed Central

Inga Jácome, Martha Cecilia; Morales Chacòn, Lilia Maria; Vera Cuesta, Hector; Maragoto Rizo, Carlos; Whilby Santiesteban, Mabel; Ramos Hernandez, Lesyanis; Noris García, Elena; González Fraguela, Maria Elena; Fernandez Verdecia, Caridad Ivette; Vegas Hurtado, Yamilé; Siniscalco, Dario; Gonçalves, Carlos Alberto; Robinson-Agramonte, Maria de los Angeles

2016-01-01

This study evaluates the contribution of peripheral biomarkers to comorbidities and clinical findings in autism. Seventeen autistic children and age-matched typically developing (AMTD), between three to nine years old were evaluated. The diagnostic followed the Diagnostic and Statistical Manual of Mental Disorders 4th Edition (DMS-IV) and the Childhood Autism Rating Scale (CARS) was applied to classify the severity. Cytokine profile was evaluated in plasma using a sandwich type ELISA. Paraclinical events included electroencephalography (EEG) record. Statistical analysis was done to explore significant differences in cytokine profile between autism and AMTD groups and respect clinical and paraclinical parameters. Significant differences were found to IL-1β, IL-6, IL-17, IL-12p40, and IL-12p70 cytokines in individuals with autism compared with AMTD (p < 0.05). All autistic patients showed interictalepileptiform activity at EEG, however, only 37.5% suffered epilepsy. There was not a regional focalization of the abnormalities that were detectable with EEG in autistic patients with history of epilepsy. A higher IL-6 level was observed in patients without history of epilepsy with interictalepileptiform activity in the frontal brain region, p < 0.05. In conclusion, peripheral inflammatory markers might be useful as potential biomarkers to predict comorbidities in autism as well as reinforce and aid informed decision-making related to EEG findings in children with Autism spectrum disorders (ASD). PMID:27983615

Circulating Inflammatory Mediators in Patients with Fever: Predicting Bloodstream Infection

PubMed Central

Groeneveld, A. B. Johan; Bossink, Ailko W. J.; van Mierlo, Gerard J.; Hack, C. Erik

2001-01-01

The systemic host response to microbial infection involves clinical signs and symptoms of infection, including fever and elevated white blood cell (WBC) counts. In addition, inflammatory mediators are released, including activated complement product C3a, interleukin 6 (IL-6), and the acute-phase reactant secretory phospholipase A2 (sPLA2). To compare the value of the latter with the former in predicting (the degree of) microbial infection at the bedside, we determined clinical variables and took blood samples daily for 3 consecutive days in 300 patients with a new fever (>38.0°C rectally or >38.3°C axillary). Microbiological culture results for 7 days after inclusion were collected. Patients were divided into clinical and microbial categories: those without and with a clinical focus of infection and those with negative cultures, with positive local cultures or specific stains for fungal (n = 13) or tuberculous infections (n = 1), and with positive blood cultures, including one patient with malaria parasitemia. The area under the curve (AUC) of the receiver operating characteristic (ROC) for prediction of positive cultures was 0.60 (P < 0.005) for peak temperature and 0.59 (P < 0.01) for peak WBC count, 0.60 (P < 0.005) for peak C3a, 0.63 (P < 0.001) for peak IL-6, and 0.61 (P < 0.001) for peak sPLA2. The AUC under the ROC curve for prediction of positive blood cultures was 0.68 (P < 0.001) for peak temperature and 0.56 for peak WBC count (P < 0.05). The AUC for peak C3a was 0.69, that for peak IL-6 was 0.70, and that for sPLA2 was 0.67 (for all, P < 0.001). The degree of microbial invasion is thus a major determinant of the clinical and inflammatory host response in patients with fever. Moreover, circulating inflammatory mediators such as C3a and IL-6 may help to predict positive blood cultures, together with clinical signs and symptoms of the host response to microbial infection, even before culture results are available. This may help in the designing of entry criteria for therapeutic intervention studies. PMID:11687462

Histopathological Parameters predicting Occult Nodal Metastases in Tongue Carcinoma Cases: An Indian Perspective.

PubMed

Jacob, Tina Elizabeth; Malathi, N; Rajan, Sharada T; Augustine, Dominic; Manish, N; Patil, Shankargouda

2016-01-01

It is a well-established fact that in squamous cell carcinoma cases, the presence of lymph node metastases decreased the 5-year survival rate by 50% and also caused the recurrence of the primary tumor with development of distant metastases. Till date, the predictive factors for occult cervical lymph nodes metastases in cases of tongue squamous cell carcinoma remain inconclusive. Therefore, it is imperative to identify patients who are at the greatest risk for occult cervical metastases. This study was thus performed with the aim to identify various histopathologic parameters of the primary tumor that predict occult nodal metastases. The clinicopathologic features of 56 cases of lateral tongue squamous cell carcinoma with cT1NoMo/cT2NoMo as the stage and without prior radiotherapy or chemotherapy were considered. The surgical excision of primary tumor was followed by elective neck dissection. The glossectomy specimen along with the neck nodes were fixed in formalin and 5 urn thick sections were obtained. The hematoxylin & eosin stained sections were then subjected to microscopic examination. The primary tumor characteristics that were analyzed include tumor grade, invading front, depth of tumor, lymphovascular invasion, perineural invasion and inflammatory response. The nodes were examined for possible metastases using hematoxylin & eosin followed by cytokeratin immunohistochemistry. A total of 12 cases were found with positive occult nodal metastases. On performing univariate analysis, the histopathologic parameters that were found to be statistically significant were lymphovascular invasion (p = 0.004) and perineural invasion (p = 0.003) along with a cut-off depth of infiltration more than 5 mm (p = 0.01). Histopathologic assessment of the primary tumor specimen therefore continues to provide information that is central to guide clinical management, particularly in cases of occult nodal metastases. Clinical significance The study highlights the importance of extensive histopathological screening, which holds the key for establishing occult metastases. Pathological upgrading of tumors is possible following histopathological studies similar to the present one. Presence of occult metastases justify neck dissection in these clinically N0 cases. In an Indian setting, histopathological evaluation assumes a bigger role than other expensive and advanced techniques.

Improved HPLC method with the aid of chemometric strategy: determination of loxoprofen in pharmaceutical formulation.

PubMed

Venkatesan, P; Janardhanan, V Sree; Muralidharan, C; Valliappan, K

2012-06-01

Loxoprofen belongs to a class of Nonsteroidal anti-inflammatory drug acts by inhibiting isoforms of cyclo-oxygenase 1 and 2. In this study an improved RP-HPLC method was developed for the quantification of loxoprofen in pharmaceutical dosage form. For that purpose an experimental design approach was employed. Factors-independent variables (organic modifier, pH of the mobile phase and flow rate) were extracted from the preliminary study and as dependent variables three responses (loxoprofen retention factor, resolution between loxoprofen probenecid and retention time of probenecid) were selected. For the improvement of method development and optimization step, Derringer's desirability function was applied to simultaneously optimize the chosen three responses. The procedure allowed deduction of optimal conditions and the predicted optimum was acetonitrile: water (53:47, v/v), pH of the mobile phase adjusted at to 2.9 with ortho phosphoric acid. The separation was achieved in less than 4minutes. The method was applied in the quality control of commercial tablets. The method showed good agreement between the experimental data and predictive value throughout the studied parameter space. The optimized assay condition was validated according to International conference on harmonisation guidelines to confirm specificity, linearity, accuracy and precision.

Suppression of inflammatory reactions by terpinen-4-ol, a main constituent of tea tree oil, in a murine model of oral candidiasis and its suppressive activity to cytokine production of macrophages in vitro.

PubMed

Ninomiya, Kentaro; Hayama, Kazumi; Ishijima, Sanae A; Maruyama, Naho; Irie, Hiroshi; Kurihara, Junichi; Abe, Shigeru

2013-01-01

The onset of oral candidiasis is accompanied by inflammatory symptoms such as pain in the tongue, edema or tissue damage and lowers the quality of life (QOL) of the patient. In a murine oral candidiasis model, the effects were studied of terpinen-4-ol (T-4-ol), one of the main constituents of tea tree oil, Melaleuca alternifolia, on inflammatory reactions. When immunosuppressed mice were orally infected with Candida albicans, their tongues showed inflammatory symptoms within 24 h after the infection, which was monitored by an increase of myeloperoxidase activity and macrophage inflammatory protein-2 in their tongue homogenates. Oral treatment with 50 µL of 40 mg/mL terpinen-4-ol 3h after the Candida infection clearly suppressed the increase of these inflammatory parameters. In vitro analysis of the effects of terpinen-4-ol on cytokine secretion of macrophages indicated that 800 µg/mL of this substance significantly inhibited the cytokine production of the macrophages cultured in the presence of heat-killed C. albicans cells. Based on these findings, the role of the anti-inflammatory action of T-4-ol in its therapeutic activity against oral candidiasis was discussed.

Periodontal disease as a potential factor for systemic inflammatory response in the dog.

PubMed

Kouki, M I; Papadimitriou, S A; Kazakos, G M; Savas, I; Bitchava, D

2013-01-01

Periodontal disease is an inflammatory disease that has numerous consequences both locally and systemically The aim of this study was to assess whether periodontal disease causes systemic inflammatory response in otherwise healthy, adult dogs. We estimated the total mouth periodontal score (TMPS), measured the concentration of C-reactive protein (CRP), hematocrit, and albumin, and determined the white blood cell (WBC) and polymorphonuclear cell (PMN) counts in client-owned dogs. There was a statistically significant relationship between the gingival bleeding index (TMPS-G) and CRP concentration, and WBC and PMN counts, possibly during the active periods of periodontal tissue destruction. No correlation was found between the periodontal destruction index (TMPS-P) and the measured blood parameters. We conclude that chronic periodontal disease does not cause anemia or a reduction in serum albumin. However, active periods of periodontal inflammation may be associated with laboratory values suggestive of a systemic inflammatory response.

Serum lipoproteins are not associated with the severity of asthma.

PubMed

Scaduto, Federica; Giglio, Rosaria Vincenza; Benfante, Alida; Nikolic, Dragana; Montalto, Giuseppe; Rizzo, Manfredi; Scichilone, Nicola

2018-06-01

Asthma is a chronic inflammatory disorder of the bronchi with a complicated and largely unknown pathogenesis. In this context, an emerging role is attributed to the apolipoproteins which serve as structural components of plasma lipoproteins. Low density lipoproteins (LDL) may be involved in the inflammatory pathways of the asthmatic airways; in particular, small dense LDL (sdLDL) particles were associated with increased oxidative susceptibility compared to medium and large sized LDL. In our previous study, we found a positive correlation between forced expiratory volume 1 s (FEV 1 ) % predicted and larger LDL particles (LDL-1), and an inverse correlation between FEV 1 % predicted and sdLDL (LDL-3) in mild, untreated asthmatics. Although LDL appear to be important modulators of inflammation, data on their clinical implications are still lacking. The aim of the study is to investigate whether LDL subclasses correlate with the severity of asthma, assuming that the atherogenic and most pro-inflammatory LDL contribute to ignite and perpetuate the airway inflammatory processes. The study was conducted in one visit, and included clinical and lung functional assessments, as well as measurements of serum concentrations of the LDL subclasses. Non-denaturing, linear polyacrylamide gel electrophoresis was used to separate and measure LDL subclasses, with the LipoPrint © System (Quantimetrix Corporation, Redondo Beach, CA, USA). LDL subclasses were distributed as seven bands (LDL-1 to LDL-7), LDL-1 and -2 being defined as large LDL (least pro-inflammatory), and LDL-3 to 7 defined as sdLDL (most pro-inflammatory). 70 asthmatics under inhaled treatment (M/F: 35/35) were enrolled; 10 healthy subjects (M/F: 3/7) served as controls. In the asthmatic group, FEV 1 % predicted was 81 ± 22% (mean ± SD), vital capacity (VC) % predicted was 97 ± 18%, and FEV 1 /FVC was 0.68 ± 0.1. The mean asthma control test (ACT) score was 18 ± 5. LDL-1 were significantly lower in asthmatics as compared to controls (18 ± 4% vs. 22 ± 4%, p = 0.008). On the contrary, LDL-2 (12 ± 4% vs. 12 ± 5%) and LDL-3 (3 ± 3% vs. 2 ± 2%) were not statistically different between the two groups; smaller subclasses were undetectable. To comply with the design of the study, subjects were classified according to their degree of severity into the 5 Global Initiative for Asthma (GINA) steps: Step 1 (M/F: 4/3, 44 ± 12 yrs), Step 2 (M/F: 1/2, 37 ± 11 yrs), Step 3 (M/F: 12/7, 47 ± 12 yrs), Step 4 (M/F: 8/15, 54 ± 12 yrs), and Step 5 (M/F: 7/9, 56 ± 9 yrs). None of the LDL subclasses showed significant differences between classes of severity: LDL-1 were 16.1 ± 5.6% in Step 1, 18 ± 2.8% in Step 2, 16.7 ± 3.7% in Step 3, 18 ± 3.3% in Step 4, and 19.5 ± 3.2% in Step 5 (p = NS); LDL2 were 14 ± 3.6%, 15 ± 3.4%, 12.4 ± 5.3%, 12.7 ± 4.4% and 11.3 ± 4.2%, respectively (p = NS); LDL3 were 5 ± 5.2%, 4.4 ± 2.6%, 3.3 ± 3.6%, 3.2 ± 2.6% and 2.4 ± 1.8%, p = NS. Finally, no relationship was detected between LDL subclasses and lung function parameters as well as the ACT scores. The current findings confirm a role of LDL as a potential biomarker in the diagnostic process for asthma, and suggest that LDL cannot be used as marker of severity of the disease. Copyright © 2018. Published by Elsevier Ltd.

Low-level laser therapy (LLLT) reduces inflammatory infiltrate and enhances skeletal muscle repair: Histomorphometric parameters

NASA Astrophysics Data System (ADS)

Paiva-Oliveira, E. L.; Lima, N. C.; Silva, P. H.; Sousa, N. T. A.; Barbosa, F. S.; Orsini, M.; Silva, J. G.

2012-09-01

Low level laser therapy (LLLT) has been suggested as an effective therapeutics in inflammatory processes modulation and tissue repairing. However, there is a lack of studies that analyze the anti-inflammatory effects of the infrared lasers in muscular skeletal injury. The aim of this study was to investigate the effects of low-level laser therapy 904 nm in the repair process of skeletal muscle tissue. Swiss mice were submitted to cryoinjury and divided in test (LLLT-treated) and control groups. Histological sections were stained with hematoxylin-eosin to assess general morphology and inflammatory influx, and Picrossirus to quantify collagen fibers deposition. Our results showed significant reduction in inflammatory infiltrated in irradiated mice after 4 days of treatment compared to control ( p = 0.01). After 8 days, the irradiated group showed high levels at regenerating myofibers with significant statistically differences in relation at control group ( p < 0.01). Collagen deposition was significantly increased in the final stages of regeneration at test group, when compared with control group ( p = 0.05). Our data suggests that LLLT reduces the inflammatory response in the initial stages of injury and accelerates the process of muscular tissue repair.

An inflammation-based cumulative prognostic score system in patients with diffuse large B cell lymphoma in rituximab era.

PubMed

Sun, Feifei; Zhu, Jia; Lu, Suying; Zhen, Zijun; Wang, Juan; Huang, Junting; Ding, Zonghui; Zeng, Musheng; Sun, Xiaofei

2018-01-02

Systemic inflammatory parameters are associated with poor outcomes in malignant patients. Several inflammation-based cumulative prognostic score systems were established for various solid tumors. However, there is few inflammation based cumulative prognostic score system for patients with diffuse large B cell lymphoma (DLBCL). We retrospectively reviewed 564 adult DLBCL patients who had received rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) therapy between Nov 1 2006 and Dec 30 2013 and assessed the prognostic significance of six systemic inflammatory parameters evaluated in previous studies by univariate and multivariate analysis:C-reactive protein(CRP), albumin levels, the lymphocyte-monocyte ratio (LMR), the neutrophil-lymphocyte ratio(NLR), the platelet-lymphocyte ratio(PLR)and fibrinogen levels. Multivariate analysis identified CRP, albumin levels and the LMR are three independent prognostic parameters for overall survival (OS). Based on these three factors, we constructed a novel inflammation-based cumulative prognostic score (ICPS) system. Four risk groups were formed: group ICPS = 0, ICPS = 1, ICPS = 2 and ICPS = 3. Advanced multivariate analysis indicated that the ICPS model is a prognostic score system independent of International Prognostic Index (IPI) for both progression-free survival (PFS) (p < 0.001) and OS (p < 0.001). The 3-year OS for patients with ICPS =0, ICPS =1, ICPS =2 and ICPS =3 were 95.6, 88.2, 76.0 and 62.2%, respectively (p < 0.001). The 3-year PFS for patients with ICPS = 0-1, ICPS = 2 and ICPS = 3 were 84.8, 71.6 and 54.5%, respectively (p < 0.001). The prognostic value of the ICPS model indicated that the degree of systemic inflammatory status was associated with clinical outcomes of patients with DLBCL in rituximab era. The ICPS model was shown to classify risk groups more accurately than any single inflammatory prognostic parameters. These findings may be useful for identifying candidates for further inflammation-related mechanism research or novel anti-inflammation target therapies.

Predictive Value of IL-8 for Sepsis and Severe Infections after Burn Injury - A Clinical Study

PubMed Central

Kraft, Robert; Herndon, David N; Finnerty, Celeste C; Cox, Robert A; Song, Juquan; Jeschke, Marc G

2014-01-01

The inflammatory response induced by burn injury contributes to increased incidence of infections, sepsis, organ failure, and mortality. Thus, monitoring post-burn inflammation is of paramount importance but so far there are no reliable biomarkers available to monitor and/or predict infectious complications after burn. As IL-8 is a major mediator for inflammatory responses, the aim of our study was to determine whether IL-8 expression can be used to predict post-burn sepsis, infections, and mortality other outcomes post-burn. Plasma cytokines, acute phase proteins, constitutive proteins, and hormones were analyzed during the first 60 days post injury from 468 pediatric burn patients. Demographics and clinical outcome variables (length of stay, infection, sepsis, multiorgan failure (MOF), and mortality were recorded. A cut-off level for IL-8 was determined using receiver operating characteristic (ROC) analysis. Statistical significance is set at (p<0.05). ROC analysis identified a cut-off level of 234 pg/ml for IL-8 for survival. Patients were grouped according to their average IL-8 levels relative to this cut off and stratified into high (H) (n=133) and low (L) (n=335) groups. In the L group, regression analysis revealed a significant predictive value of IL-8 to percent of total body surface area (TBSA) burned and incidence of MOF (p<0.001). In the H group IL-8 levels were able to predict sepsis (p<0.002). In the H group, elevated IL-8 was associated with increased inflammatory and acute phase responses compared to the L group (p<0.05). High levels of IL-8 correlated with increased MOF, sepsis, and mortality. These data suggest that serum levels of IL-8 may be a valid biomarker for monitoring sepsis, infections, and mortality in burn patients. PMID:25514427

A nomogram to predict prognostic values of various inflammatory biomarkers in patients with esophageal squamous cell carcinoma

PubMed Central

Liu, Jin-Shi; Huang, Ying; Yang, Xun; Feng, Ji-Feng

2015-01-01

Background: Inflammation plays an important role in cancer progression and prognosis. However, the prognostic values of inflammatory biomarkers in esophageal cancer (EC) were not established. In the present study, therefore, we initially used a nomogram to predict prognostic values of various inflammatory biomarkers in patients with esophageal squamous cell carcinoma (ESCC). Methods: A total of 326 ESCC patients were included in this retrospective study. Glasgow prognostic score (GPS), neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR) and lymphocyte monocyte ratio (LMR) were analyzed in the current study. Kaplan-Meier method was used to calculate the cancer-specific survival (CSS). Cox regression analysis was also performed to evaluate the prognostic factors. A nomogram was established to predict the prognosis for CSS. Results: Patients were divided into 3 groups according to GPS (GPS 0, 1 and 2) and 2 groups according to NLR (≤3.45 and >3.45), PLR (≤166.5 and >166.5) and LMR (≤2.30 and >2.30). The 5-year CSS in patients with GPS 0, 1 and 2 were 49.2%, 26.8% and 11.9%, respectively (P<0.001). In addition, patients with NLR (>3.45), PLR (>166.5) and LMR (≤2.30) were significantly associated with decreased CSS, respectively (P<0.001). Multivariate analysis revealed that GPS (P<0.001), PLR (P=0.002) and LMR (P=0.002) were independent prognostic factors in patients with ESCC. In addition, a nomogram was established according to all significantly independent factors for CSS. The Harrell’s c-index for CSS prediction was 0.72. Conclusion: GPS, PLR and LMR were potential prognostic biomarkers in patients with ESCC. The nomogram based on CSS could be used as an accurately prognostic prediction for patients with ESCC. PMID:26328248

[Effect of naphthalan and therapeutic mud applications on clinical and roentgenological characteristics in patients with protracted pneumonia].

PubMed

Rassulova, M A; Siziakova, L A; Aĭrapetova, N S

2009-01-01

The influence of application of naftalan and therapeutic muds on clinical and roentgenological parameters, external respiration function, biochemical and immunological characteristics of the inflammatory process was studied in 82 patients presenting with protracted pneumonia and compared with the outcome of therapy using no physical factors. The application of naftalan and therapeutic muds was shown to reduce activity of inflammatory processes, improve airway patency and the state ofbronchial mucosa. Naftalan produced better therapeutic effect than muds.

Neutrophil-to-lymphocyte ratio as a predictor of worsening renal function in diabetic patients (3-year follow-up study).

PubMed

Azab, Basem; Daoud, Jacques; Naeem, Fahad Ben; Nasr, Rabih; Ross, Jennifer; Ghimire, Pratima; Siddiqui, Ayesha; Azzi, Nadine; Rihana, Nancy; Abdallah, Marie; Azzi, Nassif; Patel, Parishram; Kleiner, Morton; El-Sayegh, Suzanne

2012-01-01

Previous studies have demonstrated the role of inflammation in diabetic nephropathy (DN). Neutrophil to lymphocyte ratio (NLR) rather than other white cell parameters was found to be a useful inflammatory marker to predict adverse outcomes in medical and surgical conditions. Nevertheless, the value of NLR in predicting DN has not been elucidated. An observational study included 338 diabetic patients, who were followed at our clinic between 2007 and 2009. We arranged our patients into tertiles according to their 2007 NLR. The primary outcome was continuous decrease of GFR >12 mL/min between 2007 and 2009 with the last GFR <60 mL/min. The lowest NLR tertile had fewer patients (2.7%) with primary outcome (i.e., worsening renal function) compared with middle and highest NLR tertiles, which had more patients with primary outcomes (8.7% and 11.5%, respectively) with a significant p-value 0.0164. When other potential confounders were individually analyzed with NLR tertile, the NLR tertiles remained a significant predictor of poor GFR outcome in the presence of other variables (hemoglobin A1C, systolic blood pressure, diastolic blood pressure, age, and congestive heart failure with p-values 0.018, 0.019, 0.017, 0.033, and 0.022, respectively). NLR predicted the worsening of the renal function in diabetic patients. Further studies are needed to confirm this result.

Neutrophil to lymphocyte ratio predicts appropriate therapy in idiopathic dilated cardiomyopathy patients with primary prevention implantable cardioverter defibrillator

PubMed Central

Uçar, Fatih M.; Açar, Burak

2017-01-01

Objectives: To investigate whether an inflammatory marker of neutrophil to lymphocyte ratio (NLR) predicts appropriate implantable cardioverter defibrillator (ICD) therapy (shock or anti tachycardia pacing) in idiopathic dilated cardiomyopathy (IDC) patients. Methods: We retrospectively examined IDC patients (mean age: 58.3 ± 11.8 years, 81.5% male) with ICD who admitted to outpatient clinic for pacemaker control at 2 tertiary care hospitals in Ankara and Edirne, Turkey from January 2013-2015. All ICDs were implanted for primary prevention. Hematological and biochemical parameters were measured prior procedure. Results: Over a median follow-up period of 43 months (Range 7-125), 68 (33.1%) patients experienced appropriate ICD therapy. The NLR was increased in patients that received appropriate therapy (4.39 ± 2.94 versus 2.96 ± 1.97, p<0.001). To identify independent risk factors for appropriate therapy, a multivariate linear regression model was conducted and age (β=0.163, p=0.013), fasting glucose (β=0.158, p=0.017), C-reactive protein (CRP) (β=0.289, p<0.001) and NLR (β=0.212, p<0.008) were found to be independent risk factors for appropriate ICD therapy. Conclusions: Before ICD implantation by using NLR and CRP, arrhythmic episodes may be predictable and better antiarrhythmic medical therapy optimization may protect these IDC patients from unwanted events. PMID:28133686

The dynamics of health in wild field vole populations: a haematological perspective

PubMed Central

Beldomenico, Pablo M.; Telfer, Sandra; Gebert, Stephanie; Lukomski, Lukasz; Bennett, Malcolm; Begon, Michael

2010-01-01

Summary Pathogens have been proposed as potentially important drivers of population dynamics, but while a few studies have investigated the impact of specific pathogens, the wealth of information provided by general indices of health has hardly been exploited. By evaluating haematological parameters in wild populations, our knowledge of the dynamics of health and infection may be better understood. Here, haematological dynamics in natural populations of field voles are investigated to determine environmental and host factors associated with indicators of inflammatory response (counts of monocytes and neutrophils) and of condition: measures of immunological investment (lymphocyte counts) and aerobic capacity (red blood cell counts). Individuals from three field vole populations were sampled monthly for 2 years. Comparisons with individuals kept under controlled conditions facilitated interpretation of field data. Mixed effects models were developed for each cell type to evaluate separately the effects of various factors on post-juvenile voles and mature breeding females. There were three well-characterized ‘physiological’ seasons. The immunological investment appeared lowest in winter (lowest lymphocyte counts), but red blood cells were at their highest levels and indices of inflammatory response at their lowest. Spring was characterized by a fall in red blood cell counts and peaks in indicators of inflammatory response. During the course of summer—autumn, red blood cell counts recovered, the immunological investment increased and the indicators of inflammatory response decreased. Poor body condition appeared to affect the inflammatory response (lower neutrophil and monocyte peaks) and the immunological investment (lower lymphocyte counts), providing evidence that the capacity to fight infection is dependent upon host condition. Breeding early in the year was most likely in females in better condition (high lymphocyte and red blood cell counts). All the haematological parameters were affected adversely by high population densities. PMID:18564292

Differential effects of subcutaneous electrical stimulation (SQS) and transcutaneous electrical nerve stimulation (TENS) in rodent models of chronic neuropathic or inflammatory pain.

PubMed

Vera-Portocarrero, Louis P; Cordero, Toni; Billstrom, Tina; Swearingen, Kim; Wacnik, Paul W; Johanek, Lisa M

2013-01-01

Electrical stimulation has been used for many years for the treatment of pain. Present-day research demonstrates that stimulation targets and parameters impact the induction of specific pain-modulating mechanisms. New targets are increasingly being investigated clinically, but the scientific rationale for a particular target is often not well established. This present study compares the behavioral effects of targeting peripheral axons by electrode placement in the subcutaneous space vs. electrode placement on the surface of the skin in a rodent model. Rodent models of inflammatory and neuropathic pain were used to investigate subcutaneous electrical stimulation (SQS) vs. transcutaneous electrical nerve stimulation (TENS). Electrical parameters and relative location of the leads were held constant under each condition. SQS had cumulative antihypersensitivity effects in both inflammatory and neuropathic pain rodent models, with significant inhibition of mechanical hypersensitivity observed on days 3-4 of treatment. In contrast, reduction of thermal hyperalgesia in the inflammatory model was observed during the first four days of treatment with SQS, and reduction of cold allodynia in the neuropathic pain model was seen only on the first day with SQS. TENS was effective in the inflammation model, and in agreement with previous studies, tolerance developed to the antihypersensitivity effects of TENS. With the exception of a reversal of cold hypersensitivity on day 1 of testing, TENS did not reveal significant analgesic effects in the neuropathic pain rodent model. The results presented show that TENS and SQS have different effects that could point to unique biologic mechanisms underlying the analgesic effect of each therapy. Furthermore, this study is the first to demonstrate in an animal model that SQS attenuates neuropathic and inflammatory-induced pain behaviors. © 2013 Medtronic, Inc.

The antioxidant and anti-inflammatory efficiency of hyaluronic acid after third molar extraction.

PubMed

Gocmen, Gokhan; Gonul, Onur; Oktay, Nihal Sehkar; Yarat, Aysen; Goker, Kamil

2015-09-01

Hyaluronic acid (HA) has a number of clinical applications in current practice. Therefore, correlation of HA with free radicals and inflammatory cells is clinically important. The purpose of this study is to measure the efficacy of high molecular weight HA on the oxidative stress of oral wounds (glutathione (GSH) and lipid peroxidation (LPO) levels), the inflammatory reaction (leucocytes, collagen and angiogenesis content), pain (visual analogue scale (VAS) records) and trismus (maximum interincisal opening (MIO) records) after third molar (M3) extraction. 40 patients were included in this study. 0.2 ml 0.8% HA was applied immediately after surgery within the HA group (n = 20). Nothing was applied to the control group (n = 20). The primary outcome variables were the changes in the inflammatory reaction (leucocyte, angiogenesis and collagen content), oxidative stress (GSH, LPO) and clinical parameters (VAS, MIO). Results were compared immediately after extraction (T0) and 1 week after surgery (T1). Bivariate analyses were used to assess the differences between the HA and control groups for each study variable. There was a statistically significant difference of leucocyte infiltration and angiogenesis between the groups at T1. The HA group showed less leucocyte infiltration and more angiogenesis than the control group. There was no statistically significant difference in oxidative stress, VAS or MIO levels between the groups. Our results confirm the hypothesis that HA has an anti-inflammatory effect following M3 extraction. However, the oxidative stress levels and clinical outcomes were similar after one week. Further studies examining these parameters at different times are necessary. Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Comparison of Tear Osmolarity in Rheumatoid Arthritis Patients With and Without Secondary Sjogren Syndrome.

PubMed

Ng, Alex L K; Choy, Bonnie N K; Chan, Tommy C Y; Wong, Ian Y H; Lai, Jimmy S M; Mok, Mo Yin

2017-07-01

To compare tear osmolarity (TO) and other dry eye parameters in rheumatoid arthritis (RA) patients with or without secondary Sjogren syndrome (sSS). Consecutive patients with RA were divided into a sSS group and no-sSS group using conventional diagnostic criteria by rheumatologists using symptomatology, Schirmer test score, and anti-Ro or anti-La autoantibody status. The TO, Ocular Surface Disease Index, dry eye disease (DED) parameters [such as tear breakup time (TBUT) and corneal staining score] and the systemic inflammatory markers [erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)] were compared. Correlation analyses between TO and the DED parameters and inflammatory markers were also performed. A total of 42 cases with mean age 54.8 ± 12.3 were included, with 12 patients (29%) having sSS and 30 (71%) without sSS. TO was increased in both groups (329 ± 20 and 319 ± 25 mOsm/L, respectively), but no statistically significant difference was found between the 2 groups (P = 0.126). RA with sSS had significantly shorter TBUT, higher corneal staining score, and ESR CRP levels (P < 0.05). TO did not correlate with the Schirmer test score, but had significant positive correlations with age, corneal staining score, ESR, and CRP levels, and a significant negative correlation with TBUT. TO was increased in RA patients with or without sSS. There was no significant correlation between TO and the Schirmer test score, and the physician could not use TO to diagnose sSS. However, TO correlated well with both DED parameters (TBUT and corneal staining score) and systemic inflammatory markers (ESR and CRP).

Effects of clopidogrel, prasugrel and ticagrelor on endothelial function, inflammatory and oxidative stress parameters and platelet function in patients undergoing coronary artery stenting for an acute coronary syndrome. A randomised, prospective, controlled study

PubMed Central

Schnorbus, Boris; Daiber, Andreas; Jurk, Kerstin; Warnke, Silke; König, Jochem; Krahn, Ulrike; Lackner, Karl; Munzel, Thomas; Gori, Tommaso

2014-01-01

Introduction Particularly in the setting of acute coronary syndromes, the interplay between vascular and platelet function has been postulated to have direct clinical implications. The present trial is designed to test the effect of clopidogrel, prasugrel and ticagrelor on multiple parameters of vascular function, platelet aggregation, oxidative and inflammatory stress before and up to 4 weeks after coronary artery stenting. Methods and analysis The study is designed as a three-arm, parallel design, randomised, investigator-blinded study. Patients with unstable angina or non-ST elevation myocardial infarction undergoing coronary intervention with a drug-eluting stent will be randomised to receive 600 mg clopidogrel, 60 mg prasugrel or 180 mg ticagrelor followed by oral therapy with the same drug. The primary endpoint of the trial is the impact of antiplatelet treatments on endothelial function as assessed by flow-mediated dilation at 1 day, 1 week and 1 month in patients who have undergone stenting. Secondary endpoints include the impact of study medications on parameters of macrovascular and microvascular function, platelet reactivity, oxidative and inflammatory stress. The study recruitment is currently ongoing and, after an interim analysis which was performed at 50% of the initially planned population, it is planned to continue until July 2015. Ethics and dissemination The protocol was approved by the local ethics committee. The trial will provide important pathophysiological insight on the relationship between platelet aggregation and endothelial function, two parameters that have been shown to influence patients’ prognosis. Trial registration number ClinicalTrials.gov Identifier: NCT01700322; EudraCT-Nr.: 2011-005305-73. Current V.1.3, from 24 February 2014. PMID:24801283

The impact of major depression on heart rate variability and endothelial dysfunction in patients with stable coronary artery disease.

PubMed

Aydin Sunbul, Esra; Sunbul, Murat; Gulec, Huseyin

Depression is an independent risk factor in cardiovascular diseases. Changes in the cardiac autonomic functions and pro-inflammatory processes are potential biological factors. Endothelial dysfunction plays an important role in the etiopathogenesis of atherosclerosis. Our objective was to evaluate the impact of major depression on heart rate variability and endothelial dysfunction in patients with stable CAD. The study group included 65 CAD patients with a diagnosis of major depression and 54 CAD patients without major depression. All study population underwent transthoracic echocardiography, measurement of flow mediated dilatation (FMD) and 24-h holter recording for heart rate variability (HRV). Blood samples were drawn to determine the inflammatory parameters. Severity of depressive episode was assessed by Montgomery-Asberg Depression Scale (MADRS). The distribution of age and sex was similar in the patient and control groups (P=0.715, 0.354, respectively). There was no significant difference in medications used between the groups. Echocardiographic parameters were similar between the groups. Inflammatory parameters were also similar between the groups. HRV parameters were significantly lower in the patient group than controls. The absolute FMD value and percentage FMD were significantly lower in the patient group than controls (P<0.001). The MADRS score correlated with pNN50 in both groups (P<0.05), and with FMD in the control group (P<0.001), even after adjusting for age and gender (P<0.001). MADRS score was an independent predictor of pNN50 level, percentage and absolute FMD values regardless of age and gender. Clinician should pay more attention for evaluation of depressive patients with CAD. Copyright © 2016 Elsevier Inc. All rights reserved.

Prediction of disease course in inflammatory bowel diseases

PubMed Central

Lakatos, Peter Laszlo

2010-01-01

Clinical presentation at diagnosis and disease course of both Crohn’s disease (CD) and ulcerative colitis are heterogeneous and variable over time. Since most patients have a relapsing course and most CD patients develop complications (e.g. stricture and/or perforation), much emphasis has been placed in the recent years on the determination of important predictive factors. The identification of these factors may eventually lead to a more personalized, tailored therapy. In this TOPIC HIGHLIGHT series, we provide an update on the available literature regarding important clinical, endoscopic, fecal, serological/routine laboratory and genetic factors. Our aim is to assist clinicians in the everyday practical decision-making when choosing the treatment strategy for their patients suffering from inflammatory bowel diseases. PMID:20518078

Avoidance-related EEG asymmetry predicts circulating interleukin-6.

PubMed

Shields, Grant S; Moons, Wesley G

2016-03-01

Recent research has linked avoidance-oriented motivational states to elevated pro-inflammatory cytokine levels. According to one of many theories regarding the association between avoidance and cytokine levels, because the evolutionarily basic avoidance system may be activated when an organism is threatened or overwhelmed, an associated inflammatory response may be adaptive for dealing with potential injury in such threatening situations. To examine this hypothesis, we tested whether the neural correlate of avoidance motivation associates with baseline levels of the circulating pro-inflammatory cytokine interleukin-6 (IL-6). Controlling for covariates, greater resting neural activity in the right frontal cortex relative to the left frontal cortex-the neural correlate of avoidance motivation-was associated with baseline IL-6. These results thus support the hypothesis that the avoidance motivational system may be closely linked to systemic inflammatory activity. (c) 2016 APA, all rights reserved).

Increased serum procalcitonin levels in pregnant patients with asymptomatic bacteriuria.

PubMed

Bilir, Filiz; Akdemir, Nermin; Ozden, Selcuk; Cevrioglu, A Serhan; Bilir, Cemil

2013-09-05

Among the pregnancy urinary tract infections, asymptomatic bacteriuria (ASB) is the most common one. Untreated ASB can progress to pyelonephritis in 30-50% of the patients and can also result in prematurity in 27% of the pregnancy so it needs immediate diagnosis and treatment. In this study, we wanted to evaluate procalcitonin levels, compared to other inflammatory in pregnant women with ASB. The study was designed between the period of January 2012 and February 2013 at Sakarya University School of Medicine, Department of Gynecology and Obstetrics. The study population included 30 pregnant patients with asymptomatic bacteriuria and 39 healthy pregnant controls. Mean age was 28 (SD, 5.5) of the study population; mean maternal weight was 70 (SD, 8) kilogram. There were no statically significant differences between the groups according to the routine biochemical parameters, but gestational age was significantly lower in the ASB group compared to the controls (20.4 vs 28.6, respectively; p < 0.001). Serum procalcitonin levels were negative in all of the controls. In ASB group, 9 (30%) patients had procalcitonin levels greater than >0.05 ng/ml and 21(70%) patients had negative procalcitonin levels (Chi-squrae, p < 0.001). The sensitivity and specificity of procalcitonin assay for ASB was calculated as 30% and 100%, respectively. The positive predictive value was 100% and the negative predictive value was 65%. The most frequent microorganisms in the urine culture were Escherichia coli (26 patients, 87%), Proteus mirabilis (3 patients, 10%) and Klebsiella (1 patient, 3%) in the ASB group. We experienced four (44%) recurrences among nine positive procalcitonin in ASB patients after completion of treatment of the first ASB diagnosis. Procalcitonin levels were significantly higher in ASB group than the control group and serum procalcitonin levels were higher in pregnant women with recurrent ASB. This finding is an important result revealed that high procalcitonin level can predict the further urinary tract infection risk. Finally, serum procalcitonin levels were normal in healthy pregnant women while other inflammatory markers such as WBC, ESR and CRP levels were higher.

Increased serum procalcitonin levels in pregnant patients with asymptomatic bacteriuria

PubMed Central

2013-01-01

Background Among the pregnancy urinary tract infections, asymptomatic bacteriuria (ASB) is the most common one. Untreated ASB can progress to pyelonephritis in 30-50% of the patients and can also result in prematurity in 27% of the pregnancy so it needs immediate diagnosis and treatment. In this study, we wanted to evaluate procalcitonin levels, compared to other inflammatory in pregnant women with ASB. Methods The study was designed between the period of January 2012 and February 2013 at Sakarya University School of Medicine, Department of Gynecology and Obstetrics. The study population included 30 pregnant patients with asymptomatic bacteriuria and 39 healthy pregnant controls. Results Mean age was 28 (SD, 5.5) of the study population; mean maternal weight was 70 (SD, 8) kilogram. There were no statically significant differences between the groups according to the routine biochemical parameters, but gestational age was significantly lower in the ASB group compared to the controls (20.4 vs 28.6, respectively; p < 0.001). Serum procalcitonin levels were negative in all of the controls. In ASB group, 9 (30%) patients had procalcitonin levels greater than >0.05 ng/ml and 21(70%) patients had negative procalcitonin levels (Chi-squrae, p < 0.001). The sensitivity and specificity of procalcitonin assay for ASB was calculated as 30% and 100%, respectively. The positive predictive value was 100% and the negative predictive value was 65%. The most frequent microorganisms in the urine culture were Escherichia coli (26 patients, 87%), Proteus mirabilis (3 patients, 10%) and Klebsiella (1 patient, 3%) in the ASB group. We experienced four (44%) recurrences among nine positive procalcitonin in ASB patients after completion of treatment of the first ASB diagnosis. Discussion Procalcitonin levels were significantly higher in ASB group than the control group and serum procalcitonin levels were higher in pregnant women with recurrent ASB. This finding is an important result revealed that high procalcitonin level can predict the further urinary tract infection risk. Finally, serum procalcitonin levels were normal in healthy pregnant women while other inflammatory markers such as WBC, ESR and CRP levels were higher. PMID:24006912

CCL11 (Eotaxin-1) Levels Predict Long-Term Functional Outcomes in Patients Following Ischemic Stroke.

PubMed

Roy-O'Reilly, Meaghan; Ritzel, Rodney M; Conway, Sarah E; Staff, Ilene; Fortunato, Gilbert; McCullough, Louise D

2017-12-01

Circulating levels of the pro-inflammatory cytokine C-C motif chemokine 11 (CCL11, also known as eotaxin-1) are increased in several animal models of neuroinflammation, including traumatic brain injury and Alzheimer's disease. Increased levels of CCL11 have also been linked to decreased neurogenesis in mice. We hypothesized that circulating CCL11 levels would increase following ischemic stroke in mice and humans, and that higher CCL11 levels would correlate with poor long-term recovery in patients. As predicted, circulating levels of CCL11 in both young and aged mice increased significantly 24 h after experimental stroke. However, ischemic stroke patients showed decreased CCL11 levels compared to controls 24 h after stroke. Interestingly, lower post-stroke CCL11 levels were predictive of increased stroke severity and independently predictive of poorer functional outcomes in patients 12 months after ischemic stroke. These results illustrate important differences in the peripheral inflammatory response to ischemic stroke between mice and human patients. In addition, it suggests CCL11 as a candidate biomarker for the prediction of acute and long-term functional outcomes in ischemic stroke patients.

Noninvasive scoring system for significant inflammation related to chronic hepatitis B

NASA Astrophysics Data System (ADS)

Hong, Mei-Zhu; Ye, Linglong; Jin, Li-Xin; Ren, Yan-Dan; Yu, Xiao-Fang; Liu, Xiao-Bin; Zhang, Ru-Mian; Fang, Kuangnan; Pan, Jin-Shui

2017-03-01

Although a liver stiffness measurement-based model can precisely predict significant intrahepatic inflammation, transient elastography is not commonly available in a primary care center. Additionally, high body mass index and bilirubinemia have notable effects on the accuracy of transient elastography. The present study aimed to create a noninvasive scoring system for the prediction of intrahepatic inflammatory activity related to chronic hepatitis B, without the aid of transient elastography. A total of 396 patients with chronic hepatitis B were enrolled in the present study. Liver biopsies were performed, liver histology was scored using the Scheuer scoring system, and serum markers and liver function were investigated. Inflammatory activity scoring models were constructed for both hepatitis B envelope antigen (+) and hepatitis B envelope antigen (-) patients. The sensitivity, specificity, positive predictive value, negative predictive value, and area under the curve were 86.00%, 84.80%, 62.32%, 95.39%, and 0.9219, respectively, in the hepatitis B envelope antigen (+) group and 91.89%, 89.86%, 70.83%, 97.64%, and 0.9691, respectively, in the hepatitis B envelope antigen (-) group. Significant inflammation related to chronic hepatitis B can be predicted with satisfactory accuracy by using our logistic regression-based scoring system.

Can Contrast-Enhanced Sonography Detect Bowel Wall Fibrosis in Mixed Inflammatory and Fibrotic Crohn Disease Lesions in an Animal Model?

PubMed

Dillman, Jonathan R; Rubin, Jonathan M; Johnson, Laura A; Moons, David S; Higgins, Peter D R

2017-03-01

To determine whether contrast-enhanced sonographic quantitative perfusion parameters can detect bowel wall fibrosis in the setting of mixed inflammatory and fibrotic lesions in a Crohn disease animal model. This study was approved by the institutional Committee on the Use and Care of Animals. Multiple (range, 1-5) 2,4,6-trinitrobenzenesulfonic acid-ethanol enemas were used to create intestinal inflammatory lesions with variable fibrosis in female Lewis rats. Low-mechanical index contrast-enhanced sonography was performed 3 days after the final enema using a 0.2-mL bolus of sulfur hexafluoride microbubbles injected through a tail vein. Contrast-enhanced sonographic data were analyzed with software that converts video data into echo-power (linearized) data. Colorectal lesions were scored for histopathologic inflammation and fibrosis; bowel wall collagen was quantified by Western blotting. The Spearman correlation was used to assess associations between contrast-enhanced sonographic quantitative parameters and bowel wall collagen; the Kruskal-Wallis test was used to compare continuous results between histopathologic groups. Thirty-one animals were included in our analysis. Animals were placed into 3 histopathologic cohorts: (1) severe bowel wall inflammation/minimal or no fibrosis (n = 11); (2) severe bowel wall inflammation/moderate fibrosis (n = 9); and (3) severe bowel wall inflammation/severe fibrosis (n = 11). Western blotting showed a significant difference in bowel wall collagen between histopathologic cohorts (P = .0001). There was no correlation between any contrast-enhanced sonographic quantitative parameter and bowel wall collagen (P > .05). There was no difference between histopathologic cohorts for any contrast-enhanced sonographic quantitative parameter (P > .05). Contrast-enhanced sonographic quantitative perfusion parameters failed to effectively detect bowel wall fibrosis in the setting of superimposed inflammation in a Crohn disease animal model. © 2017 by the American Institute of Ultrasound in Medicine.

Apparent diffusion coefficient (ADC) does not correlate with different serological parameters in myositis and myopathy.

PubMed

Meyer, Hans-Jonas; Ziemann, Oliver; Kornhuber, Malte; Emmer, Alexander; Quäschling, Ulf; Schob, Stefan; Surov, Alexey

2018-06-01

Background Magnetic resonance imaging (MRI) is widely used in several muscle disorders. Diffusion-weighted imaging (DWI) is an imaging modality, which can reflect microstructural tissue composition. The apparent diffusion coefficient (ADC) is used to quantify the random motion of water molecules in tissue. Purpose To investigate ADC values in patients with myositis and non-inflammatory myopathy and to analyze possible associations between ADC and laboratory parameters in these patients. Material and Methods Overall, 17 patients with several myositis entities, eight patients with non-inflammatory myopathies, and nine patients without muscle disorder as a control group were included in the study (mean age = 55.3 ± 14.3 years). The diagnosis was confirmed by histopathology in every case. DWI was obtained in a 1.5-T scanner using two b-values: 0 and 1000 s/mm 2 . In all patients, the blood sample was acquired within three days to the MRI. The following serological parameters were estimated: C-reactive protein, lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, creatine kinase, and myoglobine. Results The estimated mean ADC value for the myositis group was 1.89 ± 0.37 × 10 -3  mm 2 /s and for the non-inflammatory myopathy group was 1.79 ± 0.33 × 10 -3  mm 2 /s, respectively. The mean ADC values (1.15 ± 0.37 × 10 -3  mm 2 /s) were significantly higher to unaffected muscles (vs. myositis P = 0.0002 and vs. myopathy P = 0.0021). There were no significant correlations between serological parameters and ADC values. Conclusion Affected muscles showed statistically significantly higher ADC values than normal muscles. No linear correlations between ADC and serological parameters were identified.

Fluid overload in hemodialysis patients: a cross-sectional study to determine its association with cardiac biomarkers and nutritional status

PubMed Central

2013-01-01

Background Chronic fluid overload is associated with higher mortality in dialysis patients; however, the link with cardiovascular morbidity has not formally been established and may be influenced by subclinical inflammation. We hypothesized that a relationship exists between fluid overload and [i] cardiovascular laboratory parameter as well as between fluid overload and [ii] inflammatory laboratory parameters. In addition, we aimed to confirm whether volume status correlates with nutritional status. Methods We recorded baseline characteristics of 244 hemodialysis patients at three hemodialysis facilities in Vienna (Austria) and determined associations with volume measurements using the body composition monitor (Fresenius/Germany). In one facility comprising 126 patients, we further analyzed cardiovascular, inflammatory and nutritional parameters. Results We detected predialysis fluid overload (FO) in 39% of all patients (n = 95) with FO defined as ≥15% of extracellular water (ECW). In this subgroup, the absolute FO was 4.4 +/-1.5 L or 22.9 ± 4.8% of ECW. A sub-analysis of patients from one center showed that FO was negatively associated with body mass index (r = -0.371; p = <0.001), while serum albumin was significantly lower in fluid overloaded patients (p = 0.001). FO was positively associated with D-Dimer (r = 0.316; p = 0.001), troponin T (r = 0.325; p < 0.001), and N-terminal pro-B-type natriuretic peptide (r = 0.436; p < 0.001), but not with investigated inflammatory parameters. Conclusions Fluid overload in HD patients was found to be lower in patients with high body mass index, indicating that dry weight was inadequately prescribed and/or difficult to achieve in overweight patients. The association with parameters of cardiovascular compromise and/or damage suggests that fluid overload is a biomarker for cardiovascular risk. Future studies should determine if this applies to patients prior to end-stage renal disease. PMID:24295522

Differentiation between inflammatory and neoplastic orbital conditions based on computed tomographic signs.

PubMed

Lederer, Kristina; Ludewig, Eberhard; Hechinger, Harald; Parry, Andrew T; Lamb, Christopher R; Kneissl, Sibylle

2015-07-01

To identify computed tomographic (CT) signs that could be used to differentiate inflammatory from neoplastic orbital conditions in small animals. Fifty-two animals (25 cats, 21 dogs, 4 rabbits, and 2 rodents). Case-control study in which CT images of animals with histopathologic diagnosis of inflammatory (n = 11), neoplastic orbital conditions (n = 31), or normal control animals (n = 10) were reviewed independently by five observers without the knowledge of the history or diagnosis. Observers recorded their observations regarding specific anatomical structures within the orbit using an itemized form containing the following characteristics: definitely normal; probably normal; equivocal; probably abnormal; and definitely abnormal. Results were statistically analyzed using Fleiss' kappa and logistic regression analyses. The overall level of agreement between observers about the presence or absence of abnormal CT signs in animals with orbital disease was poor to moderate, but was highest for observations concerning orbital bones (κ = 0.62) and involvement of the posterior segment (κ = 0.52). Significant associations between abnormalities and diagnosis were found for four structures: Abnormalities affecting orbital bones (odds ratio [OR], 1.7) and anterior ocular structures (OR, 1.5) were predictive of neoplasia, while abnormalities affecting extraconal fat (OR, 1.7) and skin (OR, 1.4) were predictive of inflammatory conditions. Orbital CT is an imaging test with high specificity. Fat stranding, a CT sign not previously emphasized in veterinary medicine, was significantly associated with inflammatory conditions. Low observer agreement probably reflects the limited resolution of CT for small orbital structures. © 2014 American College of Veterinary Ophthalmologists.

Pro-inflammatory cytokines and structural biomarkers are effective to categorize osteoarthritis phenotype and progression in Standardbred racehorses over five years of racing career.

PubMed

Bertuglia, Andrea; Pagliara, Eleonora; Grego, Elena; Ricci, Alessandro; Brkljaca-Bottegaro, Nika

2016-11-08

Joint impact injuries initiate a progressive articular damage finally leading to post-traumatic osteoarthritis (PTOA). Racehorses represent an ideal, naturally available, animal model of the disease. Standardbred racehorses developing traumatic osteoarthritis of the fetlock joint during the first year of their career were enrolled in our study. Age-matched controls were contemporarily included. Biomarker levels of equine osteoarthritis were measured in serum and synovial fluid (SF) at baseline, and repeated yearly over the next 4 years of training (from T1 to T4). The effect of time and disease on the biomarker concentrations were analysed, and their relationship with clinical and radiographic parameters were assessed. We hypothesized that the kinetics of pro-inflammatory cytokines and structural biomarkers of joint disease would demonstrate progression of degenerative joint status during post-traumatic osteoarthritis and clarify the effect of early joint trauma. The concentrations of IL1-ß, IL-6, TNF-α in the SF of PTOA group peaked at T0, decreased at T1, and then progressively increased with time, reaching levels higher than those observed at baseline starting from T3. CTXII and COMP levels were similar in PTOA and control horses at baseline, and increased in serum and synovial fluid of PTOA horses starting from T2 (serum and synovial CTXII, and serum COMP) or T3 (synovial COMP). The percentual change of TNF-α in the SF of the affected joints independently contributed to explaining the radiological changes at T3 vs T2 and T4 vs T3. Temporal changes of selected biomarkers in STBRs with an acute episode of traumatic fetlock OA demonstrated that long-term increased concentrations of inflammatory cytokines, type II collagen fragments and COMP, in the SF and serum, are related to PTOA. Based on the observed decrease in inflammatory merkers at T1, we hypothesize that the progression of PTOA could be effectively modulated by proper treatment strategies. Annual variations of synovial concentration of TNF-α can reliably predict radiographic progression of PTOA.

Performance Comparison of Systemic Inflammatory Response Syndrome with Logistic Regression Models to Predict Sepsis in Neonates

PubMed Central

Thakur, Jyoti; Pahuja, Sharvan Kumar; Pahuja, Roop

2017-01-01

In 2005, an international pediatric sepsis consensus conference defined systemic inflammatory response syndrome (SIRS) for children <18 years of age, but excluded premature infants. In 2012, Hofer et al. investigated the predictive power of SIRS for term neonates. In this paper, we examined the accuracy of SIRS in predicting sepsis in neonates, irrespective of their gestational age (i.e., pre-term, term, and post-term). We also created two prediction models, named Model A and Model B, using binary logistic regression. Both models performed better than SIRS. We also developed an android application so that physicians can easily use Model A and Model B in real-world scenarios. The sensitivity, specificity, positive likelihood ratio (PLR) and negative likelihood ratio (NLR) in cases of SIRS were 16.15%, 95.53%, 3.61, and 0.88, respectively, whereas they were 29.17%, 97.82%, 13.36, and 0.72, respectively, in the case of Model A, and 31.25%, 97.30%, 11.56, and 0.71, respectively, in the case of Model B. All models were significant with p < 0.001. PMID:29257099

[Association of age, inflammatory markers and subclinical atherosclerosis in subjects free from cardiovascular disease].

PubMed

Páramo, José A; Orbe, Josune; Beloqui, Oscar; Colina, Inmaculada; Benito, Alberto; Rodríguez, José A; Díez, Javier

2008-09-27

We assessed whether an independent association between inflammatory markers and age-related subclinical atherosclerosis could be found in subjects free from cardiovascular disease. Metabolic parameters, inflammatory and endothelial markers, such as high-sensitivity C-reactive protein, interleukin-6, fibrinogen and von Willebrand factor, as well as the carotid intima-media thickness were assessed in 890 asymptomatic subjects (mean age: 55 years; range: 20-80 years; 80% men) with cardiovascular risk factors. Subjects in the upper quartile (age 61-80 years) showed a significant increase of traditional risk factors, particularly arterial pressure and glucose levels (p < 0.01) as compared with lower quartiles. We also found a significant increase in the levels on inflammatory and endothelial markers (p < 0.001) and intima-media thickness (p < 0.001) in older adults. In the multivarate analysis, after adjustment for cardiovascular risk factors, intima-media thickness was independently associated with inflammation and endothelial dysfunction in older adults (p < 0.01). Besides age, systemic inflammation and vascular damage are associated with subclinical atherosclerosis in asymptomatic subjects. The age-related inflammatory profile may predispose to cardiovascular complications.

Immediate effects of chest physiotherapy on hemodynamic, metabolic, and oxidative stress parameters in subjects with septic shock.

PubMed

dos Santos, Rafael S; Donadio, Márcio V F; da Silva, Gabriela V; Blattner, Clarissa N; Melo, Denizar A S; Nunes, Fernanda B; Dias, Fernando S; Squizani, Eamim D; Pedrazza, Leonardo; Gadegast, Isabella; de Oliveira, Jarbas R

2014-09-01

Septic shock presents as a continuum of infectious events, generating tissue hypoxia and hypovolemia, and increased oxidative stress. Chest physiotherapy helps reduce secretion, improving dynamic and static compliance, as well as improving secretion clearance and preventing pulmonary complications. The purpose of this study was to evaluate the immediate effect of chest physiotherapy on hemodynamic, metabolic, inflammatory, and oxidative stress parameters in subjects in septic shock. We conducted a quasi-experimental study in 30 subjects in septic shock, who underwent chest physiotherapy, without associated heart diseases and with vasopressors < 0.5 μg/kg/min. Venous and arterial blood gases, clinical and hemodynamic data, inflammatory data, lactate, and oxidative stress were evaluated before and 15 min after physiotherapy. Thirty subjects with a mean age of 61.8 ± 15.9 y and Sequential Organ Failure Assessment of 8 (range 6-10) were included. Chest physiotherapy caused a normalization of pH (P = .046) and P(aCO2) (P = .008); reduction of lactate (P = .001); and an increase in P(aO2) (P = .03), arterial oxygen saturation (P = .02), and P(aO2)/F(IO2) (P = .034), 15 min after it was applied. The results indicate that chest physiotherapy has immediate effects, improving oxygenation and reducing lactate and oxidative damage in subjects in septic shock. However, it does not cause alterations in the inflammatory and hemodynamic parameters. Copyright © 2014 by Daedalus Enterprises.

Helicobacter pylori in sedentary men is linked to higher heart rate, sympathetic activity, and insulin resistance but not inflammation or oxidative stress

PubMed Central

Cherkas, Andriy; Eckl, Peter; Guéraud, Françoise; Abrahamovych, Orest; Serhiyenko, Victoria; Yatskevych, Ostap; Pliatsko, Mykhailo; Golota, Sergii

2016-01-01

Aim To compare anthropometric parameters, body composition, hormonal and inflammatory profiles, oxidative stress indices, and heart rate variability (HRV) in Heliobacter pylori (H.pylori) positive and negative healthy sedentary participants. Methods Among 30 recruited apparently healthy male participants (age between 20 and 40) enrolled in this cross-sectional study, 18 were H.pylori negative and 12 were positive (stool antigen test). Participants underwent routine physical examination and body composition determination. The following biochemical parameters were determined in blood: fasting whole blood glucose, glycated hemoglobin, insulin, C-peptide, cortisol, aldosterone, testosterone, thyroid stimulating hormone, C-reactive protein, interleukins 6 and 10, tumor necrosis factor-α, and the urinary level of 1,4-dihydroxynonane mercapturic acid. For HRV evaluation, electrocardiogram in supine position and in orthostatic test was performed. Results H.pylori contamination was not significantly associated with any changes in anthropometric parameters, body composition, blood pressure, fasting glucose, or glycated hemoglobin levels. No significant difference was found for inflammatory markers as well as 1,4-dihydroxynonane mercapturic acid. H.pylori-positive participants, however, had significantly higher heart rate (P = 0.009), sympathetic/parasympathetic balance in orthostatic test (P = 0.029), fasting insulin level (P = 0.037), and HOMA-index (P = 0.047). Conclusions H.pylori contamination is linked to a significantly higher heart rate, sympathetic activation, and increased insulin resistance, while inflammatory and oxidative stress markers remain unaffected in healthy sedentary male subjects. PMID:27106356

Lead intoxication under environmental hypoxia impairs oral health.

PubMed

Terrizzi, Antonela R; Fernandez-Solari, Javier; Lee, Ching M; Martínez, María Pilar; Conti, María Ines

2014-01-01

We have reported that chronic lead intoxication under hypoxic environment induces alveolar bone loss that can lead to periodontal damage with the subsequent loss of teeth. The aim of the present study was to assess the modification of oral inflammatory parameters involved in the pathogenesis of periodontitis in the same experimental model. In gingival tissue, hypoxia increased inducible nitric oxid synthase (iNOS) activity (p < .01) and meanwhile lead decreased prostaglandin E2 (PGE2) content (p < .05). In submandibular gland (SMG), iNOS activity was enhanced by lead and PGE2 content was increased by both lead and hypoxia (p < .01) and even more by combined treatments (p < .001). In the SMG, hypoxia stimulated angiogenesis (p < .01) with blood extravasation. Adrenal glands were 22% bigger in those animals exposed to lead under hypoxic conditions. Results suggest a wide participation of inflammatory markers that mediate alveolar bone loss induced by these environmental conditions. The lack of information regarding oral health in lead-contaminated populations that coexist with hypoxia induced us to evaluate the alteration of inflammatory parameters in rat oral tissues to elucidate the link between periodontal damage and these environmental conditions.

Decreased Circulating mtDNA Levels in Professional Male Volleyball Players.

PubMed

Nasi, Milena; Cristani, Alessandro; Pinti, Marcello; Lamberti, Igor; Gibellini, Lara; De Biasi, Sara; Guazzaloca, Alessandro; Trenti, Tommaso; Cossarizza, Andrea

2016-01-01

Exercise exerts various effects on the immune system, and evidence is emerging on its anti-inflammatory effects; the mechanisms on the basis of these modifications are poorly understood. Mitochondrial DNA (mtDNA) released from damaged cells acts as a molecule containing the so-called damage-associated molecular patterns and can trigger sterile inflammation. Indeed, high plasma levels of mtDNA are associated to several inflammatory conditions and physiological aging and longevity. The authors evaluated plasma mtDNA in professional male volleyball players during seasonal training and the possible correlation between mtDNA levels and clinical parameters, body composition, and physical performance. Plasma mtDNA was quantified by real-time PCR every 2 mo in 12 professional volleyball players (PVPs) during 2 consecutive seasons. As comparison, 20 healthy nonathlete male volunteers (NAs) were analyzed. The authors found lower levels of mtDNA in plasma of PVPs than in NAs. However, PVPs showed a decrease of circulating mtDNA only in the first season, while no appreciable variations were observed during the second season. No correlation was observed among mtDNA, hematochemical, and anthropometric parameters. Regular physical activity appeared associated with lower levels of circulating mtDNA, further confirming the protective, anti-inflammatory effect of exercise.

Anti-inflammatory and anti-oxidative effects of alpha-lipoic acid in experimentally induced acute otitis media.

PubMed

Tatar, A; Korkmaz, M; Yayla, M; Gozeler, M S; Mutlu, V; Halici, Z; Uslu, H; Korkmaz, H; Selli, J

2016-07-01

To investigate the anti-inflammatory, anti-oxidative and tissue protective effects, as well as the potential therapeutic role, of alpha-lipoic acid in experimentally induced acute otitis media. Twenty-five guinea pigs were assigned to one of five groups: a control (non-otitis) group, and otitis-induced groups treated with saline, penicillin G, alpha-lipoic acid, or alpha-lipoic acid plus penicillin G. Tissue samples were histologically analysed, and oxidative parameters in tissue samples were measured and compared between groups. The epithelial integrity was better preserved, and histological signs of inflammation and secretory metaplasia were decreased, in all groups compared to the saline treated otitis group. In the alpha-lipoic acid plus penicillin G treated otitis group, epithelial integrity was well preserved and histological findings of inflammation were significantly decreased compared to the saline, penicillin G and alpha-lipoic acid treated otitis groups. The most favourable oxidative parameters were observed in the control group, followed by the alpha-lipoic acid plus penicillin G treated otitis group. Alpha-lipoic acid, with its antioxidant, anti-inflammatory and tissue protective properties, may decrease the clinical sequelae and morbidity associated with acute otitis media.

Exercise Training positively modulates the Ectonucleotidase Enzymes in Lymphocytes of Metabolic Syndrome Patients.

PubMed

Martins, C C; Bagatini, M D; Cardoso, A M; Zanini, D; Abdalla, F H; Baldissarelli, J; Dalenogare, D P; Dos Santos, D L; Schetinger, M R C; Morsch, V M M

2016-11-01

In this study, we investigated the cardiovascular risk factors as well as ectonucleotidase activities in lymphocytes of metabolic syndrome (MetS) patients before and after an exercise intervention. 20 MetS patients, who performed regular concurrent exercise training for 30 weeks, 3 times/week, were studied. Anthropometric, biochemical, inflammatory and hepatic parameters and hydrolysis of adenine nucleotides and nucleoside in lymphocytes were collected from patients before and after 15 and 30 weeks of the exercise intervention as well as from participants of the control group. An increase in the hydrolysis of ATP and ADP, and a decrease in adenosine deamination in lymphocytes of MetS patients before the exercise intervention were observed (P<0.001). However, these alterations were reversed by exercise training after 30 weeks of intervention. Additionally, exercise training reduced the inflammatory and hepatic markers to baseline levels after 30 weeks of exercise. Our results clearly indicated alteration in ectonucleotidase enzymes in lymphocytes in the MetS, whereas regular exercise training had a protective effect on the enzymatic alterations and on inflammatory and hepatic parameters, especially if it is performed regularly and for a long period. © Georg Thieme Verlag KG Stuttgart · New York.

Pilot Mental Workload with Predictive System Status Information

NASA Technical Reports Server (NTRS)

Trujillo, Anna C.

1998-01-01

Research has shown a strong pilot preference for predictive information of aircraft system status in the flight deck. However, the mental workload associated with using this predictive information has not been ascertained. The study described here attempted to measure mental workload. In this simulator experiment, three types of predictive information (none, whether a parameter was changing abnormally, and the time for a parameter to reach an alert range) and four initial times to a parameter alert range (1 minute, 5 minutes, 15 minutes, and ETA+45 minutes) were tested to determine their effects on subjects mental workload. Subjective workload ratings increased with increasing predictive information (whether a parameter was changing abnormally or the time for a parameter to reach an alert range). Subjective situation awareness decreased with more predictive information but it became greater with increasing initial times to a parameter alert range. Also, subjective focus changed depending on the type of predictive information. Lastly, skin temperature fluctuated less as the initial time to a parameter alert range increased.

Construct Validation of the Dietary Inflammatory Index among Postmenopausal Women

PubMed Central

Tabung, Fred K.; Steck, Susan E.; Zhang, Jiajia; Ma, Yunsheng; Liese, Angela D.; Agalliu, Ilir; Hingle, Melanie; Hou, Lifang; Hurley, Thomas G.; Jiao, Li; Martin, Lisa W.; Millen, Amy E.; Park, Hannah L.; Rosal, Milagros C.; Shikany, James M.; Shivappa, Nitin; Ockene, Judith K.; Hebert, James R.

2015-01-01

Purpose Many dietary factors have either pro- or anti-inflammatory properties. We previously developed a dietary inflammatory index (DII) to assess the inflammatory potential of diet. In this study we conducted a construct validation of the DII based on data from a food frequency questionnaire and three inflammatory biomarkers in a subsample of 2,567 postmenopausal women in the Women’s Health Initiative Observational Study. Methods We used multiple linear and logistic regression models, controlling for potential confounders, to test whether baseline DII predicted concentrations of interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor alpha receptor 2 (TNFα-R2), or an overall biomarker score combining all three inflammatory biomarkers. Results The DII was associated with the four biomarkers with beta estimates (95%CI) comparing the highest with lowest DII quintiles as follows: IL-6: 1.26 (1.15, 1.38), Ptrend<0.0001; TNFα-R2: 81.43 (19.15, 143.71), Ptrend=0.004; dichotomized hs-CRP (odds ratio for higher versus lower hs-CRP): 1.30 (0.97, 1.67), Ptrend=0.34); and the combined inflammatory biomarker score: 0.26 (0.12, 0.40), Ptrend=0.0001. Conclusion The DII was significantly associated with inflammatory biomarkers. Construct validity of the DII indicates its utility for assessing the inflammatory potential of diet and for expanding its use to include associations with common chronic diseases in future studies. PMID:25900255

Inflammation and sarcopenia: A systematic review and meta-analysis.

PubMed

Bano, Giulia; Trevisan, Caterina; Carraro, Sara; Solmi, Marco; Luchini, Claudio; Stubbs, Brendon; Manzato, Enzo; Sergi, Giuseppe; Veronese, Nicola

2017-02-01

Inflammatory cytokines have been shown to prompt muscle wasting, ultimately stimulating protein catabolism and suppressing muscle synthesis. However, the possible association between inflammatory parameters and sarcopenia is poorly understood. We therefore aimed to summarize the current evidence about this topic with a meta-analysis of studies reporting serum inflammatory parameters in patients with sarcopenia vs. people without sarcopenia (controls). An electronic PubMed and Scopus search through to 09/01/2016 and meta-analysis of cross-sectional studies comparing serum levels of inflammatory cytokines between patients with sarcopenia and controls was made, calculating random-effects standardized mean differences (SMDs) ±95% confidence intervals (CIs) as the effect size. Out of 1370 initial hits, 17 studies with a total of 11249 participants (3072 with sarcopenia and 8177 without) were meta-analyzed. Sarcopenic participants had significantly higher levels of CRP (SMD=0.51; 95%CI 0.26, 0.77; p<0.0001; I 2 =96%) than controls. Conversely, serum IL6 levels were not significantly different (SMD=0.35; 95%CI: -0.19, 0.89; p=0.21; I 2 =97%) in people with sarcopenia versus controls. Sarcopenic people did not have higher levels of TNF-α than controls (SMD=0.28; 95%CI -0.26, 0.83; p=0.31; I 2 =97%). In conclusion, sarcopenia seems to be associated with elevated serum CRP levels; future longitudinal studies are needed to clarify this relationship. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Brazilian nut consumption by healthy volunteers improves inflammatory parameters.

PubMed

Colpo, Elisângela; Dalton D A Vilanova, Carlos; Reetz, Luiz Gustavo B; Duarte, Marta M M F; Farias, Iria Luiza G; Meinerz, Daiane F; Mariano, Douglas O C; Vendrusculo, Raquel G; Boligon, Aline A; Dalla Corte, Cristiane L; Wagner, Roger; Athayde, Margareth L; da Rocha, João Batista T

2014-04-01

The aim of this study was to investigate the effect of a single dose of Brazil nuts on the inflammatory markers of healthy individuals. A randomized crossover study was conducted with 10 healthy individuals (mean age 24.7 ± 3.4 y). Each individual was tested four times regarding intake of different portions of Brazil nuts: 0, 5, 20 and 50 g. At each testing period, peripheral blood was collected before and at 1, 3, 6, 9, 24, and 48 h after intake of nuts, as well as at 5 and 30 d after intake of various Brazil nut portions. Blood samples were tested for high-sensitivity to C-reactive protein, interleukin (IL)-1, IL-6, IL-10, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ, aspartate and alanine aminotransferases, albumin, total protein, alkaline phosphatase, gamma-glutamyltransferase, urea, and creatinine. Consumption of nuts did not affect biochemical parameters for liver and kidney function, indicating absence of hepatic and renal toxicity. A single intake of Brazil nuts (20 or 50 g) caused a significant decrease in serum IL-1, IL-6, TNF-α, and IFN-γ levels (P < 0.05), whereas serum levels of IL-10 were significantly increased (P < 0.05). The results indicate a long-term decrease in inflammatory markers after a single intake of large portions of Brazil nuts in healthy volunteers. Therefore, the long-term effect of regular Brazil nut consumption on inflammatory markers should be better investigated. Copyright © 2014 Elsevier Inc. All rights reserved.

Toxicological evaluation and anti-inflammatory potential of an ethanolic extract from Bromelia balansae (Bromeliaceae) fruit.

PubMed

da Silva Balin, Paola; Zanatta, Flavia Carina; Jorge, Bárbara Campos; Leitão, Maicon; Kassuya, Roberto Mikio; Cardoso, Claudia Andrea Lima; Kassuya, Cândida Aparecida Leite; Arena, Arielle Cristina

2018-05-03

Bromelia balansae is a relatively unexplored medicinal species that is used for nutritional purposes and in folk medicine to treat cough or wounds. This study assessed the anti-inflammatory activity of the ethanolic extract obtained from Bromelia balansae fruit (EEBB) as well as the toxicological potential of this extract after single and repeated exposure. Male rats (Wistar) were gavaged with 2000 mg/kg of extract from the fruit of B. balansae for the acute toxicity test and with 25, 100, or 400 mg/kg of EEBB for the subacute toxicity test. The anti-inflammatory effect of EEBB was evaluated in vivo (30, 100, or 300 mg/kg) by carrageenan (Cg) induced-oedema and pleurisy in Swiss mice. A single oral dose of EEBB did not result in toxicity, demonstrating that the LD 50 of this extract was greater than 2000 mg/kg. In the subacute toxicity test, the tested doses produced no significant changes in the haematological, biochemical or histopathological parameters of treated animals. Similarly, there were no statistically significant differences in the sperm parameters. A dose of 300 mg/kg of EEBB significantly reduced oedema formation, Cg-induced mechanical hypersensitivity and cold sensitivity, as well as leukocyte migration in the pleurisy model. These results show that EEBB has an anti-inflammatory potential without causing acute or subacute toxicity. These data may contribute to the advancement of biopharmaceutical applications for this species. Copyright © 2018 Elsevier B.V. All rights reserved.

Systemic inflammatory response syndrome (SIRS)

PubMed Central

Balk, Robert A

2014-01-01

The concept of a systemic inflammatory response syndrome (SIRS) to describe the complex pathophysiologic response to an insult such as infection, trauma, burns, pancreatitis, or a variety of other injuries came from a 1991 consensus conference charged with the task of developing an easy-to-apply set of clinical parameters to aid in the early identification of potential candidates to enter into clinical trials to evaluate new treatments for sepsis. There was recognition that a diverse group of injuries produced a common inflammatory response in the host and provided attractive targets for new anti-inflammatory molecules designed to prevent further propagation and/or provide specific treatment. Effective application of these new anti-inflammatory strategies necessitated identification of early clinical markers that could be assessed in real-time and were likely to define a population of patients that would have a beneficial response to the targeted intervention. It was felt that early clinical manifestations might be more readily available to clinicians than more sophisticated and specific assays for inflammatory substances that were systemically released by the network of injurious inflammatory events. Therefore, the early definition of a systemic inflammatory response syndrome (SIRS) was built upon a foundation of basic clinical and laboratory abnormalities that were readily available in almost all clinical settings. With further refinement, it was hoped, that this definition would have a high degree of sensitivity, coupled with a reasonable degree of specificity. This manuscript reviews the derivation, application, utilization, potential benefits, and speculation regarding the future of the SIRS definition. PMID:24280933

Seasonal variation in onset and relapse of IBD and a model to predict the frequency of onset, relapse, and severity of IBD based on artificial neural network.

PubMed

Peng, Jiang Chen; Ran, Zhi Hua; Shen, Jun

2015-09-01

Previous research has yielded conflicting data as to whether the natural history of inflammatory bowel disease follows a seasonal pattern. The purpose of this study was (1) to determine whether the frequency of onset and relapse of inflammatory bowel disease follows a seasonal pattern and (2) to establish a model to predict the frequency of onset, relapse, and severity of inflammatory bowel disease (IBD) with meteorological data based on artificial neural network (ANN). Patients with diagnosis of ulcerative colitis (UC) or Crohn's disease (CD) between 2003 and 2011 were investigated according to the occurrence of onset and flares of symptoms. The expected onset or relapse was calculated on a monthly basis over the study period. For artificial neural network (ANN), patients from 2003 to 2010 were assigned as training cohort and patients in 2011 were assigned as validation cohort. Mean square error (MSE) and mean absolute percentage error (MAPE) were used to evaluate the predictive accuracy. We found no seasonal pattern of onset (P = 0.248) and relapse (P = 0.394) among UC patients. But, the onset (P = 0.015) and relapse (P = 0.004) of CD were associated with seasonal pattern, with a peak in July and August. ANN had average accuracy to predict the frequency of onset (MSE = 0.076, MAPE = 37.58%) and severity of IBD (MSE = 0.065, MAPE = 42.15%) but high accuracy in predicting the frequency of relapse of IBD (MSE = 0.009, MAPE = 17.1%). The frequency of onset and relapse in IBD showed seasonality only in CD, with a peak in July and August, but not in UC. ANN may have its value in predicting the frequency of relapse among patients with IBD.

The role of adipokines in the rapid antidepressant effects of ketamine.

PubMed

Machado-Vieira, R; Gold, P W; Luckenbaugh, D A; Ballard, E D; Richards, E M; Henter, I D; De Sousa, R T; Niciu, M J; Yuan, P; Zarate, C A

2017-01-01

We previously found that body mass index (BMI) strongly predicted response to ketamine. Adipokines have a key role in metabolism (including BMI). They directly regulate inflammation and neuroplasticity pathways and also influence insulin sensitivity, bone metabolism and sympathetic outflow; all of these have been implicated in mood disorders. Here, we sought to examine the role of three key adipokines-adiponectin, resistin and leptin-as potential predictors of response to ketamine or as possible transducers of its therapeutic effects. Eighty treatment-resistant subjects who met DSM-IV criteria for either major depressive disorder (MDD) or bipolar disorder I/II and who were currently experiencing a major depressive episode received a single ketamine infusion (0.5 mg kg -1 for 40 min). Plasma adipokine levels were measured at three time points (pre-infusion baseline, 230 min post infusion and day 1 post infusion). Overall improvement and response were assessed using percent change from baseline on the Montgomery-Asberg Depression Rating Scale and the Hamilton Depression Rating Scale. Lower baseline levels of adiponectin significantly predicted ketamine's antidepressant efficacy, suggesting an adverse metabolic state. Because adiponectin significantly improves insulin sensitivity and has potent anti-inflammatory effects, this finding suggests that specific systemic abnormalities might predict positive response to ketamine. A ketamine-induced decrease in resistin was also observed; because resistin is a potent pro-inflammatory compound, this decrease suggests that ketamine's anti-inflammatory effects may be transduced, in part, by its impact on resistin. Overall, the findings suggest that adipokines may either predict response to ketamine or have a role in its possible therapeutic effects.

Genome sequencing elucidates Sardinian genetic architecture and augments association analyses for lipid and blood inflammatory markers

PubMed Central

Zoledziewska, Magdalena; Mulas, Antonella; Pistis, Giorgio; Steri, Maristella; Danjou, Fabrice; Kwong, Alan; Ortega del Vecchyo, Vicente Diego; Chiang, Charleston W. K.; Bragg-Gresham, Jennifer; Pitzalis, Maristella; Nagaraja, Ramaiah; Tarrier, Brendan; Brennan, Christine; Uzzau, Sergio; Fuchsberger, Christian; Atzeni, Rossano; Reinier, Frederic; Berutti, Riccardo; Huang, Jie; Timpson, Nicholas J; Toniolo, Daniela; Gasparini, Paolo; Malerba, Giovanni; Dedoussis, George; Zeggini, Eleftheria; Soranzo, Nicole; Jones, Chris; Lyons, Robert; Angius, Andrea; Kang, Hyun M.; Novembre, John; Sanna, Serena; Schlessinger, David; Cucca, Francesco; Abecasis, Gonçalo R

2015-01-01

We report ~17.6M genetic variants from whole-genome sequencing of 2,120 Sardinians; 22% are absent from prior sequencing-based compilations and enriched for predicted functional consequence. Furthermore, ~76K variants common in our sample (frequency >5%) are rare elsewhere (<0.5% in the 1000 Genomes Project). We assessed the impact of these variants on circulating lipid levels and five inflammatory biomarkers. Fourteen signals, including two major new loci, were observed for lipid levels, and 19, including two novel loci, for inflammatory markers. New associations would be missed in analyses based on 1000 Genomes data, underlining the advantages of large-scale sequencing in this founder population. PMID:26366554

Ability of commonly used prediction equations to predict resting energy expenditure in children with inflammatory bowel disease.

PubMed

Hill, Rebecca J; Lewindon, Peter J; Withers, Geoffrey D; Connor, Frances L; Ee, Looi C; Cleghorn, Geoffrey J; Davies, Peter S W

2011-07-01

Paediatric onset inflammatory bowel disease (IBD) may cause alterations in energy requirements and invalidate the use of standard prediction equations. Our aim was to evaluate four commonly used prediction equations for resting energy expenditure (REE) in children with IBD. Sixty-three children had repeated measurements of REE as part of a longitudinal research study yielding a total of 243 measurements. These were compared with predicted REE from Schofield, Oxford, FAO/WHO/UNU, and Harris-Benedict equations using the Bland-Altman method. Mean (±SD) age of the patients was 14.2 (2.4) years. Mean measured REE was 1566 (336) kcal per day compared with 1491 (236), 1441 (255), 1481 (232), and 1435 (212) kcal per day calculated from Schofield, Oxford, FAO/WHO/UNU, and Harris-Benedict, respectively. While the Schofield equation demonstrated the least difference between measured and predicted REE, it, along with the other equations tested, did not perform uniformly across all subjects, indicating greater errors at either end of the spectrum of energy expenditure. Smaller differences were found for all prediction equations for Crohn's disease compared with ulcerative colitis. Of the commonly used equations, the equation of Schofield should be used in pediatric patients with IBD when measured values are not able to be obtained. Copyright © 2010 Crohn's & Colitis Foundation of America, Inc.

Inflammatory macrophage-associated 3-gene signature predicts subclinical allograft injury and graft survival.

PubMed

Azad, Tej D; Donato, Michele; Heylen, Line; Liu, Andrew B; Shen-Orr, Shai S; Sweeney, Timothy E; Maltzman, Jonathan Scott; Naesens, Maarten; Khatri, Purvesh

2018-01-25

Late allograft failure is characterized by cumulative subclinical insults manifesting over many years. Although immunomodulatory therapies targeting host T cells have improved short-term survival rates, rates of chronic allograft loss remain high. We hypothesized that other immune cell types may drive subclinical injury, ultimately leading to graft failure. We collected whole-genome transcriptome profiles from 15 independent cohorts composed of 1,697 biopsy samples to assess the association of an inflammatory macrophage polarization-specific gene signature with subclinical injury. We applied penalized regression to a subset of the data sets and identified a 3-gene inflammatory macrophage-derived signature. We validated discriminatory power of the 3-gene signature in 3 independent renal transplant data sets with mean AUC of 0.91. In a longitudinal cohort, the 3-gene signature strongly correlated with extent of injury and accurately predicted progression of subclinical injury 18 months before clinical manifestation. The 3-gene signature also stratified patients at high risk of graft failure as soon as 15 days after biopsy. We found that the 3-gene signature also distinguished acute rejection (AR) accurately in 3 heart transplant data sets but not in lung transplant. Overall, we identified a parsimonious signature capable of diagnosing AR, recognizing subclinical injury, and risk-stratifying renal transplant patients. Our results strongly suggest that inflammatory macrophages may be a viable therapeutic target to improve long-term outcomes for organ transplantation patients.

Therapeutic intent of proton pump inhibitor prescription among elderly nonsteroidal anti-inflammatory drug users.

PubMed

Dries, A M; Richardson, P; Cavazos, J; Abraham, N S

2009-09-15

Prescription of proton pump inhibitors (PPIs) has increased dramatically. To assess therapeutic intent of PPI prescription among elderly veterans prescribed nonsteroidal anti-inflammatory drugs. Medical-record abstraction identified therapeutic intent of PPI prescription. An 'appropriate therapeutic intent' was defined as symptomatic gastro-oesophageal reflux disease or endoscopic oesophagitis, Zollinger-Ellison disease, dyspepsia, upper gastrointestinal event, Helicobacter pylori infection or nonsteroidal anti-inflammatory drug gastroprotection. Logistic regression predicted the outcome while adjusting for clinical characteristics. Of 1491 patients [mean 73 years (s.d. 5.6), 73% white and 99.8% men], among those charts which did document a therapeutic indication, 88.8% were appropriate. Prior gastroscopy was predictive of an appropriate therapeutic intent (OR 2.7; 95% CI: 1.9-3.7). Prescription to patients who used VA pharmacy services only, to in-patients, or by a cardiologist or an otolaryngologist were less likely to be appropriate. Gastroprotection was poorly recognized as an indication for PPI prescription, except by rheumatologists (OR 46.7; 95% CI: 15.9-136.9), or among highly co-morbid patients (OR 1.8; 95% CI: 1.1-2.9). Among in-patients, 45% of PPI prescriptions were initiated for unknown or inappropriate reasons. Type of provider predicts appropriate PPI use. In-patient prescription is associated with poor recognition of necessary gastroprotection and unknown therapeutic intent.

Periodontal Inflammatory Conditions Among Smokers and Never-Smokers With and Without Type 2 Diabetes Mellitus.

PubMed

Javed, Fawad; Al-Kheraif, Abdulaziz A; Salazar-Lazo, Karem; Yanez-Fontenla, Virginia; Aldosary, Khalid M; Alshehri, Mohammed; Malmstrom, Hans; Romanos, Georgios E

2015-07-01

There is a dearth of studies regarding the influence of cigarette smoking on periodontal inflammatory conditions among patients with type 2 diabetes mellitus (T2DM). The aim of the present study is to assess periodontal inflammatory conditions among smokers and never-smokers with and without T2DM. One hundred individuals (50 patients with T2DM [25 smokers and 25 never-smokers] and 50 controls [25 smokers and 25 never-smokers]) were included. Information regarding age, sex, duration and daily frequency of smoking, duration and treatment of diabetes, and oral hygiene was recorded using a questionnaire. Periodontal parameters (plaque index [PI], bleeding on probing [BOP], probing depth [PD], clinical attachment loss [AL], and marginal bone loss [MBL]) were measured. Hemoglobin A1c (HbA1c) levels were also recorded. Mean age, monthly income status, and education levels were comparable among smokers and never-smokers with and without T2DM. Mean HbA1c levels were significantly higher among patients with T2DM (8.2% ± 0.1%) compared with controls (4.4% ± 0.3%) (P <0.05). Smokers in the control group were smoking significantly greater numbers of cigarettes (15.5 ± 2.5 cigarettes daily) compared with smokers with T2DM (6.2 ± 2.1 cigarettes daily) (P <0.05). Periodontal parameters were comparable among smokers and never-smokers with T2DM. Among controls, periodontal parameters (PI [P <0.05], AL [P <0.05], PD ≥4 mm [P <0.05], and MBL [P <0.05]) were significantly higher in smokers than never-smokers. Never-smokers with T2DM had worse periodontal status than smokers and never-smokers in the control group (P <0.05). Periodontal inflammatory conditions are comparable among smokers and never-smokers with T2DM. Among controls, periodontal inflammation is worse among smokers than never-smokers.

Cognitive models of risky choice: parameter stability and predictive accuracy of prospect theory.

PubMed

Glöckner, Andreas; Pachur, Thorsten

2012-04-01

In the behavioral sciences, a popular approach to describe and predict behavior is cognitive modeling with adjustable parameters (i.e., which can be fitted to data). Modeling with adjustable parameters allows, among other things, measuring differences between people. At the same time, parameter estimation also bears the risk of overfitting. Are individual differences as measured by model parameters stable enough to improve the ability to predict behavior as compared to modeling without adjustable parameters? We examined this issue in cumulative prospect theory (CPT), arguably the most widely used framework to model decisions under risk. Specifically, we examined (a) the temporal stability of CPT's parameters; and (b) how well different implementations of CPT, varying in the number of adjustable parameters, predict individual choice relative to models with no adjustable parameters (such as CPT with fixed parameters, expected value theory, and various heuristics). We presented participants with risky choice problems and fitted CPT to each individual's choices in two separate sessions (which were 1 week apart). All parameters were correlated across time, in particular when using a simple implementation of CPT. CPT allowing for individual variability in parameter values predicted individual choice better than CPT with fixed parameters, expected value theory, and the heuristics. CPT's parameters thus seem to pick up stable individual differences that need to be considered when predicting risky choice. Copyright © 2011 Elsevier B.V. All rights reserved.

Associations between three specific a-cellular measures of the oxidative potential of particulate matter and markers of acute airway and nasal inflammation in healthy volunteers.

PubMed

Janssen, Nicole A H; Strak, Maciej; Yang, Aileen; Hellack, Bryan; Kelly, Frank J; Kuhlbusch, Thomas A J; Harrison, Roy M; Brunekreef, Bert; Cassee, Flemming R; Steenhof, Maaike; Hoek, Gerard

2015-01-01

We evaluated associations between three a-cellular measures of the oxidative potential (OP) of particulate matter (PM) and acute health effects. We exposed 31 volunteers for 5 h to ambient air pollution at five locations: an underground train station, two traffic sites, a farm and an urban background site. Each volunteer visited at least three sites. We conducted health measurements before exposure, 2 h after exposure and the next morning. We measured air pollution on site and characterised the OP of PM2.5 and PM10 using three a-cellular assays; dithiotreitol (OP(DTT)), electron spin resonance (OP(ESR)) and ascorbic acid depletion (OP(AA)). In single-pollutant models, all measures of OP were significantly associated with increases in fractional exhaled nitric oxide and increases in interleukin-6 in nasal lavage 2 h after exposure. These OP associations remained significant after adjustment for co-pollutants when only the four outdoor sites were included, but lost significance when measurements at the underground site were included. Other health end points including lung function and vascular inflammatory and coagulation parameters in blood were not consistently associated with OP. We found significant associations between three a-cellular measures of OP of PM and markers of airway and nasal inflammation. However, consistency of these effects in two-pollutant models depended on how measurements at the underground site were considered. Lung function and vascular inflammatory and coagulation parameters in blood were not consistently associated with OP. Our study, therefore, provides limited support for a role of OP in predicting acute health effects of PM in healthy young adults. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Platelet-derived growth factor predicts prolonged relapse-free period in multiple sclerosis.

PubMed

Stampanoni Bassi, Mario; Iezzi, Ennio; Marfia, Girolama A; Simonelli, Ilaria; Musella, Alessandra; Mandolesi, Georgia; Fresegna, Diego; Pasqualetti, Patrizio; Furlan, Roberto; Finardi, Annamaria; Mataluni, Giorgia; Landi, Doriana; Gilio, Luana; Centonze, Diego; Buttari, Fabio

2018-04-14

In the early phases of relapsing-remitting multiple sclerosis (RR-MS), a clear correlation between brain lesion load and clinical disability is often lacking, originating the so-called clinico-radiological paradox. Different factors may contribute to such discrepancy. In particular, synaptic plasticity may reduce the clinical expression of brain damage producing enduring enhancement of synaptic strength largely dependent on neurotrophin-induced protein synthesis. Cytokines released by the immune cells during acute inflammation can alter synaptic transmission and plasticity possibly influencing the clinical course of MS. In addition, immune cells may promote brain repair during the post-acute phases, by secreting different growth factors involved in neuronal and oligodendroglial cell survival. Platelet-derived growth factor (PDGF) is a neurotrophic factor that could be particularly involved in clinical recovery. Indeed, PDGF promotes long-term potentiation of synaptic activity in vitro and in MS and could therefore represent a key factor improving the clinical compensation of new brain lesions. The aim of the present study is to explore whether cerebrospinal fluid (CSF) PDGF concentrations at the time of diagnosis may influence the clinical course of RR-MS. At the time of diagnosis, we measured in 100 consecutive early MS patients the CSF concentrations of PDGF, of the main pro- and anti-inflammatory cytokines, and of reliable markers of neuronal damage. Clinical and radiological parameters of disease activity were prospectively collected during follow-up. CSF PDGF levels were positively correlated with prolonged relapse-free survival. Radiological markers of disease activity, biochemical markers of neuronal damage, and clinical parameters of disease progression were instead not influenced by PDGF concentrations. Higher CSF PDGF levels were associated with an anti-inflammatory milieu within the central nervous system. Our results suggest that PDGF could promote a more prolonged relapse-free period during the course of RR-MS, without influencing inflammation reactivation and inflammation-driven neuronal damage and likely enhancing adaptive plasticity.

Herb-drug interaction of Andrographis paniculata (Nees) extract and andrographolide on pharmacokinetic and pharmacodynamic of naproxen in rats.

PubMed

Balap, Aishwarya; Lohidasan, Sathiyanarayanan; Sinnathambi, Arulmozhi; Mahadik, Kakasaheb

2017-01-04

Andrographis paniculata Nees (Acanthacae) have broad range of pharmacological effects such as hepatoprotective, antifertility, antimalarial, antidiabetic, suppression of various cancer cells and anti-inflammatory properties and is widely used medicinal plant in the traditional Unani and Ayurvedic medicinal systems. Andrographolide (AN) is one of the active constituent of the A. paniculata Nees extract (APE). They have been found in many traditional herbal formulations in India and proven to be effective as anti-inflammatory drug. To evaluate the pharmacokinetic and pharmacodynamic (anti arthritic) herb-drug interactions of A. paniculata Nees extract (APE) and pure andrographolide (AN) with naproxen (NP) after oral co-administration in wistar rats. After oral co-administration of APE (200mg/Kg) and AN (60mg/kg) with NP (7.5mg/kg) in rats, drug concentrations in plasma were determined using HPLC method. The main pharmacokinetic parameters of C max , t max , t 1/2 , MRT, Vd, CL, and AUC were calculated by non-compartment model. Change in paw volume, mechanical nociceptive threshold, mechanical hyperalgesia, histopathology and hematological parameters were evaluated to study antiarthritic activity. Co-administration of NP with APE and pure AN decreased systemic exposure level of NP in vivo. The C max , t max, AUC 0-t of NP was decreased. In pharmacodynamic study, NP (10mg/kg) alone and NP+AN (10+60mg/kg) groups exhibited significant synergistic anti-arthritic activity as compared to groups NP+APE, APE and AN alone. The results obtained from this study suggested that NP, APE and pure AN existed pharmacokinetic herb-drug interactions in rat which is correlated with anti-arthritic study. The knowledge regarding possible herb-drug interaction of NP might be helpful for physicians as well as patients using AP. So further studies should be done to understand the effect of other herbal ingredients of APE on NP as well as to predict the herb-drug interaction in humans. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Preparation, spectroscopic, thermal, antihepatotoxicity, hematological parameters and liver antioxidant capacity characterizations of Cd(II), Hg(II), and Pb(II) mononuclear complexes of paracetamol anti-inflammatory drug

NASA Astrophysics Data System (ADS)

El-Megharbel, Samy M.; Hamza, Reham Z.; Refat, Moamen S.

2014-10-01

Keeping in view that some metal complexes are found to be more potent than their parent drugs, therefore, our present paper aimed to synthesized Cd(II), Hg(II) and Pb(II) complexes of paracetamol (Para) anti-inflammatory drug. Paracetamol complexes with general formula [M(Para)2(H2O)2]·nH2O have been synthesized and characterized on the basis of elemental analysis, conductivity, IR and thermal (TG/DTG), 1H NMR, electronic spectral studies. The conductivity data of these complexes have non-electrolytic nature. Comparative antimicrobial (bacteria and fungi) behaviors and molecular weights of paracetamol with their complexes have been studied. In vivo the antihepatotoxicity effect and some liver function parameters levels (serum total protein, ALT, AST, and LDH) were measured. Hematological parameters and liver antioxidant capacities of both Para and their complexes were performed. The Cd2+ + Para complex was recorded amelioration of antioxidant capacities in liver homogenates compared to other Para complexes treated groups.

Dynamic imaging of adaptive stress response pathway activation for prediction of drug induced liver injury.

PubMed

Wink, Steven; Hiemstra, Steven W; Huppelschoten, Suzanne; Klip, Janna E; van de Water, Bob

2018-05-01

Drug-induced liver injury remains a concern during drug treatment and development. There is an urgent need for improved mechanistic understanding and prediction of DILI liabilities using in vitro approaches. We have established and characterized a panel of liver cell models containing mechanism-based fluorescent protein toxicity pathway reporters to quantitatively assess the dynamics of cellular stress response pathway activation at the single cell level using automated live cell imaging. We have systematically evaluated the application of four key adaptive stress pathway reporters for the prediction of DILI liability: SRXN1-GFP (oxidative stress), CHOP-GFP (ER stress/UPR response), p21 (p53-mediated DNA damage-related response) and ICAM1 (NF-κB-mediated inflammatory signaling). 118 FDA-labeled drugs in five human exposure relevant concentrations were evaluated for reporter activation using live cell confocal imaging. Quantitative data analysis revealed activation of single or multiple reporters by most drugs in a concentration and time dependent manner. Hierarchical clustering of time course dynamics and refined single cell analysis allowed the allusion of key events in DILI liability. Concentration response modeling was performed to calculate benchmark concentrations (BMCs). Extracted temporal dynamic parameters and BMCs were used to assess the predictive power of sub-lethal adaptive stress pathway activation. Although cellular adaptive responses were activated by non-DILI and severe-DILI compounds alike, dynamic behavior and lower BMCs of pathway activation were sufficiently distinct between these compound classes. The high-level detailed temporal- and concentration-dependent evaluation of the dynamics of adaptive stress pathway activation adds to the overall understanding and prediction of drug-induced liver liabilities.

Clostridium difficile Associated Risk of Death Score (CARDS): A novel severity score to predict mortality among hospitalized patients with Clostridium difficile infection

PubMed Central

Kassam, Zain; Fabersunne, Camila Cribb; Smith, Mark B.; Alm, Eric J.; Kaplan, Gilaad G.; Nguyen, Geoffrey C.; Ananthakrishnan, Ashwin N.

2016-01-01

Background Clostridium difficile infection (CDI) is public health threat and associated with significant mortality. However, there is a paucity of objectively derived CDI severity scoring systems to predict mortality. Aims To develop a novel CDI risk score to predict mortality entitled: Clostridium difficile Associated Risk of Death Score (CARDS). Methods We obtained data from the United States 2011 Nationwide Inpatient Sample (NIS) database. All CDI-associated hospitalizations were identified using discharge codes (ICD-9-CM, 008.45). Multivariate logistic regression was utilized to identify independent predictors of mortality. CARDS was calculated by assigning a numeric weight to each parameter based on their odds ratio in the final logistic model. Predictive properties of model discrimination were assessed using the c-statistic and validated in an independent sample using the 2010 NIS database. Results We identified 77,776 hospitalizations, yielding an estimate of 374,747 cases with an associated diagnosis of CDI in the United States, 8% of whom died in the hospital. The 8 severity score predictors were identified on multivariate analysis: age, cardiopulmonary disease, malignancy, diabetes, inflammatory bowel disease, acute renal failure, liver disease and ICU admission, with weights ranging from −1 (for diabetes) to 5 (for ICU admission). The overall risk score in the cohort ranged from 0 to 18. Mortality increased significantly as CARDS increased. CDI-associated mortality was 1.2% with a CARDS of 0 compared to 100% with CARDS of 18. The model performed equally well in our validation cohort. Conclusion CARDS is a promising simple severity score to predict mortality among those hospitalized with CDI. PMID:26849527

Systems Pharmacology Dissection of the Anti-Inflammatory Mechanism for the Medicinal Herb Folium Eriobotryae

PubMed Central

Zhang, Jingxiao; Li, Yan; Chen, Su-Shing; Zhang, Lilei; Wang, Jinghui; Yang, Yinfeng; Zhang, Shuwei; Pan, Yanqiu; Wang, Yonghua; Yang, Ling

2015-01-01

Inflammation is a hallmark of many diseases like diabetes, cancers, atherosclerosis and arthritis. Thus, lots of concerns have been raised toward developing novel anti-inflammatory agents. Many alternative herbal medicines possess excellent anti-inflammatory properties, yet their precise mechanisms of action are yet to be elucidated. Here, a novel systems pharmacology approach based on a large number of chemical, biological and pharmacological data was developed and exemplified by a probe herb Folium Eriobotryae, a widely used clinical anti-inflammatory botanic drug. The results show that 11 ingredients of this herb with favorable pharmacokinetic properties are predicted as active compounds for anti-inflammatory treatment. In addition, via systematic network analyses, their targets are identified to be 43 inflammation-associated proteins including especially COX2, ALOX5, PPARG, TNF and RELA that are mainly involved in the mitogen-activated protein kinase (MAPK) signaling pathway, the rheumatoid arthritis pathway and NF-κB signaling pathway. All these demonstrate that the integrated systems pharmacology method provides not only an effective tool to illustrate the anti-inflammatory mechanisms of herbs, but also a new systems-based approach for drug discovery from, but not limited to, herbs, especially when combined with further experimental validations. PMID:25636035

Numerical weather prediction model tuning via ensemble prediction system

NASA Astrophysics Data System (ADS)

Jarvinen, H.; Laine, M.; Ollinaho, P.; Solonen, A.; Haario, H.

2011-12-01

This paper discusses a novel approach to tune predictive skill of numerical weather prediction (NWP) models. NWP models contain tunable parameters which appear in parameterizations schemes of sub-grid scale physical processes. Currently, numerical values of these parameters are specified manually. In a recent dual manuscript (QJRMS, revised) we developed a new concept and method for on-line estimation of the NWP model parameters. The EPPES ("Ensemble prediction and parameter estimation system") method requires only minimal changes to the existing operational ensemble prediction infra-structure and it seems very cost-effective because practically no new computations are introduced. The approach provides an algorithmic decision making tool for model parameter optimization in operational NWP. In EPPES, statistical inference about the NWP model tunable parameters is made by (i) generating each member of the ensemble of predictions using different model parameter values, drawn from a proposal distribution, and (ii) feeding-back the relative merits of the parameter values to the proposal distribution, based on evaluation of a suitable likelihood function against verifying observations. In the presentation, the method is first illustrated in low-order numerical tests using a stochastic version of the Lorenz-95 model which effectively emulates the principal features of ensemble prediction systems. The EPPES method correctly detects the unknown and wrongly specified parameters values, and leads to an improved forecast skill. Second, results with an atmospheric general circulation model based ensemble prediction system show that the NWP model tuning capacity of EPPES scales up to realistic models and ensemble prediction systems. Finally, a global top-end NWP model tuning exercise with preliminary results is published.

Diagnostic and prognostic value of history-taking and physical examination in undifferentiated peripheral inflammatory arthritis: a systematic review.

PubMed

Kuriya, Bindee; Villeneuve, Edith; Bombardier, Claire

2011-03-01

To review the diagnostic and prognostic value of history/physical examination among patients with undifferentiated peripheral inflammatory arthritis (UPIA). We conducted a systematic review evaluating the association between history/physical examination features and a diagnostic or prognostic outcome. Nineteen publications were included. Advanced age, female sex, and morning stiffness were predictive of a diagnosis of rheumatoid arthritis (RA) from UPIA. A higher number of tender and swollen joints, small/large joint involvement in the upper/lower extremities, and symmetrical involvement were associated with progression to RA. Similar features were associated with persistent disease and erosions, while disability at baseline and extraarticular features were predictive of future disability. History/physical examination features are heterogeneously reported. Several features predict progression from UPIA to RA or a poor prognosis. Continued measurements in the UPIA population are needed to determine if these features are valid and reliable predictors of outcomes, especially as new definitions for RA and disease states emerge.

Reaction-Diffusion-Delay Model for EPO/TNF-α Interaction in articular cartilage lesion abatement

PubMed Central

2012-01-01

Background Injuries to articular cartilage result in the development of lesions that form on the surface of the cartilage. Such lesions are associated with articular cartilage degeneration and osteoarthritis. The typical injury response often causes collateral damage, primarily an effect of inflammation, which results in the spread of lesions beyond the region where the initial injury occurs. Results and discussion We present a minimal mathematical model based on known mechanisms to investigate the spread and abatement of such lesions. The first case corresponds to the parameter values listed in Table 1, while the second case has parameter values as in Table 2. In particular we represent the "balancing act" between pro-inflammatory and anti-inflammatory cytokines that is hypothesized to be a principal mechanism in the expansion properties of cartilage damage during the typical injury response. We present preliminary results of in vitro studies that confirm the anti-inflammatory activities of the cytokine erythropoietin (EPO). We assume that the diffusion of cytokines determine the spatial behavior of injury response and lesion expansion so that a reaction diffusion system involving chemical species and chondrocyte cell state population densities is a natural way to represent cartilage injury response. We present computational results using the mathematical model showing that our representation is successful in capturing much of the interesting spatial behavior of injury associated lesion development and abatement in articular cartilage. Further, we discuss the use of this model to study the possibility of using EPO as a therapy for reducing the amount of inflammation induced collateral damage to cartilage during the typical injury response. Table 1 Model Parameter Values for Results in Figure 5 Table of Parameter Values Corresponding to Simulations in Figure 5 Parameter Value Units Reason D R 0.1 c m 2 day Determined from [13] D M 0.05 c m 2 day Determined from [13] D F 0.05 c m 2 day Determined from [13] D P 0.005 c m 2 day Determined from [13] δ R 0.01 1 day Approximated δ M 0.6 1 day Approximated δ F 0.6 1 day Approximated δ P 0.0087 1 day Approximated δ U 0.0001 1 day Approximated σ R 0.0001 micromolar ⋅ c m 2 day ⋅ cells Approximated σ M 0.00001 micromolar ⋅ c m 2 day ⋅ cells Approximated σ F 0.0001 micromolar ⋅ c m 2 day ⋅ cells Approximated σ P 0 micromolar ⋅ c m 2 day ⋅ cells Case with no anti-inflammatory response Λ 10 micromolar Approximated λ R 10 micromolar Approximated λ M 10 micromolar Approximated λ F 10 micromolar Approximated λ P 10 micromolar Approximated α 0 1 day Case with no anti-inflammatory response β 1 100 1 day Approximated Β 2 50 1 day Approximated γ 10 1 day Approximated ν 0.5 1 day Approximated μ S A 1 1 day Approximated μ D N 0.5 1 day Approximated τ 1 0.5 days Taken from [5] τ 2 1 days Taken from [5] Table 2 Model Parameter Values for Results in Figure 6 Table of Parameter Values Corresponding to Simulations in Figure 6 Parameter Value Units Reason D R 0.1 c m 2 day Determined from [13] D M 0.05 c m 2 day Determined from [13] D F 0.05 c m 2 day Determined from [13] DP 0.005 c m 2 day Determined from [13] δ R 0.01 1 day Approximated δ M 0.6 1 day Approximated δ F 0.6 1 day Approximated δ P 0.0087 1 day Approximated δ U 0.0001 1 day Approximated σ R 0.0001 micromolar ⋅ c m 2 day ⋅ cells Approximated σ M 0.00001 micromolar ⋅ c m 2 day ⋅ cells Approximated σ F 0.0001 micromolar ⋅ c m 2 day ⋅ cells Approximated σ P 0.001 micromolar ⋅ c m 2 day ⋅ cells Approximated Λ 10 micromolar Approximated λ R 10 micromolar Approximated λ M 10 micromolar Approximated λ F 10 micromolar Approximated λ P 10 micromolar Approximated α 10 1 day Approximated β 1 100 1 day Approximated β 2 50 1 day Approximated γ 10 1 day Approximated ν 0.5 1 day Approximated μ S A 1 1 day Approximated μ D N 0.5 1 day Approximated τ 1 0.5 days Taken from [5] τ 2 1 days Taken from [5] Conclusions The mathematical model presented herein suggests that not only are anti-inflammatory cy-tokines, such as EPO necessary to prevent chondrocytes signaled by pro-inflammatory cytokines from entering apoptosis, they may also influence how chondrocytes respond to signaling by pro-inflammatory cytokines. Reviewers This paper has been reviewed by Yang Kuang, James Faeder and Anna Marciniak-Czochra. PMID:22353555

A statistical analysis of RNA folding algorithms through thermodynamic parameter perturbation.

PubMed

Layton, D M; Bundschuh, R

2005-01-01

Computational RNA secondary structure prediction is rather well established. However, such prediction algorithms always depend on a large number of experimentally measured parameters. Here, we study how sensitive structure prediction algorithms are to changes in these parameters. We found already that for changes corresponding to the actual experimental error to which these parameters have been determined, 30% of the structure are falsely predicted whereas the ground state structure is preserved under parameter perturbation in only 5% of all the cases. We establish that base-pairing probabilities calculated in a thermal ensemble are viable although not a perfect measure for the reliability of the prediction of individual structure elements. Here, a new measure of stability using parameter perturbation is proposed, and its limitations are discussed.

[Determination by thermometric titrimetry of the thermodynamic parameters of water/n-octanol transfer of several non-steroidal anti-inflammatory drugs].

PubMed

Burgot, G; Burgot, J L

1995-01-01

The calorimetric determination by thermometric titrimetry of the water/n-octanol transfer enthalpies of some non steroidic anti-inflammatory compounds is described. By combining the values obtained with that of the free enthalpies of transfer issuing from the values of corresponding log P, it is possible to determinate the transfer entropies of the solutes. The whole results of the show that almost the transfers are both enthalpy and entropy driven. They demonstrate the occurrence of three different mechanisms of transfer.

Clinical Response to Vedolizumab in Ulcerative Colitis Patients Is Associated with Changes in Integrin Expression Profiles.

PubMed

Fuchs, Friederike; Schillinger, Daniela; Atreya, Raja; Hirschmann, Simon; Fischer, Sarah; Neufert, Clemens; Atreya, Imke; Neurath, Markus F; Zundler, Sebastian

2017-01-01

Despite large clinical success, deeper insights into the immunological effects of vedolizumab therapy for inflammatory bowel diseases are scarce. In particular, the reasons for differential clinical response in individual patients, the precise impact on the equilibrium of integrin-expressing T cell subsets, and possible associations between these issues are not clear. Blood samples from patients receiving clinical vedolizumab therapy were sequentially collected and analyzed for expression of integrins and chemokine receptors on T cells. Moreover, clinical and laboratory data from the patients were collected, and changes between homing marker expression and clinical parameters were analyzed for possible correlations. While no significant correlation of changes in integrin expression and changes in outcome parameters were identified in Crohn's disease (CD), increasing α4β7 levels in ulcerative colitis (UC) seemed to be associated with favorable clinical development, whereas increasing α4β1 and αEβ7 correlated with negative changes in outcome parameters. Changes in α4β1 integrin expression after 6 weeks were significantly different in responders and non-responders to vedolizumab therapy as assessed after 16 weeks with a cutoff of +4.2% yielding 100% sensitivity and 100% specificity in receiver-operator-characteristic analysis. Our data show that clinical response to vedolizumab therapy in UC but not in CD is associated with specific changes in integrin expression profiles opening novel avenues for mechanistic research and possibly prediction of response to therapy.

NWP model forecast skill optimization via closure parameter variations

NASA Astrophysics Data System (ADS)

Järvinen, H.; Ollinaho, P.; Laine, M.; Solonen, A.; Haario, H.

2012-04-01

We present results of a novel approach to tune predictive skill of numerical weather prediction (NWP) models. These models contain tunable parameters which appear in parameterizations schemes of sub-grid scale physical processes. The current practice is to specify manually the numerical parameter values, based on expert knowledge. We developed recently a concept and method (QJRMS 2011) for on-line estimation of the NWP model parameters via closure parameter variations. The method called EPPES ("Ensemble prediction and parameter estimation system") utilizes ensemble prediction infra-structure for parameter estimation in a very cost-effective way: practically no new computations are introduced. The approach provides an algorithmic decision making tool for model parameter optimization in operational NWP. In EPPES, statistical inference about the NWP model tunable parameters is made by (i) generating an ensemble of predictions so that each member uses different model parameter values, drawn from a proposal distribution, and (ii) feeding-back the relative merits of the parameter values to the proposal distribution, based on evaluation of a suitable likelihood function against verifying observations. In this presentation, the method is first illustrated in low-order numerical tests using a stochastic version of the Lorenz-95 model which effectively emulates the principal features of ensemble prediction systems. The EPPES method correctly detects the unknown and wrongly specified parameters values, and leads to an improved forecast skill. Second, results with an ensemble prediction system emulator, based on the ECHAM5 atmospheric GCM show that the model tuning capability of EPPES scales up to realistic models and ensemble prediction systems. Finally, preliminary results of EPPES in the context of ECMWF forecasting system are presented.

Quantifying model-structure- and parameter-driven uncertainties in spring wheat phenology prediction with Bayesian analysis

DOE PAGES

Alderman, Phillip D.; Stanfill, Bryan

2016-10-06

Recent international efforts have brought renewed emphasis on the comparison of different agricultural systems models. Thus far, analysis of model-ensemble simulated results has not clearly differentiated between ensemble prediction uncertainties due to model structural differences per se and those due to parameter value uncertainties. Additionally, despite increasing use of Bayesian parameter estimation approaches with field-scale crop models, inadequate attention has been given to the full posterior distributions for estimated parameters. The objectives of this study were to quantify the impact of parameter value uncertainty on prediction uncertainty for modeling spring wheat phenology using Bayesian analysis and to assess the relativemore » contributions of model-structure-driven and parameter-value-driven uncertainty to overall prediction uncertainty. This study used a random walk Metropolis algorithm to estimate parameters for 30 spring wheat genotypes using nine phenology models based on multi-location trial data for days to heading and days to maturity. Across all cases, parameter-driven uncertainty accounted for between 19 and 52% of predictive uncertainty, while model-structure-driven uncertainty accounted for between 12 and 64%. Here, this study demonstrated the importance of quantifying both model-structure- and parameter-value-driven uncertainty when assessing overall prediction uncertainty in modeling spring wheat phenology. More generally, Bayesian parameter estimation provided a useful framework for quantifying and analyzing sources of prediction uncertainty.« less

Fluorine 18 fluorodeoxyglucose PET/CT volume-based indices in locally advanced non-small cell lung cancer: prediction of residual viable tumor after induction chemotherapy.

PubMed

Soussan, Michael; Cyrta, Joanna; Pouliquen, Christelle; Chouahnia, Kader; Orlhac, Fanny; Martinod, Emmanuel; Eder, Véronique; Morère, Jean-François; Buvat, Irène

2014-09-01

To study whether volume-based indices of fluorine 18 fluorodeoxyglucose positron emission tomographic (PET)/computed tomographic (CT) imaging is an accurate tool to predict the amount of residual viable tumor after induction chemotherapy in patients with locally advanced non-small cell lung cancer (NSCLC). This study was approved by institutional review board with waivers of informed consent. Twenty-two patients with locally advanced NSCLC underwent surgery after induction chemotherapy. All had pre- and posttreatment FDG PET/CT scans. CT largest diameter, CT volume, maximum standardized uptake value (SUVmax), mean SUV (SUVmean), metabolic tumor volume (TV), and total lesion glycolysis of primary tumor were calculated. Changes in tumor measurements were determined by dividing follow-up by baseline measurement (ratio index). Amounts of residual viable tumor, necrosis, fibrous tissue, inflammatory infiltrate, and Ki-67 proliferative index were estimated on resected tumor. Correlations between imaging indices and histologic parameters were estimated by using Spearman correlation coefficients or Mann-Whitney tests. No baseline or posttreatment indices correlated with percentage of residual viable tumor. TV ratio was the only index that correlated with percentage of residual viable tumor (r = 0.61 [95% confidence interval: 0.24, 0.81]; P = .003). Conversely, SUVmax and SUVmean ratios were only indices correlated with Ki-67 (r = 0.62 [95% confidence interval: 0.24, 0.82]; P = .003; and r = 0.60 [95% confidence interval: 0.21, 0.81]; P = .004, respectively). Total lesion glycolysis ratio was moderately correlated with residual viable tumor (r = 0.53 [95% confidence interval: 0.13, 0.78]; P = .01) and with Ki-67 (r = 0.57 [95% confidence interval: 0.18, 0.80]; P = .006). No ratios were correlated with presence of inflammatory infiltrate or foamy macrophages. TV and total lesion glycolysis ratios were the only indices correlated with residual viable tumor after induction chemotherapy in locally advanced NSCLC.

The predictive value of mean platelet volume, plateletcrit and red cell distribution width in the differentiation of autoimmune gastritis patients with and without type I gastric carcinoid tumors.

PubMed

Tüzün, Ali; Keskin, Onur; Yakut, Mustafa; Kalkan, Cagdas; Soykan, Irfan

2014-01-01

Autoimmune gastritis is an autoimmune and inflammatory condition that may predispose to gastric carcinoid tumors or adenocarcinomas. The early diagnosis of these tumors is important in order to decrease morbidity and mortality. Platelet indices such as mean platelet volume and plateletcrit levels increase in inflammatory, infectious and malign conditions. The primary aim of this study was to explore wheter platelet indices and red cell distribution width have any predictive role in the discrimination of autoimmune gastritis patients with and without gastric carcinoid tumors. Also secondary aim of this study was to investigate whether any changes exist betwenn autoimmune gastritis and functional dyspepsia patients by means of platelet indices. Plateletcrit (0.22 ± 0.06 vs. 0.20 ± 0.03%, p < 0.001) and red cell distribution width (16.11 ± 3.04 vs. 13.41 ± 0.95%, p < 0.001) were significantly higher in autoimmune gastritis patients compared to control group. Receiver operating curve analysis suggested that optimum plateletcrit cut-off point was 0.20% (AUC: 0.646), and 13.95% as the cut off value for red cell distribution width (AUC: 0.860). Although plateletcrit (0.22 ± 0.06 vs. 0.21 ± 0.04%, p = 0.220) and mean platelet volume (8.94 ± 1.44 vs. 8.68 ± 0.89 fl, p = 0.265) were higher in autoimmune gastritis patients without carcinoid tumor compared to patients with carcinoid tumors, these parameters were not statistically significant. Changes in plateletcrit and red cell distribution width values may be used as a marker in the discrimination of autoimmune gastritis and fucntional dyspepsia patients but not useful in patients with gastric carcinoid tumor type I.

Correlation of total serum immunoglobulin E level, sputum, and peripheral eosinophil count in assessing the clinical severity in bronchial asthma.

PubMed

Kumar, Roshan M; Pajanivel, R; Koteeswaran, G; Menon, Surendra K; Charles, Pravin Mv

2017-01-01

Asthma is a chronic inflammatory disorder of the airway with involvement of various cellular populations and release of many inflammatory mediators. Eosinophils and serum immunoglobulin E (IgE) are considered a good marker of airway inflammation in asthma. The correlation of clinical assessment with various markers of airway inflammation in asthma is not well established in the Indian population. This study aims to study the correlation of serum IgE, sputum eosinophil count, and peripheral eosinophil count with clinical severity of Asthma. This is a cross-sectional study involving 76 stable asthmatic patients of 18-60 years of age attending the pulmonary medicine OPD. Spirometry measured at baseline. Participants were categorized according to the GINA criteria based on clinical symptoms and pulmonary function test. Blood samples were collected for peripheral eosinophil count, serum IgE levels, and sputum samples for eosinophil count. All three parameters were compared with severity of asthma. The correlation of sputum eosinophil count, peripheral eosinophil count, and serum IgE with severity of asthma was analyzed by Pearson's Chi-square test, Fisher's exact test, and the correlation coefficient was reported together with standard error of the estimate. The mean age of patients in our study was 37.42 years and 56.6% were male. There was a significant inverse correlation between serum IgE levels and predicted forced expiratory volume 1 s (FEV1). Sputum eosinophilia was significantly seen in severe persistent asthma patients (19.7%). There was a significant inverse correlation between sputum eosinophil count and predicted FEV1and forced vital capacity. We also found there was a significant association between peripheral eosinophil count, sputum eosinophil count, and elevated serum IgE (g100 IU/mL) with severe persistent asthma. The assessment of sputum eosinophil count is simple, inexpensive, noninvasive, and direct measurement of airway inflammation. It could be the preferred method in monitoring airway inflammation and guided management in day-to-day practice.

Early reduction of matrix metalloproteinase-8 serum levels is associated with leptin drop and predicts diabetes remission after bariatric surgery.

PubMed

Liberale, Luca; Bonaventura, Aldo; Carbone, Federico; Bertolotto, Maria; Contini, Paola; Scopinaro, Nicola; Camerini, Giovanni Bruno; Papadia, Francesco Saverio; Cordera, Renzo; Camici, Giovanni Guido; Dallegri, Franco; Adami, Gian Franco; Montecucco, Fabrizio

2017-10-15

We aimed at investigating whether the acute abrogation of leptin after bariatric surgery is able to reduce neutrophil activation and potentially affect type 2 diabetes mellitus (T2DM) remission. Metabolic and inflammatory parameters (i.e. leptin, IL-6 and neutrophil products) were compared at baseline (before bariatric surgery), one month, one and three years after surgery in morbid obese (MOB) T2DM patients (n=12) and non-MOB controls (n=32). In vitro, the effects of leptin on Il-6-induced human neutrophil degranulation and integrin upregulation were assessed. At baseline, MOB T2DM patients had a similar demographic, lipid and glycemic profiles than non-MOB T2DM controls, but higher levels of inflammatory mediators, such as CRP, fibrinogen, neutrophil-to-lymphocyte ratio (NLR), matrix metalloproteinase (MMP)-8 and leptin. One month after surgery, CRP, fibrinogen and MMP-8 were reduced only in MOB T2DM patients, while serum leptin was reduced in both groups. In the overall cohort, leptin and MMP-8 drops from baseline to one month post-surgery were positively correlated (Δleptin vs. ΔMMP8: r=0.391, p=0.025). Moreover, ΔMMP8 inversely correlated with fasting glucose levels at one-year follow-up and with glycated hemoglobin at both one- and three-year. At the cut-off point identified by ROC curve analysis (>0ng/mL), ΔMMP8 predicted complete T2DM remission at 3-year follow-up. In vitro, leptin increased IL-6-induced MMP-8 release and abrogated CD18 up-regulation. Bariatric surgery is associated to an acute abrogation of leptin that could affect MMP-8 levels, particularly in MOB T2DM patients. This beneficial event is associated with T2DM remission at 3-year follow-up. Copyright © 2017 Elsevier B.V. All rights reserved.

Predictive comparisons of procalcitonin (PCT) level, arterial ketone body ratio (AKBR), APACHE III score and multiple organ dysfunction score (MODS) in systemic inflammatory response syndrome (SIRS).

PubMed

Lee, Young-Joo; Park, Chan-Hee; Yun, Jang-Woon; Lee, Young-Suk

2004-02-29

Procalcitonin (PCT) is a newly introduced marker of systemic inflammation and bacterial infection. A marked increase in circulating PCT level in critically ill patients has been related with the severity of illness and poor survival. The goal of this study was to compare the prognostic power of PCT and three other parameters, the arterial ketone body ratio (AKBR), the acute physiology, age, chronic health evaluation (APACHE) III score and the multiple organ dysfunction score (MODS), in the differentiation between survivors and nonsurvivors of systemic inflammatory response syndrome (SIRS). The study was performed in 95 patients over 16 years of age who met the criteria of SIRS. PCT and AKBR were assayed in arterial blood samples. The APACHE III score and MODS were recorded after the first 24 hours of surgical ICU (SICU) admission and then daily for two weeks or until either discharge or death. The patients were divided into two groups, survivors (n=71) and nonsurvivors (n=24), in accordance with the ICU outcome. They were also divided into three groups according to the trend of PCT level: declining, increasing or no change. Significant differences between survivors and nonsurvivors were found in APACHE III score and MODS throughout the study period, but in PCT value only up to the 7th day and in AKBR only up to the 3rd day. PCT values of the three groups were not significantly different on the first day between survivors and nonsurvivors. Receiver operating characteristic (ROC) curves for prediction of mortality by PCT, AKBR, APACHE III score and MODS were 0.690, 0.320, 0.915 and 0.913, respectively, on the admission day. In conclusion, PCT could have some use as a mortality predictor in SIRS patients but was less reliable than APACHE III score or MODS.

Relationship of Th17/Treg Cells and Radiation Pneumonia in Locally Advanced Esophageal Carcinoma.

PubMed

Wang, Yan; Xu, Gang; Wang, Jie; Li, Xin-Hua; Sun, Ping; Zhang, Wei; Li, Jun-Xia; Wu, Chao-Yang

2017-08-01

Radiation pneumonia is a main side-effect that has limited the clinical usage of radiotherapy in locally advanced esophageal carcinoma. T helper cells 17 (Th 17) and T regulatory cells (Tregs) play an important role in inflammatory diseases. The balance between Treg and Th17 cells is a key factor in the progression of many inflammatory and autoimmune diseases. Whether Tregs and Th17 cells are predictive factors of radiation pneumonia has not yet been reported. In this study, we investigated the relationships of Treg/Th17 cells and radiation pneumonia in patients with locally advanced esophageal cancer who received radiotherapy. One hundred and forty-eight patients with locally advanced esophageal cancer who received radical and palliative radiotherapy were enrolled. The levels of Th17 and Treg cells in the blood of patients were detected using flow cytometry at the time point of pre-radiotherapy, 1st, 2nd, 3rd, 4th, 5th and 6th week from the start of radiation and 4 weeks after completion of radiotherapy. Radiation pneumonia was evaluated according to Radiation Therapy Oncology Group's acute radiation pneumonia standards, with the endpoint being grade 2 or above radiation pneumonia. There were 24 cases of radiation pneumonia in 148 cases of locally advanced esophageal cancer patients who underwent radiotherapy. Th17 cells increased and, in contrast, Treg cells decreased in the radiation pneumonia group. The change in the ratio of Th17/Treg was more pronounced and the difference was statistically significant from the 5th week after irradiation compared to patients with no radiation pneumonia (p<0.05). There was no significant difference in dosimetric parameters, including V5, V20, V30 and mean lung dose (MLD) and clinical factors, such as gender, age, smoking history, history of surgery and chemotherapy. The ratio of Th17/Treg cells may be an effective predictive factor of radiation pneumonia. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

[Importance of electromiographic examination in diagnostification and monitoring of chronic inflammatory demyelinating polyneuropathy].

PubMed

Damjan, Igor; Cvijanović, Milan; Erak, Marko

2010-01-01

Polyneuropathies or peripheral neuropathies present a dysfunction or disease of larger number of peripheral nerves or their dysfunction. Considering their morbidity - mortality characteristics they present an important aspect in daily clinical practice. One particular polyneuropathy that deserves special review is chronic inflammatory demyelinating polyneuropathy, which, due to its clinical-laboratory presentation, does not include the group of "simple" neuropathies, thus requiring further examinations. Neurophysiological testing should be performed using the protocol for neuropathy examinations. Neurophysiological examination, during the electroneurographic examination, shows neurographic parameters referring to polyneuropatic demyelinating type of lesion, while the electromyographic finding records the presence of neuropathic lesions (denervation activity, great action potentials with a reduced sample). A 54-year-old patient was diagnosed to have a "complicated" demyelinating polyneuropathy according to the clinical-laboratory findings and electromyographic examination. Exclusion criteria, targeted diagnostic examinations, considering the mentioned peripheral neuropathies, pointed to acute inflammatory demyelinating polyneuropathy. However, the chronic inflammatory demyelinating polyneuropathy was finally differentiated during the clinical and electromyographic monitoring.

Fisetin attenuates cerulein-induced acute pancreatitis through down regulation of JNK and NF-κB signaling pathways.

PubMed

Jo, Il-Joo; Bae, Gi-Sang; Choi, Sun Bok; Kim, Dong-Goo; Shin, Joon-Yeon; Seo, Seung-Hee; Choi, Mee-Ok; Kim, Tae-Hyeon; Song, Ho-Joon; Park, Sung-Joo

2014-08-15

Acute pancreatitis (AP) is a complicated disease which is largely undiscovered. Fisetin, a natural flavonoid from fruits and vegetables, has been shown to have anti-inflammatory, antioxidant, and anti-cancer activities in various disease models. However, the effects of fisetin on AP have not been determined. Pre- and post- treatment of mice with fisetin reduced the severity of AP and pancreatitis-associated lung injury and inhibited several biochemical parameters (pancreatic weight to body weight ratio, amylase, lipase, and myeloperoxidase activity) and production of inflammatory cytokines. In pancreatic acinar cells, fisetin also inhibited cell death and production of inflammatory cytokines. In addition, fisetin inhibited activation of c-Jun NH2-terminal kinase (JNK) and nuclear factor (NF)-κB in vivo and in vitro. In conclusion, these results suggest that fisetin exhibits anti-inflammatory effect on AP and could be a beneficial agent in the treatment of AP and its pulmonary complications. Copyright © 2014 Elsevier B.V. All rights reserved.

Mango Supplementation Has No Effects on Inflammatory Mediators in Obese Adults

PubMed Central

Evans, Shirley F; Beebe, Maureen; Mahmood, Maryam; Janthachotikun, Sawanya; Eldoumi, Heba; Peterson, Sandra; Payton, Mark; Perkins-Veazie, Penelope; Smith, Brenda J; Lucas, Edralin A

2017-01-01

This pilot study examined the effects of freeze-dried mango (Mangifera indica L.) supplementation on anthropometric measurements, lipid parameters, and inflammatory mediators in obese individuals. A total of 20 obese (body mass index [BMI]: 30-35 kg/m2) adults (11 men and 9 women), aged 20 to 50 years, received 10 g/d of ground freeze-dried mango pulp for 12 weeks. Anthropometrics, lipids, and inflammatory mediators were assessed at baseline and after 12 weeks of mango supplementation. There were no differences between baseline and final visits in inflammatory mediators, lipids, diet, physical activity, and anthropometrics. Relationships were present at baseline and final visits between adiponectin and high-density lipoprotein cholesterol and between leptin and fat mass. Correlations were found after 12 weeks of mango supplementation between leptin and the following variables: waist-to-height ratio, BMI, percent fat, and fat mass. Our findings demonstrate that 12-week consumption of freeze-dried mango by obese individuals has no impact on obesity-related inflammation. PMID:28983188

Mulberry extract supplements ameliorate the inflammation-related hematological parameters in carrageenan-induced arthritic rats.

PubMed

Kim, Ae-Jung; Park, Soojin

2006-01-01

Mulberry fruit (Morus Lhou Koidz.), a rich source of the major anthocyanin, cyanidin 3-glucoside (C3G), has traditionally been used for the treatment of inflammatory conditions including rheumatic arthritis. In this study, we evaluated the efficacy of orally administrated methanolic mulberry fruit extract (ME) in carrageenan-induced arthritic rats, based on previously observed in vitro antioxidant and anti-inflammatory activities. A significant attenuation of hind paw inflammation characterized by fluid accumulation, uric acid production, and rheumatoid factors induced by carrageenan was observed following the intake of both ME (50 mg/kg of body weight) and C3G (10 mg/kg of body weight). Moreover, alterations in hematological parameters such as serum triglyceride, high-density lipoprotein-cholesterol, and atherogenic index following carrageenan administration were partially reversed by the administration of ME. It is concluded that dietary mulberry fruit extracts elicited protection against carrageenan-induced inflammation.

Better cognitive control of emotional information is associated with reduced pro-inflammatory cytokine reactivity to emotional stress.

PubMed

Shields, Grant S; Kuchenbecker, Shari Young; Pressman, Sarah D; Sumida, Ken D; Slavich, George M

2016-01-01

Stress is strongly associated with several mental and physical health problems that involve inflammation, including asthma, cardiovascular disease, certain types of cancer, and depression. It has been hypothesized that better cognitive control of emotional information may lead to reduced inflammatory reactivity to stress and thus better health, but to date no studies have examined whether differences in cognitive control predict pro-inflammatory cytokine responses to stress. To address this issue, we conducted a laboratory-based experimental study in which we randomly assigned healthy young-adult females to either an acute emotional stress (emotionally evocative video) or no-stress (control video) condition. Salivary levels of the key pro-inflammatory cytokines IL-1β, IL-6, and IL-8 were measured before and after the experimental manipulation, and following the last cytokine sample, we assessed participants' cognitive control of emotional information using an emotional Stroop task. We also assessed participants' cortisol levels before and after the manipulation to verify that documented effects were specific to cytokines and not simply due to increased nonwater salivary output. As hypothesized, the emotional stressor triggered significant increases in IL-1β, IL-6, and IL-8. Moreover, even in fully adjusted models, better cognitive control following the emotional (but not control) video predicted less pronounced cytokine responses to that stressor. In contrast, no effects were observed for cortisol. These data thus indicate that better cognitive control specifically following an emotional stressor is uniquely associated with less pronounced pro-inflammatory cytokine reactivity to such stress. These findings may therefore help explain why superior cognitive control portends better health over the lifespan.

Deriving a cardiac ageing signature to reveal MMP-9-dependent inflammatory signalling in senescence.

PubMed

Ma, Yonggang; Chiao, Ying Ann; Clark, Ryan; Flynn, Elizabeth R; Yabluchanskiy, Andriy; Ghasemi, Omid; Zouein, Fouad; Lindsey, Merry L; Jin, Yu-Fang

2015-06-01

Cardiac ageing involves the progressive development of cardiac fibrosis and diastolic dysfunction coordinated by MMP-9. Here, we report a cardiac ageing signature that encompasses macrophage pro-inflammatory signalling in the left ventricle (LV) and distinguishes biological from chronological ageing. Young (6-9 months), middle-aged (12-15 months), old (18-24 months), and senescent (26-34 months) mice of both C57BL/6J wild type (WT) and MMP-9 null were evaluated. Using an identified inflammatory pattern, we were able to define individual mice based on their biological, rather than chronological, age. Bcl6, Ccl24, and Il4 were the strongest inflammatory markers of the cardiac ageing signature. The decline in early-to-late LV filling ratio was most strongly predicted by Bcl6, Il1r1, Ccl24, Crp, and Cxcl13 patterns, whereas LV wall thickness was most predicted by Abcf1, Tollip, Scye1, and Mif patterns. With age, there was a linear increase in cardiac M1 macrophages and a decrease in cardiac M2 macrophages in WT mice; of which, both were prevented by MMP-9 deletion. In vitro, MMP-9 directly activated young macrophage polarization to an M1/M2 mid-transition state. Our results define the cardiac ageing inflammatory signature and assign MMP-9 roles in mediating the inflammaging profile by indirectly and directly modifying macrophage polarization. Our results explain early mechanisms that stimulate ageing-induced cardiac fibrosis and diastolic dysfunction. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Anti-inflammatory use may not negatively impact oncologic outcomes following intravesical BCG for high-grade non-muscle-invasive bladder cancer.

PubMed

Singla, Nirmish; Haddad, Ahmed Q; Passoni, Niccolo M; Meissner, Matthew; Lotan, Yair

2017-01-01

To evaluate whether anti-inflammatory agents affect outcomes in patients receiving intravesical BCG therapy for high-grade (HG) non-muscle-invasive bladder cancer (NMIBC). We reviewed the records of 203 patients in a prospective database of HG NMIBC from 2006 to 2012 at a single institution. Patients who had muscle-invasive disease (n = 32), low-grade pathology (n = 4), underwent early cystectomy within 3 months (n = 25), had <3 months of follow-up (n = 11), or did not receive an induction course of intravesical BCG (n = 32) were excluded. Clinicopathologic data were tabulated including demographics, comorbidities, pathologic stage and grades, intravesical therapy, and concomitant use of aspirin, NSAIDs, COX inhibitors, and statins. Multivariate Cox regression analysis explored predictive factors for recurrence, progression (stage progression or progression to cystectomy), cancer-specific survival (CSS), and overall survival (OS). Ninety-nine patients with HG NMIBC who received at least one induction course of intravesical BCG were identified, with median follow-up of 31.4 months. There were 20 (20.2 %) deaths, including 6 (6.1 %) patients with bladder cancer-related mortality. 13 % patients experienced tumor progression and 27 % underwent cystectomy following failure of intravesical therapy. Anti-inflammatory use included statins (65 %), aspirin (63 %), or non-aspirin NSAIDs/COX inhibitors (26 %). Anti-inflammatory use was not significantly predictive of recurrence, progression, or mortality outcomes on Cox regression. CIS stage was associated with higher progression, while age, BMI, and Charlson score were independent predictors of overall mortality. Despite speculation of inhibitory effects on BCG immunomodulation there was no evidence that anti-inflammatory agents impacted oncologic outcomes in patients receiving BCG for HG NMIBC.

Fatigue in out-patients with inflammatory bowel disease: Prevalence and predictive factors.

PubMed

Villoria, Albert; García, Víctor; Dosal, Angelina; Moreno, Laura; Montserrat, Antònia; Figuerola, Ariadna; Horta, Diana; Calvet, Xavier; Ramírez-Lázaro, María José

2017-01-01

Fatigue is a common and bothersome symptom in inflammatory bowel disease (IBD) patients. The study was aimed to determine the relationship of biological and psychological factors with IBD-related fatigue. Consecutive clinically inactive IBD outpatients receiving immunosuppressants or biological drugs were enrolled between January and December 2013. Patients completed a Fatigue score (FACIT-F), various psychological, quality of life (IBDQ-9), and IBD activity scores. Biological parameters were assessed, including levels of interleukins (IL-5, IL-8 and IL-12) and micronutrients. We prospectively recruited 202 patients (28% ulcerative colitis and 72% Crohn's disease) for the study. Fatigue measured by FACIT-F score was prevalent in the studied population (54%, 96/177) and higher than in the general population. In the univariate analysis no relation was found between IL levels or micronutrient deficiencies and fatigue. Fatigue was significantly related to female sex, Crohn's disease, joint disorders, body mass index (BMI), psychological tests, thiopurine use, and anti-TNF treatment. All these variables were included in the multivariate analysis. Female sex (OR: 4.8), high BMI (OR:1.2) and higher depression rates (OR:1.2) were predictors of increased fatigue. High IBDQ-9 score (OR: 0.82) was significantly related to lower degrees of fatigue. Fatigue was prevalent in quiescent IBD patients with moderate-to-severe disease. It was associated with high levels of depression, low quality of life, and female sex. No association was found with the other biological and psychological factors evaluated.

Relationship of Salmonella infection and inflammatory intestinal response with hematological and serum biochemical values in laying hens.

PubMed

Soria, Mario Alberto; Bonnet, María Agustina; Bueno, Dante Javier

2015-06-15

There are few studies about the blood serum of laying hens infected with Salmonella. The differential leukocyte count and blood chemistry values are an important aid in the diagnosis of human diseases, but blood parameters in the avian species are not well known. On the other hand, invasive forms of bacterial gastroenteritis, like Salmonella, often cause intestinal inflammation so this study was undertaken to find a biomarker of Salmonella infection and inflammatory intestinal response in the hematological or serum biochemical parameters in laying hens. Furthermore, we evaluated the association of some farm characteristics with Salmonella infection and fecal leukocytes (FL). A fecal sample with at least one fecal leukocyte per field was considered positive for inflammatory intestinal response. False positive serum reactions for Salmonella infection, by serum plate agglutination (SPA) test, were reduced by heating the sample to 56°C for 30 min and then diluting it 5-fold. The range of hematological and biochemical parameter values was very wide, in addition, there was a poor agreement between the SPA and FL results. Comparison of the positive and negative samples in SPA and FL showed that 1.3% and 79.8% of the laying hens were positive and negative in both tests, respectively. Hens with a positive SPA result showed a higher percentage of monocytes than those with a negative SPA result. Hens with a positive FL test had a higher percentage of heterophils, ratio of heterophils to lymphocytes and aspartate aminotransferase values, while the percentage of lymphocytes was significantly lower (P < 0.05) than those with a negative FL test. The risk of Salmonella infection increased when the age of laying hens and the number of hens per poultry house was greater than or equal to 18 months old and 10,000 laying hens, compared to less than 18 months old and 10,000 laying hens, respectively. On the other hand, the risk of inflammatory intestinal response was higher in laying hens ≥ 18 months old than in hens < 18 months old. Despite the fact that we did not find any specific biomarker of Salmonella infection, this is the first report about the change of Salmonella infection and inflammatory response in hematological/serum biochemical values for laying hens. Copyright © 2015 Elsevier B.V. All rights reserved.

Combining Early Coagulation and Inflammatory Status Improves Prediction of Mortality in Burned and Nonburned Trauma Patients

DTIC Science & Technology

2008-02-01

clinician to distinguish between the effects of treatment and the effects of disease. Several different prediction models for multiple or- gan failure...treat- ment protocols and allow a clinician to distinguish the effect of treatment from effect of disease. In this study, our model predicted in...TNF produces a decrease in protein C activation by down regulating the expression of endothelial cell protein C receptor and thrombomodulin, both of

Ocimum basilicum affects tracheal responsiveness, lung inflammatory cells and oxidant-antioxidant biomarkers in sensitized rats.

PubMed

Eftekhar, Naeima; Moghimi, Ali; Hossein Boskabady, Mohammad; Kaveh, Mahsa; Shakeri, Farzaneh

2018-04-23

The anti-inflammatory and antioxidant effects of Ocimum basilicum (O. basilicum) was shown previously. In the present study, the effect of O. basilicum on tracheal responsiveness (TR) to methacholine and ovalbumin (OVA), bronchoalveolar lavage fluid (BALF) levels of oxidant-antioxidant biomarkers as well as total and differential white blood cell (WBC) in sensitized rats was examined. Six groups of rats including control (group C), sensitized rats to OVA (group S), S groups treated with three concentrations of O. basilicum (0.75, 1.50, and 3.00 mg/ml) and one concentration of dexamethasone (1.25 μg/ml) (n = 8 for all groups) were studied. TR to methacholine and OVA, total WBC count, percentages of eosinophils, monocytes, neutrophils, and levels of oxidant biomarkers were significantly increased but other measured parameters were significantly decreased in group S compared to group C. TR to methacholine and OVA, percentages of eosinophils, monocytes, neutrophils, and levels of oxidant biomarkers were significantly decreased but lymphocytes and antioxidant biomarkers were significantly increased in S groups treated with dexamethasone and at least two higher concentrations of the extract compared to group S. Total WBC count was also decreased in treated S groups with dexamethasone and high extract concentration. The effect of extract on most measured parameters was significantly lower than dexamethasone treatment. The effects of two higher concentrations of the extract on most variables were significantly higher than the effect of low extract concentration. These results showed the concentration-dependent effect of O. basilicum on tracheal responses, lung inflammatory cells, and oxidant-antioxidant parameters in sensitized rats.

Genetic variants of interferon-gamma and its mRNA expression and inflammatory parameters in the pathogenesis of vitiligo.

PubMed

Karam, Rehab A; Zidan, Haidy E; Khater, Mohamed H

2017-08-01

Although genetics plays an essential role in the pathogenesis of vitiligo, vitiligo pathogenesis is still unclear. Our aim was to investigate the role of IFN-γ expression and polymorphism in vitiligo susceptibility and whether intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor (TNF)-α, and TNF-β play a role in vitiligo pathogenesis as important inflammatory parameters. Eighty-five patients with vitiligo and 90 controls were investigated for IFN-γ gene expression by quantitative real-time PCR and genotyped for IFN-γ +874T/A (rs2430561) and IFN-γ +2109A/G (rs1861494) gene polymorphisms by sequence-specific primer (SSP)-PCR and PCR-restriction fragment length polymorphism (RFLP), respectively. Serum levels of inflammatory parameters were measured using ELISA. Frequencies of the +874 TT genotype and T allele were significantly higher in patients with active vitiligo than in stable patients (P = 0.01 and 0.03, respectively). Calculation of odds ratio suggested a 1.7-fold increased risk of vitiligo in individuals having the TA haplotype. We observed overexpression of IFN-γ mRNA with elevated serum levels of IFN-γ, ICAM-1, TNF-α, and TNF-β in patients with vitiligo when compared with the control group (P = 0.001, for all). In addition, these levels were elevated in patients with active vitiligo compared with stable patients with vitiligo (P = 0.008, 0.006, 0.01, 0.01, and 0.03, respectively), which suggests the involvement of these cytokines in disease activity. In conclusion, IFN-γ is a promising immunological marker in vitiligo pathogenesis.

The importance of intestinal ultrasound and elastographic techniques in inflammatory bowel diseases.

PubMed

Marin, Andreea; Tribus, Laura; Fierbinteanu-Braticevici, Carmen

2018-05-02

Inflammatory bowel diseases have an important impact upon the economic and social status due to their increasing incidence and prevalence, often affecting young people. At the moment, the therapeutic goal goes beyond the improvement of symptoms and laboratory parameters, being represented by endoscopic mucosal healing, changing the disease's natural history. Even though endoscopy is the gold standard for the assessment of mucosal healing, it is an invasive maneuver and it lacks good repeatability. These patients require frequent evaluation; therefore, interest for noninvasive techniques has risen.As a consequence, the importance of intestinal ultrasound has increased lately and recent studies support its use to assess the degree of inflammation, to differentiate between remission and relapse, to monitor therapy response and guide treatment, to evaluate prognosis, and to diagnose complications. Another promising noninvasive imagistic technique is elastography which has gained interest because of its capacity to discriminate between inflammatory and fibrotic tissue, taking into account the different therapeutic options for the fibrotic strictures compared to inflammatory processes. This review summarizes the actual recommendations regarding the use of intestinal ultrasound and elastographic techniques for the diagnosis and monitoring of inflammatory bowel diseases.

Ovariectomy shortens the life span of female mice

PubMed Central

Benedusi, Valeria; Martini, Elisa; Kallikourdis, Marinos; Villa, Alessandro; Meda, Clara; Maggi, Adriana

2015-01-01

This study shows that lack of ovarian activity has a negative impact on the life span of female mice. The extent to which this phenomenon could be associated with the anti-inflammatory effect of estrogens was analyzed in metabolic organs and aorta, by quantitative analysis of mRNAs encoding proteins in the inflammatory cascade. We demonstrate that the TNFα, IL-1β, MCP-1, MIP-2 and IL-6 mRNA contents are increased in the liver, adipose tissue and aorta 7 months after ovariectomy (ovx) and this increased basal inflammation is maintained as the mice aged. In contrast, the extent of inflammatory gene expression is directly proportional to age in sham-operated mice. As a consequence, at 22 months, most of the inflammatory parameters examined were higher in the sham-operated group compared with the ovx group. These observations led us to propose that the decreased longevity of ovx mice may be due to an acceleration of the basal state of inflammation in metabolic organs, which is likely driven by the combination of a lack of estrogen-mediated anti-inflammatory activity and the loss of gonadal control of energy metabolism. PMID:25719423

Folate-targeted nanoparticles show efficacy in the treatment of inflammatory arthritis

PubMed Central

Thomas, Thommey P.; Goonewardena, Sascha N.; Majoros, Istvan; Kotlyar, Alina; Cao, Zhengyi; Leroueil, Pascale R.; Baker, James R.

2011-01-01

Objective To investigate the uptake of a poly(amidoamine) dendrimer (generation 5 (G5)) nanoparticle covalently conjugated to polyvalent folic acid (FA) as the targeting ligand into macrophages, and the activity of a FA- and methotrexate-conjugated dendrimer (G5-FA-MTX) as a therapeutic for the inflammatory disease of arthritis. Methods In vitro studies were performed in macrophage cell lines and in isolated mouse macrophages to check the cellular uptake of fluorescently tagged G5-FA nanoparticles, using flow cytometry and confocal microscopy. In vivo studies were conducted in a rat model of collagen-induced arthritis to evaluate the therapeutic potential of G5-FA-MTX. Results Folate targeted dendrimer bound and internalized in a receptor-specific manner into both folate receptor β-expressing macrophage cell lines and primary mouse macrophages. The G5-FA-MTX acts as a potent anti-inflammatory agent and reduces arthritis-induced inflammatory parameters such as ankle swelling, paw volume, cartilage damage, bone resorption and body weight decrease. Conclusion The use of folate-targeted nanoparticles to specifically target MTX into macrophages may provide an effective clinical approach for anti-inflammatory therapy in rheumatoid arthritis. PMID:21618461

Improving hot region prediction by parameter optimization of density clustering in PPI.

PubMed

Hu, Jing; Zhang, Xiaolong

2016-11-01

This paper proposed an optimized algorithm which combines density clustering of parameter selection with feature-based classification for hot region prediction. First, all the residues are classified by SVM to remove non-hot spot residues, then density clustering of parameter selection is used to find hot regions. In the density clustering, this paper studies how to select input parameters. There are two parameters radius and density in density-based incremental clustering. We firstly fix density and enumerate radius to find a pair of parameters which leads to maximum number of clusters, and then we fix radius and enumerate density to find another pair of parameters which leads to maximum number of clusters. Experiment results show that the proposed method using both two pairs of parameters provides better prediction performance than the other method, and compare these two predictive results, the result by fixing radius and enumerating density have slightly higher prediction accuracy than that by fixing density and enumerating radius. Copyright © 2016. Published by Elsevier Inc.

Prediction of stream volatilization coefficients

USGS Publications Warehouse

Rathbun, Ronald E.

1990-01-01

Equations are developed for predicting the liquid-film and gas-film reference-substance parameters for quantifying volatilization of organic solutes from streams. Molecular weight and molecular-diffusion coefficients of the solute are used as correlating parameters. Equations for predicting molecular-diffusion coefficients of organic solutes in water and air are developed, with molecular weight and molal volume as parameters. Mean absolute errors of prediction for diffusion coefficients in water are 9.97% for the molecular-weight equation, 6.45% for the molal-volume equation. The mean absolute error for the diffusion coefficient in air is 5.79% for the molal-volume equation. Molecular weight is not a satisfactory correlating parameter for diffusion in air because two equations are necessary to describe the values in the data set. The best predictive equation for the liquid-film reference-substance parameter has a mean absolute error of 5.74%, with molal volume as the correlating parameter. The best equation for the gas-film parameter has a mean absolute error of 7.80%, with molecular weight as the correlating parameter.

Homology modeling and in silico prediction of Ulcerative colitis associated polymorphisms of NOD1.

PubMed

Majumdar, Ishani; Nagpal, Isha; Paul, Jaishree

2017-10-01

Cytosolic pattern recognition receptors play key roles in innate immune response. Nucleotide binding and oligomerisation domain containing protein 1 (NOD1) belonging to the Nod-like receptor C (NLRC) sub-family of Nod-like receptors (NLRs) is important for detection and clearance of intra-cellular Gram negative bacteria. NOD1 is involved in activation of pro-inflammatory pathways. Limited structural data is available for NOD1. Using different templates for each domain of NOD1, we determined the full-length homology model of NOD1. ADP binding amino acids within the nucleotide binding domain (NBD) of NOD1 were also predicted. Key residues in inter-domain interaction were identified by sequence comparison with Oryctolagus cuniculus NOD2, a related protein. Interactions between NBD and winged helix domain (WHD) were found to be conserved in NOD1. Functional and structural effect of single nucleotide polymorphisms within the NOD1 NBD domain associated with susceptibility risk to Ulcerative colitis (UC), an inflammatory disorder of the colon was evaluated by in silico studies. Mutations W219R and L349P were predicted to be damaging and disease associated by prediction programs SIFT, PolyPhen2, PANTHER, SNP&GO, PhD SNP and SNAP2. We further validated the effect of W219R and L349P mutation on NOD1 function in vitro. Elevated mRNA expression of pro-inflammatory cytokines IL8 and IL-1β was seen as compared to the wild type NOD1 in intestinal epithelial cell line HT29 when stimulated with NOD1 ligand. Thus, these mutations may indeed have a bearing on pathogenesis of inflammation during UC. Copyright © 2017 Elsevier Ltd. All rights reserved.

Prevalence of Coxitis and its Correlation with Inflammatory Activity in Rheumatoid Arthritis.

PubMed

Bajraktari, Ismet H; Krasniqi, Blerim; Rexhepi, Sylejman; Bexheti, Sadi; Bahtiri, Elton; Bajraktari, Halit; Luri, Besim

2018-02-15

Rheumatoid arthritis (RA) is an autoimmune inflammatory disease characterised by intra-articular and extra-articular manifestations but very rarely with coxitis. This study aimed to investigate the prevalence of coxitis, clinical changes, and its correlation with the parameters of inflammatory activity. A cohort of 951 patients diagnosed with ACR/EULAR (American College of Rheumatology/European League against Rheumatism) 2010 criteria was enrolled in this prospective, observational and analytic research study. The CBC (Complete Blood Count), ESR (Erythrocyte sedimentation rate), CRP(C - reactive protein), Anti CCP (Antibodies to cyclic citrullinated peptides), X-ray examination of palms and pelvis, and the activity of the disease as measured by DAS - 28 (28 - joint disease activity score) were carried out in all subjects. Independent samples t-test was used to compare the group's characteristics, whereas Pearson correlation test was used to analyse the correlation between study variables. Of the total number of the subjects, 730 (76.8 %) were females, whereas 221 (23.2%) were males. The average age was 51.3, y/o while the most of them were between 40 - 49 y/o (32.6%). The prevalence of coxitis was 14.2%, mostly found in males (19.46%). The echosonografic prevalence of changes was 21.45%, while the radiological changes were 16.3%; in both cases, the changes were more expressed in males. The analysis showed that inflammatory parameters were significantly higher in patients with coxitis. Coxitis has high economic cost because it ends up with a mandatory need for a total hip joint prosthesis. Thus the results of this study can serve to plan and initiate early preventive measures.

Disruption of erythrocyte antioxidant defense system, hematological parameters, induction of pro-inflammatory cytokines and DNA damage in liver of co-exposed rats to aluminium and acrylamide.

PubMed

Ghorbel, Imen; Maktouf, Sameh; Kallel, Choumous; Ellouze Chaabouni, Semia; Boudawara, Tahia; Zeghal, Najiba

2015-07-05

The individual toxic effects of aluminium and acrylamide are well known but there are no data on their combined effects. The present study was undertaken to determine (i) hematological parameters during individual and combined chronic exposure to aluminium and acrylamide (ii) correlation of oxidative stress in erythrocytes with pro-inflammatory cytokines expression, DNA damage and histopathological changes in the liver. Rats were exposed to aluminium (50 mg/kg body weight) in drinking water and acrylamide (20 mg/kg body weight) by gavage, either individually or in combination for 3 weeks. Exposure rats to AlCl3 or/and ACR provoked an increase in MDA, AOPP, H2O2 and a decrease in GSH and NPSH levels in erythrocytes. Activities of catalase, glutathione peroxidase and superoxide dismutase were decreased in all treated rats. Our results showed that all treatments induced an increase in WBC, erythrocyte osmotic fragility and a decrease in RBC, Hb and Ht. While MCV, MCH, MCHC remained unchanged. Hepatic pro-inflammatory cytokines expression including tumor necrosis factor-α, interleukin-6, interleukin-1β was increased suggesting leucocytes infiltration in the liver. A random DNA degradation was observed on agarose gel only in the liver of co-exposed rats to AlCl3 and ACR treatment. Interestingly, co-exposure to these toxicants exhibited synergism based on physical and biochemical variables in erythrocytes, pro-inflammatory cytokines and DNA damage in liver. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Impact of acute exacerbations on platelet reactivity in chronic obstructive pulmonary disease patients.

PubMed

Muñoz-Esquerre, Mariana; Ferreiro, José Luis; Huertas, Daniel; Marcano, Ana Lucrecia; López-Sánchez, Marta; Roura, Gerard; Gómez-Hospital, Joan Antoni; Dorca, Jordi; Cequier, Angel; Santos, Salud

2018-01-01

A higher risk of atherothrombotic cardiovascular events, which are platelet-driven processes, has been described during acute exacerbations of chronic obstructive pulmonary disease (AECOPD). However, the relevance of platelet reactivity during AECOPD and whether this is affected by antiplatelet agents are not fully elucidated to date. This study aimed to evaluate whether platelet reactivity is augmented during an exacerbation in COPD patients with and without antiplatelet therapy and its association with systemic inflammatory parameters. Prospective, observational, ex vivo investigation was conducted in consecutive patients suffering an exacerbation of COPD. Platelet reactivity was assessed during AECOPD and at stable state. Platelet function assays included: 1) vasodilator-stimulated phosphoprotein assay expressed as P2Y 12 reactivity index (PRI), 2) multiple electrode aggregometry and 3) optical aggregometry. Systemic inflammatory parameters such as leukocyte count, interleukin-6 and fibrinogen were also assessed. Higher platelet reactivity was observed during AECOPD compared to stability measured by vasodilator-stimulated phosphoprotein (PRI: 75.2%±1.9% vs 68.8%±2.4%, p =0.001). This augmented platelet aggregability was also observed in the subset of patients on antiplatelet therapy (PRI: 72.8%±3.1% vs 61.7%±7.5%, p =0.071). Consistent findings were observed with all other platelet function tests. Patients with greater enhancement of inflammatory markers during AECOPD were more likely to present a higher increase in platelet reactivity. Platelet reactivity is increased during AECOPD, which may contribute to the augmented cardiovascular risk of these patients. Additionally, the increase in platelet reactivity might be associated with an increment in inflammatory markers during exacerbations.

Ceramic modifications of porous titanium: effects on macrophage activation.

PubMed

Scislowska-Czarnecka, A; Menaszek, E; Szaraniec, B; Kolaczkowska, E

2012-12-01

Porous titanium is one of the most widely used implant materials because of its mechanical properties, however, it is also characterised by low bioactivity. To improve the above parameter we prepared three modifications of the porous (30 wt%) titanium (Ti) surface by covering it with bioactive hydroxyapatite (HA), bioglass (BG) and calcium silicate (CS). Subsequently we tested the impact of the modifications on macrophages directing the inflammatory response that might compromise the implant bioactivity. In the study we investigated the in vitro effects of the materials on murine cell line RAW 264.7 macrophage adherence, morphology and activation (production/release of metalloproteinase MMP-9 and pro- and anti-inflammatory cytokines). CS Ti decreased the macrophage adherence and up-regulated the release of several pro-inflammatory mediators, including TNF-α, IL-6, IL-12. Also HA Ti reduced the cell adherence but other parameters were generally not increased, except of TNF-α. In contrast, BG Ti improved macrophage adherence and either decreased production of multiple mediators (MMP-9, TNF-α, IFN-γ, MCP-1) or did not change it in comparison to the porous titanium. We can conclude that analyzing the effects on the inflammatory response initiated by macrophages in vitro, calcium silicate did not improve the biological properties of the porous titanium. The improved bioactivity of titanium was, however, achieved by the application of the hydroxyapatite and bioglass layers. The present in vitro results suggest that these materials, HA Ti and especially BG Ti, may be suitable for in vivo application and thus justify their further investigation. Copyright © 2012 Elsevier Ltd. All rights reserved.

New therapeutic activity of metabolic enhancer piracetam in treatment of neurodegenerative disease: Participation of caspase independent death factors, oxidative stress, inflammatory responses and apoptosis.

PubMed

Verma, Dinesh Kumar; Gupta, Sonam; Biswas, Joyshree; Joshi, Neeraj; Singh, Abhishek; Gupta, Parul; Tiwari, Shubhangini; Sivarama Raju, K; Chaturvedi, Swati; Wahajuddin, M; Singh, Sarika

2018-06-01

Piracetam, a nootropic drug that has been clinically used for decades but remains enigmatic due to no distinct understanding of its mechanism of action. The present study aimed to investigate the role of caspase independent pathway in piracetam mediated neuroprotection. LPS administration caused significant alterations in oxidative stress related parameters like glutathione, glutathione reductase and increased lipid peroxidation. LPS administration also caused augmented expression of inflammatory cytokines and astrocytes activation. Piracetam treatment offered significant protection against LPS induced oxidative and inflammatory parameters and inhibited astrocytes activation. LPS administration caused augmented level of reactive oxygen species and depleted mitochondrial membrane potential which were attenuated with piracetam treatment. This study for the first time demonstrates the role of caspase independent death factors in piracetam induced neuroprotective effects in rat brain. Translocation of mitochondrial resident apoptosis inducing factor and endonuclease G to nucleus through cytosol after LPS administration was significantly blocked with piracetam treatment. Further, LPS induced DNA fragmentation along with up regulated Poly [ADP-ribose] polymerase 1 (PARP1) levels were also inhibited with piracetam treatment. Apoptotic death was confirmed by the cleavage of caspase 3 as well as histological alteration in rat brain regions. LPS administration caused significantly increased level of cleaved caspase 3, altered neuronal morphology and decreased neuronal density which were restored with piracetam treatment. Collectively our findings indicate that piracetam offered protection against LPS induced inflammatory responses and cellular death including its antioxidative antiapoptotic activity with its attenuation against mitochondria mediated caspase independent pathway. Copyright © 2018 Elsevier B.V. All rights reserved.

The impact of fish oil and wheat germ oil combination on mineral-bone and inflammatory markers in maintenance hemodialysis patients: a randomized, double-blind, placebo-controlled clinical trial.

PubMed

Zakaria, Hadeer; Mostafa, Tarek M; El-Azab, Gamal A; Abd El Wahab, Ahmed M; Elshahawy, Heba; Sayed-Ahmed, Nagy Ah

2017-10-01

This study aimed to examine the impact of combined supplementation of fish oil (FO) with antioxidants like wheat germ oil (WGO) on mineral-bone and inflammatory markers in maintenance HD patients. This randomized, double-blind, placebo-controlled trial involved 46 HD patients who were randomly assigned into two groups to receive daily 3000 mg of FO [1053 mg omega-3 fatty acids (ω-3 FAs)] plus 300 mg of WGO [0.765 mg vitamin E] or placebo for 4 months. Blood concentrations of hemoglobin (Hgb), white blood cells, mineral-bone parameters including serum calcium (Ca), phosphorus, calcium-phosphorus product, parathyroid hormone, alkaline phosphatase, and osteoprotegerin and serum concentrations of inflammatory markers including high-sensitivity C-reactive protein, ferritin, and uric acid were measured before and after the intervention. Eighty-seven percentage of patients in each group completed the study. The mean serum Ca levels increased significantly in the supplemented group at the end of study (p = 0.0016), and this increment was also significant as compared to placebo group (p = 0.0418). No significant alterations were observed in the other measured parameters within each group during the study (as p values were >0.05). FO plus WGO supplementation showed beneficial effect on serum Ca levels of HD patients without any statistically significant effect on other mineral-bone and inflammatory markers. Further investigations are required to confirm it.

Hemoadsorption by CytoSorb in septic patients: a case series.

PubMed

Kogelmann, Klaus; Jarczak, Dominik; Scheller, Morten; Drüner, Matthias

2017-03-27

Septic shock, defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, is a highly lethal condition that causes substantial morbidity and mortality among critically ill patients. One of the hallmarks of sepsis is the excessive release of cytokines and other inflammatory mediators causing refractory hypotension, tissue damage, metabolic acidosis and ultimately multiple organ failure. In this context, cytokine reduction by hemoadsorption represents a new concept for blood purification, developed to attenuate the overwhelming systemic levels of pro-inflammatory and anti-inflammatory mediators released in the early phase of sepsis. In the present case series, we evaluated the impact of a new hemoadsorption device (CytoSorb) used as adjunctive therapy, on hemodynamics and clinically relevant outcome parameters in 26 critically ill patients with septic shock and in need of renal replacement therapy. We found that treatment of these patients with septic shock was associated with hemodynamic stabilization and a reduction in blood lactate levels. Actual mortality in the overall patient population was lower than mortality predicted by acute physiology and chronic health evaluation II (APACHE II). These effects seem to be more pronounced in patients in whom therapy started within 24 h of sepsis diagnosis, whereas a delay in the start of therapy was associated with a poor response to therapy in terms of reduction of catecholamine demand and survival. Moreover, from our patient population, medical patients seemed to benefit more than post-surgical patients in terms of survival. Treatment using the CytoSorb device was safe and well-tolerated with no device-related adverse events during or after the treatment sessions. Hemoadsorption using CytoSorb resulted in rapid hemodynamic stabilization and increased survival, particularly in patients in whom therapy was started early. Given the positive clinical experience of this case series, randomized controlled trials are urgently needed to define the potential benefits of this new treatment option.

Serum C-reactive protein levels predict regional brain responses to noxious cold stimulation of the hand in chronic whiplash associated disorders.

PubMed

Sterling, Michele; Head, Jessica; Cabot, Peter J; Farrell, Michael

2016-04-01

Whiplash Associated Disorders (WAD) are a costly health burden. The condition is characterised by sensory disturbances such as widespread hyperalgesia likely indicative of central hyperexcitability. Recently elevated levels of pro-inflammatory biomarkers have also found in acute and chronic WAD. The aim of this cross-sectional study was to investigate the relationship between inflammatory biomarkers and pain processing in people with persistent whiplash associated disorders (WAD). Twenty one participants with chronic whiplash (>3 months) were recruited. Venous blood samples were collected and assays performed for C-reactive protein (CRP) and TNF-α. Blood oxygen level-dependent (BOLD) contrast images of the brain were acquired with a Siemens 1.5T MRI scanner during repeated 24s stimulus blocks of innocuous or painful stimuli (thumbnail pressure and cold stimulation of dorsum of hand) separated by 36s inter-stimulus intervals. Stimulus intensities used during scanning were at the level of participants' thresholds for moderate pain. Parameter estimates representing BOLD signal increases during painful events from each participant were tested for associations with inflammatory biomarkers. Clinically relevant levels of CRP and TNF-α were found in 33% and 38% of participants. Levels of CRP showed a positive correlation with levels of cold pain activation in brain regions including the anterior insula, posterior parietal cortex, caudate and thalamus (p corrected <0.05). Levels of TNF-α were not related to activation levels during either noxious pressure or cold. Pressure pain activations also did not show a relationship with CRP levels. Shared variance between inflammation and increased levels of regional pain-related activation in people with persistent whiplash symptoms is apparent for cold, but not pressure stimuli. The results highlight cold pain processing as an important aspect of whiplash chronicity, although the implications of this modality-specific effect are not readily apparent. Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.

Diagnostic efficiency of amylase and type IV collagen in predicting chronic pancreatitis.

PubMed

Das, Subir Kumar; Varadhan, Sowmya; Dhanya, L; Mukherjee, Sukhes; Mohana, S; Balakrishnan, V; Vasudevan, D M

2009-01-01

Chronic pancreatitis, an irreversible inflammatory disease of the pancreas, is associated with the replacement of the destroyed parenchyma by extended development of fibrosis. Despite marked progress in diagnostic tools, no consensus has been reached in diagnosis of chronic pancreatitis. In this study we examined the hematological and biochemical parameters among 40 chronic pancreatitis patients within 18 to 67 yrs. ESR level and ALP activity was elevated in 40% cases. Serum amylase activity increased in 32 patients and it showed significant correlation with ALP (r=0.458, p=0.003), CA-19.9 (r=0.556, p<0.001), and calcium level (r=-0.472, p=0.002). Type IV collagen level in chronic pancreatitis also elevated (164.4 ± 55.5 ng/ml) and showed negative significant correlation with calcium level (r= -0.505, p=0.001). However, no significant correlation was observed between amylase activity and type IV collagen (r=0.289, p= 0.07).

Microwave-assisted extraction and pharmacological evaluation of polysaccharides from Posidonia oceanica.

PubMed

Ben Salem, Yosra; Abdelhamid, Amal; Mkadmini Hammi, Khaoula; Le Cerf, Didier; Bouraoui, Abderrahman; Majdoub, Hatem

2017-10-01

Microwave-assisted extraction was employed for the isolation of polysaccharides from Posidonia oceanica (PPO). The extracting parameters were optimized adopting response surface methodology. The highest polysaccharide yield (2.55 ± 0.09%), which is in concordance with the predicted value (2.76%), was obtained under the following conditions: extraction time 60 s, liquid-solid ratio of 50:1 (mL/g) and power of 800 W. This polysaccharide, with molecular weight of 524 KDa, characterized by gas chromatography-mass spectrometry showed that PPO was mainly composed of galactose, glucose, and arabinose with molar percentages 25.38, 24.37, and 21.64%, respectively. The pharmacological evaluation of PPO using animal models at the dose of 100 mg/kg indicated a significant anti-inflammatory activity with a percentage of inhibition of edema of 54.65% and a significant antinociceptive activity with 78.91% inhibition of writhing for peripheral analgesic activity and an increase in the hot plate reaction time for central analgesic activity.

Plasma fatty acid-binding protein 4 (FABP4) as a novel biomarker to predict gestational diabetes mellitus.

PubMed

Ning, Hui; Tao, Hong; Weng, Zhanping; Zhao, Xingbo

2016-12-01

Fatty acid-binding protein 4 (FABP4) is mainly expressed in adipocytes and macrophages and is demonstrated to be elevated in diabetes patients. The aim of this study was to evaluate the possible role of FABP4 in the diagnosis of GDM and to investigate the relationship between FABP4 and overweight, insulin resistance and inflammatory marker TNF-α. A total of 46 women with GDM and 55 age-matched pregnant women without GDM (non-GDM) were eligible for the study. Demographic and biochemical parameters and fasting venous blood samples of two groups were collected from all cases. Serum concentrations of FABP4 were determined using enzyme-linked immunosorbent assay (ELISA). The predictive value of Serum FABP4 level was evaluated using receiver operating characteristic curve (ROC curve) analysis. We found that the serum FABP4 levels were significantly higher in GDM compared to the non-GDM group. The area under the ROC curve assay yielded a satisfactory result of 0.94 (95 % confidence interval 0.90-0.98; p < 0.001). The best compromise between 86.96 % specificity and 89.09 % sensitivity was obtained with a cutoff value of 1.96 ng/mL for GDM diagnosis. Moreover, a significant positive correlation was observed between FABP4 and overweight, insulin resistance and TNF-α in pregnant women with GDM. These results suggest that serum FABP4 may potentially serve as a novel biomarker for the prediction of GDM.

Mathematical modeling of cell adhesion in shear flow: application to targeted drug delivery in inflammation and cancer metastasis.

PubMed

Jadhav, Sameer; Eggleton, Charles D; Konstantopoulos, Konstantinos

2007-01-01

Cell adhesion plays a pivotal role in diverse biological processes that occur in the dynamic setting of the vasculature, including inflammation and cancer metastasis. Although complex, the naturally occurring processes that have evolved to allow for cell adhesion in the vasculature can be exploited to direct drug carriers to targeted cells and tissues. Fluid (blood) flow influences cell adhesion at the mesoscale by affecting the mechanical response of cell membrane, the intercellular contact area and collisional frequency, and at the nanoscale level by modulating the kinetics and mechanics of receptor-ligand interactions. Consequently, elucidating the molecular and biophysical nature of cell adhesion requires a multidisciplinary approach involving the synthesis of fundamentals from hydrodynamic flow, molecular kinetics and cell mechanics with biochemistry/molecular cell biology. To date, significant advances have been made in the identification and characterization of the critical cell adhesion molecules involved in inflammatory disorders, and, to a lesser degree, in cancer metastasis. Experimental work at the nanoscale level to determine the lifetime, interaction distance and strain responses of adhesion receptor-ligand bonds has been spurred by the advent of atomic force microscopy and biomolecular force probes, although our current knowledge in this area is far from complete. Micropipette aspiration assays along with theoretical frameworks have provided vital information on cell mechanics. Progress in each of the aforementioned research areas is key to the development of mathematical models of cell adhesion that incorporate the appropriate biological, kinetic and mechanical parameters that would lead to reliable qualitative and quantitative predictions. These multiscale mathematical models can be employed to predict optimal drug carrier-cell binding through isolated parameter studies and engineering optimization schemes, which will be essential for developing effective drug carriers for delivery of therapeutic agents to afflicted sites of the host.

Neural Networks for Nodal Staging of Non–Small Cell Lung Cancer with FDG PET and CT: Importance of Combining Uptake Values and Sizes of Nodes and Primary Tumor

PubMed Central

Vesselle, Hubert J.

2014-01-01

Purpose To evaluate the effect of adding lymph node size to three previously explored artificial neural network (ANN) input parameters (primary tumor maximum standardized uptake value or tumor uptake, tumor size, and nodal uptake at N1, N2, and N3 stations) in the structure of the ANN. The goal was to allow the resulting ANN structure to relate lymph node uptake for size to primary tumor uptake for size in the determination of the status of nodes as human readers do. Materials and Methods This prospective study was approved by the institutional review board, and informed consent was obtained from all participants. The authors developed a back-propagation ANN with one hidden layer and eight processing units. The data set used to train the network included node and tumor size and uptake from 133 patients with non–small cell lung cancer with surgically proved N status. Statistical analysis was performed with the paired t test. Results The ANN correctly predicted the N stage in 99.2% of cases, compared with 72.4% for the expert reader (P < .001). In categorization of N0 and N1 versus N2 and N3 disease, the ANN performed with 99.2% accuracy versus 92.2% for the expert reader (P < .001). Conclusion The ANN is 99.2% accurate in predicting surgical-pathologic nodal status with use of four fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT)–derived parameters. Malignant and benign inflammatory lymph nodes have overlapping appearances at FDG PET/CT but can be differentiated by ANNs when the crucial input of node size is used. © RSNA, 2013 Online supplemental material is available for this article. PMID:24056403

Synthesis, biological evaluation and molecular modeling of novel series of pyridine derivatives as anticancer, anti-inflammatory and analgesic agents

NASA Astrophysics Data System (ADS)

Helal, M. H.; El-Awdan, S. A.; Salem, M. A.; Abd-elaziz, T. A.; Moahamed, Y. A.; El-Sherif, A. A.; Mohamed, G. A. M.

2015-01-01

This paper presents a combined synthesis; characterization, computational and biological activity studies of novel series of pyridines heterocyclic compounds. The compounds have been characterized by elemental analyses and spectral like IR, 1H NMR, 13C NMR and MS studies. Michael addition of substituted-2-methoxycarbonylacetanilide 2a,b on the α-substituted cinnamonitriles 3a-d gave the corresponding 2-pyridone derivatives 5-10. Structures of the titled compounds cited in this article were elucidated by spectrometric data (IR, 1H NMR, 13C NMR and MS). The molecular modeling of the synthesized compounds has been drawn and their molecular parameters were calculated. Also, valuable information is obtained from the calculation of molecular parameters including electronegativity, net dipole moment of the compounds, total energy, electronic energy, binding energy, HOMO and LUMO energy. Various in vitro antitumor as well as in vivo anti-inflammatory and analgesic activities of the synthesized compounds were investigated. Evaluation of anti-inflammatory activity of test compounds was performed using carrageenan induced paw edema in rats. All the tested compounds showed moderate to good activity. The SAR results indicate that all compounds showed moderate to good activity, among these 7 and 10 compounds having -N(CH3)2 group are most effective.

Evaluation of hyaluronan gel (Gengigel(®) ) as a topical applicant in the treatment of gingivitis.

PubMed

Sapna, Nadiger; Vandana, Kharidi Laxman

2011-08-01

  To clinically and histopathologically evaluate the anti-inflammatory effect of 0.2% hyaluronan gel alone and with mechanical therapy on gingivitis. The argyrophilic nucleolar organizer region staining technique was attempted to routinely determine its diagnostic and prognostic dependability for periodontal lesions.   In each of the 28 gingivitis patients, the four quadrants were subjected to different treatments: scaling, scaling + topical hyaluronan gel, only topical hyaluronan gel, and topical + intrasulcular hyaluronan gel. Clinical parameters were recorded at baseline, and on days 7, 14, and 21. Biopsies were taken from each quadrant, inflammatory infiltrates were graded, and the argyrophilic nucleolar organizer region count was measured before and after treatment.   A significant reduction was seen in clinical parameters, inflammatory infiltrates, and the argyrophilic nucleolar organizer region count within the groups. The effect of topical + intrasulcular gel was equivalent to scaling (P > 0.05). Topical + intrasulcular hyaluronan gel application demonstrated a better reduction than topical hyaluronan gel alone.   Hyaluronan gel is an effective topical agent for treating gingivitis, along with scaling and intrasulcular application. The argyrophilic nucleolar organizer region count can be used as a histopathological indicator in cases of non-responsive gingivitis to assess the severity of gingival inflammation. © 2011 Blackwell Publishing Asia Pty Ltd.

Diterpenoid alkaloids of Aconitum laciniatum and mitigation of inflammation by 14-O-acetylneoline in a murine model of ulcerative colitis

PubMed Central

Wangchuk, Phurpa; Navarro, Severine; Shepherd, Catherine; Keller, Paul A.; Pyne, Stephen G.; Loukas, Alex

2015-01-01

Aconitum laciniatum is used in Bhutanese traditional medicine for treating various chronic infections and inflammatory conditions. We carried out in-depth isolation and characterization of the phytochemicals from the root component and determined the anti-inflammatory effects of the isolated compounds against chemically-induced colitis in mice. Five diterpenoid alkaloids - pseudaconitine, 14-veratroylpseudaconine, 14-O-acetylneoline, neoline, and senbusine A - were isolated from A. laciniatum for the first time. Two of the alkaloids were tested for anti-inflammatory properties in the TNBS-induced colitis model in mice. Various parameters were measured to assess pathology including weight loss, clinical and macroscopic scores, histological structure and IFN-γ production in the gut. Of the two alkaloids tested, 14-O-acetylneoline showed significant protection against different parameters of colitic inflammation. Compared to control mice that received TNBS alone, mice treated with 14-O-acetylneoline experienced significantly less weight loss and had significantly lower clinical scores, macroscopic pathology and grades of histological inflammation. Moreover, colonic IFN-γ mRNA levels were significantly reduced in mice that received 14-O-acetylneoline compared to control mice that received TNBS alone. This alkaloid is now considered a novel anti-colitis drug lead compound. PMID:26240038

Impact of vitamin D supplementation on endothelial and inflammatory markers in adults: A systematic review.

PubMed

Agbalalah, Tari; Hughes, Stephen F; Freeborn, Ellen J; Mushtaq, Sohail

2017-10-01

This systematic review aims to evaluate randomised controlled trials (RCTs) investigating the effect of vitamin D supplementation on endothelial function and inflammation in adults. An electronic search of published randomised controlled trials, using Cochrane, Pubmed and Medline databases was conducted, with the search terms related to vitamin D and endothelial function. Inclusion criteria were RCTs in adult humans with a measure of vitamin D status using serum/plasma 25(OH)D and studies which administered the intervention through the oral route. Among the 1107 studies retrieved, 29 studies met the full inclusion criteria for this systematic review. Overall, 8 studies reported significant improvements in the endothelial/inflammatory biomarkers/parameters measured. However, in 2 out of the 8 studies, improvements were reported at interim time points, but improvements were absent post-intervention. The remaining 21 trial studies did not show significant improvements in the markers of interest measured. Evidence from the studies included in this systematic review did not demonstrate that vitamin D supplementation in adults, results in an improvement in circulating inflammatory and endothelial function biomarkers/parameters. This systematic review does not therefore support the use of vitamin D supplementation as a therapeutic or preventative measure for CVD in this respect. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Implications of polymorphonuclear neutrophils for ischemic stroke and intracerebral hemorrhage: Predictive value, pathophysiological consequences and utility as therapeutic target.

PubMed

Hermann, Dirk M; Kleinschnitz, Christoph; Gunzer, Matthias

2018-04-24

Polymorphonuclear neutrophil granulocytes (PMN) orchestrate the removal of cell debris in ischemic stroke and intracerebral hemorrhage. In both pathologies, high neutrophil to lymphocyte ratios in peripheral blood are predictive of poor outcome in human stroke patients. Following earlier studies indicating that the cerebral microvasculature forms an efficient barrier that impedes neutrophil brain entry, intravital microscopy and immunohistochemistry in the meantime unequivocally revealed the accumulation of PMN in the ischemic and hemorrhagic brain parenchyma. These studies provide definite evidence that PMN contribute to the degradation of the blood-brain barrier, predisposing the brain to secondary injury, edema, hemorrhage formation, hemorrhage growth and poor neurological recovery. Recent studies demonstrated the role of pro-inflammatory N1 neutrophils in brain edema and neurotoxicity, whereas anti-inflammatory N2 neutrophils were found to limit this excessive immune response, promoting neuronal survival and successful brain remodeling. In view of the recent failure of anti-inflammatory immunotherapies in clinical trials, strategies specifically modulating the brain accumulation, differentiation and action of PMN may open promising perspectives for stroke treatment. Copyright © 2018 Elsevier B.V. All rights reserved.

Combined use of serum MCP-1/IL-10 ratio and uterine artery Doppler index significantly improves the prediction of preeclampsia.

PubMed

Cui, Shihong; Gao, Yanan; Zhang, Linlin; Wang, Yuan; Zhang, Lindong; Liu, Pingping; Liu, Ling; Chen, Juan

2017-10-01

Monocyte chemotactic protein-1 (MCP-1, or CCL2) is a member of the chemokine subfamily involved in recruitment of monocytes in inflammatory tissues. IL-10 is a key regulator for maintaining the balance of anti-inflammatory and pro-inflammatory milieu at the feto-maternal interface. Doppler examination has been routinely performed for the monitoring and management of preeclampsia patients. This study evaluates the efficiency of these factors alone, or in combination, for the predication of preeclampsia. The serum levels of MCP-1 and IL-10 in 78 preeclampsia patients and 143 age-matched normal controls were measured. The Doppler ultrasonography was performed and Artery Pulsatility Index (PI) and Resistance Index (RI) were calculated for the same subjects. It was found that while the second-trimester serum MCP-1, IL-10, MCP-1/IL-10 ratio, PI, and RI showed some power in predicting preeclampsia, the combination of MCP-1/IL-10 and PI and RI accomplishes the highest efficiency, achieving an AUC of 0.973 (95% CI, 0.000-1.000, P<0.001), a sensitivity of 94%, and a specificity of 80%. The use of MCP-1/IL-10 ratio in combination with ultrasound findings appears to provide a promising modality for predicting preeclampsia. Future studies using a larger sample can be conducted to construct an algorithm capable of quantitative assessment on the risk of preeclampsia. Copyright © 2016 Elsevier B.V. All rights reserved.

C-reactive protein as a prognostic marker after lacunar stroke: levels of inflammatory markers in the treatment of stroke study.

PubMed

Elkind, Mitchell S V; Luna, Jorge M; McClure, Leslie A; Zhang, Yu; Coffey, Christopher S; Roldan, Ana; Del Brutto, Oscar H; Pretell, Edwin Javier; Pettigrew, L Creed; Meyer, Brett C; Tapia, Jorge; White, Carole; Benavente, Oscar R

2014-03-01

Inflammatory biomarkers predict incident and recurrent cardiac events, but their relationship to stroke prognosis is uncertain. We hypothesized that high-sensitivity C-reactive protein (hsCRP) predicts recurrent ischemic stroke after recent lacunar stroke. Levels of Inflammatory Markers in the Treatment of Stroke (LIMITS) was an international, multicenter, prospective ancillary biomarker study nested within Secondary Prevention of Small Subcortical Strokes (SPS3), a phase III trial in patients with recent lacunar stroke. Patients were assigned in factorial design to aspirin versus aspirin plus clopidogrel, and higher versus lower blood pressure targets. Patients had blood samples collected at enrollment and hsCRP measured using nephelometry at a central laboratory. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for recurrence risks before and after adjusting for demographics, comorbidities, and statin use. Among 1244 patients with lacunar stroke (mean age, 63.3±10.8 years), median hsCRP was 2.16 mg/L. There were 83 recurrent ischemic strokes (including 45 lacunes) and 115 major vascular events (stroke, myocardial infarction, and vascular death). Compared with the bottom quartile, those in the top quartile (hsCRP>4.86 mg/L) were at increased risk of recurrent ischemic stroke (unadjusted HR, 2.54; 95% CI, 1.30-4.96), even after adjusting for demographics and risk factors (adjusted HR, 2.32; 95% CI, 1.15-4.68). hsCRP predicted increased risk of major vascular events (top quartile adjusted HR, 2.04; 95% CI, 1.14-3.67). There was no interaction with randomized antiplatelet treatment. Among recent lacunar stroke patients, hsCRP levels predict the risk of recurrent strokes and other vascular events. hsCRP did not predict the response to dual antiplatelets. http://www.clinicaltrials.gov. Unique identifier: NCT00059306.

Sarcopenia in Elderly Diabetic Patients: Role of Dipeptidyl Peptidase 4 Inhibitors.

PubMed

Rizzo, Maria Rosaria; Barbieri, Michelangela; Fava, Ilaria; Desiderio, Manuela; Coppola, Carla; Marfella, Raffaele; Paolisso, Giuseppe

2016-10-01

Our study aimed to investigate the effect of dipeptidyl peptidase 4 inhibitors (DPP4-I) on sarcopenic parameters in elderly type 2 diabetic patients. All elderly diabetic patients were invited to present themselves at our outpatient Geriatric Centre to undergo to evaluation of glycemic, inflammatory, and sarcopenic parameters and to perform a meal test for glucagon-like peptide-1 analogue (GLP-1) activity evaluation. According to European Working Group on Sarcopenia in Older People (EWGSOP) criteria, sarcopenic parameters were assessed by bioelectrical impedance analysis (BIA) and Kern dynamometer and 4-m gait speed tests. All patients received standardized meals for the assessment of postprandial levels of GLP-1 activity. Data of 80 elderly diabetic patients treated with oral glucose-lowering drugs (DPP4-I or Sulfonylureas Group) for at least 24 months before enrollment were analyzed. The DPP4-I Group showed appropriate glycemic control, lower levels of inflammatory parameters, a significant and greater increase, during interprandial periods, of GLP-1 activity, and better sarcopenic parameters (fat-free mass, skeletal muscle mass, and related indices, muscle strength, and gait speed) compared with the Sulfonylureas Group. Univariate analysis showed that sarcopenic parameters correlated with glycemic control and with GLP-1 area under the curve values. Multivariate analysis confirms these relationships. The results are consistent with the hypothesis that DPP4-I use might have a positive effect on the loss of muscle mass and its function. Copyright © 2016 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

Dietary Inflammatory Index and Colorectal Cancer Risk-A Meta-Analysis.

PubMed

Shivappa, Nitin; Godos, Justyna; Hébert, James R; Wirth, Michael D; Piuri, Gabriele; Speciani, Attilio F; Grosso, Giuseppe

2017-09-20

Diet and chronic inflammation of the colon have been suggested to be risk factors in the development of colorectal cancer (CRC). The possible link between inflammatory potential of diet, measured through the Dietary Inflammatory Index (DII ® ), and CRC has been investigated in several populations across the world. The aim of this study was to conduct a meta-analysis on studies exploring this association. Data from nine studies were eligible, of which five were case-control and four were cohort studies. Results from meta-analysis showed a positive association between increasing DII scores, indicating a pro-inflammatory diet, and CRC. Individuals in the highest versus the lowest (reference) DII category showed an overall 40% increased risk of CRC with moderate evidence of heterogeneity [relative risk (RR) = 1.40, 95% confidence interval (CI): 1.26, 1.55; I ² = 69%, p < 0.001]. When analyzed as a continuous variable, results showed an increased risk of CRC of 7% for a 1-point increase in the DII score. Results remained unchanged when analyses were restricted to the four prospective studies. Results of our meta-analysis support the importance of adopting a healthier anti-inflammatory diet in preventing CRC. These results further substantiate the utility of DII as tool to characterize the inflammatory potential of diet and to predict CRC.

Exercise training improves autonomic function and inflammatory pattern in women with polycystic ovary syndrome (PCOS).

PubMed

Giallauria, Francesco; Palomba, Stefano; Maresca, Luigi; Vuolo, Laura; Tafuri, Domenico; Lombardi, Gaetano; Colao, Annamaria; Vigorito, Carlo; Francesco, Orio

2008-11-01

Polycystic ovary syndrome (PCOS) is a common female reproductive-age endocrine disease predominantly characterized by chronic anovulation, hyperandrogenism, insulin-resistance and low-grade inflammatory status. Exercise training (ET) favourably modulates cardiopulmonary function and insulin-sensitivity markers in PCOS women. The present study investigated the effects of ET on autonomic function and inflammatory pattern in PCOS women. Prospective baseline uncontrolled clinical study. One-hundred and eighty five PCOS women referred to our department were screened for the inclusion into the study protocol from March 2004 to July 2007. One-hundred and twenty four PCOS women met the criteria for the inclusion into the study protocol and were subdivided into two groups each composed of 62 patients: PCOS-T (trained) group underwent 3-month ET program, whereas PCOS-UnT (untrained) group did not. At baseline and at 3-month follow-up, hormonal and metabolic profile, cardiopulmonary parameters, autonomic function (as expressed by heart rate recovery, HRR) and inflammatory pattern [as expressed by C-reactive protein (CRP) and white blood cells (WBCs) count] were evaluated. PCOS-T showed a significant (P < 0.05) improvement in maximal oxygen consumption (VO(2max)) and in post-exercise HRR, and a significant (P < 0.001) decrease in CRP and WBCs; whereas no statistically significant changes of the same parameters were observed in PCOS-UnT. Multiple linear regression analysis showed that 3-month HRR is linearly related to the inclusion in training group (beta = 0.316, P < 0.001), VO(2max) (beta = 0.151, P = 0.032) and the ratio between glucose and insulin area under curve (AUC) (beta = 0.207, P = 0.003), and inversely related to body mass index (beta = -0.146, P = 0.046), insulin AUC (beta = -0.152, P = 0.032), CRP (beta = -0.165, P < 0.021), and WBCs count (beta = -0.175, P = 0.039). Exercise training improves autonomic function and inflammatory pattern in PCOS women.

Lipoxin A4 inhibits UV radiation-induced skin inflammation and oxidative stress in mice.

PubMed

Martinez, R M; Fattori, V; Saito, P; Melo, C B P; Borghi, S M; Pinto, I C; Bussmann, A J C; Baracat, M M; Georgetti, S R; Verri, W A; Casagrande, R

2018-04-27

Lipoxin A4 (LXA 4 ) is a metabolic product of arachidonic acid. Despite potent anti-inflammatory and pro-resolution activities, it remains to be determined if LXA 4 has effect on ultraviolet (UV) radiation-induced skin inflammation. To investigate the effects of systemic administration with LXA 4 on UV radiation-induced inflammation and oxidative damage in the skin of mice. Varied parameters of inflammation and oxidative stress in the skin of mice were evaluated after UV radiation (4.14 J/cm 2 ). Pretreatment with LXA 4 significantly inhibited UV radiation-induced skin edema and myeloperoxidase activity. LXA 4 efficacy was enhanced by increasing the time of pre-treatment to up to 72 h. LXA 4 reduced UV radiation-induced skin edema, neutrophil recruitment (myeloperoxidase activity and LysM-eGFP + cells), MMP-9 activity, deposition of collagen fibers, epidermal thickness, sunburn cell counts, and production of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-33). Depending on the time point, LXA 4 increased the levels of anti-inflammatory cytokines (TGF-β and IL-10). LXA 4 significantly attenuated UV radiation-induced oxidative damage returning the oxidative status to baseline levels in parameters such as ferric reducing ability, scavenging of free radicals, GSH levels, catalase activity and superoxide anion production. LXA 4 also reduced UV radiation-induced gp91 phox [nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) subunit] mRNA expression and enhanced nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream target enzyme nicotinamide adenine dinucleotide (phosphate) quinone oxidoreductase (Nqo1) mRNA expression. LXA 4 inhibited UV radiation-induced skin inflammation by diminishing pro-inflammatory cytokine production and oxidative stress as well as inducing anti-inflammatory cytokines and Nrf2. Copyright © 2018. Published by Elsevier B.V.

Influence of glucoregulation quality on C-reactive protein, interleukin-6 and tumor necrosis factor-alpha level in patients with diabetes type 1.

PubMed

Mitrović, Milena; Ilić, Tatjana; Stokić, Edita; Paro, Jovanka Novaković; Naglić, Dragana Tomić; Bajkin, Ivana; Icin, Tijana

2011-09-01

Results of studies which have proved an increased inflammatory activity in diabetes type 1, have been published over recent years. One of possible mechanisms that are used to explain chronic inflammation in diabetes is the state of hyperglycemia leading to the enhanced synthesis of glycosylation end products (AGEs) which activate macrophages, increase the oxidative stress and affect the synthesis of interleukins (IL-1, IL-6), tumor necrosis factor-alpha (TNF-alpha) and C-reactive protein (CRP). The aim of the study was to determine the inflammatory markers (CRP, IL-6, TNF-alpha) in patients with diabetes type 1 and to establish their correlation with glucoregulation parameters and other cardiovascular risk factors as well as to compare them with the healthy controls. The study included 76 patients with diabetes type 1 and 30 healthy controls. We determined values of inflammatory markers (CRP, IL-6, TNF-alpha) and glucoregulation parameters (fasting glucose HbA(1c)). The values of CRP (p = 0.014), IL-6 (p = 0.020) and TNF-alpha (p = 0.037) were statistically significantly higher in the diabetic patients than in the healthy controls. There was a positive correlation between CRP with postprandial glycemia (p = 0.004); the multivariate regression analysis revealed a statistically significant correlation between CRP and age (p = 0.001), smoking (p = 0.055), fasting glucose (p = 0.021) and triglycerides (p = 0.048) as well as between IL-6 and LDL-cholesterol (p = 0.009). No statistically significant correlations were found between glycosilated hemoglobin (HbA(1c)) and the inflammatory markers (CRP, IL-6 and TNF-alpha). The patients with type 1 diabetes were found to have a low level of inflammatory activity manifested by the increased values of CRP, IL-6 and TNF-alpha.

Anti-inflammatory and antioxidant activities of aqueous extract of Cecropia glaziovii leaves.

PubMed

Müller, Simony Davet; Florentino, Drielly; Ortmann, Caroline Flach; Martins, Fernanda Amélia; Danielski, Lucineia Gainski; Michels, Monique; de Souza Constantino, Larissa; Petronilho, Fabricia; Reginatto, Flavio Henrique

2016-06-05

Cecropia glaziovii Sneth leaves extract is widely used as a traditional folk medicine in Brazil, especially for the treatment of diabetes, and as an antihypertensive and antiinflammatory agent. To investigate the anti-inflammatory and antioxidant properties of crude aqueous extract (CAE) of C. glaziovii leaves. The in vivo anti-inflammatory and antioxidant effect of the CAE (10-300mg/kg, intragastrically) was investigated in the animal model of pleurisy. The cell migration, proinflammatory cytokines (TNF-α, IL-1β and IL-6), nitrite/nitrate concentration, myeloperoxidase (MPO) activity, oxidative damage in lipids and proteins, lactate dehydrogenase (LDH) activity and total protein content were also analyzed. Furthermore, the in vitro antioxidant activity of CAE was evaluated by the inhibition of formation of thiobarbituric acid reactive substances (TBARS), induced by free radical generators (H2O2, FeSO4 and AAPH) on a lipid-rich substrate. Hence, the chemical characterizarion of CAE by HPLC was therefore performed. The results showed that the inflammatory process caused by the administration of carragenin (Cg) into the pleural cavity resulted in a substantial increase in inflammatory parameters and oxidative damage. These levels seems to be reversed after CAE treatment in animals with similar results to Dexamethasone (Dex) treatment. Further, the CAE was effective in reducing proinflammatory cytokines, cell infiltrate, MPO activity, nitrite/nitrate concentration, LDH activity, and total protein levels with concomitant attenuation of all parameters associated with oxidative damage induced by Cg. Finally, the CAE presented in vitro antioxidant activity induced by free radical generators at all the concentrations investigated. HPLC analysis confirmed the presence of chlorogenic acid and C-glycosylflavonoids (isoorientin and isovitexin) as the major compounds of the CAE. CAE of C. glaziovii exerts significant antiinflammatory and antioxidant activities and this effect can be attributed, at least in part, to the presence of chlorogenic acid and the C-glycosylflavonoids. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Seismic activity prediction using computational intelligence techniques in northern Pakistan

NASA Astrophysics Data System (ADS)

Asim, Khawaja M.; Awais, Muhammad; Martínez-Álvarez, F.; Iqbal, Talat

2017-10-01

Earthquake prediction study is carried out for the region of northern Pakistan. The prediction methodology includes interdisciplinary interaction of seismology and computational intelligence. Eight seismic parameters are computed based upon the past earthquakes. Predictive ability of these eight seismic parameters is evaluated in terms of information gain, which leads to the selection of six parameters to be used in prediction. Multiple computationally intelligent models have been developed for earthquake prediction using selected seismic parameters. These models include feed-forward neural network, recurrent neural network, random forest, multi layer perceptron, radial basis neural network, and support vector machine. The performance of every prediction model is evaluated and McNemar's statistical test is applied to observe the statistical significance of computational methodologies. Feed-forward neural network shows statistically significant predictions along with accuracy of 75% and positive predictive value of 78% in context of northern Pakistan.

trans-Chalcone, a flavonoid precursor, inhibits UV-induced skin inflammation and oxidative stress in mice by targeting NADPH oxidase and cytokine production.

PubMed

Martinez, Renata M; Pinho-Ribeiro, Felipe A; Steffen, Vinicius S; Caviglione, Carla V; Fattori, Victor; Bussmann, Allan J C; Bottura, Carolina; Fonseca, Maria J V; Vignoli, Josiane A; Baracat, Marcela M; Georgetti, Sandra R; Verri, Waldiceu A; Casagrande, Rubia

2017-07-01

trans-Chalcone is a plant flavonoid precursor, which lacks broad investigation on its biological activity in inflammatory processes. In the present study, anti-inflammatory and antioxidant mechanisms of systemic administration with trans-chalcone, a flavonoid precursor, on ultraviolet (UV) irradiation-induced skin inflammation and oxidative stress in hairless mice were investigated by the following parameters: skin edema, myeloperoxidase activity (neutrophil marker), matrix metalloproteinase-9 activity, reduced glutathione levels, catalase activity, lipid peroxidation products, superoxide anion production, gp 91phox (NADPH oxidase subunit) mRNA expression by quantitative PCR and cytokine production by ELISA. Systemic treatment with trans-chalcone inhibited skin inflammation by reducing skin edema and neutrophil recruitment, and also inhibited matrix metalloproteinase-9 activity. trans-Chalcone also inhibited oxidative stress, gp 91phox mRNA expression, and the production of a wide range of pro-inflammatory cytokines, while it did not affect anti-inflammatory cytokines induced by UV irradiation. However, trans-chalcone did not prevent oxidative stress in vitro, suggesting that its in vivo effect is more related to anti-inflammatory properties rather than a direct antioxidant effect. In conclusion, treatment with trans-chalcone inhibited UV-induced skin inflammation resulting in oxidative stress inhibition in vivo. Therefore, systemic supplementation with this compound may represent an important therapeutic approach in inflammatory skin diseases induced by UV irradiation.

Immune, inflammatory and cardiovascular consequences of sleep restriction and recovery.

PubMed

Faraut, Brice; Boudjeltia, Karim Zouaoui; Vanhamme, Luc; Kerkhofs, Myriam

2012-04-01

In addition to its effects on cognitive function, compelling evidence links sleep loss to alterations in the neuroendocrine, immune and inflammatory systems with potential negative public-health ramifications. The evidence to suggest that shorter sleep is associated with detrimental health outcomes comes from both epidemiological and experimental sleep deprivation studies. This review will focus on the post-sleep deprivation and recovery changes in immune and inflammatory functions in well-controlled sleep restriction laboratory studies. The data obtained indicate non-specific activation of leukocyte populations and a state of low-level systemic inflammation after sleep loss. Furthermore, one night of recovery sleep does not allow full recovery of a number of these systemic immune and inflammatory markers. We will speculate on the mechanism(s) that link(s) sleep loss to these responses and to the progression of cardiovascular disease. The immune and inflammatory responses to chronic sleep restriction suggest that chronic exposure to reduced sleep (<6 h/day) and insufficient time for recovery sleep could have gradual deleterious effects, over years, on cardiovascular pathogenesis with a heightened risk in women and in night and shift workers. Finally, we will examine countermeasures, e.g., napping or sleep extension, which could improve the recovery processes, in terms of alertness and immune and inflammatory parameters, after sleep restriction. Copyright © 2011 Elsevier Ltd. All rights reserved.

Inflammatory potential of diet, weight gain, and incidence of overweight/obesity: The SUN cohort.

PubMed

Ramallal, Raúl; Toledo, Estefanía; Martínez, J Alfredo; Shivappa, Nitin; Hébert, James R; Martínez-González, Miguel A; Ruiz-Canela, Miguel

2017-06-01

This study prospectively assessed the association of the inflammatory potential of a diet using the dietary inflammatory index (DII) with average yearly weight changes and incident overweight/obesity. Seven thousand and twenty-seven university graduates with body mass index <25 from the Seguimiento Universidad de Navarra (SUN) cohort were followed up during a median of 8.1 years. The DII, a validated tool based on scientific evidence to appraise the relationship between dietary parameters and inflammatory biomarkers, was used. A validated food-frequency questionnaire was used to assess intake of total energy, food, and nutrients, from which DII scores were calculated at baseline and after 10 years of follow-up. After a median follow-up of 8.1 years, 1,433 incident cases of overweight or obesity were observed. Hazard ratios for overweight/obesity were calculated, including multivariable time-dependent Cox regression models with repeated measures of diet. The hazard ratio for subjects in the highest quartile (most pro-inflammatory diet) was 1.32 (95% confidence interval 1.08-1.60) compared with participants in the lowest quartile (most anti-inflammatory diet), with a significant linear dose-response relationship (P = 0.004). Consistently, increases in average yearly weight gains were significantly associated with proinflammatory diets. A proinflammatory diet was significantly associated with a higher annual weight gain and higher risk of developing new-onset overweight or obesity. © 2017 The Obesity Society.

Evaluation of nonsurgical periodontal therapy in chronic periodontitis patients with anemia by estimating hematological parameters and high-sensitivity C-reactive protein levels

PubMed Central

Musalaiah, S. V. V. S.; Anupama, M.; Nagasree, M.; Krishna, Ch. Murali; Kumar, Aravind; Kumar, P. Mohan

2014-01-01

Background: Periodontal tissues mount an immune inflammatory response to bacteria and their products. Certain inflammatory cytokines produced during periodontal inflammation increase the production of acute phase proteins like high‑sensitivity C‑reactive protein (hs‑CRP) and can depress erythropoietin production leading to the development of anemia. Aim: The aim of this study is to investigate the efficacy of nonsurgical periodontal therapy on red blood cell (RBC) parameters and hs-CRP in chronic periodontitis patients with anemia. Materials and Methods: This is a longitudinal, interventional study with 6-month follow-up. A total of 30 subjects with anemia and chronic periodontitis with age group of 33-55 years were selected by screening hemoglobin (Hb) levels and examining periodontal findings. The clinical parameters plaque index (PI), gingival index (GI), probing pocket depth (PPD) and clinical attachment level (CAL) were recorded at baseline. Laboratory blood investigations were performed to evaluate RBC count, Hb, packed cell volume (PCV), erythrocyte sedimentation rate (ESR) and red cell indices, hs-CRP at baseline. Nonsurgical periodontal therapy was performed for all patients. Patients were recalled after 6 months. The clinical and hematological parameters were re-evaluated to analyze the changes after nonsurgical periodontal therapy. Results: The results showed that there was a significant increase in Hb levels, RBC count and PCV from baseline to 6 months after nonsurgical periodontal therapy. There is significant decrease in levels of ESR and hs-CRP levels after nonsurgical periodontal therapy indicating resolution of periodontal inflammation. There is a significant decrease in PPD, scores of PI and GI and significant increase in CAL gain. Minimal changes in mean corpuscular volume, mean corpuscular hemoglobin (MCH) and MCH concentration indicated that the lower values of red cell parameters are not due to any vitamin and mineral deficiencies, but secondary to the chronic inflammatory changes associated with chronic periodontal disease. Conclusion: The present study strengthens the hypothesis that chronic periodontitis may lead to anemia and provides evidence that nonsurgical periodontal therapy can improve the anemic status and reduce levels of hs-CRP in patients with chronic periodontitis. PMID:25210388

Evaluation of nonsurgical periodontal therapy in chronic periodontitis patients with anemia by estimating hematological parameters and high-sensitivity C-reactive protein levels.

PubMed

Musalaiah, S V V S; Anupama, M; Nagasree, M; Krishna, Ch Murali; Kumar, Aravind; Kumar, P Mohan

2014-07-01

Periodontal tissues mount an immune inflammatory response to bacteria and their products. Certain inflammatory cytokines produced during periodontal inflammation increase the production of acute phase proteins like high‑sensitivity C‑reactive protein (hs‑CRP) and can depress erythropoietin production leading to the development of anemia. The aim of this study is to investigate the efficacy of nonsurgical periodontal therapy on red blood cell (RBC) parameters and hs-CRP in chronic periodontitis patients with anemia. This is a longitudinal, interventional study with 6-month follow-up. A total of 30 subjects with anemia and chronic periodontitis with age group of 33-55 years were selected by screening hemoglobin (Hb) levels and examining periodontal findings. The clinical parameters plaque index (PI), gingival index (GI), probing pocket depth (PPD) and clinical attachment level (CAL) were recorded at baseline. Laboratory blood investigations were performed to evaluate RBC count, Hb, packed cell volume (PCV), erythrocyte sedimentation rate (ESR) and red cell indices, hs-CRP at baseline. Nonsurgical periodontal therapy was performed for all patients. Patients were recalled after 6 months. The clinical and hematological parameters were re-evaluated to analyze the changes after nonsurgical periodontal therapy. The results showed that there was a significant increase in Hb levels, RBC count and PCV from baseline to 6 months after nonsurgical periodontal therapy. There is significant decrease in levels of ESR and hs-CRP levels after nonsurgical periodontal therapy indicating resolution of periodontal inflammation. There is a significant decrease in PPD, scores of PI and GI and significant increase in CAL gain. Minimal changes in mean corpuscular volume, mean corpuscular hemoglobin (MCH) and MCH concentration indicated that the lower values of red cell parameters are not due to any vitamin and mineral deficiencies, but secondary to the chronic inflammatory changes associated with chronic periodontal disease. The present study strengthens the hypothesis that chronic periodontitis may lead to anemia and provides evidence that nonsurgical periodontal therapy can improve the anemic status and reduce levels of hs-CRP in patients with chronic periodontitis.

Protective Effect of Tropisetron on Rodent Hepatic Injury after Trauma-Hemorrhagic Shock through P38 MAPK-Dependent Hemeoxygenase-1 Expression

PubMed Central

Hwang, Tsong-Long; Tsai, Yung-Fong

2012-01-01

Tropisetron can decrease inflammatory cell responses and alleviate organ damage caused by trauma-hemorrhage, but the mechanism of these effects remains unknown. The p38 mitogen-activated protein kinase/hemeoxygenase-1 (p38 MAPK/HO-1) pathway exerts anti-inflammatory effects on different tissues. The aim of this study was to investigate whether p38 MAPK/HO-1 plays any role in the tropisetron-mediated attenuation of hepatic injury after trauma-hemorrhage. Male Sprague-Dawley rats underwent trauma-hemorrhage (mean blood pressure maintained at approximately 35–40 mmHg for 90 min), followed by fluid resuscitation. During resuscitation, several treatment regimens were administered: four doses of tropisetron alone (0.1, 0.3, 1, 3 mg/kg body weight), or a single dose of tropisetron (1 mg/kg body weight) with and without a p38 MAPK inhibitor (SB-203580, 2 mg/kg body weight) or HO antagonist (chromium-mesoporphyrin, 2.5 mg/kg body weight). Various parameters were measured, and the animals were sacrificed at 24 h post-resuscitation. The results showed that trauma-hemorrhage increased the following parameters: plasma concentrations of aspartate (AST) and alanine aminotransferases (ALT), hepatic myeloperoxidase (MPO) activity, and levels of cytokine-induced neutrophil chemoattractant-1 and -3 (CINC-1 and CINC-3), intercellular adhesion molecule-1 (ICAM-1), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and macrophage inflammatory protein-1α (MIP-1α). These parameters were significantly improved in the tropisetron-treated rats subjected to trauma-hemorrhage. Tropisetron treatment also increased hepatic p38 MAPK and HO-1 expression compared with vehicle-treated trauma-hemorrhaged rats. Co-administration of SB-203580 or chromium-mesoporphyrin with tropisetron abolished the tropisetron-induced beneficial effects on the above parameters and hepatic injury. These results suggest that the protective effect of tropisetron administration on alleviation of hepatic injury after trauma-hemorrhage is likely mediated through p38 MAPK-dependent HO-1 expression. PMID:23285267

Protective effect of tropisetron on rodent hepatic injury after trauma-hemorrhagic shock through P38 MAPK-dependent hemeoxygenase-1 expression.

PubMed

Liu, Fu-Chao; Yu, Huang-Ping; Hwang, Tsong-Long; Tsai, Yung-Fong

2012-01-01

Tropisetron can decrease inflammatory cell responses and alleviate organ damage caused by trauma-hemorrhage, but the mechanism of these effects remains unknown. The p38 mitogen-activated protein kinase/hemeoxygenase-1 (p38 MAPK/HO-1) pathway exerts anti-inflammatory effects on different tissues. The aim of this study was to investigate whether p38 MAPK/HO-1 plays any role in the tropisetron-mediated attenuation of hepatic injury after trauma-hemorrhage. Male Sprague-Dawley rats underwent trauma-hemorrhage (mean blood pressure maintained at approximately 35-40 mmHg for 90 min), followed by fluid resuscitation. During resuscitation, several treatment regimens were administered: four doses of tropisetron alone (0.1, 0.3, 1, 3 mg/kg body weight), or a single dose of tropisetron (1 mg/kg body weight) with and without a p38 MAPK inhibitor (SB-203580, 2 mg/kg body weight) or HO antagonist (chromium-mesoporphyrin, 2.5 mg/kg body weight). Various parameters were measured, and the animals were sacrificed at 24 h post-resuscitation. The results showed that trauma-hemorrhage increased the following parameters: plasma concentrations of aspartate (AST) and alanine aminotransferases (ALT), hepatic myeloperoxidase (MPO) activity, and levels of cytokine-induced neutrophil chemoattractant-1 and -3 (CINC-1 and CINC-3), intercellular adhesion molecule-1 (ICAM-1), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and macrophage inflammatory protein-1α (MIP-1α). These parameters were significantly improved in the tropisetron-treated rats subjected to trauma-hemorrhage. Tropisetron treatment also increased hepatic p38 MAPK and HO-1 expression compared with vehicle-treated trauma-hemorrhaged rats. Co-administration of SB-203580 or chromium-mesoporphyrin with tropisetron abolished the tropisetron-induced beneficial effects on the above parameters and hepatic injury. These results suggest that the protective effect of tropisetron administration on alleviation of hepatic injury after trauma-hemorrhage is likely mediated through p38 MAPK-dependent HO-1 expression.

Biochemical parameters as monitoring markers of the inflammatory reaction by patients with chronic obstructive pulmonary disease (COPD)

PubMed

Lenártová, Petra; Kopčeková, Jana; Gažarová, Martina; Mrázová, Jana; Wyka, Joanna

Chronic obstructive pulmonary disease (COPD) is an airway inflammatory disease caused by inhalation of toxic particles, mainly cigarette smoking, and now is accepted as a disease associated with systemic characteristics. The aim of this work was to investigate and compare selected biochemical parameters in patients with and without COPD. Observation group consisted of clinically stable patients with COPD (n = 60). The control group was healthy persons from the general population, without COPD, who were divided into two subgroups – smokers (n = 30) and non-smokers (n = 30). Laboratory parameters were investigated by automated clinical chemistry analyzer LISA 200th. Albumin in our measurements showed an average value of 39.55 g.l-1 in the patient population; 38.89 g.l-1 in smokers and in non-smokers group 44.65 g.l-1. The average value of pre-albumin in the group of patients was 0.28 ± 0.28 g.l-1 and 0.30 ± 0.04 g.l-1 in smokers group. The average value of the orosomucoid in patients was about 1.11 ± 0.90 mg.ml-1. In the group of smokers, the mean value of orosomucoid was 0.60 ± 0.13 mg.ml-1. The level of C-reactive protein (CRP) in the patient group reached an average value of 15.31 ± 22.04 mg.l-1, in the group of smokers was 5.18 ± 4.58 mg. l-1. Prognostic inflammatory and nutritional index (PINI) in the group of patients showed a mean value of 4.65 ± 10.77 and 0.026 ± 0.025 in smokers. The results of this work show, that the values of index PINI in COPD patients are significantly higher than in smokers (P <0.001). This along with other monitored parameters indicative inflammation as well as a catabolic process that occurs in the organism of patients with COPD.

Prediction of compressibility parameters of the soils using artificial neural network.

PubMed

Kurnaz, T Fikret; Dagdeviren, Ugur; Yildiz, Murat; Ozkan, Ozhan

2016-01-01

The compression index and recompression index are one of the important compressibility parameters to determine the settlement calculation for fine-grained soil layers. These parameters can be determined by carrying out laboratory oedometer test on undisturbed samples; however, the test is quite time-consuming and expensive. Therefore, many empirical formulas based on regression analysis have been presented to estimate the compressibility parameters using soil index properties. In this paper, an artificial neural network (ANN) model is suggested for prediction of compressibility parameters from basic soil properties. For this purpose, the input parameters are selected as the natural water content, initial void ratio, liquid limit and plasticity index. In this model, two output parameters, including compression index and recompression index, are predicted in a combined network structure. As the result of the study, proposed ANN model is successful for the prediction of the compression index, however the predicted recompression index values are not satisfying compared to the compression index.

Inflammatory licensed equine MSCs are chondroprotective and exhibit enhanced immunomodulation in an inflammatory environment.

PubMed

Cassano, Jennifer M; Schnabel, Lauren V; Goodale, Margaret B; Fortier, Lisa A

2018-04-03

Inflammatory licensed mesenchymal stem cells (MSCs) have the ability to promote functional tissue repair. This study specifically sought to understand how the recipient tissue environment reciprocally affects MSC function. Inflammatory polarized macrophages, modeling an injured tissue environment, were exposed to licensed MSCs, and the resultant effects of MSC immunomodulation and functionality of the MSC secretome on chondrocyte homeostasis were studied. Inflammatory licensed MSCs were generated through priming with either IFN-γ or polyinosinic:polycytidylic acid (poly I:C). Macrophages were polarized to an inflammatory phenotype using IFN-γ. Licensed MSCs were co-cultured with inflammatory macrophages and immunomodulation of MSCs was assessed in a T-cell proliferation assay. MSC gene expression was analyzed for changes in immunogenicity (MHC-I, MHC-II), immunomodulation (IDO, PTGS2, NOS2, TGF-β1), cytokine (IL-6, IL-8), and chemokine (CCL2, CXCL10) expression. Macrophages were assessed for changes in cytokine (IL-6, IL-10, TNF-α, IFN-γ) and chemokine (CCL2, CXCL10) expression. Conditioned medium representing the secretome from IFN-γ or poly I:C-primed MSCs was applied to IL-1β-stimulated chondrocytes, which were analyzed for catabolic (IL-6, TNF-α, CCL2, CXCL10, MMP-13, PTGS2) and matrix synthesis (ACAN, COL2A1) genes. IFN-γ-primed MSCs had a superior ability to suppress T-cell proliferation compared to naïve MSCs, and this ability was maintained following exposure to proinflammatory macrophages. In naïve and licensed MSCs exposed to inflammatory macrophages, MHC-I and MHC-II gene expression was upregulated. The secretome from licensed MSCs was chondroprotective and downregulated inflammatory gene expression in IL-1β-stimulated chondrocytes. In-vitro inflammatory licensing agents enhanced the immunomodulatory ability of MSCs exposed to inflammatory macrophages, and the resultant secretome was biologically active, protecting chondrocytes from catabolic stimulation. Use of licensing agents produced a more consistent immunomodulatory MSC population compared to exposure to inflammatory macrophages. The clinical implications of this study are that in-vitro licensing prior to therapeutic application could result in a more predictable immunomodulatory and reparative response to MSC therapy compared to in-vivo inflammatory licensing by the recipient environment.

The Effect of Nondeterministic Parameters on Shock-Associated Noise Prediction Modeling

NASA Technical Reports Server (NTRS)

Dahl, Milo D.; Khavaran, Abbas

2010-01-01

Engineering applications for aircraft noise prediction contain models for physical phenomenon that enable solutions to be computed quickly. These models contain parameters that have an uncertainty not accounted for in the solution. To include uncertainty in the solution, nondeterministic computational methods are applied. Using prediction models for supersonic jet broadband shock-associated noise, fixed model parameters are replaced by probability distributions to illustrate one of these methods. The results show the impact of using nondeterministic parameters both on estimating the model output uncertainty and on the model spectral level prediction. In addition, a global sensitivity analysis is used to determine the influence of the model parameters on the output, and to identify the parameters with the least influence on model output.

Uncertainty quantification and propagation in dynamic models using ambient vibration measurements, application to a 10-story building

NASA Astrophysics Data System (ADS)

Behmanesh, Iman; Yousefianmoghadam, Seyedsina; Nozari, Amin; Moaveni, Babak; Stavridis, Andreas

2018-07-01

This paper investigates the application of Hierarchical Bayesian model updating for uncertainty quantification and response prediction of civil structures. In this updating framework, structural parameters of an initial finite element (FE) model (e.g., stiffness or mass) are calibrated by minimizing error functions between the identified modal parameters and the corresponding parameters of the model. These error functions are assumed to have Gaussian probability distributions with unknown parameters to be determined. The estimated parameters of error functions represent the uncertainty of the calibrated model in predicting building's response (modal parameters here). The focus of this paper is to answer whether the quantified model uncertainties using dynamic measurement at building's reference/calibration state can be used to improve the model prediction accuracies at a different structural state, e.g., damaged structure. Also, the effects of prediction error bias on the uncertainty of the predicted values is studied. The test structure considered here is a ten-story concrete building located in Utica, NY. The modal parameters of the building at its reference state are identified from ambient vibration data and used to calibrate parameters of the initial FE model as well as the error functions. Before demolishing the building, six of its exterior walls were removed and ambient vibration measurements were also collected from the structure after the wall removal. These data are not used to calibrate the model; they are only used to assess the predicted results. The model updating framework proposed in this paper is applied to estimate the modal parameters of the building at its reference state as well as two damaged states: moderate damage (removal of four walls) and severe damage (removal of six walls). Good agreement is observed between the model-predicted modal parameters and those identified from vibration tests. Moreover, it is shown that including prediction error bias in the updating process instead of commonly-used zero-mean error function can significantly reduce the prediction uncertainties.

Characterization of atopic skin and the effect of a hyperforin-rich cream by laser scanning microscopy.

PubMed

Meinke, Martina C; Richter, Heike; Kleemann, Anke; Lademann, Juergen; Tscherch, Kathrin; Rohn, Sascha; Schempp, Christoph M

2015-05-01

Atopic dermatitis (AD) is a multifactorial inflammatory skin disease that affects both children and adults in an increasing manner. The treatment of AD often reduces subjective skin parameters, such as itching, dryness, and tension, but the inflammation cannot be cured. Laser scanning microscopy was used to investigate the skin surface, epidermal, and dermal characteristics of dry and atopic skin before and after treatment with an ointment rich in hyperforin, which is known for its anti-inflammatory effects. The results were compared to subjective parameters and transepidermal water loss, stratum corneum moisture, and stratum corneum lipids. Using biophysical methods, in particular laser scanning microscopy, it was found that atopic skin has distinct features compared to healthy skin. Treatment with a hyperforin-rich ointment resulted in an improvement of the stratum corneum moisture, skin surface dryness, skin lipids, and the subjective skin parameters, indicating that the barrier is stabilized and improved by the ointment. But in contrast to the improved skin surface, the inflammation in the deeper epidermis/dermis often continues to exist. This could be clearly shown by the reflectance confocal microscopy (RCM) measurements. Therefore, RCM measurements could be used to investigate the progress in treatment of atopic dermatitis.

Characterization of atopic skin and the effect of a hyperforin-rich cream by laser scanning microscopy

NASA Astrophysics Data System (ADS)

Meinke, Martina C.; Richter, Heike; Kleemann, Anke; Lademann, Juergen; Tscherch, Kathrin; Rohn, Sascha; Schempp, Christoph M.

2015-05-01

Atopic dermatitis (AD) is a multifactorial inflammatory skin disease that affects both children and adults in an increasing manner. The treatment of AD often reduces subjective skin parameters, such as itching, dryness, and tension, but the inflammation cannot be cured. Laser scanning microscopy was used to investigate the skin surface, epidermal, and dermal characteristics of dry and atopic skin before and after treatment with an ointment rich in hyperforin, which is known for its anti-inflammatory effects. The results were compared to subjective parameters and transepidermal water loss, stratum corneum moisture, and stratum corneum lipids. Using biophysical methods, in particular laser scanning microscopy, it was found that atopic skin has distinct features compared to healthy skin. Treatment with a hyperforin-rich ointment resulted in an improvement of the stratum corneum moisture, skin surface dryness, skin lipids, and the subjective skin parameters, indicating that the barrier is stabilized and improved by the ointment. But in contrast to the improved skin surface, the inflammation in the deeper epidermis/dermis often continues to exist. This could be clearly shown by the reflectance confocal microscopy (RCM) measurements. Therefore, RCM measurements could be used to investigate the progress in treatment of atopic dermatitis.

Nasal lavage, blood or sputum: Which is best for phenotyping asthma?

PubMed

de Farias, Camyla F; Amorim, Maria M F; Dracoulakis, Michel; Caetano, Lilian B; Santoro, Ilka L; Fernandes, Ana L G

2017-05-01

Determination of asthma phenotypes, particularly inflammatory phenotypes, helps guide treatment and management of this heterogeneous disease. Induced sputum cytology has been the gold standard for determination of inflammatory phenotypes, but sputum induction is fairly invasive and technically challenging. Blood and nasal lavage cytology have been suggested as substitutes, but have not been fully verified. The aim of this study is to determine the accuracy of blood and nasal lavage cytometry as indicators of inflammatory phenotypes in asthma. Clinical evaluation, Asthma Control Questionnaire (ACQ) and spirometry were performed for 121 adult asthma patients, and blood, nasal lavage and induced sputum samples were taken. Eosinophils and neutrophils were counted in three samples from each subject. Inflammatory phenotypes (eosinophilic, neutrophilic, mixed and paucicellular) and cells counts were analysed using Venn diagram and receiver operating characteristic (ROC) curve, respectively. ACQ score, spirometry and bronchodilator response did not differ among subjects with different inflammatory phenotypes. Inflammatory phenotypes defined by nasal lavage cytometry were in better concordance than those defined by blood cell counts with phenotypes determined by sputum cytology, and were significantly correlated with sputum phenotypes. For eosinophilia, nasal lavage cytology showed better accuracy than blood cytology (area under the curve (AUC): 0.89 vs 0.65). For all phenotypes, sensitivity and positive and negative predictive power were higher for nasal lavage cytometry than for blood. Blood cell counts gave a high level of false positives for all inflammatory phenotypes. We recommend nasal lavage cytology over blood cell count as a substitute for sputum cytology to identify inflammatory phenotypes in asthma. © 2016 Asian Pacific Society of Respirology.

Anti-inflammatory effects of nitric oxide-releasing hydrocortisone NCX 1022, in a murine model of contact dermatitis

PubMed Central

Hyun, Eric; Bolla, Manlio; Steinhoff, Martin; Wallace, John L; Soldato, Piero del; Vergnolle, Nathalie

2004-01-01

The concept that nitric oxide (NO) release can be beneficial in inflammatory conditions has raised more attention in the recent years, particularly with the development of nitric oxide-releasing anti-inflammatory drugs. There is considerable evidence that NO is capable of enhancing the anti-inflammatory benefits of conventional anti-inflammatory drugs. Since hydrocortisone is the most widely used anti-inflammatory drug for the treatment of skin inflammation, we compared the anti-inflammatory effects of hydrocortisone to an NO-releasing derivative of hydrocortisone, NCX 1022, in a murine model of irritant contact dermatitis, induced by epidermal application of benzalkonium chloride. Topical pre- and post-treatment with NCX 1022 (3 nmol) in C57BL6 mice not only reduced ear oedema formation in a dose-dependent manner, but also was significantly more effective than the parent compound during the initial stages of inflammation (from 1 to 5 h). NCX 1022, but not hydrocortisone, significantly inhibited granulocyte recruitment (tissue myeloperoxidase activity). Histological samples of mouse ears treated with NCX 1022 showed significant reduction in both the number of infiltrated cells and disruption of the tissue architecture compared to hydrocortisone-treated tissues. With intravital microscopy, we observed that both pre- and post-treatments with NCX 1022 were more effective than hydrocortisone in terms of inhibiting benzalkonium chloride-induced leukocyte adhesion to the endothelium, without affecting the flux of rolling leukocytes or venule diameter. These results suggest that by releasing NO, NCX 1022 modulates one of the early events of skin inflammation: the recruitment of leukocytes to the site of inflammation. Overall, we have shown that NO-hydrocortisone provided faster and greater protective effects, reducing major inflammatory parameters (leukocyte adhesion and recruitment, oedema formation, tissue disruption) compared to its parental compound. PMID:15313880

Phytochemical Composition, Antioxidant, Antimicrobial and in Vivo Anti-inflammatory Activity of Traditionally Used Romanian Ajuga laxmannii (Murray) Benth. (“Nobleman’s Beard” – Barba Împăratului)

PubMed Central

Toiu, Anca; Mocan, Andrei; Vlase, Laurian; Pârvu, Alina E.; Vodnar, Dan C.; Gheldiu, Ana-Maria; Moldovan, Cadmiel; Oniga, Ilioara

2018-01-01

In the Romanian folk medicine, aerial parts of Ajuga laxmannii (“nobleman’s beard,” Romanian – “barba boierului” or “avrămească” or “creştinească”) are traditionally used as galactagogue and anti-inflammatory agents. The present study aimed to evaluate the chemical composition (polyphenols, iridoids, and phytosterols), antioxidant, antimicrobial and in vivo anti-inflammatory activity of different extracts of A. laxmannii aerial parts. The major identified bioactive compounds were rutin, 8-O-acetylharpagide and β-sitosterol. The antioxidant activity of A. laxmannii extracts was evaluated using several methods, and the results showed good antiradical effects. Moreover, the antimicrobial evaluation showed a potent antifungal activity against C. albicans and P. funiculosum. Furthermore, the anti-inflammatory effect was determined by monitoring some parameters involved in the inflammatory process. The results obtained showed differences between the analyzed extracts; and therefore the importance of choosing the best solvent in order to extract the appropriate amount of bioactive compounds. A. laxmannii ethanol extract showed an anti-inflammatory effect by reducing total leukocytes, PMN, phagocytosis, and oxidative stress. Compared to diclofenac, only the 50 mg/mL A. laxmannii extract had better anti-inflammatory and anti-oxidative stress effects, and this could justify the importance of a correlation between the activity and the used concentration. These findings strongly suggest that A. laxmannii could be considered as a valuable source of bioactive compounds, which could be further valued as anti-inflammatory agents in the composition of several herbal drugs. PMID:29551972

Anti-inflammatory effects of nitric oxide-releasing hydrocortisone NCX 1022, in a murine model of contact dermatitis.

PubMed

Hyun, Eric; Bolla, Manlio; Steinhoff, Martin; Wallace, John L; Soldato, Piero Del; Vergnolle, Nathalie

2004-11-01

1 The concept that nitric oxide (NO) release can be beneficial in inflammatory conditions has raised more attention in the recent years, particularly with the development of nitric oxide-releasing anti-inflammatory drugs. There is considerable evidence that NO is capable of enhancing the anti-inflammatory benefits of conventional anti-inflammatory drugs. 2 Since hydrocortisone is the most widely used anti-inflammatory drug for the treatment of skin inflammation, we compared the anti-inflammatory effects of hydrocortisone to an NO-releasing derivative of hydrocortisone, NCX 1022, in a murine model of irritant contact dermatitis, induced by epidermal application of benzalkonium chloride. 3 Topical pre- and post-treatment with NCX 1022 (3 nmol) in C57BL6 mice not only reduced ear oedema formation in a dose-dependent manner, but also was significantly more effective than the parent compound during the initial stages of inflammation (from 1 to 5 h). NCX 1022, but not hydrocortisone, significantly inhibited granulocyte recruitment (tissue myeloperoxidase activity). Histological samples of mouse ears treated with NCX 1022 showed significant reduction in both the number of infiltrated cells and disruption of the tissue architecture compared to hydrocortisone-treated tissues. 4 With intravital microscopy, we observed that both pre- and post-treatments with NCX 1022 were more effective than hydrocortisone in terms of inhibiting benzalkonium chloride-induced leukocyte adhesion to the endothelium, without affecting the flux of rolling leukocytes or venule diameter. 5 These results suggest that by releasing NO, NCX 1022 modulates one of the early events of skin inflammation: the recruitment of leukocytes to the site of inflammation. Overall, we have shown that NO-hydrocortisone provided faster and greater protective effects, reducing major inflammatory parameters (leukocyte adhesion and recruitment, oedema formation, tissue disruption) compared to its parental compound.

CALCULATION OF NONLINEAR CONFIDENCE AND PREDICTION INTERVALS FOR GROUND-WATER FLOW MODELS.

USGS Publications Warehouse

Cooley, Richard L.; Vecchia, Aldo V.

1987-01-01

A method is derived to efficiently compute nonlinear confidence and prediction intervals on any function of parameters derived as output from a mathematical model of a physical system. The method is applied to the problem of obtaining confidence and prediction intervals for manually-calibrated ground-water flow models. To obtain confidence and prediction intervals resulting from uncertainties in parameters, the calibrated model and information on extreme ranges and ordering of the model parameters within one or more independent groups are required. If random errors in the dependent variable are present in addition to uncertainties in parameters, then calculation of prediction intervals also requires information on the extreme range of error expected. A simple Monte Carlo method is used to compute the quantiles necessary to establish probability levels for the confidence and prediction intervals. Application of the method to a hypothetical example showed that inclusion of random errors in the dependent variable in addition to uncertainties in parameters can considerably widen the prediction intervals.

Negative Emotions Predict Elevated Interleukin-6 in the United States but not in Japan

PubMed Central

Miyamoto, Yuri; Boylan, Jennifer Morozink; Coe, Christopher L.; Curhan, Katherine B.; Levine, Cynthia S.; Markus, Hazel Rose; Park, Jiyoung; Kitayama, Shinobu; Kawakami, Norito; Karasawa, Mayumi; Love, Gayle D.; Ryff, Carol D.

2013-01-01

Previous studies conducted in Western cultures have shown that negative emotions predict higher levels of pro-inflammatory biomarkers, specifically interleukin-6 (IL-6). This link between negative emotions and IL-6 may be specific to Western cultures where negative emotions are perceived to be problematic and thus may not extend to Eastern cultures where negative emotions are seen as acceptable and normal. Using samples of 1044 American and 382 Japanese middle-aged and older adults, we investigated whether the relationship between negative emotions and IL-6 varies by cultural context. Negative emotions predicted higher IL-6 among American adults, whereas no association was evident among Japanese adults. Furthermore, the interaction between culture and negative emotions remained even after controlling for demographic variables, psychological factors (positive emotions, neuroticism, extraversion), health behaviors (smoking status, alcohol consumption), and health status (chronic conditions, BMI). These findings highlight the role of cultural context in shaping how negative emotions affect inflammatory physiology and underscore the importance of cultural ideas and practices relevant to negative emotions for understanding of the interplay between psychology, physiology, and health. PMID:23911591

Computational Prediction and Validation of BAHD1 as a Novel Molecule for Ulcerative Colitis

NASA Astrophysics Data System (ADS)

Zhu, Huatuo; Wan, Xingyong; Li, Jing; Han, Lu; Bo, Xiaochen; Chen, Wenguo; Lu, Chao; Shen, Zhe; Xu, Chenfu; Chen, Lihua; Yu, Chaohui; Xu, Guoqiang

2015-07-01

Ulcerative colitis (UC) is a common inflammatory bowel disease (IBD) producing intestinal inflammation and tissue damage. The precise aetiology of UC remains unknown. In this study, we applied a rank-based expression profile comparative algorithm, gene set enrichment analysis (GSEA), to evaluate the expression profiles of UC patients and small interfering RNA (siRNA)-perturbed cells to predict proteins that might be essential in UC from publicly available expression profiles. We used quantitative PCR (qPCR) to characterize the expression levels of those genes predicted to be the most important for UC in dextran sodium sulphate (DSS)-induced colitic mice. We found that bromo-adjacent homology domain (BAHD1), a novel heterochromatinization factor in vertebrates, was the most downregulated gene. We further validated a potential role of BAHD1 as a regulatory factor for inflammation through the TNF signalling pathway in vitro. Our findings indicate that computational approaches leveraging public gene expression data can be used to infer potential genes or proteins for diseases, and BAHD1 might act as an indispensable factor in regulating the cellular inflammatory response in UC.

Multiaxial Fatigue Damage Parameter and Life Prediction without Any Additional Material Constants

PubMed Central

Yu, Zheng-Yong; Liu, Qiang; Liu, Yunhan

2017-01-01

Based on the critical plane approach, a simple and efficient multiaxial fatigue damage parameter with no additional material constants is proposed for life prediction under uniaxial/multiaxial proportional and/or non-proportional loadings for titanium alloy TC4 and nickel-based superalloy GH4169. Moreover, two modified Ince-Glinka fatigue damage parameters are put forward and evaluated under different load paths. Results show that the generalized strain amplitude model provides less accurate life predictions in the high cycle life regime and is better for life prediction in the low cycle life regime; however, the generalized strain energy model is relatively better for high cycle life prediction and is conservative for low cycle life prediction under multiaxial loadings. In addition, the Fatemi–Socie model is introduced for model comparison and its additional material parameter k is found to not be a constant and its usage is discussed. Finally, model comparison and prediction error analysis are used to illustrate the superiority of the proposed damage parameter in multiaxial fatigue life prediction of the two aviation alloys under various loadings. PMID:28792487

Multiaxial Fatigue Damage Parameter and Life Prediction without Any Additional Material Constants.

PubMed

Yu, Zheng-Yong; Zhu, Shun-Peng; Liu, Qiang; Liu, Yunhan

2017-08-09

Based on the critical plane approach, a simple and efficient multiaxial fatigue damage parameter with no additional material constants is proposed for life prediction under uniaxial/multiaxial proportional and/or non-proportional loadings for titanium alloy TC4 and nickel-based superalloy GH4169. Moreover, two modified Ince-Glinka fatigue damage parameters are put forward and evaluated under different load paths. Results show that the generalized strain amplitude model provides less accurate life predictions in the high cycle life regime and is better for life prediction in the low cycle life regime; however, the generalized strain energy model is relatively better for high cycle life prediction and is conservative for low cycle life prediction under multiaxial loadings. In addition, the Fatemi-Socie model is introduced for model comparison and its additional material parameter k is found to not be a constant and its usage is discussed. Finally, model comparison and prediction error analysis are used to illustrate the superiority of the proposed damage parameter in multiaxial fatigue life prediction of the two aviation alloys under various loadings.

Parameters of Microcirculation in the Broad Ligament of the Uterus in Wistar Rats after Injection of Autologous Biomedical Cell Product.

PubMed

Dergacheva, T I; Lykov, A P; Shurlygina, A V; Starkova, E V; Poveshchenko, O V; Bondarenko, N A; Kim, I I; Tenditnik, M V; Borodin, Yu I; Konenkov, V I

2015-10-01

We studied the effects of autologous biomedical cell product (bone marrow multipotent mesenchymal stromal cells and their conditioned media) on the parameters of the microcirculatory bed in the broad ligament of the uterus of normal Wistar rats were studied. The parameters of microcirculation and lymph drainage in the broad ligament changed in opposite directions in response to injection of autologous biomedical cell product via different routes. This fact should be taken into consideration when prescribing cell therapy for inflammatory degenerative processes in the pelvic organs.

Prediction of High-Grade Vesicoureteral Reflux after Pediatric Urinary Tract Infection: External Validation Study of Procalcitonin-Based Decision Rule

PubMed Central

Leroy, Sandrine; Bouissou, François; Fernandez-Lopez, Anna; Gurgoze, Metin K.; Karavanaki, Kyriaki; Ulinski, Tim; Bressan, Silvia; Vaos, Geogios; Leblond, Pierre; Coulais, Yvon; Cubells, Carlos Luaces; Aygun, A. Denizmen; Stefanidis, Constantinos J.; Bensman, Albert; DaDalt, Liviana; Gardikis, Stefanos; Bigot, Sandra; Gendrel, Dominique; Bréart, Gérard; Chalumeau, Martin

2011-01-01

Background Predicting vesico-ureteral reflux (VUR) ≥3 at the time of the first urinary tract infection (UTI) would make it possible to restrict cystography to high-risk children. We previously derived the following clinical decision rule for that purpose: cystography should be performed in cases with ureteral dilation and a serum procalcitonin level ≥0.17 ng/mL, or without ureteral dilatation when the serum procalcitonin level ≥0.63 ng/mL. The rule yielded a 86% sensitivity with a 46% specificity. We aimed to test its reproducibility. Study Design A secondary analysis of prospective series of children with a first UTI. The rule was applied, and predictive ability was calculated. Results The study included 413 patients (157 boys, VUR ≥3 in 11%) from eight centers in five countries. The rule offered a 46% specificity (95% CI, 41–52), not different from the one in the derivation study. However, the sensitivity significantly decreased to 64% (95%CI, 50–76), leading to a difference of 20% (95%CI, 17–36). In all, 16 (34%) patients among the 47 with VUR ≥3 were misdiagnosed by the rule. This lack of reproducibility might result primarily from a difference between derivation and validation populations regarding inflammatory parameters (CRP, PCT); the validation set samples may have been collected earlier than for the derivation one. Conclusions The rule built to predict VUR ≥3 had a stable specificity (ie. 46%), but a decreased sensitivity (ie. 64%) because of the time variability of PCT measurement. Some refinement may be warranted. PMID:22216314

Chemotherapy of colorectal liver metastases induces a rapid rise in intermediate blood monocytes which predicts treatment response

PubMed Central

Schauer, Dominic; Starlinger, Patrick; Alidzanovic, Lejla; Zajc, Philipp; Maier, Thomas; Feldman, Alexandra; Padickakudy, Robin; Buchberger, Elisabeth; Elleder, Vanessa; Spittler, Andreas; Stift, Judith; Pop, Lorand; Gruenberger, Birgit; Gruenberger, Thomas; Brostjan, Christine

2016-01-01

ABSTRACT We have previously reported that intermediate monocytes (CD14++/CD16+) were increased in colorectal cancer (CRC) patients, while the subset of pro-angiogenic TIE2-expressing monocytes (TEMs) was not significantly elevated. This study was designed to evaluate changes in frequency and function of intermediate monocytes and TEMs during chemotherapy and anti-angiogenic cancer treatment and their relation to treatment response. Monocyte populations were determined by flow cytometry in 60 metastasized CRC (mCRC) patients who received neoadjuvant chemotherapy with or without bevacizumab. Blood samples were taken before treatment, after two therapy cycles, at the end of neoadjuvant therapy and immediately before surgical resection of liver metastases. Neoadjuvant treatment resulted in a significant increase in circulating intermediate monocytes which was most pronounced after two cycles and positively predicted tumor response (AUC = 0.875, p = 0.005). With a cut-off value set to 1% intermediate monocytes of leukocytes, this parameter showed a predictive sensitivity and specificity of 75% and 88%. Anti-angiogenic therapy with bevacizumab had no impact on monocyte populations including TEMs. In 15 patients and six healthy controls, the gene expression profile and the migratory behavior of monocyte subsets was evaluated. The profile of intermediate monocytes suggested functions in antigen presentation, inflammatory cytokine production, chemotaxis and was remarkably stable during chemotherapy. Intermediate monocytes showed a preferential migratory response to tumor-derived signals in vitro and correlated with the level of CD14+/CD16+ monocytic infiltrates in the resected tumor tissue. In conclusion, the rapid rise of intermediate monocytes during chemotherapy may offer a simple marker for response prediction and a timely change in regimen. PMID:27471631

Airline Transport Pilot Preferences for Predictive Information

NASA Technical Reports Server (NTRS)

Trujillo, Anna C.

1996-01-01

This experiment assessed certain issues about the usefulness of predictive information: (1) the relative time criticality of failures, (2) the subjective utility of predictive information for different parameters or sensors, and (3) the preferred form and prediction time for displaying predictive information. To address these issues, three separate tasks were administered to 22 airline pilots. As shown by the data, these pilots preferred predictive information on parameters they considered vital to the safety of the flight. These parameters were related to the checklists performed first for alert messages. These pilots also preferred to know whether a parameter was changing abnormally and the time to a certain value being reached. Furthermore, they considered this information most useful during the cruise, the climb, and the descent phases of flight. Lastly, these pilots preferred the information to predict as far ahead as possible.

Approaches to highly parameterized inversion: A guide to using PEST for model-parameter and predictive-uncertainty analysis

USGS Publications Warehouse

Doherty, John E.; Hunt, Randall J.; Tonkin, Matthew J.

2010-01-01

Analysis of the uncertainty associated with parameters used by a numerical model, and with predictions that depend on those parameters, is fundamental to the use of modeling in support of decisionmaking. Unfortunately, predictive uncertainty analysis with regard to models can be very computationally demanding, due in part to complex constraints on parameters that arise from expert knowledge of system properties on the one hand (knowledge constraints) and from the necessity for the model parameters to assume values that allow the model to reproduce historical system behavior on the other hand (calibration constraints). Enforcement of knowledge and calibration constraints on parameters used by a model does not eliminate the uncertainty in those parameters. In fact, in many cases, enforcement of calibration constraints simply reduces the uncertainties associated with a number of broad-scale combinations of model parameters that collectively describe spatially averaged system properties. The uncertainties associated with other combinations of parameters, especially those that pertain to small-scale parameter heterogeneity, may not be reduced through the calibration process. To the extent that a prediction depends on system-property detail, its postcalibration variability may be reduced very little, if at all, by applying calibration constraints; knowledge constraints remain the only limits on the variability of predictions that depend on such detail. Regrettably, in many common modeling applications, these constraints are weak. Though the PEST software suite was initially developed as a tool for model calibration, recent developments have focused on the evaluation of model-parameter and predictive uncertainty. As a complement to functionality that it provides for highly parameterized inversion (calibration) by means of formal mathematical regularization techniques, the PEST suite provides utilities for linear and nonlinear error-variance and uncertainty analysis in these highly parameterized modeling contexts. Availability of these utilities is particularly important because, in many cases, a significant proportion of the uncertainty associated with model parameters-and the predictions that depend on them-arises from differences between the complex properties of the real world and the simplified representation of those properties that is expressed by the calibrated model. This report is intended to guide intermediate to advanced modelers in the use of capabilities available with the PEST suite of programs for evaluating model predictive error and uncertainty. A brief theoretical background is presented on sources of parameter and predictive uncertainty and on the means for evaluating this uncertainty. Applications of PEST tools are then discussed for overdetermined and underdetermined problems, both linear and nonlinear. PEST tools for calculating contributions to model predictive uncertainty, as well as optimization of data acquisition for reducing parameter and predictive uncertainty, are presented. The appendixes list the relevant PEST variables, files, and utilities required for the analyses described in the document.

Type of Renal Replacement Therapy (Hemodialysis versus Peritoneal Dialysis) Does Not Affect Cytokine Gene Expression or Clinical Parameters of Renal Transplant Candidates

PubMed Central

Kamińska, Dorota; Kościelska-Kasprzak, Katarzyna; Chudoba, Paweł; Mazanowska, Oktawia; Banasik, Mirosław; Żabinska, Marcelina; Boratyńska, Maria; Lepiesza, Agnieszka; Korta, Krzysztof; Gomółkiewicz, Agnieszka; Dzięgiel, Piotr; Klinger, Marian

2015-01-01

Patients with renal failure suffer from immune disturbances, caused by uremic toxins and influenced by dialysis treatment. The aim of the present study was to reveal whether type of dialysis modality (hemodialysis, HD, versus peritoneal dialysis, PD) differentially affects the immunocompetence, particularly the expression of genes involved in the immune response. Material. 87 renal transplant candidates (66 HD, 21 PD) were included in the study. Methods. The peripheral blood RNA samples were obtained with the PAXgene Blood system just before transplantation. The gene expression of CASP3, FAS, TP53, FOXP3, IFNG, IL2, IL6, IL8, IL10, IL17, IL18, LCN2, TGFB1, and TNF was assessed with real-time PCR on custom-designed low density arrays (TaqMan). Gene expression data were analyzed in relation to pretransplant clinical parameters. Results. The mean expression of examined genes showed no significant differences between PD and HD with the exception of FAS, expression of which was 30% higher in PD patients compared to the HD group. There was nonsignificantly higher expression of proinflammatory cytokines in the PD group. The clinical inflammatory parameters (CRP, albumin, cholesterol, and hemoglobin levels) did not differ between the groups. Conclusion. Type of renal replacement therapy exerts no differential effect on cytokine gene expression or inflammatory clinical parameters. PMID:26236736

Pulp Inflammation Diagnosis from Clinical to Inflammatory Mediators: A Systematic Review.

PubMed

Zanini, Marjorie; Meyer, Elisabeth; Simon, Stéphane

2017-07-01

Similar to other tissues, the dental pulp mounts an inflammatory reaction as a way to eliminate pathogens and stimulate repair. Pulp inflammation is prerequisite for dentin pulp complex repair and regeneration; otherwise, chronic disease or pulp necrosis occurs. Evaluation of pulp inflammation severity is necessary to predict the clinical success of maintaining pulp vitality. Clinical limitations to evaluating in situ inflammatory status are well-described. A molecular approach that aids clinical distinction between reversible and irreversible pulpitis could improve the success rate of vital pulp therapy. The aim of this article is to review inflammatory mediator expression in the context of clinical diagnosis. We searched PubMed and Cochrane databases for articles published between 1970 and December 2016. Only published studies of inflammatory mediator expression related to clinical diagnosis were eligible for inclusion and analysis. Thirty-two articles were analyzed. Two molecular approaches were described by study methods, protein expression analysis and gene expression analysis. Our review indicates that interleukin-8, matrix metalloproteinase 9, tumor necrosis factor-α, and receptor for advanced glycation end products expression increase at both the gene and protein levels during inflammation. Clinical irreversible pulpitis is related to specific levels of inflammatory mediator expression. The difference in expression between reversible and irreversible disease is both quantitative and qualitative. On the basis of our analysis, in situ quantification of inflammatory mediators may aid in the clinical distinction between reversible and irreversible pulpitis. Copyright © 2017 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Dietary Inflammatory Index and Cardiovascular Risk and Mortality-A Meta-Analysis.

PubMed

Shivappa, Nitin; Godos, Justyna; Hébert, James R; Wirth, Michael D; Piuri, Gabriele; Speciani, Attilio F; Grosso, Giuseppe

2018-02-12

Diet and chronic inflammation have been suggested to be risk factors in the development of cardiovascular disease (CVD) and related mortality. The possible link between the inflammatory potential of diet measured through the Dietary Inflammatory Index (DII ® ) and CVD has been investigated in several populations across the world. The aim of this study was to conduct a meta-analysis on studies exploring this association. Data from 14 studies were eligible, of which two were case-control, eleven were cohort, and one was cross-sectional. Results from the random-effects meta-analysis showed a positive association between increasing DII, indicating a pro-inflammatory diet, and CVD. Individuals in the highest versus the lowest (reference) DII category showed a 36% increased risk of CVD incidence and mortality, with moderate evidence of heterogeneity (relative risk (RR) = 1.36, 95% confidence interval (CI): 1.19, 1.57; heterogeneity index I ² = 69%, p < 0.001). When analyzed as a continuous variable, results showed an increased risk of CVD risk and mortality of 8% for each one-point increase in the DII score. Results remained unchanged when analyses were restricted to the prospective studies. Results of our meta-analysis support the importance of adopting a healthier anti-inflammatory diet for preventing CVD incidence and related mortality. In conclusion, a pro-inflammatory diet is associated with increased risk of CVD and CVD mortality. These results further substantiate the utility of DII as tool to characterize the inflammatory potential of diet and to predict CVD incidence and mortality.

Anxiety, not anger, induces inflammatory activity: An avoidance/approach model of immune system activation.

PubMed

Moons, Wesley G; Shields, Grant S

2015-08-01

Psychological stressors reliably trigger systemic inflammatory activity as indexed by levels of proinflammatory cytokines. This experiment demonstrates that one's specific emotional reaction to a stressor may be a significant determinant of whether an inflammatory reaction occurs in response to that stressor. Based on extant correlational evidence and theory, a causal approach was used to determine whether an avoidant emotion (anxiety) triggers more inflammatory activity than an approach emotion (anger). In an experimental design (N = 40), a 3-way Emotion Condition × Time × Analyte interaction revealed that a writing-based anxiety induction, but not a writing-based anger induction, increased mean levels of interferon-γ (IFN- γ) and interleukin-1β (IL-1β), but not interleukin-6 (IL-6) in oral mucous, F(2, 54) = 4.64, p = .01, ηp(²) = .15. Further, self-reported state anxiety predicted elevated levels of proinflammatory cytokines, all ΔR(²) >.06, ps <.04, but self-reported state anger did not. These results constitute the first evidence to our knowledge that specific negative emotions can differentially cause inflammatory activity and support a theoretical model explaining these effects based on the avoidance or approach motivations associated with emotions. (c) 2015 APA, all rights reserved).

Predicting the Occurrence of Oxygenation Impairment in Patients with Type-B Acute Aortic Dissection

PubMed Central

Tomita, Kazunori; Hata, Noritake; Kobayashi, Nobuaki; Shinada, Takuro; Shirakabe, Akihiro

2014-01-01

Complicated respiratory failure requiring mechanical ventilation in patients with type-B acute aortic dissection (AAD) has been previously reported, and inflammatory reactions have been found to be associated with the occurrence of oxygenation impairment (OI). However, the possibility of predicting the occurrence of OI in patients with type-B AAD has not yet been evaluated. This study was performed to investigate the possibility of predicting the occurrence of OI in type-B AAD. In this study, 79 type-B AAD patients were enrolled to investigate the possibility of predicting the occurrence of OI. OI was defined as Po 2/Fio 2 ≤ 200. Patient characteristics, type of AAD, vital signs on admission, and the presence of inflammatory reactions obtained on admission day were evaluated. OI occurred in 39 patients (49%) on hospital day 2.5 ± 1.4 on average. Younger age, male gender, nonslender frame (body mass index ≥ 22 kg/m2), a relatively high maximum body temperature on the admission day (≥ 36.5°C), DeBakey IIIb type, patent false lumen, and lower Po 2/Fio 2 on admission were found to be associated with the occurrence of OI. Multivariate analysis revealed that nonslender frame, relatively high body temperature on the admission day, and lower Po 2/Fio 2 on admission were reliable for predicting the occurrence of oxygen impairment. The occurrence of OI in type-B AAD can be predicted in the clinical setting. PMID:24627618

Evaluation of anti-inflammatory effect of statins in chronic periodontitis.

PubMed

Suresh, Snophia; Narayana, Satya; Jayakumar, P; Sudhakar, Uma; Pramod, V

2013-01-01

Statins are the group of lipid-lowering drugs commonly used to control cardiovascular and cerebrovascular diseases. Statins have potential anti-inflammatory effect by blocking the intermediate metabolites of the mevalonate pathway. The objective of this study was to evaluate the anti-inflammatory effect of statin medication in chronic periodontitis patients. Thirty patients of age group between 40 and 60 years were selected from the outpatient pool of Department of Periodontics, Thaimoogambigai Dental College and Hospital, Chennai. Thirty patients selected were grouped into two groups, Group-I consists of patients with generalized chronic periodontitis and on statin medication and Group-II consists of patients with generalized chronic periodontitis. Clinical parameters were recorded and gingival crevicular fluid (GCF) samples were analyzed for interleukin (IL)-1β using commercially available enzyme-linked immunosorbent assay. The mean GCF IL-1β levels in generalized chronic periodontitis patients who are on statin medication (Group-I) were lower than the generalized chronic periodontitis patients without statin medication (Group-II). Reduction of GCF IL-1β levels in statin users indicate that statins have anti-inflammatory effect on periodontal disease.

Administration of a leptin antagonist during the neonatal leptin surge induces alterations in the redox and inflammatory state in peripubertal /adolescent rats.

PubMed

Mela, Virginia; Hernandez, Oskarina; Hunsche, Caroline; Diaz, Francisca; Chowen, Julie A; De la Fuente, Mónica

2017-10-15

The importance of the neonatal leptin surge in rodents in neurodevelopmental processes has aroused curiosity in its implication in other physiological systems. Given the role of leptin in neuro-immune interactions, we hypothesized that the neonatal leptin surge could have an effect on the oxidative and inflammatory stress situations of both systems. We blocked the neonatal leptin surge by a leptin antagonist and measured several parameters of oxidative and inflammatory stress in the spleen, hypothalamus and adipose tissue of peripubertal/adolescent rats. The treated rats showed lower activity of several antioxidant enzymes in the spleen and their leukocytes released lower levels of mitogen-stimulated IL-10 and IL-13 and higher levels of TNF-alpha. In conclusion, the neonatal leptin surge may have a key role in the establishment of adequate redox and inflammatory states in the immune system, which is important for the generation of adequate immune responses and to obtain and maintain good health. Copyright © 2017 Elsevier B.V. All rights reserved.

The studies of anti-inflammatory and analgesic activities and pharmacokinetics of Oxytropis falcate Bunge extraction after transdermal administration in rats.

PubMed

Chen, Zhi-peng; Qu, Min-ming; Chen, Hong-xuan; Liu, Dan; Xiao, Yan-yu; Chen, Jun; Lu, Tu-lin; Cai, Bao-chang

2011-04-01

The aim of this study was to evaluate the activities of anti-inflammatory and analgesic of the total flavonoids extraction from Oxytropis falcate Bunge (FEO) after transdermal administration. The pharmacokinetics and absolute bioavailability of FEO in rat, furthermore, was studied. Firstly, the anti-inflammatory and analgesic effects of the FEO were studied by xylene-induced ear edema, adjuvant-induced joint inflammation law in rats, acetic acid-induced writhing and hot-plate tests in mice. Secondly, we developed a sensitive and specific HPLC method to analyze 2', 4'-dihydroxychalcone (TFC, the mainly ingredient of FEO) in rat plasma to study the pharmacokinetic of TEC. The results showed FEO has anti-inflammatory and analgesic property in a dose-dependent manner, and that the high dose group (90.6 mg/kg) of FEO appeared more significantly effective than the positive drug. From the pharmacokinetic studies of TFC in rats, we got the main pharmacokinetic parameters of TFC, providing a basis for the future studies in clinic. Copyright © 2010 Elsevier B.V. All rights reserved.

[Met-enkephalin in the cerebrospinal fluid as an indicator of central nervous system injury in meningitis and encephalitis].

PubMed

Cieśla, Andrzej; Pierzchała-Koziec, Krystyna; Mach, Tomasz; Garlicki, Aleksander; Bociaga-Jasik, Monika

2005-05-01

Assessment of met-enkephalin level in the cerebrospinal fluid (CSF) of patients with inflammatory process of the central nervous system (CNS) was performed to estimate the role of opioid system in viral and bacterial meningitis, and encephalitis. The met-enkephalin level, protein concentration and pleocytosis were analysed in the CSF of 53 patients with viral or bacterial meningitis, encephalitis, and in the control group of patients without inflammatory disease of the CNS. The biggest differences have been observed between the groups of patients with bacterial meningitis and those without inflammatory disease of the CNS, but they were statistically insignificant. There was a lack of correlation between met-enkephalin level and some factors of inflammatory process in CSF, such as pleocytosis and protein concentration. We have not revealed any correlation between etiological agent of CNS infection and opioid system of the brain. Despite the fact that, we observed in the study statistically insignificant changes, we suggest to continue investigations, including additional parameters which are characteristic for the CNS diseases.

Quercetin attenuates zymosan-induced arthritis in mice.

PubMed

Guazelli, Carla F S; Staurengo-Ferrari, Larissa; Zarpelon, Ana C; Pinho-Ribeiro, Felipe A; Ruiz-Miyazawa, Kenji W; Vicentini, Fabiana T M C; Vignoli, Josiane A; Camilios-Neto, Doumit; Georgetti, Sandra R; Baracat, Marcela M; Casagrande, Rubia; Verri, Waldiceu A

2018-06-01

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by articular lesions, recruitment of inflammatory cells and increased levels of pro-inflammatory cytokine. The intra-articular administration of zymosan is an experimental model that promotes inflammatory parameters resembling RA. Therefore, this model was used to investigate the efficacy of quercetin as a treatment of articular inflammation. Treatment with quercetin dose-dependently reduced zymosan-induced hyperalgesia, articular edema and the recruitment of neutrophils to the knee joint cavity. Histological analysis confirmed that quercetin inhibited zymosan-induced arthritis. The treatment with quercetin also inhibited zymosan-induced depletion of reduced glutathione (GSH) levels, TNFα and IL-1β production, and gp91 phox , prepro-endothelin-1 (preproET-1), and cyclooxygenase-2 mRNA expression. These molecular effects of quercetin were related to the inhibition of the nuclear factor kappa-B and induction of Nuclear factor erythroid 2- related factor (Nrf2)/home oxygenase (HO-1) pathway. Thus, quercetin exerted anti-inflammatory, analgesic and antioxidant effects in experimental arthritis, suggesting quercetin is a possible candidate for arthritis treatment. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Longitudinal Assessment of Systemic and Genital Tract Inflammatory Markers and Endogenous Genital Tract E. coli Inhibitory Activity in HIV-Infected and Uninfected Women.

PubMed

Keller, Marla J; McGinn, Aileen P; Lo, Yungtai; Huber, Ashley; Espinoza, Lilia; Minkoff, Howard; Colie, Christine; Nowicki, Marek J; D'Souza, Gypsyamber; Anastos, Kathryn

2016-06-01

Stability over time of systemic and mucosal immunity and their associations with bacterial vaginosis (BV) and HIV-specific parameters were assessed. Immune mediators and HIV viral load in plasma and cervicovaginal lavage (CVL), E. coli inhibition, and Nugent score were measured at three semiannual visits among 94 participants in the Women's Interagency HIV Study. Mixed models identified the factors associated with immune mediators. There was higher E. coli inhibition and lower inflammation over time in the genital tract and systemically. BV was consistently associated with higher CVL inflammatory mediators and lower CVL E. coli inhibition. HIV-infected women with higher CD4 counts had lower systemic and genital inflammatory mediators, and genital HIV shedding was associated with higher CVL inflammatory mediators. Use of antiretroviral therapy (ART) was associated with lower plasma and CVL mediators, but higher E. coli inhibition. HIV and BV are linked to inflammation, and ART may be associated with improved vaginal health. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Systematic review and meta-analysis of lactose digestion, its impact on intolerance and nutritional effects of dairy food restriction in inflammatory bowel diseases.

PubMed

Szilagyi, Andrew; Galiatsatos, Polymnia; Xue, Xiaoqing

2016-07-13

Relationships between inflammatory bowel disease and lactose containing foods remain controversial and poorly defined regarding symptoms, nutritional outcomes, and epidemiologic associations for lactose maldigestion. A literature review was performed using Pub Med, Cochrane library and individual references, to extract data on lactose maldigestion prevalence in inflammatory bowel diseases. A meta-analysis was done using selected articles, to determine odds ratios of maldigestion. Information was collected about symptoms, impact on pattern of dairy food consumption, as well as the effects of dairy foods on the course of inflammatory bowel diseases. A total of 1022 articles were evaluated, 35 articles were retained and 5 studies were added from review articles. Of these 17 were included in meta-analysis which showed overall increased lactose maldigestion in both diseases. However increased risk on sub analysis was only found in Crohn's in patients with small bowel involvement. Nine additional studies were reviewed for symptoms, with variable outcomes due to confounding between lactose intolerance and lactose maldigestion. Fourteen studies were evaluated for dairy food effects. There was a suggestion that dairy foods may protect against inflammatory bowel disease. Nutritional consequences of dairy restrictions might impact adversely on bone and colonic complications. Lactose maldigestion in inflammatory bowel disease is dependent on ethnic makeup of the population and usually not disease. No bias of increased disease prevalence was noted between lactase genotypes. Intolerance symptoms depend on several parameters besides lactose maldigestion. Dairy foods may decrease risks of inflammatory bowel disease. Dairy restrictions may adversely affect disease outcome.

Andrographis paniculata decreases fatigue in patients with relapsing-remitting multiple sclerosis: a 12-month double-blind placebo-controlled pilot study.

PubMed

Bertoglio, J C; Baumgartner, M; Palma, R; Ciampi, E; Carcamo, C; Cáceres, D D; Acosta-Jamett, G; Hancke, J L; Burgos, R A

2016-05-23

Andrographis paniculata (A. paniculata), a medicinal plant, has shown anti-inflammatory, neuroprotective and antifibrotic effects in animal models as well as clinical efficacy in different studies, including an anti-fatigue effect in autoimmune diseases such as rheumatoid arthritis. In multiple sclerosis (MS), fatigue is rated as one of the most common and disabling symptoms. In the present trial, we investigated the effect of A. paniculata on relapse rate and fatigue in relapsing-remitting MS (RRMS) patients receiving interferon beta. A randomised double-blind placebo-controlled trial assessed the effects of 170 mg of A. paniculata dried extract tablet b.i.d. p.o. on relapse rate and fatigue using the Fatigue Severity Scores (FSS) over 12 months in RRMS patients receiving interferon. The Expanded Disability Status Scale (EDSS) score, inflammatory parameters and radiological findings were also investigated. Twenty-five patients were enrolled, and twenty-two patients were ultimately analysed and randomised to the active or placebo group. Patients treated with A. paniculata showed a significant reduction in their FSS score as compared to the placebo, equivalent to a 44 % reduction at 12 months. No statistically significant differences were observed for relapse rate, EDSS or inflammatory parameters, with a trend in reducing new lesions among the A. paniculata group. One patient in the A. paniculata group presented with a mild and transient skin rash, which was alleviated with anti-histamine treatment for three weeks. A. paniculata was well tolerated in patients and no changes in clinical parameters were observed. A. paniculata significantly reduces fatigue in patients with RRMS receiving interferon beta in comparison to placebo and only interferon beta treatment. ClinicalTrials.gov Identifier: NCT02280876 ; Trial registration date: 20.10.2014.

Change in inflammatory parameters in prefrail and frail persons obtaining physical training and nutritional support provided by lay volunteers: A randomized controlled trial.

PubMed

Haider, Sandra; Grabovac, Igor; Winzer, Eva; Kapan, Ali; Schindler, Karin Emmi; Lackinger, Christian; Titze, Sylvia; Dorner, Thomas Ernst

2017-01-01

The aim of the study was to compare the effects of home visits with physical training and nutritional support on inflammatory parameters to home visits with social support alone within a randomized controlled trial. Prefrail and frail persons received home visits from lay volunteers twice a week for 12 weeks. Participants in the physical training and nutritional intervention group (PTN, n = 35) conducted two sets of six strength exercises and received nutritional support. The social support group (SoSu, n = 23) received visits only. TNF-α, IL-6, CRP, and total leukocyte count were assessed at baseline and after 12 weeks. Changes over time within groups were analyzed with paired t-tests; differences between groups were analyzed with ANCOVA for repeated measurements. In the PTN group, IL-6 and CRP remained stable, whereas in the SoSu group, IL-6 increased significantly from a median value of 2.6 pg/l (min-max = 2.0-10.2) to 3.0 pg/l (min-max = 2.0-20.8), and CRP rose from 0.2 mg/dl (min-max = 0.1-0.9) to 0.3 mg/dl (min-max = 0.1-3.0) after 12 weeks. In CRP, a significant difference between groups was found. TNF-α and total leukocyte count did not change in either the PTN group or the SoSu group. Persons showing an increase in physical performance (OR 4.54; 95% CI = 1.33-15.45) were more likely to have constant or decreased IL-6 values than persons who showed no improvement. In conclusion, in non-robust older adults, a physical training and nutritional support program provided by lay volunteers can delay a further increase in some inflammatory parameters.

Lean body mass and creatine kinase are associated with reduced inflammation in obesity.

PubMed

Bekkelund, Svein I; Jorde, Rolf

2017-11-01

Obesity is associated with inflammation, but the role of lean mass and creatine kinase (CK) on the inflammatory process is less known. We investigated the associations between lean mass, CK and fat mass upon inflammatory parameters in an overweight and obese adult population. Body composition examined by dual-energy X-ray absorptiometry, high-sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), CK and supplementary clinical parameters were measured in 454 overweight and obese individuals. This is a secondary analysis from a cohort of obese individuals treated with Vitamin D. Mean age was 47·6 ± 11·4 years and mean body mass index 34·6 ± 3·9 kg/m 2 . Lean mass correlated negatively with hs-CRP (r = -0·127, P = 0·042) and ESR (r = -0·381, P < 0·001). Median lean mass in the lower ESR quartile was significantly higher than in the upper quartile (P < 0·001) but not between lower and upper hs-CRP quartiles (P = 0·114). CK was negatively correlated with hs-CRP (r = -0·151, P < 0·001) and ESR (r = -0·240, P < 0·001). Median CK in the lower hs-CRP and ESR quartiles were significantly higher than in the upper quartiles (P < 0·001 for both). Conversely, fat mass was positively associated with hs-CRP and ESR. Inflammatory parameters were related to reduced lean mass and CK in an overweight and obese population. Hypothetically, lean mass has a favourable effect on obesity-related inflammation, and CK may play a role as an inhibitor of inflammation in obesity. © 2017 Stichting European Society for Clinical Investigation Journal Foundation.

Evaluation of the biochemical, inflammatory and oxidative profile of obese patients given clinical treatment and bariatric surgery.

PubMed

Schmatz, Roberta; Bitencourt, Mariana R; Patias, Luciana D; Beck, Maristela; da C Alvarez, Glauco; Zanini, Daniela; Gutierres, Jessié M; Diehl, Lia Natália; Pereira, Luciane B; Leal, Claudio Alberto; Duarte, Marta Frescura; Schetinger, Maria Rosa; Morsch, Vera Maria

2017-02-01

We investigated the biochemical and inflammatory parameters as well as biomarkers of oxidative stress in morbidly obese patients before and after bariatric surgery and clinical treatment. This study was conducted using 60 individuals (10 men and 50 women) distributed into 3 groups: the control group, 20 non-diabetic obese patients given clinical treatment, the bariatric group, 20 non-diabetic obese patients given a Roux-en-Y bypass gastroplasty, and the bariatric diabetic group, 20 diabetic obese patients given a Roux-en-Y bypass gastroplasty. Measurements were made before and 1, 3, 6, and 12months after surgery and clinical treatment. We showed a significant decrease in body weight, body mass index (BMI) and waist circumference, accompanied by a decrease in the lipid profile and glucose and glycated hemoglobin concentrations in the groups that received bariatric surgery. The concentrations of lipid peroxidation, carbonyl protein and NPSH, as well as superoxide dismutase (SOD) and catalase (CAT) activity, significantly decreased in both groups after surgery. The concentrations of inteleukin-6, inteleukin-1, TNF-α and resistin were also significantly lower, while adiponectin concentrations significantly increased 12months after bariatric surgery. No significant alterations were observed in the biochemical, inflammatory or oxidative parameters of the control group. Our findings demonstrate a decrease in body mass and a subsequent improvement in biochemical, metabolic and anthropometric parameters in patients given bariatric surgery. This may contribute to the reduction of oxidative damage in these patients and consequently a reduction in the risk of the development and progression of multiple co-morbidities associated with obesity. Copyright © 2016 Elsevier B.V. All rights reserved.

Overexpression of alpha(1)-acid glycoprotein in transgenic mice leads to sensitisation to acute colitis.

PubMed

Hochepied, T; Wullaert, A; Berger, F G; Baumann, H; Brouckaert, P; Steidler, L; Libert, C

2002-09-01

alpha(1)-Acid glycoprotein (alpha(1)-AGP) is an acute phase protein in most mammalian species whose concentration rises 2-5-fold during an acute phase reaction. Its serum concentration has often been used as a marker of disease, including inflammatory bowel disease (IBD). High alpha(1)-AGP levels were found to have a prognostic value for an increased risk of relapse in IBD. To investigate a possible role for increased serum levels of alpha(1)-AGP in the development of IBD. Dextran sodium sulphate (DSS) 2% was added to the drinking water of transgenic mice, overexpressing the rat alpha(1)-AGP gene, to induce acute colitis, thus mimicking the conditions of relapse. Clinical parameters, inflammatory parameters, and histological analyses on colon sections were performed. Homozygous alpha(1)-AGP-transgenic mice started losing weight and showed rectal bleeding significantly earlier than heterozygous transgenic or wild-type mice. Survival time of homozygous transgenic mice was significantly shorter compared with heterozygous and wild-type mice. The higher susceptibility of homozygous alpha(1)-AGP-transgenic mice to DSS induced acute colitis was also reflected in higher local myeloperoxidase levels, higher inflammation scores of the colon, and higher systemic levels of interleukin 6 and serum amyloid P component. Local inflammatory parameters were also significantly different in heterozygous transgenic mice compared with wild-type mice, indicating a local dosage effect. In homozygous transgenic mice, significantly higher amounts of bacteria were found in organs but IgA levels were only slightly lower than those of control mice. Sufficiently high serum levels of alpha(1)-AGP result in a more aggressive development of acute colitis.

Evaluation of the effects of glimepiride (Amaryl) and repaglinide (novoNorm) on atherosclerosis progression in high cholesterol-fed male rabbits.

PubMed

Hadi, Najah R; Al-Amran, Fadhil; Hussein, Mohammad A A; Rezeg, Fadhil A

2012-01-01

Atherosclerosis is an inflammatory disease of the blood vessel wall, characterized in early stages by endothelial dysfunction, recruitment and activation of monocyte/macrophages. Glimepiride is one of the third generation sulphonylurea drugs, useful for control of diabetes mellitus type two and it may exert anti inflammatory activity, by induction of nitric oxide production or through selective suppression of the cyclooxygenase pathway. Repaglinide is a new hypoglycemic agent, and a member of the carbamoylmethyl benzoic acid family. Some results from the literature demonstrate that repaglinide has favorable effects on the parameters of antioxidative balance. The objective of the present study was to assess the effect of glimepiride and repaglinide on atherosclerosis via interfering with the inflammatory and oxidative pathways. Twenty four local domestic male rabbits were involved in this study. The animals were randomly divided into four groups; Group I rabbits fed normal chow (oxiod) diet for 10 weeks. Group II rabbits were fed with 1% cholesterol enriched diet. Group III rabbits were fed with 1% cholesterol enriched diet together with Glimepiride (0.1 mg/kg once daily before morning feed). Group IV rabbits were fed with 1% cholesterol enriched diet together with Repaglinide (0.3 mg/kg once daily before morning feed). Blood samples were collected before (0 time) and every two weeks of experimental diets for measurement of serum triglycerides (TG), total cholesterol (TC), High-density lipoprotein cholesterol (HDL-C), high sensitive C - reactive protein (hsCRP), Interleukin - 6 (IL-6) and Tumor Necrosis Factor alpha (TNF-α) levels. At the end of 10 weeks, the aorta was removed for measurement of aortic Malondialdehyde (MDA), reduced glutathione (GSH) and aortic intimal thickness. Glimepiride and repaglinide treatment did show significant effect on lipid parameters compared with induced untreated group (P < 0.05). Also, they significantly reduced the elevation in hsCRP, IL-6, TNF-α, aortic MDA and aortic intimal thickness compared with induced untreated group (P < 0.05), and they helped to restore the aortic GSH levels (P < 0.05). Glimepiride and repaglinide may reduce atherosclerosis progression in hypercholesterolemic rabbits by interfering with the inflammatory and oxidative pathways without affecting lipid parameters.

The predictive consequences of parameterization

NASA Astrophysics Data System (ADS)

White, J.; Hughes, J. D.; Doherty, J. E.

2013-12-01

In numerical groundwater modeling, parameterization is the process of selecting the aspects of a computer model that will be allowed to vary during history matching. This selection process is dependent on professional judgment and is, therefore, inherently subjective. Ideally, a robust parameterization should be commensurate with the spatial and temporal resolution of the model and should include all uncertain aspects of the model. Limited computing resources typically require reducing the number of adjustable parameters so that only a subset of the uncertain model aspects are treated as estimable parameters; the remaining aspects are treated as fixed parameters during history matching. We use linear subspace theory to develop expressions for the predictive error incurred by fixing parameters. The predictive error is comprised of two terms. The first term arises directly from the sensitivity of a prediction to fixed parameters. The second term arises from prediction-sensitive adjustable parameters that are forced to compensate for fixed parameters during history matching. The compensation is accompanied by inappropriate adjustment of otherwise uninformed, null-space parameter components. Unwarranted adjustment of null-space components away from prior maximum likelihood values may produce bias if a prediction is sensitive to those components. The potential for subjective parameterization choices to corrupt predictions is examined using a synthetic model. Several strategies are evaluated, including use of piecewise constant zones, use of pilot points with Tikhonov regularization and use of the Karhunen-Loeve transformation. The best choice of parameterization (as defined by minimum error variance) is strongly dependent on the types of predictions to be made by the model.

Predicting CYP2C19 Catalytic Parameters for Enantioselective Oxidations Using Artificial Neural Networks and a Chirality Code

PubMed Central

Hartman, Jessica H.; Cothren, Steven D.; Park, Sun-Ha; Yun, Chul-Ho; Darsey, Jerry A.; Miller, Grover P.

2013-01-01

Cytochromes P450 (CYP for isoforms) play a central role in biological processes especially metabolism of chiral molecules; thus, development of computational methods to predict parameters for chiral reactions is important for advancing this field. In this study, we identified the most optimal artificial neural networks using conformation-independent chirality codes to predict CYP2C19 catalytic parameters for enantioselective reactions. Optimization of the neural networks required identifying the most suitable representation of structure among a diverse array of training substrates, normalizing distribution of the corresponding catalytic parameters (kcat, Km, and kcat/Km), and determining the best topology for networks to make predictions. Among different structural descriptors, the use of partial atomic charges according to the CHelpG scheme and inclusion of hydrogens yielded the most optimal artificial neural networks. Their training also required resolution of poorly distributed output catalytic parameters using a Box-Cox transformation. End point leave-one-out cross correlations of the best neural networks revealed that predictions for individual catalytic parameters (kcat and Km) were more consistent with experimental values than those for catalytic efficiency (kcat/Km). Lastly, neural networks predicted correctly enantioselectivity and comparable catalytic parameters measured in this study for previously uncharacterized CYP2C19 substrates, R- and S-propranolol. Taken together, these seminal computational studies for CYP2C19 are the first to predict all catalytic parameters for enantioselective reactions using artificial neural networks and thus provide a foundation for expanding the prediction of cytochrome P450 reactions to chiral drugs, pollutants, and other biologically active compounds. PMID:23673224

Is it possible to claim or refute sputum eosinophils ≥ 3% in asthmatics with sufficient accuracy using biomarkers?

PubMed

Demarche, Sophie F; Schleich, Florence N; Paulus, Virginie A; Henket, Monique A; Van Hees, Thierry J; Louis, Renaud E

2017-07-03

The concept of asthma inflammatory phenotypes has proved to be important in predicting response to inhaled corticosteroids. Induced sputum, which has been pivotal in the development of the concept of inflammatory phenotypes, is however not widely available. Several studies have proposed to use surrogate exhaled or blood biomarkers, like fractional exhaled nitric oxide (FENO), blood eosinophils and total serum immunoglobulin E (IgE). However, taken alone, each of these biomarkers has moderate accuracy to identify sputum eosinophilia. Here, we propose a new approach based on the likelihood ratio to study which thresholds of these biomarkers, taken alone or in combination, were able to rule in or rule out sputum eosinophils ≥3%. We showed in a large population of 869 asthmatics that combining FENO, blood eosinophils and total serum IgE could accurately predict sputum eosinophils ≥ or <3% in 58% of our population.

Modeling the NF-κB mediated inflammatory response predicts cytokine waves in tissue

PubMed Central

2011-01-01

Background Waves propagating in "excitable media" is a reliable way to transmit signals in space. A fascinating example where living cells comprise such a medium is Dictyostelium D. which propagates waves of chemoattractant to attract distant cells. While neutrophils chemotax in a similar fashion as Dictyostelium D., it is unclear if chemoattractant waves exist in mammalian tissues and what mechanisms could propagate them. Results We propose that chemoattractant cytokine waves may naturally develop as a result of NF-κB response. Using a heuristic mathematical model of NF-κB-like circuits coupled in space we show that the known characteristics of NF-κB response favor cytokine waves. Conclusions While the propagating wave of cytokines is generally beneficial for inflammation resolution, our model predicts that there exist special conditions that can cause chronic inflammation and re-occurrence of acute inflammatory response. PMID:21771307

[Value of sepsis single-disease manage system in predicting mortality in patients with sepsis].

PubMed

Chen, J; Wang, L H; Ouyang, B; Chen, M Y; Wu, J F; Liu, Y J; Liu, Z M; Guan, X D

2018-04-03

Objective: To observe the effect of sepsis single-disease manage system on the improvement of sepsis treatment and the value in predicting mortality in patients with sepsis. Methods: A retrospective study was conducted. Patients with sepsis admitted to the Department of Surgical Intensive Care Unit of Sun Yat-Sen University First Affiliated Hospital from September 22, 2013 to May 5, 2015 were enrolled in this study. Sepsis single-disease manage system (Rui Xin clinical data manage system, China data, China) was used to monitor 25 clinical quality parameters, consisting of timeliness, normalization and outcome parameters. Based on whether these quality parameters could be completed or not, the clinical practice was evaluated by the system. The unachieved quality parameter was defined as suspicious parameters, and these suspicious parameters were used to predict mortality of patients with receiver operating characteristic curve (ROC). Results: A total of 1 220 patients with sepsis were enrolled, included 805 males and 415 females. The mean age was (59±17) years, and acute physiology and chronic health evaluation (APACHE Ⅱ) scores was 19±8. The area under ROC curve of total suspicious numbers for predicting 28-day mortality was 0.70; when the suspicious parameters number was more than 6, the sensitivity was 68.0% and the specificity was 61.0% for predicting 28-day mortality. In addition, the area under ROC curve of outcome suspicious number for predicting 28-day mortality was 0.89; when the suspicious outcome parameters numbers was more than 1, the sensitivity was 88.0% and the specificity was 78.0% for predicting 28-day mortality. Moreover, the area under ROC curve of total suspicious number for predicting 90-day mortality was 0.73; when the total suspicious parameters number was more than 7, the sensitivity was 60.0% and the specificity was 74.0% for predicting 90-day mortality. Finally, the area under ROC curve of outcome suspicious numbers for predicting 90-day mortality was 0.92; when suspicious outcome parameters numbers was more than 1, the sensitivity was 88.0% and the specificity was 81.0% for predicting 90-day mortality. Conclusion: The single center study suggests that this sepsis single-disease manage system could be used to monitor the completion of clinical practice for intensivist in managing sepsis, and the number of quality parameters failed to complete could be used to predict the mortality of the patients.

Parameter prediction based on Improved Process neural network and ARMA error compensation in Evaporation Process

NASA Astrophysics Data System (ADS)

Qian, Xiaoshan

2018-01-01

The traditional model of evaporation process parameters have continuity and cumulative characteristics of the prediction error larger issues, based on the basis of the process proposed an adaptive particle swarm neural network forecasting method parameters established on the autoregressive moving average (ARMA) error correction procedure compensated prediction model to predict the results of the neural network to improve prediction accuracy. Taking a alumina plant evaporation process to analyze production data validation, and compared with the traditional model, the new model prediction accuracy greatly improved, can be used to predict the dynamic process of evaporation of sodium aluminate solution components.

Rational selection of experimental readout and intervention sites for reducing uncertainties in computational model predictions.

PubMed

Flassig, Robert J; Migal, Iryna; der Zalm, Esther van; Rihko-Struckmann, Liisa; Sundmacher, Kai

2015-01-16

Understanding the dynamics of biological processes can substantially be supported by computational models in the form of nonlinear ordinary differential equations (ODE). Typically, this model class contains many unknown parameters, which are estimated from inadequate and noisy data. Depending on the ODE structure, predictions based on unmeasured states and associated parameters are highly uncertain, even undetermined. For given data, profile likelihood analysis has been proven to be one of the most practically relevant approaches for analyzing the identifiability of an ODE structure, and thus model predictions. In case of highly uncertain or non-identifiable parameters, rational experimental design based on various approaches has shown to significantly reduce parameter uncertainties with minimal amount of effort. In this work we illustrate how to use profile likelihood samples for quantifying the individual contribution of parameter uncertainty to prediction uncertainty. For the uncertainty quantification we introduce the profile likelihood sensitivity (PLS) index. Additionally, for the case of several uncertain parameters, we introduce the PLS entropy to quantify individual contributions to the overall prediction uncertainty. We show how to use these two criteria as an experimental design objective for selecting new, informative readouts in combination with intervention site identification. The characteristics of the proposed multi-criterion objective are illustrated with an in silico example. We further illustrate how an existing practically non-identifiable model for the chlorophyll fluorescence induction in a photosynthetic organism, D. salina, can be rendered identifiable by additional experiments with new readouts. Having data and profile likelihood samples at hand, the here proposed uncertainty quantification based on prediction samples from the profile likelihood provides a simple way for determining individual contributions of parameter uncertainties to uncertainties in model predictions. The uncertainty quantification of specific model predictions allows identifying regions, where model predictions have to be considered with care. Such uncertain regions can be used for a rational experimental design to render initially highly uncertain model predictions into certainty. Finally, our uncertainty quantification directly accounts for parameter interdependencies and parameter sensitivities of the specific prediction.

Establishing a Th17 based mouse model for preclinical assessment of the toxicity of candidate microbicides.

PubMed

Li, Liang-Zhu; Yang, Yu; Yuan, Song-Hua; Wan, Yan-Min; Qiu, Chao; Feng, Yan-Ling; Xu, Jian-Qing; Zhang, Xiao-Yan

2010-12-01

To effectively block the invasion of human immunodeficiency virus (HIV)-1 on mucosal surface, vaginal anti-HIV-1 microbicides should avoid inflammatory responses and disruption of mucosa integrity because these will facilitate transepithelial viral penetration and replication. However, existing models fail to predict and evaluate vaginal mucosal toxicity induced by microbicides, and most importantly, they are unable to identify subtle or subclinical inflammatory reactions. This study was designed to develop a cost-effective in vivo model to evaluate microbicide safety in a preclinical study which can recapitulate the mucosal topical reaction. A murine model was employed with nonoxynol-9 (N-9) as the topical stimulant within the vagina. Different concentrations of N-9 (1%, 3%, and 4%) were topically applied to the vagina for five consecutive days. A panel of inflammatory cytokines including interleukine-2 (IL-2), IL-4, IL-6, IL-17A, interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and immuno-regulatory IL-10 were assayed in vaginal lavage. Cytokines were quantified by using cytometric bead array (CBA) and reverse transcript (RT) real-time PCR. Histopathological evaluation of vaginal tissues was conducted on hematoxylin-eosin stained slides and scored with a semi-quantitative system according to the severity of epithelial disruption, leucocyte infiltration, edema, and vascular injection. The association between the cytokines and histopathological scores was assessed by linear regression analysis. All three concentrations of N-9 induced inflammatory cytokine production. The 4% N-9 application resulted in a consistent production of cytokines in a time-dependent manner. The cytokines reached peak expression on day three with the exception of IL-4 which reached its peak on day one. Histopathological examination of 4% N-9 treated cervicovaginal tissues on day three showed intensive damage in four mice (sores: 10 - 13) and moderate damage in one mouse (score: 8), which were significantly associated with both inflammatory cytokines IL-17A and IL-6 and anti-inflammatory cytokines IL-4 and IL-10. Interestingly, IL-17A showed significant positive association with inflammatory cytokine TNF-α (r = 0.739; P < 0.05), anti-inflammatory cytokines IL-10 (r = 0.804; P < 0.01) and IL-4 (r = 0.668; P < 0.05). Our data demonstrate that a panel of cytokines (IL-17A, IL-6, IL-4 and IL-10) could be used as surrogate biomarkers to predict the histopathological damage. Th17 may play a central role in orchestrating inflammatory cytokine responses. This Th17 based mouse model is cost-effective and suitable to assess the toxicity of candidate microbicides in preclinical studies.

Prevalence of Coxitis and its Correlation with Inflammatory Activity in Rheumatoid Arthritis

PubMed Central

Bajraktari, Ismet H.; Krasniqi, Blerim; Rexhepi, Sylejman; Bexheti, Sadi; Bahtiri, Elton; Bajraktari, Halit; Luri, Besim

2018-01-01

BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune inflammatory disease characterised by intra-articular and extra-articular manifestations but very rarely with coxitis. AIM: This study aimed to investigate the prevalence of coxitis, clinical changes, and its correlation with the parameters of inflammatory activity. METHODS: A cohort of 951 patients diagnosed with ACR/EULAR (American College of Rheumatology/European League against Rheumatism) 2010 criteria was enrolled in this prospective, observational and analytic research study. The CBC (Complete Blood Count), ESR (Erythrocyte sedimentation rate), CRP(C - reactive protein), Anti CCP (Antibodies to cyclic citrullinated peptides), X-ray examination of palms and pelvis, and the activity of the disease as measured by DAS - 28 (28 - joint disease activity score) were carried out in all subjects. Independent samples t-test was used to compare the group’s characteristics, whereas Pearson correlation test was used to analyse the correlation between study variables. RESULTS: Of the total number of the subjects, 730 (76.8 %) were females, whereas 221 (23.2%) were males. The average age was 51.3, y/o while the most of them were between 40 - 49 y/o (32.6%). The prevalence of coxitis was 14.2%, mostly found in males (19.46%). The echosonografic prevalence of changes was 21.45%, while the radiological changes were 16.3%; in both cases, the changes were more expressed in males. The analysis showed that inflammatory parameters were significantly higher in patients with coxitis. CONCLUSION: Coxitis has high economic cost because it ends up with a mandatory need for a total hip joint prosthesis. Thus the results of this study can serve to plan and initiate early preventive measures. PMID:29531599

Recommendations for improved use of the murine TNBS-induced colitis model in evaluating anti-inflammatory properties of lactic acid bacteria: technical and microbiological aspects.

PubMed

Foligné, Benoit; Nutten, Sophie; Steidler, Lothar; Dennin, Véronique; Goudercourt, Denise; Mercenier, Annick; Pot, Bruno

2006-02-01

Probiotic bacteria have been shown to exert promising beneficial effects in different types of intestinal disorders, including chronic inflammation. In this context, animal models of inflammatory bowel disease are useful in studying the possible prophylactic role of candidate probiotic strains. This study aimed at evaluating the critical technological and microbiological parameters as well as the robustness of the murine trinitrobenzene sulfonic acid (TNBS)-induced model of colitis, after intragastric administration of lactic acid bacteria (LAB) preparations. A standardized methodology was applied to assess the protective effect achieved by various bacterial concentrations and culture conditions of the reference strain Lactobacillus plantarum NCIMB 8826. Not only was protection found to vary in function in different levels of colitis, but also repeated experiments showed a clear bacterial dose-dependent attenuation of colitis. The physiological stage of bacteria was shown to impact as well, with substantial, mild, or reduced improvement of inflammatory scores for exponentially growing, stationary-phase, or killed bacteria, respectively. A recombinant strain, secreting murine interleukin-10 (IL-10) and previously reported to successfully treat colitis in two different models of murine colitis (dextran sulfate sodium [DSS] and IL-10-deficient mice), was used to validate the final experimental conditions. In conclusion, we identified and optimized some of the key parameters that need to be controlled in order to ensure reliable comparison of results generated over a long period of time or independent experiments. The recommendations for an improved model presented here will prove to be helpful for reproducible, independent comparison of the anti-inflammatory potential of wild-type or recombinant candidate probiotic strains, whether administered as pure cultures or as blends.

The Effects of Diode Laser Therapy as an Adjunct to Scaling and Root Planing in the Treatment of Aggressive Periodontitis: A 1-Year Randomized Controlled Clinical Trial.

PubMed

Matarese, Giovanni; Ramaglia, Luca; Cicciù, Marco; Cordasco, Giancarlo; Isola, Gaetano

2017-12-01

The aim of this study was to investigate and compare the clinical, microbial, and inflammatory effects of a diode laser as an adjunct to scaling and root planing (SRP) versus SRP alone for the treatment of generalized aggressive periodontitis (GAgP). Using a split-mouth design, 31 patients with GAgP were enrolled in the study. The maxillary right and left quadrants were randomly assigned to SRP+diode laser or SRP alone. Patients were examined on a regular basis for clinical, microbiological, and inflammatory mediator changes over a 1-year period. Clinical attachment level (CAL) was the primary outcome variable chosen. In addition, subgingival biofilm samples and gingival crevicular fluid (GCF) inflammatory mediators were analyzed at each follow-up session. Compared to baseline, both treatments demonstrated an improvement in periodontal parameters at 1 year. However, SRP+diode laser produced a significant improvement in probing depth (PD; 2.56 ± 0.44 vs. 3.36 ± 0.51 mm, p < 0.05) and CAL (3.47 ± 0.25 vs. 4.11 ± 0.26 mm, p < 0.05) values compared to SRP alone. Similarly, in the SRP+diode laser group, the bacteria of orange complex group were significantly reduced at 30 and 60 days compared to SRP alone. Moreover, SRP+diode laser determined a reduction in mean GCF level of interleukin (IL)-1β and IL-1β/IL-10 ratio at 15 and 30 days compared to SRP alone (p < 0.05). At 1 year, SRP+diode laser yielded a significant reduction in some clinical parameters, while microbial and inflammatory mediator changes were not significantly reduced compared to SRP alone.

The effect of balneotherapy on antioxidant, inflammatory, and metabolic indices in patients with cardiovascular risk factors (hypertension and obesity)--a randomised, controlled, follow-up study.

PubMed

Oláh, Mihály; Koncz, Ágnes; Fehér, Judit; Kálmánczhey, Judit; Oláh, Csaba; Nagy, György; Bender, Tamás

2011-11-01

The primary objective of our study was to explore the changes of antioxidant, inflammatory, and metabolic parameters in obese and hypertension people patients during balneotherapy and to evaluate the safety of balneotherapy in these participants. Following randomisation, 22 obese and 20 hypertensive patients underwent balneotherapy with thermal water of 38°C temperature, in 15 sessions of 30 minutes. An additional 22 obese and 20 hypertensive patients served as controls. Antioxidant, inflammatory, and metabolic parameters were determined at baseline, as well as post-treatment and at the end of follow-up (at 15 weeks). As regards changes observed in hypertensive patients subjected to balneotherapy, differences could be detected between baseline and post-treatment albumin and haemoglobin A(1c) levels only; however, these were no longer significant after 3 months. Although the difference between transferrin levels determined at the end of balneotherapy and 3 months later was significant, it remained within the physiological range, as well as it was accompanied by normal serum iron level and therefore, it was considered irrelevant. C-reactive protein levels of balneotherapy patients decreased significantly after treatment. In obese patients, haemoglobin A(1c) level decreased after balneotherapy, but this difference was not observed either after 3 months. Similarly, both transferrin and C-reactive protein levels changed from baseline, but not between groups. This study contributes important information regarding the safety of balneotherapy in hypertensive and obese diabetics by showing no alterations of antioxidant, inflammatory, or metabolic indices. The findings of this study confirm that balneotherapy is not contraindicated for hypertensive or obese patients. Copyright © 2011 Elsevier Inc. All rights reserved.

Effects of short-term dietary restriction and glutamine supplementation in vitro on the modulation of inflammatory properties.

PubMed

C de Oliveira, Dalila; Santos, Ed Wilson; Nogueira-Pedro, Amanda; Xavier, José Guilherme; Borelli, Primavera; Fock, Ricardo Ambrósio

2018-04-01

Dietary restriction (DR) is a nutritional intervention that exerts profound effects on biochemical and immunologic parameters, modulating some inflammatory properties. Glutamine (GLN) is a conditionally essential amino acid that can modulate inflammatory properties. However, there is a lack of data evaluating the effects of DR and GLN supplementation, especially in relation to inflammatory cytokine production and the expression of transcription factors such as nuclear factor (NF)-κB. We subjected 3-mo-old male Balb/c mice to DR by reducing their food intake by 30%. DR animals lost weight and showed reduced levels of serum triacylglycerols, glucose, cholesterol, and calcium as well as a reduction in bone density. Additionally, blood, peritoneal, and spleen cellularity were reduced, lowering the number of peritoneal F4/80- and CD86-positive cells and the total number of splenic CD4- and CD8-positive cells. The production of interleukin (IL)-10 and the expression of NF-κB in splenic cells were not affected by DR or by GLN supplementation. However, peritoneal macrophages from DR animals showed reduced IL-12 and tumor necrosis factor-α production and increased IL-10 production with reduced phosphorylation of NF-κB expression. Additionally, GLN was able to modulate cytokine production by peritoneal cells from the control group, although no effects were observed in cells from the DR group. DR induces biochemical and immunologic changes, in particular by reducing IL-12 and tumor necrosis factor-α production by macrophages and clearly upregulating IL-10 production, whereas GLN supplementation did not modify these parameters in cells from DR animals. Copyright © 2017 Elsevier Inc. All rights reserved.

[Upper gastrointestinal hemorrhage caused by anti-inflammatory agents].

PubMed

Duhamel, C; Czernichow, P; Dechelotte, P; Ducrotte, P; Lerebours, E; Colin, R

1989-03-01

The aim of this study was to describe the clinical and evolutive characteristics of gastroduodenal bleeding occurring in patients receiving nonsteroidal anti-inflammatory (NSAI) drugs, containing salicylates or not, and to determine the relative toxicity of the NSAI drugs without salicylates. Eight hundred and fourty-five consecutive patients with upper gastrointestinal bleeding related to endoscopically proven peptic ulcer or gastroduodenal erosions were admitted between 1983 and June 1987 to an intensive care unit for digestive tract hemorrhage. Of these, 267 were using anti-inflammatory drugs; 151 (56 p. 100) were taking NSAI drugs other than salicylates, 97 salicylates (36 p. 100) and 10, steroids (4 p. 100). Patients taking nonsteroidal drugs without or with salicylates were compared with patients bleeding from gastroduodenal ulcer or erosion not receiving anti-inflammatory therapy. Patients receiving nonsteroidal drugs not containing salicylates were older (70 p. 100 over 65 years of age vs 46 p. 100, p less than 0.001) and the proportion of female patients was greater (54 p. 100 vs 33 p. 100, p less than 0.001) than in the other group. No significant difference was observed with regard to the following parameters: percentage of gastric lesions, concomitant anticoagulant therapy, need for surgical hemostasis, or mortality. Patients taking aspirin had more gastric lesions (75 p. 100 vs 64 p. 100, p less than 0.05) and less need for surgical hemostasis (7 p. 100 vs 15 p. 100, p less than 0.05); the other parameters did not differ. NSAI drugs other than salicylates were taken more often for osteoarthritis than salicylates (33.6 p. 100 vs 17.4 p. 100, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Cross-shift changes in blood inflammatory markers occur in the absence of airway obstruction in workers exposed to grain dust.

PubMed

Borm, P J; Schins, R P; Derhaag, T J; Kant, I; Jorna, T H

1996-04-01

Grain dust is well known to cause both acute and chronic respiratory disorders, and endotoxins are considered key components in this. Since endotoxins are known to elicit proinflammatory mediators, we investigated cytokine (tumor necrosis factor [TNF], interleukin-6, interleukin-8) release and a number of proinflammatory and anti-inflammatory proteins (soluble TNF receptors, lipopolysaccharide (LPS) binding protein, bactericidal permeability increasing protein (BPI), C-reactive protein) in plasma of workers exposed to grain dust. In two surveys during 1 week, lung function was measured daily before and after the shift, using flow-volume curves and/or forced oscillation measurements. On Monday and Friday, blood samples (30 mL) were drawn and cytokine release was determined by enzyme-linked immunosorbent assay in supernatant of isolated monocytes or whole blood culture, either unstimulated or on the ex vivo stimulation with 3 ng/mL or 1,000 ng/mL endotoxin. Individual exposures were determined from stationary dust measurements at every workplace combined with personal task analysis during all shifts. In both surveys, no cross-week change in lung function parameters was observed. In the first survey (average exposure: 20.2 mg/m3), monocyte spontaneous TNF release was increased sevenfold cross week (p<0.001) and was significantly related both to individual dust exposure (r=0.62) of that week and the increase in soluble TNF receptor 75 kD (r=0.85). In the second survey, where average exposure was much lower (3.67 mg/m3), impedance parameters indicated a significant improvement of airway function, and cross-week changes in inflammatory markers were minimal. Therefore, we conclude that inflammatory events can be used to monitor adverse respiratory effects of moderate grain dust exposure.

Prediction of the explosion effect of aluminized explosives

NASA Astrophysics Data System (ADS)

Zhang, Qi; Xiang, Cong; Liang, HuiMin

2013-05-01

We present an approach to predict the explosion load for aluminized explosives using a numerical calculation. A code to calculate the species of detonation products of high energy ingredients and those of the secondary reaction of aluminum and the detonation products, velocity of detonation, pressure, temperature and JWL parameters of aluminized explosives has been developed in this study. Through numerical calculations carried out with this code, the predicted JWL parameters for aluminized explosives have been compared with those measured by the cylinder test. The predicted JWL parameters with this code agree with those measured by the cylinder test. Furthermore, the load of explosion for the aluminized explosive was calculated using the numerical simulation by using the JWL equation of state. The loads of explosion for the aluminized explosive obtained using the predicted JWL parameters have been compared with those using the measured JWL parameters. Both of them are almost the same. The numerical results using the predicted JWL parameters show that the explosion air shock wave is the strongest when the mass fraction of aluminum powder in the explosive mixtures is 30%. This result agrees with the empirical data.

High prevalence of low bone mineral density in patients with Inflammatory Bowel Disease in the setting of a peripheral Dutch hospital.

PubMed

Van Schaik, Fiona D M; Verhagen, Marc A M T; Siersema, Peter D; Oldenburg, Bas

2008-09-01

Osteopenia and osteoporosis are frequently encountered in patients with Inflammatory Bowel Disease (IBD). Our aims were to evaluate the actual practice of screening for low bone mineral density (BMD) by dual energy X-ray absorptiometry (DEXA), to determine the prevalence of low BMD and to investigate the risk factors associated with a low BMD in the IBD population of a regional Dutch hospital. A retrospective chart review was performed in 474 patients (259 with ulcerative colitis, 210 with Crohn's disease and 5 with indeterminate colitis). DEXA results and potential predictive factors of low BMD were documented. Predictive factors of low BMD were assessed by logistic regression. DEXA was performed in 168 IBD patients (35.4%). A low BMD (T-score<-1) was present in 64.3%. Osteoporosis (T-score<-2.5) was found in 23.8%. Low BMI, older age at the moment of diagnosis and male gender were found to be predictive factors of low BMD. For patients with osteoporosis, disease duration was an additional predictive factor. After subgroup analysis predictive factors were found to be the same in patients with Crohn's disease. The prevalence of osteopenia and osteoporosis in IBD patients in a regional centre is as high as the prevalence rates reported from tertiary referral centres. A low BMI, an older age at the moment of diagnosis and male gender were predictive factors of low BMD. Prediction of osteoporosis and osteopenia using risk factors identified in this and previous studies is presently not feasible.

Strychnine inhibits inflammatory angiogenesis in mice via down regulation of VEGF, TNF-α and TGF-β.

PubMed

Saraswati, Sarita; Agarwal, S S

2013-05-01

Strychnine is known to possess anti-inflammatory and antitumour activity, but its roles in tumour angiogenesis, the key step involved in tumour growth and metastasis, and the involved molecular mechanism are still unknown. We aimed to investigate the effects of strychnine on key components of inflammatory angiogenesis in the murine cannulated sponge implant angiogenesis model. Polyester-polyurethane sponges, used as a framework for fibrovascular tissue growth, were implanted in Swiss albino mice and strychnine (0.25, and 0.5 mg/kg/day) was given through installed cannulas for 9 days. The implants collected at day 9 postimplantation were processed for the assessment of haemoglobin (Hb), myeloperoxidase (MPO), N-acetylglucosaminidase (NAG) and collagen used as indexes for angiogenesis, neutrophil and macrophage accumulation and extracellular matrix deposition, respectively. Relevant inflammatory, angiogenic and fibrogenic cytokines were also determined. Strychnine treatment attenuated the main components of the fibrovascular tissue, wet weight, vascularization (Hb content), macrophage recruitment (NAG activity), collagen deposition and the levels of vascular endothelial growth factor (VEGF), tumour necrosis factor (TNF)-α and transforming growth factor (TGF-β). A regulatory function of strychnine on multiple parameters of main components of inflammatory angiogenesis has been revealed giving insight into the potential therapeutic underlying the actions of strychnine. Copyright © 2013 Elsevier Inc. All rights reserved.

Acute and Chronic Effects of Endurance Running on Inflammatory Markers: A Systematic Review

PubMed Central

Barros, Edilberto S.; Nascimento, Dahan C.; Prestes, Jonato; Nóbrega, Otávio T.; Córdova, Claúdio; Sousa, Fernando; Boullosa, Daniel A.

2017-01-01

In order to understand the effect of endurance running on inflammation, it is necessary to quantify the extent to which acute and chronic running affects inflammatory mediators. The aim of this study was to summarize the literature on the effects of endurance running on inflammation mediators. Electronic searches were conducted on PubMED and Science Direct with no limits of date and language of publication. Randomized controlled trials (RCTs) and non-randomized controlled trials (NRCTs) investigating the acute and chronic effects of running on inflammation markers in runners were reviewed by two researchers for eligibility. The modified Downs and Black checklist for the assesssments of the methodological quality of studies was subsequently used. Fifty-one studies were finally included. There were no studies with elite athletes. Only two studies were chronic interventions. Results revealed that acute and chronic endurance running may affect anti- and pro-inflammatory markers but methodological differences between studies do not allow comparisons or generalization of the results. The information provided in this systematic review would help practitioners for better designing further studies while providing reference values for a better understanding of inflammatory responses after different running events. Further longitudinal studies are needed to identify the influence of training load parameters on inflammatory markers in runners of different levels and training background. PMID:29089897

In Vivo Evaluation of the Anti-Inflammatory Effect of Pistacia lentiscus Fruit Oil and Its Effects on Oxidative Stress

PubMed Central

Bardaa, Sana; Sahnoun, Zouheir; Rebai, Tarek

2016-01-01

In order to find new topical anti-inflammatory agents, we had recourse to a medicinal plant. This work was designed to determine the topical anti-inflammatory effect of Pistacia lentiscus fruit oil (PLFO), using carrageenan-induced paw edema rat model, and to evaluate its effects on oxidative stress. The topical anti-inflammatory activity of PLFO was compared to Inflocine® and estimated by measuring the diameter of paw edema, for 5 hours at a 1-hour interval. After that the rats were scarified and the inflamed paw tissue was removed for the exploration of some parameters of oxidative stress and histopathology. PLFO showed a significant anti-inflammatory activity in comparison with the Inflocine. The percentages of edema inhibition were 70% and % 51.5% (p < 0.01), respectively, after five hours. The treatment with PLFO and Inflocine led to significant increases (p ≤ 0.05) in the activities of CAT, SOD, and GPX and significant decreases in the MDA level and AOPP activity in the paw tissue after Carr injection, in comparison with the Carr group. Therefore, our findings demonstrate that PLFO might accelerate the development of new drugs which could be used scientifically as a source for natural health products in the treatment of topical inflammation. PMID:28070202

Quantitative analysis of blood cells and inflammatory factors in wounds.

PubMed

Cerveró-Ferragut, S; López-Riquelme, N; Martín-Tomás, E; Massa-Domínguez, B; Pomares-Vicente, J; Soler-Pérez, M; Sánchez-Hernández, J F

2017-03-02

The aim of this study was to quantify blood cells and inflammatory markers, involved in the healing process, in exudates from wounds in different healing phases, to assess these markers in order to identify the inflammatory phase of the wounds. Patients who presented with postsurgical wounds, which closed by first and second intention, and those who presented with pressure ulcers (PUs), which were closed by second intention, were included in the study. We examined wounds from 37 patients and collected samples from 52 wounds in the inflammatory phase, 30 in the proliferative phase and 29 in the maturation phase. The number of neutrophils and platelets in the exudate collected from wounds in the inflammatory phase was significantly higher (p<0.001), while the number of lymphocytes, was significantly lower in exudate from wounds in the inflammatory phase (p<0.001). Wound c-reactive protein (CRP) and immunoglobulin G (IgG) levels were higher in the inflammatory group (p<0.001). We found a significantly positive correlation between CRP levels and the percentage of neutrophils and monocytes (r=0.346, p=0.004; r=0.293, p=0.015), and a significantly negative correlation between CRP levels and the percentage of lymphocytes (r=-0.503, p<0.001). A stepwise logistic regression analysis was used to identify an optimal combination of these biomarkers. The optimal biomarker combinations were neutrophils + monocytes + platelets + IgG + CRP, with an area under the curve (AUC) of 0.981 [confidence interval (CI) 95%: 0.955-1.000, p<0.001] for the diagnosis of wounds in the inflammatory phase. The optimal cutpoint yielded 96.9 % sensitivity and 94.6 % specificity. The biomarker combination predicted the inflammatory phase and was superior to individual biomarkers. Our findings suggest that the combination of the markers, percentage of neutrophils and monocytes, platelets, CRP and IgG levels could be useful prognostic indicators of the inflammatory phase.

Study of inflammatory responses to crocidolite and basalt wool in the rat lung.

PubMed

Adamis, Z; Kerényi, T; Honma, K; Jäckel, M; Tátrai, E; Ungváry, G

2001-03-09

The subacute effects of crocidolite and basalt wool dusts were studied by nmeans of biochemical, morphological. and histological methods 1 and .3 mo after intrabronchial instillation. The cell count, protein and phospholipid contents, and lactate dehydrogenase (LDH) activity were determined in the bronchoalveolar lavage (BAL). Both types of fibers induced a prolonged inflammatory reaction in the lung. All the parameters studied in the experimental groups were more markedly elevated after 3 mo. Relative to the control, the protein and LDH values were increased three- to fivefold, the phospholipid content twofold, and the number of free cells in the BAL exceeded the control level up to ninefold. The inflammatory responses to crocidolite and basalt wool in the lung did not differ significantly. In spite of this, basalt wool is recoinmended as an asbestos substitute, as the use of this man-nade fiber may result in a significantly lower release of dust than that from crocidolite.

Joint ultrasound baseline abnormalities predict a specific long-term clinical outcome in systemic lupus erythematosus patients.

PubMed

Corzo, P; Salman-Monte, T C; Torrente-Segarra, V; Polino, L; Mojal, S; Carbonell-Abelló, J

2017-06-01

Objective To describe long-term clinical and serological outcome in all systemic lupus erythematosus (SLE) domains in SLE patients with hand arthralgia (HA) and joint ultrasound (JUS) inflammatory abnormalities, and to compare them with asymptomatic SLE patients with normal JUS. Methods SLE patients with HA who presented JUS inflammatory abnormalities ('cases') and SLE patients without HA who did not exhibit JUS abnormalities at baseline ('controls') were included. All SLE clinical and serological domain involvement data were collected. End follow-up clinical activity and damage scores (systemic lupus erythematosus disease activity index (SLEDAI), Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR)) were recorded. JUS inflammatory abnormalities were defined based on the Proceedings of the Seventh International Consensus Conference on Outcome Measures in Rheumatology Clinical Trials (OMERACT-7) definitions. Statistical analyses were carried out to compare 'cases' and 'controls'. Results A total of 35 patients were recruited. The 'cases', n = 18/35, had a higher incidence of musculoskeletal involvement (arthralgia and/or arthritis) through the follow-up period (38.9% vs 0%, p = 0.008) and received more hydroxychloroquine (61.1% vs 25.0%, p = 0.034) and methotrexate (27.8% vs 0%, p = 0.046) compared to 'controls', n = 17/35. Other comparisons did not reveal any statistical differences. Conclusions We found SLE patients with arthralgia who presented JUS inflammatory abnormalities received more hydroxychloroquine and methotrexate, mainly due to persistent musculoskeletal involvement over time. JUS appears to be a useful technique for predicting worse musculoskeletal outcome in SLE patients.

Use of Readily Accessible Inflammatory Markers to Predict Diabetic Kidney Disease.

PubMed

Winter, Lauren; Wong, Lydia A; Jerums, George; Seah, Jas-Mine; Clarke, Michele; Tan, Sih Min; Coughlan, Melinda T; MacIsaac, Richard J; Ekinci, Elif I

2018-01-01

Diabetic kidney disease is a common complication of type 1 and type 2 diabetes and is the primary cause of end-stage renal disease in developed countries. Early detection of diabetic kidney disease will facilitate early intervention aimed at reducing the rate of progression to end-stage renal disease. Diabetic kidney disease has been traditionally classified based on the presence of albuminuria. More recently estimated glomerular filtration rate has also been incorporated into the staging of diabetic kidney disease. While albuminuric diabetic kidney disease is well described, the phenotype of non-albuminuric diabetic kidney disease is now widely accepted. An association between markers of inflammation and diabetic kidney disease has previously been demonstrated. Effector molecules of the innate immune system including C-reactive protein, interleukin-6, and tumor necrosis factor-α are increased in patients with diabetic kidney disease. Furthermore, renal infiltration of neutrophils, macrophages, and lymphocytes are observed in renal biopsies of patients with diabetic kidney disease. Similarly high serum neutrophil and low serum lymphocyte counts have been shown to be associated with diabetic kidney disease. The neutrophil-lymphocyte ratio is considered a robust measure of systemic inflammation and is associated with the presence of inflammatory conditions including the metabolic syndrome and insulin resistance. Cross-sectional studies have demonstrated a link between high levels of the above inflammatory biomarkers and diabetic kidney disease. Further longitudinal studies will be required to determine if these readily available inflammatory biomarkers can accurately predict the presence and prognosis of diabetic kidney disease, above and beyond albuminuria, and estimated glomerular filtration rate.

Oral tolerance in neonates: from basics to potential prevention of allergic disease.

PubMed

Verhasselt, V

2010-07-01

Oral tolerance refers to the observation that prior feeding of an antigen induces local and systemic immune tolerance to that antigen. Physiologically, this process is probably of central importance for preventing inflammatory responses to the numerous dietary and microbial antigens present in the gut. Defective oral tolerance can lead to gut inflammatory disease, food allergies, and celiac disease. In the last two cases, the diseases develop early in life, stressing the necessity of understanding how oral tolerance is set up in neonates. This article reviews the parameters that have been outlined in adult animal models as necessary for tolerance induction and assesses whether these factors operate in neonates. In addition, we highlight the factors that are specific for this period of life and discuss how they could have an impact on oral tolerance. We pay particular attention to maternal influence on early oral tolerance induction through breast-feeding and outline the major parameters that could be modified to optimize tolerance induction in early life and possibly prevent allergic diseases.

Simultaneously targeting inflammatory response and parasite sequestration in brain to treat Experimental Cerebral Malaria

PubMed Central

Dende, Chaitanya; Meena, Jairam; Nagarajan, Perumal; Panda, Amulya K.; Rangarajan, Pundi N.; Padmanaban, Govindarajan

2015-01-01

Malaria afflicts around 200 million people annually, with a mortality number close to 600,000. The mortality rate in Human Cerebral Malaria (HCM) is unacceptably high (15–20%), despite the availability of artemisinin-based therapy. An effective adjunct therapy is urgently needed. Experimental Cerebral Malaria (ECM) in mice manifests many of the neurological features of HCM. Migration of T cells and parasite-infected RBCs (pRBCs) into the brain are both necessary to precipitate the disease. We have been able to simultaneously target both these parameters of ECM. Curcumin alone was able to reverse all the parameters investigated in this study that govern inflammatory responses, CD8+ T cell and pRBC sequestration into the brain and blood brain barrier (BBB) breakdown. But the animals eventually died of anemia due to parasite build-up in blood. However, arteether-curcumin (AC) combination therapy even after the onset of symptoms provided complete cure. AC treatment is a promising therapeutic option for HCM. PMID:26227888

Long-Term Oral Administration of Capsicum baccatum Extracts Does Not Alter Behavioral, Hematological, and Metabolic Parameters in CF1 Mice

PubMed Central

Zimmer, Aline Rigon; Leonardi, Bianca; Kalinine, Eduardo; de Souza, Diogo Onofre; Portela, Luis Valmor; Gosmann, Grace

2012-01-01

Our group showed that crude ethanol (CE) and butanol (BUT) extracts of Capsicum baccatum presented anti-inflammatory and antioxidant properties. Furthermore, the flavonoid and total phenolic contents were positively correlated with both of these properties observed for C. baccatum extracts. The present study demonstrated that 60 days of oral administration of CE and BUT (200 mg/kg) in mice did not cause significant differences in the following parameters evaluated: hematological profile, body weight and relative weight of visceral organs, systemic lipid profile, glucose homeostasis (GTT), kidney and hepatic biochemical markers, and spontaneous locomotion and anxiety-like behavior. Altogether, these results indicate for the first time that the long-term oral administration of C. baccatum extracts does not affect specific aspects of CF1 mice physiology, suggesting their safety, building up the venue to test their efficacy in animal models underlying persistent activation of oxidative and inflammatory pathways. PMID:23320023

A comparative study of the antihyaluronidase, antiurease, antioxidant, antimicrobial and physicochemical properties of different unifloral degrees of chestnut (Castanea sativa Mill.) honeys.

PubMed

Kolayli, Sevgi; Can, Zehra; Yildiz, Oktay; Sahin, Huseyin; Karaoglu, Sengul Alpay

2016-01-01

This study was planned to investigate some physicochemical and anti-inflammatory, antioxidant, antimicrobial properties of three different degrees of unifloral characters of chestnut honeys. Antihyaluronidase, antiurease and antimicrobial activities were evaluated as anti-inflammatory characteristics. Total phenolic contents, flavonoids, tannins, phenolic profiles, ferric-reducing antioxidant power (FRAP), scavenging activities of 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS + ) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals were evaluated as antioxidant properties. Color, optical rotation, conductivity, moisture, pH and ash content were evaluated as physicochemical parameters, and some sugars content, prolin, diastase, HMF and minerals (Na, K, Ca, P, Fe, Cu and Zn) were evaluated as chemical and biochemical parameters. All studied physicochemical and biological active properties were changed in line with the unifloral character of the chestnut honeys. A higher unifloral character was found associated with greater apitherapeutic capacity of the honey, as well as biological active compounds.

Methotrexate Reduces DNA Integrity in Sperm From Men With Inflammatory Bowel Disease.

PubMed

Ley, Dana; Jones, Jeffrey; Parrish, John; Salih, Sana; Caldera, Freddy; Tirado, Edna; Leader, Benjamin; Saha, Sumona

2018-06-01

There are few data on the effects of methotrexate on reproductive capacity in men with inflammatory bowel diseases (IBDs). We performed a case-control study to determine the effects of methotrexate on sperm quality and genetic integrity. We compared sperm samples from 7 men with IBD who had been exposed to methotrexate for at least 3 months with sperm samples collected from 1912 age-matched men at fertility centers (controls) where sperm parameters would be expected to be worse than those of the general population. Sperm were evaluated by basic semen analysis and advanced sperm integrity testing. In samples from men with IBD, all basic semen analysis parameters were within normal limits. However, these samples had reduced sperm integrity, based on significant increases in levels of DNA fragmentation and damage from oxidative stress compared with controls. Our findings indicate that methotrexate can reduce DNA integrity in sperm and cause damage via oxidative stress. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Piroxicam derivatives THz classification

NASA Astrophysics Data System (ADS)

Sterczewski, Lukasz A.; Grzelczak, Michal P.; Nowak, Kacper; Szlachetko, Bogusław; Plinska, Stanislawa; Szczesniak-Siega, Berenika; Malinka, Wieslaw; Plinski, Edward F.

2016-02-01

In this paper we report a new approach to linking the terahertz spectral shapes of drug candidates having a similar molecular structure to their chemical and physical parameters. We examined 27 newly-synthesized derivatives of a well-known nonsteroidal anti-inflammatory drug Piroxicam used for treatment of inflammatory arthritis and chemoprevention of colon cancer. The testing was carried out by means of terahertz pulsed spectroscopy (TPS). Using chemometric techniques we evaluated their spectral similarity in the terahertz range and attempted to link the position on the principal component analysis (PCA) score map to the similarity of molecular descriptors. A simplified spectral model preserved 75% and 85.1% of the variance in 2 and 3 dimensions respectively, compared to the input 1137. We have found that in 85% of the investigated samples a similarity of the physical and chemical parameters corresponds to a similarity in the terahertz spectra. The effects of data preprocessing on the generated maps are also discussed. The technique presented can support the choice of the most promising drug candidates for clinical trials in pharmacological research.

Investigation of Homogeneous Relaxation Model Parameters and their Implications for Gasoline Injectors

DOE PAGES

Saha, Kaushik; Som, Sibendu; Battistoni, Michele

2017-01-01

Flash boiling is known to be a common phenomenon for gasoline direct injection (GDI) engine sprays. The Homogeneous Relaxation Model has been adopted in many recent numerical studies for predicting cavitation and flash boiling. The Homogeneous Relaxation Model is assessed in this study. Sensitivity analysis of the model parameters has been documented to infer the driving factors for the flash-boiling predictions. The model parameters have been varied over a range and the differences in predictions of the extent of flashing have been studied. Apart from flashing in the near nozzle regions, mild cavitation is also predicted inside the gasoline injectors.more » The variation in the predicted time scales through the model parameters for predicting these two different thermodynamic phenomena (cavitation, flash) have been elaborated in this study. Turbulence model effects have also been investigated by comparing predictions from the standard and Re-Normalization Group (RNG) k-ε turbulence models.« less

Characterization of Initial Parameter Information for Lifetime Prediction of Electronic Devices.

PubMed

Li, Zhigang; Liu, Boying; Yuan, Mengxiong; Zhang, Feifei; Guo, Jiaqiang

2016-01-01

Newly manufactured electronic devices are subject to different levels of potential defects existing among the initial parameter information of the devices. In this study, a characterization of electromagnetic relays that were operated at their optimal performance with appropriate and steady parameter values was performed to estimate the levels of their potential defects and to develop a lifetime prediction model. First, the initial parameter information value and stability were quantified to measure the performance of the electronics. In particular, the values of the initial parameter information were estimated using the probability-weighted average method, whereas the stability of the parameter information was determined by using the difference between the extrema and end points of the fitting curves for the initial parameter information. Second, a lifetime prediction model for small-sized samples was proposed on the basis of both measures. Finally, a model for the relationship of the initial contact resistance and stability over the lifetime of the sampled electromagnetic relays was proposed and verified. A comparison of the actual and predicted lifetimes of the relays revealed a 15.4% relative error, indicating that the lifetime of electronic devices can be predicted based on their initial parameter information.

Characterization of Initial Parameter Information for Lifetime Prediction of Electronic Devices

PubMed Central

Li, Zhigang; Liu, Boying; Yuan, Mengxiong; Zhang, Feifei; Guo, Jiaqiang

2016-01-01

Newly manufactured electronic devices are subject to different levels of potential defects existing among the initial parameter information of the devices. In this study, a characterization of electromagnetic relays that were operated at their optimal performance with appropriate and steady parameter values was performed to estimate the levels of their potential defects and to develop a lifetime prediction model. First, the initial parameter information value and stability were quantified to measure the performance of the electronics. In particular, the values of the initial parameter information were estimated using the probability-weighted average method, whereas the stability of the parameter information was determined by using the difference between the extrema and end points of the fitting curves for the initial parameter information. Second, a lifetime prediction model for small-sized samples was proposed on the basis of both measures. Finally, a model for the relationship of the initial contact resistance and stability over the lifetime of the sampled electromagnetic relays was proposed and verified. A comparison of the actual and predicted lifetimes of the relays revealed a 15.4% relative error, indicating that the lifetime of electronic devices can be predicted based on their initial parameter information. PMID:27907188

The role of animal models in the pharmacological evaluation of emerging anti-inflammatory agents for the treatment of COPD.

PubMed

Fox, J Craig; Fitzgerald, Mary F

2009-06-01

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease that has been relatively under researched compared to other inflammatory diseases. Indeed, thus far there have been no anti-inflammatory therapies specifically approved for COPD and the available anti-inflammatory therapies were originally developed for asthma. The challenges facing research in COPD are multi-faceted; the mechanisms underlying the complex and heterogeneous pathology of this disease require unravelling; the role of inflammation in disease progression needs to be confirmed and new drugs with potential to successfully treat COPD need to be identified. Many of the compounds in the clinic today have been identified through the work performed in a range of animal models of COPD. These models have provided us with an understanding of disease pathology and potential mechanistic pathways and have given us the means to prioritise new chemical entities before entry into the clinic. This review will summarise currently available models of COPD and highlight how they have been used to take a first generation of anti-inflammatory therapies for COPD into clinical development. The predictive nature of these animal models will become clear as these therapies are clinically evaluated. The recurring challenge will be to take emerging pre-clinical and clinical data and use it to continually improve animal models so that they remain a valuable tool in the drug discovery process.

Can Inhibitors of Snake Venom Phospholipases A₂ Lead to New Insights into Anti-Inflammatory Therapy in Humans? A Theoretical Study.

PubMed

Sales, Thaís A; Marcussi, Silvana; da Cunha, Elaine F F; Kuca, Kamil; Ramalho, Teodorico C

2017-10-25

Human phospholipase A₂ ( h PLA₂) of the IIA group (HGIIA) catalyzes the hydrolysis of membrane phospholipids, producing arachidonic acid and originating potent inflammatory mediators. Therefore, molecules that can inhibit this enzyme are a source of potential anti-inflammatory drugs, with different action mechanisms of known anti-inflammatory agents. For the study and development of new anti-inflammatory drugs with this action mechanism, snake venom PLA₂ ( sv PLA₂) can be employed, since the sv PLA₂ has high similarity with the human PLA₂ HGIIA. Despite the high similarity between these secretory PLA₂s , it is still not clear if these toxins can really be employed as an experimental model to predict the interactions that occur with the human PLA₂ HGIIA and its inhibitors. Thus, the present study aims to compare and evaluate, by means of theoretical calculations, docking and molecular dynamics simulations, as well as experimental studies, the interactions of human PLA₂ HGIIA and two sv PLA₂s , Bothrops toxin II and Crotoxin B (BthTX-II and CB, respectively). Our theoretical findings corroborate experimental data and point out that the human PLA₂ HGIIA and sv PLA₂ BthTX-II lead to similar interactions with the studied compounds. From our results, the sv PLA₂ BthTX-II can be used as an experimental model for the development of anti-inflammatory drugs for therapy in humans.

Efficacy of local drug delivery of Achyranthes aspera gel in the management of chronic periodontitis: A clinical study.

PubMed

Boyapati, Ramanarayana; Gojja, Prathibha; Chintalapani, Srikanth; Nagubandi, Kirankumar; Ramisetti, Arpita; Salavadhi, Shyam Sunder

2017-01-01

Periodontitis is an inflammatory disease of microbial origin. Locally delivered antimicrobials reduce subgingival flora. Achyranthes aspera gel has antimicrobial, antioxidant, anti-inflammatory, and immunostimulant effects. To evaluate the efficacy of local drug delivery of A. aspera gel in the management of chronic periodontitis. Thirty patients with chronic periodontitis were considered in the study and categorized into two equal groups (Group A: scaling and root planing (SRP) with A. aspera gel, Group B: SRP with placebo gel). Patients were enlisted from the Department of Periodontics, Mamata Dental College and Hospital. The clinical parameters (gingival index, bleeding on probing, probing pocket depth, and clinical attachment level) were recorded at baseline and 3 months. All the obtained data were sent for statistical analyses using SPSS version 18. The periodontitis and the Achyranthes were statistically analyzed. A comparison of clinical parameters for test group and control group from baseline to 3 months was done using paired t -test. Intergroup comparison for both the groups was done using independent sample t -test. A. aspera gel when delivered locally along with SRP showed a beneficial effect. A. aspera gel as a non-surgical local drug delivery system proved to be without any side effects in the management of periodontitis. A. aspera gel has strong anti-inflammatory effects in addition to its antioxidant activity.

Efficacy of local drug delivery of Achyranthes aspera gel in the management of chronic periodontitis: A clinical study

PubMed Central

Boyapati, Ramanarayana; Gojja, Prathibha; Chintalapani, Srikanth; Nagubandi, Kirankumar; Ramisetti, Arpita; Salavadhi, Shyam Sunder

2017-01-01

Context: Periodontitis is an inflammatory disease of microbial origin. Locally delivered antimicrobials reduce subgingival flora. Achyranthes aspera gel has antimicrobial, antioxidant, anti-inflammatory, and immunostimulant effects. Aims: To evaluate the efficacy of local drug delivery of A. aspera gel in the management of chronic periodontitis. Materials and Methods: Thirty patients with chronic periodontitis were considered in the study and categorized into two equal groups (Group A: scaling and root planing (SRP) with A. aspera gel, Group B: SRP with placebo gel). Patients were enlisted from the Department of Periodontics, Mamata Dental College and Hospital. The clinical parameters (gingival index, bleeding on probing, probing pocket depth, and clinical attachment level) were recorded at baseline and 3 months. Statistical Analysis Used: All the obtained data were sent for statistical analyses using SPSS version 18. Results: The periodontitis and the Achyranthes were statistically analyzed. A comparison of clinical parameters for test group and control group from baseline to 3 months was done using paired t-test. Intergroup comparison for both the groups was done using independent sample t-test. Conclusions: A. aspera gel when delivered locally along with SRP showed a beneficial effect. A. aspera gel as a non-surgical local drug delivery system proved to be without any side effects in the management of periodontitis. A. aspera gel has strong anti-inflammatory effects in addition to its antioxidant activity. PMID:29386800

Combination of arginine, glutamine, and omega-3 fatty acid supplements for perioperative enteral nutrition in surgical patients with gastric adenocarcinoma or gastrointestinal stromal tumor (GIST): A prospective, randomized, double-blind study.

PubMed

Ma, C; Tsai, H; Su, W; Sun, L; Shih, Y; Wang, J

2018-05-31

Perioperative enteral nutrition (EN) enriched with immune-modulating substrates is preferable for patients undergoing major abdominal cancer surgery. In this study, perioperative EN enriched with immune-modulating nutrients such as arginine, glutamine, and omega-3 fatty acids was evaluated for its anti-inflammatory efficacy in patients with gastric adenocarcinoma or gastrointestinal stromal tumor (GIST) receiving curative surgery. This prospective, randomized, double-blind study recruited 34 patients with gastric adenocarcinoma or gastric GIST undergoing elective curative surgery. These patients were randomly assigned to the study group, receiving immune-modulating nutrient-enriched EN, or the control group, receiving standard EN from 3 days before surgery (preoperative day 3) to up to postoperative day 14 or discharge. Laboratory and inflammatory parameters were assessed on preoperative day 3 and postoperative day 14 or at discharge. Adverse events (AEs) and clinical outcomes were documented daily and compared between groups. No significant differences were observed between the two groups in selected laboratory and inflammatory parameters, or in their net change, before and after treatment. AEs and clinical outcomes, including infectious complications, overall complications, time to first bowel action, and length of hospital stay after surgery, were comparable between treatment groups (all P > 0.05). Immune-modulating nutrient-enriched EN had no prominent immunomodulation effect compared with that of standard EN.

Serum YKL-40 as a potential biomarker of inflammation in psoriasis.

PubMed

Baran, Anna; Myśliwiec, Hanna; Szterling-Jaworowska, Malgorzata; Kiluk, Paulina; Świderska, Magdalena; Flisiak, Iwona

2018-02-01

YKL-40 is an inflammatory glycoprotein associated with atherosclerosis, cardiovascular disease, diabetes or metabolic syndrome which are common comorbidities in psoriasis. The aim of the study was to assess serum YKL-40 level in psoriasis and elucidate possible associations with disease activity, inflammatory or metabolic parameters and treatment. A total of 37 individuals with active plaque-type psoriasis and 15 healthy controls were enrolled. Blood samples were collected before and after 2 weeks of therapy. Serum YKL-40 concentrations were evaluated by enzyme-linked immunosorbent assay (ELISA). The results were correlated with Psoriasis Area and Severity Index (PASI), body mass index (BMI), inflammatory and biochemical markers, lipid profile and topical therapy. Median YKL-40 serum levels were significantly increased in psoriatic patients in comparison to the controls (p < .0001). No significant correlations between investigated protein and metabolic parameters as BMI (p = .19), glucose (p = .32) nor lipids levels were found. Significant positive relation with CRP (p = .003) or alanine aminotransferase (p = .04) and no correlation with PASI (p = .2) were noted. Serum YKL-40 level remained unchanged (p = .5) after topical treatment, despite clinical improvement. YKL-40 might be a biomarker of psoriasis and inflammation in psoriatic patients, but not a reliable indicator of metabolic conditions, severity of psoriasis nor efficacy of the treatment.

Evidence-based hydro- and balneotherapy in Hungary--a systematic review and meta-analysis.

PubMed

Bender, T; Bálint, G; Prohászka, Z; Géher, P; Tefner, I K

2014-04-01

Balneotherapy is appreciated as a traditional treatment modality in medicine. Hungary is rich in thermal mineral waters. Balneotherapy has been in extensive use for centuries and its effects have been studied in detail. Here, we present a systematic review and meta-analysis of clinical trials conducted with Hungarian thermal mineral waters, the findings of which have been published by Hungarian authors in English. The 122 studies identified in different databases include 18 clinical trials. Five of these evaluated the effect of hydro- and balneotherapy on chronic low back pain, four on osteoarthritis of the knee, and two on osteoarthritis of the hand. One of the remaining seven trials evaluated balneotherapy in chronic inflammatory pelvic diseases, while six studies explored its effect on various laboratory parameters. Out of the 18 studies, 9 met the predefined criteria for meta-analysis. The results confirmed the beneficial effect of balneotherapy on pain with weight bearing and at rest in patients with degenerative joint and spinal diseases. A similar effect has been found in chronic pelvic inflammatory disease. The review also revealed that balneotherapy has some beneficial effects on antioxidant status, and on metabolic and inflammatory parameters. Based on the results, we conclude that balneotherapy with Hungarian thermal-mineral waters is an effective remedy for lower back pain, as well as for knee and hand osteoarthritis.

Correlation of human S100A12 (EN-RAGE) and high-sensitivity C-reactive protein as gingival crevicular fluid and serum markers of inflammation in chronic periodontitis and type 2 diabetes.

PubMed

Pradeep, A R; Martande, Santosh S; Singh, Sonender Pal; Suke, Deepak Kumar; Raju, Arjun P; Naik, Savitha B

2014-04-01

The aim of the present study was to evaluate the levels and correlation of human S100A12 and high-sensitivity C-reactive protein (hs-CRP) in gingival crevicular fluid (GCF) and serum in chronic periodontitis (CP) subjects with and without type 2 diabetes mellitus (DM). A total of 44 subjects were divided into three groups: group 1 had 10 periodontally healthy subjects, group 2 consisted of 17 CP subjects and group 3 had 17 type 2 DM subjects with CP. GCF and serum levels of human S100A12 and hs-CRP were quantified using enzyme-linked immunosorbent assay and immunoturbidimetric analysis, respectively. The clinical outcomes evaluated were gingival index, probing depth and clinical attachment level and the correlations of the two inflammatory mediators with clinical parameters were evaluated. Both human S100A12 and hs-CRP levels increased from group 1 to group 2 to group 3. The GCF and serum values of both these inflammatory mediators correlated positively with each other and with the periodontal parameters evaluated (p < 0.05). Human S100A12 and hs-CRP can be considered as possible GCF and serum markers of inflammatory activity in CP and DM.

Evidence-based hydro- and balneotherapy in Hungary—a systematic review and meta-analysis

NASA Astrophysics Data System (ADS)

Bender, T.; Bálint, G.; Prohászka, Z.; Géher, P.; Tefner, I. K.

2014-04-01

Balneotherapy is appreciated as a traditional treatment modality in medicine. Hungary is rich in thermal mineral waters. Balneotherapy has been in extensive use for centuries and its effects have been studied in detail. Here, we present a systematic review and meta-analysis of clinical trials conducted with Hungarian thermal mineral waters, the findings of which have been published by Hungarian authors in English. The 122 studies identified in different databases include 18 clinical trials. Five of these evaluated the effect of hydro- and balneotherapy on chronic low back pain, four on osteoarthritis of the knee, and two on osteoarthritis of the hand. One of the remaining seven trials evaluated balneotherapy in chronic inflammatory pelvic diseases, while six studies explored its effect on various laboratory parameters. Out of the 18 studies, 9 met the predefined criteria for meta-analysis. The results confirmed the beneficial effect of balneotherapy on pain with weight bearing and at rest in patients with degenerative joint and spinal diseases. A similar effect has been found in chronic pelvic inflammatory disease. The review also revealed that balneotherapy has some beneficial effects on antioxidant status, and on metabolic and inflammatory parameters. Based on the results, we conclude that balneotherapy with Hungarian thermal-mineral waters is an effective remedy for lower back pain, as well as for knee and hand osteoarthritis.

Quality of life and time perspective in inflammatory bowel disease patients.

PubMed

Laguette, Vanessa; Apostolidis, Themis; Dany, Lionel; Bellon, Nelly; Grimaud, Jean-Charles; Lagouanelle-Simeoni, Marie-Claude

2013-12-01

Numerous studies have shown the impact of inflammatory bowel disease (IBD) on patient quality of life (QoL), but no research has yet examined the impact of time's experience in the assessment of QoL in IBD. Our goal is to explore the links between QoL and time perspective (TP) and the role of TP as a determinant of QoL. Data were collected from 156 patients who completed a questionnaire comprising a generic measure (SF-12) and a specific measure (Inflammatory Bowel Disease Questionnaire) of QoL, a measure of TP (ZTPI) and a collection of socio-demographic and medical data. Correlational analyses illustrated the links between TP and QoL. Regression analyses revealed that records of Past-negative and Present-hedonistic perspectives predicted QoL. Past-negative time perspective seemed to have a deleterious impact, while a Present-hedonistic time perspective predicted a better QoL, and this was irrespective of the level of severity of the disease. These results suggest the importance of considering TP as a determinant of psychological QoL. They corroborate earlier findings on the relationship between TP and QoL associated with other pathologies. The past-negative register, which indicates rumination, tells us about the importance of considering the psychological experience of time in order to improve the QoL of patients.

Parameter transferability within homogeneous regions and comparisons with predictions from a priori parameters in the eastern United States

NASA Astrophysics Data System (ADS)

Chouaib, Wafa; Alila, Younes; Caldwell, Peter V.

2018-05-01

The need for predictions of flow time-series persists at ungauged catchments, motivating the research goals of our study. By means of the Sacramento model, this paper explores the use of parameter transfer within homogeneous regions of similar climate and flow characteristics and makes comparisons with predictions from a priori parameters. We assessed the performance using the Nash-Sutcliffe (NS), bias, mean monthly hydrograph and flow duration curve (FDC). The study was conducted on a large dataset of 73 catchments within the eastern US. Two approaches to the parameter transferability were developed and evaluated; (i) the within homogeneous region parameter transfer using one donor catchment specific to each region, (ii) the parameter transfer disregarding the geographical limits of homogeneous regions, where one donor catchment was common to all regions. Comparisons between both parameter transfers enabled to assess the gain in performance from the parameter regionalization and its respective constraints and limitations. The parameter transfer within homogeneous regions outperformed the a priori parameters and led to a decrease in bias and increase in efficiency reaching a median NS of 0.77 and a NS of 0.85 at individual catchments. The use of FDC revealed the effect of bias on the inaccuracy of prediction from parameter transfer. In one specific region, of mountainous and forested catchments, the prediction accuracy of the parameter transfer was less satisfactory and equivalent to a priori parameters. In this region, the parameter transfer from the outsider catchment provided the best performance; less-biased with smaller uncertainty in medium flow percentiles (40%-60%). The large disparity of energy conditions explained the lack of performance from parameter transfer in this region. Besides, the subsurface stormflow is predominant and there is a likelihood of lateral preferential flow, which according to its specific properties further explained the reduced efficiency. Testing the parameter transferability using criteria of similar climate and flow characteristics at ungauged catchments and comparisons with predictions from a priori parameters are a novelty. The ultimate limitations of both approaches are recognized and recommendations are made for future research.

Antioxidant and intestinal anti-inflammatory effects of plant-derived coumarin derivatives.

PubMed

Witaicenis, Aline; Seito, Leonardo Noboru; da Silveira Chagas, Alexandre; de Almeida, Luiz Domingues; Luchini, Ana Carolina; Rodrigues-Orsi, Patrícia; Cestari, Silvia Helena; Di Stasi, Luiz Claudio

2014-02-15

Coumarins, also known as benzopyrones, are plant-derived products with several pharmacological properties, including antioxidant and anti-inflammatory activities. Based on the wide distribution of coumarin derivatives in plant-based foods and beverages in the human diet, our objective was to evaluate both the antioxidant and intestinal anti-inflammatory activities of six coumarin derivatives of plant origin (scopoletin, scoparone, fraxetin, 4-methyl-umbeliferone, esculin and daphnetin) to verify if potential intestinal anti-inflammatory activity was related to antioxidant properties. Intestinal inflammation was induced by intracolonic instillation of TNBS in rats. The animals were treated with coumarins by oral route. The animals were killed 48 h after colitis induction. The colonic segments were obtained after laparotomy and macroscopic and biochemical parameters (determination of glutathione level and myeloperoxidase and alkaline phosphatase activities) were evaluated. The antioxidant properties of these coumarins were examined by lipid peroxidation and DPPH assays. Treatment with esculin, scoparone and daphnetin produced the best protective effects. All coumarin derivatives showed antioxidant activity in the DPPH assay, while daphnetin and fraxetin also showed antioxidant activity by inhibiting lipid peroxidation. Coumarins, except 4-methyl-umbeliferone, also showed antioxidant activity through the counteraction of glutathione levels or through the inhibition of myeloperoxidase activity. The intestinal anti-inflammatory activity of coumarin derivatives were related to their antioxidant properties, suggesting that consumption of coumarins and/or foods rich in coumarin derivatives, particularly daphnetin, esculin and scoparone, could prevent intestinal inflammatory disease. Copyright © 2013 Elsevier GmbH. All rights reserved.

Association of constitutional type of Ayurveda with cardiovascular risk factors, inflammatory markers and insulin resistance

PubMed Central

Mahalle, Namita P.; Kulkarni, Mohan V.; Pendse, Narendra M.; Naik, Sadanand S.

2012-01-01

Context: Ayurveda propounds that diseases manifest from imbalance of doshas. There, have been attempts to indicate biochemical basis of constitutional types described in Ayurveda. Aims: The study was intended to assess the association of constitutional types (Prakriti) with cardiovascular risk factors, inflammatory markers and insulin resistance in subjects with coronary artery disease (CAD). Settings and Design: Hospital based cross sectional study. Materials and Methods: Three hundred patients with CAD >25 years were studied. Assessment of Prakriti was done by using Ayusoft software. Biochemical parameters, inflammatory markers (hsCRP, TNF-alpha and IL-6) and insulin resistance (HOMA-IR) were measured. Statistical Analysis: Was done using EPI INFO, version 3.5.3. Results: Mean age of patients was 60.97±12.5 years. Triglyceride, VLDL and LDL was significantly higher (P<0.0001, P<0.0001 and 0.0355, respectively) and HDL cholesterol (P<0.0001) significantly lower in vatta kapha (VK) Prakriti when compared with other constitution type. VK Prakriti was correlated with diabetes mellitus (r=0.169, P=0.003), hypertension (r=0.211, P≤0.0001) and dyslipidemia (r=0.541, P≤0.0001). Inflammatory markers; IL6, TNF alpha, hsCRP and HOMA IR was highest in VK Prakriti. Inflammatory markers were correlated positively with both VK and Kapha group. Conclusions: There is strong relation of risk factors (diabetes, hypertension, dyslipidemia), insulin resistance, and inflammatory markers with Vata Kapha and Kapha Prakriti. PMID:23125512

Treatment of acne vulgaris with fractional radiofrequency microneedling.

PubMed

Kim, Sang Tae; Lee, Kang Hoon; Sim, Hyung Jun; Suh, Kee Suck; Jang, Min Soo

2014-07-01

Fractional radiofrequency microneedling is a novel radiofrequency technique that uses insulated microneedles to deliver energy to the deep dermis at the point of penetration without destruction of the epidermis. It has been used for the treatment of various dermatological conditions including wrinkles, atrophic scars and hypertrophic scars. There have been few studies evaluating the efficacy of fractional radiofrequency microneedling in the treatment of acne, and none measuring objective parameters like the number of inflammatory and non-inflammatory acne lesions or sebum excretion levels. The safety and efficacy of fractional radiofrequency microneedling in the treatment of acne vulgaris was investigated. In a prospective clinical trial, 25 patients with moderate to severe acne were treated with fractional radiofrequency microneedling. The procedure was carried out three times at 1-month intervals. Acne lesion count, subjective satisfaction score, sebum excretion level and adverse effects were assessed at baseline and at 4, 8 and 12 weeks after the first treatment as well as 4, 8 and 12 weeks after the last treatment. Number of acne lesions (inflammatory and non-inflammatory) decreased. Sebum excretion and subjective satisfaction were more favorable at every time point compared with the baseline values (P < 0.05). Inflammatory lesions responded better than non-inflammatory lesions (P < 0.05). Adverse effects such as pinpoint bleeding, pain and erythema were noted, but were transient and not severe enough to stop treatment. Fractional radiofrequency microneedling is a safe and effective treatment for acne vulgaris. © 2014 Japanese Dermatological Association.

Vaccinium bracteatum Thunb. Exerts Anti-Inflammatory Activity by Inhibiting NF-κB Activation in BV-2 Microglial Cells.

PubMed

Kwon, Seung-Hwan; Ma, Shi-Xun; Ko, Yong-Hyun; Seo, Jee-Yeon; Lee, Bo-Ram; Lee, Taek Hwan; Kim, Sun Yeou; Lee, Seok-Yong; Jang, Choon-Gon

2016-09-01

This study was designed to evaluate the pharmacological effects of Vaccinium bracteatum Thunb. methanol extract (VBME) on microglial activation and to identify the underlying mechanisms of action of these effects. The anti-inflammatory properties of VBME were studied using lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. We measured the production of nitric oxide (NO), inducible NO synthase (iNOS), cyclooxygenase (COX)-2, prostaglandin E₂ (PGE₂), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) as inflammatory parameters. We also examined the effect of VBME on intracellular reactive oxygen species (ROS) production and the activity of nuclear factor-kappa B p65 (NF-κB p65). VBME significantly inhibited LPS-induced production of NO and PGE2 and LPS-mediated upregulation of iNOS and COX-2 expression in a dose-dependent manner; importantly, VBME was not cytotoxic. VBME also significantly reduced the generation of the pro-inflammatory cytokines TNF-α, IL-1β, and IL-6. In addition, VBME significantly dampened intracellular ROS production and suppressed NF-κB p65 translocation by blocking IκB-α phosphorylation and degradation in LPS-stimulated BV2 cells. Our findings indicate that VBME inhibits the production of inflammatory mediators in BV-2 microglial cells by suppressing NF-κB signaling. Thus, VBME may be useful in the treatment of neurodegenerative diseases due to its ability to inhibit inflammatory mediator production in activated BV-2 microglial cells.

The dual anti-inflammatory and antioxidant activities of natural honey promote cell proliferation and neural regeneration in a rat model of colitis.

PubMed

Nooh, Hanaa Z; Nour-Eldien, Nermeen M

2016-07-01

A decreased antioxidant capacity and excessive inflammation are well-known features in the pathogenesis of ulcerative colitis (UC). Recent evidence has suggested a role of honey in reducing colitis-induced inflammatory and oxidative stress markers. In this study, we examined whether the anti-inflammatory and anti-oxidative properties of honey have a beneficial effect on the enteric innervation and cellular proliferation of UC in rat. The colitis was induced in rats by dextran sodium sulphate (DSS). The effect of natural honey on induced colitis was assessed by the following parameters in colonic samples: tissue injury, inflammatory infiltration, interleukin-1β and -6, superoxide dismutase and reduced glutathione. In addition, the expression of tumour necrosis factor-α, inducible NO synthase, caspase-3, CD34, Ki67, S100, c-kit, and neuron-specific enolase were examined by immunohistochemistry. Compared to the DSS-induced colitis group, the honey-treated group had significantly improved macroscopic and microscopic scores and exhibited the down-regulation of oxidative, inflammatory, and apoptotic markers. In addition, up-regulation of intrinsic muscular innervation and epithelial cellular proliferation markers was detected. These results provide new insight into the beneficial role of natural honey in the treatment of DSS-induced colitis via the inhibition of colonic motor dysfunction and the inflammatory-oxidative-apoptotic cascade. In addition, the role of honey in epithelial regeneration was clarified. Copyright © 2016 Elsevier GmbH. All rights reserved.

Atrial Electromechanical Properties in Coeliac Disease.

PubMed

Efe, Tolga Han; Ertem, Ahmet Goktug; Coskun, Yusuf; Bilgin, Murat; Algul, Engin; Beton, Osman; Asarcikli, Lale Dinc; Erat, Mehmet; Ayturk, Mehmet; Yuksel, Ilhami; Yeter, Ekrem

2016-02-01

Coeliac disease (CD) is an autoimmune and inflammatory disorder of the small intestine. There is reasonable evidence linking inflammation to the initiation and continuation of atrial fibrillation (AF) in inflammatory conditions. Atrial electro-mechanic delay (EMD) was suggested as an early marker of AF in previous studies. The objectives of this study were to evaluate atrial electromechanical properties measured by tissue Doppler imaging and simultaneous electrocardiography (ECG) tracing in patients with CD. Thirty-nine patients with coeliac disease (CD), and 26 healthy volunteers, matched for age and sex, were enrolled in the study. Atrial electromechanical properties were measured by using transthoracic echocardiography and surface ECG. Interatrial electro-mechanic delay (EMD), left intraatrial EMD, right intratrial EMD were calculated. There was no difference between CD patients and healthy volunteers in terms of basal characteristics. Patients with CD had significantly prolonged left and right intraatrial EMDs, and interatrial EMD compared to healthy controls (p= 0.03, p= 0.02, p<0.0001, respectively). Interatrial EMD was positively correlated with age, disease duration, anti-gliadin IgG, anti-endomysium and disease status. In multiple linear regression, interatrial EMD was independently associated with disease duration, anti-endomysium and disease status after adjusting for age and sex. In the present study, atrial EMDs were found significantly higher in patients with CD compared with healthy individuals. Measurement of atrial EMD parameters might be used to predict the risk of development of AF in patients with CD. Copyright © 2015 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Fatigue in out-patients with inflammatory bowel disease: Prevalence and predictive factors

PubMed Central

Villoria, Albert; García, Víctor; Dosal, Angelina; Moreno, Laura; Montserrat, Antònia; Figuerola, Ariadna; Horta, Diana; Ramírez-Lázaro, María José

2017-01-01

Background and Aim Fatigue is a common and bothersome symptom in inflammatory bowel disease (IBD) patients. The study was aimed to determine the relationship of biological and psychological factors with IBD-related fatigue. Methods Consecutive clinically inactive IBD outpatients receiving immunosuppressants or biological drugs were enrolled between January and December 2013. Patients completed a Fatigue score (FACIT-F), various psychological, quality of life (IBDQ-9), and IBD activity scores. Biological parameters were assessed, including levels of interleukins (IL-5, IL-8 and IL-12) and micronutrients. Results We prospectively recruited 202 patients (28% ulcerative colitis and 72% Crohn’s disease) for the study. Fatigue measured by FACIT-F score was prevalent in the studied population (54%, 96/177) and higher than in the general population. In the univariate analysis no relation was found between IL levels or micronutrient deficiencies and fatigue. Fatigue was significantly related to female sex, Crohn’s disease, joint disorders, body mass index (BMI), psychological tests, thiopurine use, and anti-TNF treatment. All these variables were included in the multivariate analysis. Female sex (OR: 4.8), high BMI (OR:1.2) and higher depression rates (OR:1.2) were predictors of increased fatigue. High IBDQ-9 score (OR: 0.82) was significantly related to lower degrees of fatigue. Conclusion Fatigue was prevalent in quiescent IBD patients with moderate-to-severe disease. It was associated with high levels of depression, low quality of life, and female sex. No association was found with the other biological and psychological factors evaluated. PMID:28749985

Clinical Value of Assessing Cytokine Levels for the Differential Diagnosis of Bacterial Meningitis in a Pediatric Population

PubMed Central

Ye, Qing; Shao, Wen-Xia; Shang, Shi-Qiang; Shen, Hong-Qiang; Chen, Xue-Jun; Tang, Yong-Min; Yu, Yong-Lin; Mao, Jian-Hua

2016-01-01

Abstract We performed a prospective observational study to evaluate the utility of measuring inflammatory cytokine levels to discriminate bacterial meningitis from similar common pediatric diseases. Inflammatory cytokine levels and other cerebrospinal fluid (CSF) physicochemical indicators were evaluated in 140 patients who were diagnosed with bacterial meningitis via microbiological culture or PCR assay. The CSF concentrations of interleukin (IL)-6 and IL-10, CSF/blood IL-6 and IL-10 ratios, CSF white blood cell count, and CSF micro total protein were significantly elevated in bacterial meningitis patients compared with healthy children or patients with viral encephalitis, epilepsy, or febrile convulsions (P < 0.001). The area under the curve values for CSF concentrations of IL-6 and IL-10, CSF/blood IL-6 and IL-10 ratios, CSF white blood cell count, and CSF micro total protein to identify bacterial meningitis episodes by receiver-operating characteristic analysis were 0.988, 0.949, 0.995, 0.924, 0.945, and 0.928, respectively. The area under the curve for the combination of CSF IL-6 and CSF/blood IL-6 ratio was larger than that for either parameter alone, and the combination exhibited enhanced specificity and positive predictive value. After effective meningitis treatment, CSF IL-6 levels dropped significantly. These results suggest that CSF IL-6 and CSF/blood IL-6 ratio are good biomarkers in discriminating bacterial meningitis. Evaluating CSF IL-6 and CSF/blood IL-6 ratio in combination can improve diagnostic efficiency. Additionally, CSF IL-6 levels can be used to monitor the effects of bacterial meningitis treatment. PMID:27043692

Clinical Value of Assessing Cytokine Levels for the Differential Diagnosis of Bacterial Meningitis in a Pediatric Population.

PubMed

Ye, Qing; Shao, Wen-Xia; Shang, Shi-Qiang; Shen, Hong-Qiang; Chen, Xue-Jun; Tang, Yong-Min; Yu, Yong-Lin; Mao, Jian-Hua

2016-03-01

We performed a prospective observational study to evaluate the utility of measuring inflammatory cytokine levels to discriminate bacterial meningitis from similar common pediatric diseases. Inflammatory cytokine levels and other cerebrospinal fluid (CSF) physicochemical indicators were evaluated in 140 patients who were diagnosed with bacterial meningitis via microbiological culture or PCR assay. The CSF concentrations of interleukin (IL)-6 and IL-10, CSF/blood IL-6 and IL-10 ratios, CSF white blood cell count, and CSF micro total protein were significantly elevated in bacterial meningitis patients compared with healthy children or patients with viral encephalitis, epilepsy, or febrile convulsions (P < 0.001). The area under the curve values for CSF concentrations of IL-6 and IL-10, CSF/blood IL-6 and IL-10 ratios, CSF white blood cell count, and CSF micro total protein to identify bacterial meningitis episodes by receiver-operating characteristic analysis were 0.988, 0.949, 0.995, 0.924, 0.945, and 0.928, respectively. The area under the curve for the combination of CSF IL-6 and CSF/blood IL-6 ratio was larger than that for either parameter alone, and the combination exhibited enhanced specificity and positive predictive value. After effective meningitis treatment, CSF IL-6 levels dropped significantly. These results suggest that CSF IL-6 and CSF/blood IL-6 ratio are good biomarkers in discriminating bacterial meningitis. Evaluating CSF IL-6 and CSF/blood IL-6 ratio in combination can improve diagnostic efficiency. Additionally, CSF IL-6 levels can be used to monitor the effects of bacterial meningitis treatment.

PD-L1 is upregulated by radiochemotherapy in rectal adenocarcinoma patients and associated with a favourable prognosis.

PubMed

Hecht, Markus; Büttner-Herold, Maike; Erlenbach-Wünsch, Katharina; Haderlein, Marlen; Croner, Roland; Grützmann, Robert; Hartmann, Arndt; Fietkau, Rainer; Distel, Luitpold V

2016-09-01

The influence of neoadjuvant radiochemotherapy (RCT) on programmed death-ligand 1 (PD-L1) expression, a predictive marker for programmed cell death protein 1 (PD-1) inhibitor therapy, was studied on tumour and inflammatory cells in rectal adenocarcinoma patients along with its prognostic value. PD-L1 immunohistochemistry was performed on tissue microarrays of 103 pre-RCT biopsies and 159 post-RCT surgical specimens (central tumour, invasive front and normal tissue) of 199 patients. In 63 patients, both samples were available. Proportion and maximum intensity of PD-L1-positive (PD-L1+) cells were evaluated. RCT increased the proportion of PD-L1-expressing cancer cells from 2.1% to 7.8% in the central tumour (p < 0.001) or 9.3% in the invasive front (p < 0.001). Cancer cell PD-L1 on its own could not predict prognosis. High PD-L1 expression on pre-RCT inflammatory cells (maximum intensity: p = 0.048) and post-RCT invasive front inflammatory cells (p = 0.010) correlated with improved no evidence of disease survival. In multivariate analysis, the combination of low PD-L1 in cancer and inflammatory cells was an independent negative prognostic marker for overall survival (OS) pre-RCT (Cox's proportional hazard ratio 0.438, p = 0.045) and in the invasive front post-RCT (Cox's proportional hazard ratio 0.257, p = 0.030). Neoadjuvant RCT is associated with an increased PD-L1 expression in rectal adenocarcinoma patients, which should prompt clinical trials combining radiotherapy and PD-1/PD-L1 pathway blockade. Combined low PD-L1 expression on tumour and inflammatory cells is an independent negative prognostic marker for OS in RCT of rectal adenocarcinoma. Copyright © 2016 Elsevier Ltd. All rights reserved.

Diet-induced obesity reprograms the inflammatory response of the murine lung to inhaled endotoxin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tilton, Susan C., E-mail: susan.tilton@pnnl.gov; Waters, Katrina M.; Karin, Norman J.

The co-occurrence of environmental factors is common in complex human diseases and, as such, understanding the molecular responses involved is essential to determine risk and susceptibility to disease. We have investigated the key biological pathways that define susceptibility for pulmonary infection during obesity in diet-induced obese (DIO) and regular weight (RW) C57BL/6 mice exposed to inhaled lipopolysaccharide (LPS). LPS induced a strong inflammatory response in all mice as indicated by elevated cell counts of macrophages and neutrophils and levels of proinflammatory cytokines (MDC, MIP-1γ, IL-12, RANTES) in the bronchoalveolar lavage fluid. Additionally, DIO mice exhibited 50% greater macrophage cell counts,more » but decreased levels of the cytokines, IL-6, TARC, TNF-α, and VEGF relative to RW mice. Microarray analysis of lung tissue showed over half of the LPS-induced expression in DIO mice consisted of genes unique for obese mice, suggesting that obesity reprograms how the lung responds to subsequent insult. In particular, we found that obese animals exposed to LPS have gene signatures showing increased inflammatory and oxidative stress response and decreased antioxidant capacity compared with RW. Because signaling pathways for these responses can be common to various sources of environmentally induced lung damage, we further identified biomarkers that are indicative of specific toxicant exposure by comparing gene signatures after LPS exposure to those from a parallel study with cigarette smoke. These data show obesity may increase sensitivity to further insult and that co-occurrence of environmental stressors result in complex biosignatures that are not predicted from analysis of individual exposures. - Highlights: ► Obesity modulates inflammatory markers in BAL fluid after LPS exposure. ► Obese animals have a unique transcriptional signature in lung after LPS exposure. ► Obesity elevates inflammatory stress and reduces antioxidant capacity in the lung. ► Toxicant-specific biomarkers predict exposure independent of systemic inflammation.« less

The use of a gas chromatograph coupled to a metal oxide sensor for rapid assessment of stool samples from irritable bowel syndrome and inflammatory bowel disease patients

PubMed Central

Shepherd, S F; McGuire, N D; de Lacy Costello, B P J; Ewen, R J; Jayasena, D H; Vaughan, K; Ahmed, I; Probert, C S; Ratcliffe, N M

2016-01-01

There is much clinical interest in the development of a low cost and reliable test for diagnosing inflammatory bowel disease and irritable bowel syndrome, two very distinct diseases that can present with similar symptoms. The assessment of stool samples for the diagnosis of gastro-intestinal diseases is in principle an ideal non-invasive testing method. This paper presents an approach to stool analysis using headspace gas chromatography and a single metal oxide sensor coupled to artificial neural network (ANN) software. Currently the system is able to distinguish samples from patients with irritable bowel syndrome (IBS) from patients with inflammatory bowel disease (IBD) with a sensitivity and specificity of 76% and 88% respectively, with an overall mean predictive accuracy of 76%. PMID:24674940

Ultrasonographic imaging of inflammatory bowel disease in pediatric patients

PubMed Central

Chiorean, Liliana; Schreiber-Dietrich, Dagmar; Braden, Barbara; Cui, Xin-Wu; Buchhorn, Reiner; Chang, Jian-Min; Dietrich, Christoph F

2015-01-01

Inflammatory bowel disease (IBD) is one of the most common chronic gastrointestinal diseases in pediatric patients. Choosing the optimal imaging modality for the assessment of gastrointestinal disease in pediatric patients can be challenging. The invasiveness and patient acceptance, the radiation exposure and the quality performance of the diagnostic test need to be considered. By reviewing the literature regarding imaging in inflammatory bowel disease the value of ultrasound in the clinical management of pediatric patients is highlighted. Transabdominal ultrasound is a useful, noninvasive method for the initial diagnosis of IBD in children; it also provides guidance for therapeutic decisions and helps to characterize and predict the course of the disease in individual patients. Ultrasound techniques including color Doppler imaging and contrast-enhanced ultrasound are promising imaging tools to determine disease activity and complications. Comparative studies between different imaging methods are needed. PMID:25954096

Real­-Time Ensemble Forecasting of Coronal Mass Ejections Using the Wsa-Enlil+Cone Model

NASA Astrophysics Data System (ADS)

Mays, M. L.; Taktakishvili, A.; Pulkkinen, A. A.; Odstrcil, D.; MacNeice, P. J.; Rastaetter, L.; LaSota, J. A.

2014-12-01

Ensemble forecasting of coronal mass ejections (CMEs) provides significant information in that it provides an estimation of the spread or uncertainty in CME arrival time predictions. Real-time ensemble modeling of CME propagation is performed by forecasters at the Space Weather Research Center (SWRC) using the WSA-ENLIL+cone model available at the Community Coordinated Modeling Center (CCMC). To estimate the effect of uncertainties in determining CME input parameters on arrival time predictions, a distribution of n (routinely n=48) CME input parameter sets are generated using the CCMC Stereo CME Analysis Tool (StereoCAT) which employs geometrical triangulation techniques. These input parameters are used to perform n different simulations yielding an ensemble of solar wind parameters at various locations of interest, including a probability distribution of CME arrival times (for hits), and geomagnetic storm strength (for Earth-directed hits). We present the results of ensemble simulations for a total of 38 CME events in 2013-2014. For 28 of the ensemble runs containing hits, the observed CME arrival was within the range of ensemble arrival time predictions for 14 runs (half). The average arrival time prediction was computed for each of the 28 ensembles predicting hits and using the actual arrival time, an average absolute error of 10.0 hours (RMSE=11.4 hours) was found for all 28 ensembles, which is comparable to current forecasting errors. Some considerations for the accuracy of ensemble CME arrival time predictions include the importance of the initial distribution of CME input parameters, particularly the mean and spread. When the observed arrivals are not within the predicted range, this still allows the ruling out of prediction errors caused by tested CME input parameters. Prediction errors can also arise from ambient model parameters such as the accuracy of the solar wind background, and other limitations. Additionally the ensemble modeling sysem was used to complete a parametric event case study of the sensitivity of the CME arrival time prediction to free parameters for ambient solar wind model and CME. The parameter sensitivity study suggests future directions for the system, such as running ensembles using various magnetogram inputs to the WSA model.

Sustained elevated levels of C-reactive protein and ferritin in pulmonary tuberculosis patients remaining culture positive upon treatment initiation

PubMed Central

Oliveira, Marina G.; Mesquita, Eliene D. D.; Silva, Elisangela; Rauwerdink, Anneloek; Cobelens, Frank; Oliveira, Martha M.; Kritski, Afrânio

2017-01-01

Background Clinical trials that evaluate new anti-tubercular drugs and treatment regimens take years to complete due to the slow clearance of Mycobacterium tuberculosis infection and the lack of early biomarkers that predict treatment outcomes. Host Inflammation markers have been associated with tuberculosis (TB) pathogenesis. In the present study, we tested if circulating levels of C-reactive protein (CRP) and ferritin reflect mycobacterial loads and inflammation in pulmonary TB (PTB) patients undergoing anti-tuberculous therapy (ATT). Methods Prospective measurements of CRP and ferritin, used as readouts of systemic inflammation, were performed in cryopreserved serum samples from 165 Brazilian patients with active PTB initiating ATT. Associations between levels of these laboratory parameters with mycobacterial loads in sputum as well as with sputum conversion at day 60 of ATT were tested. Results Circulating levels of both ferritin and CRP gradually decreased over time on ATT. At pre-treatment, concentrations of these parameters were unable to distinguish patients with positive from those with negative acid-fast bacilli (AFB) in sputum cultures. However, patients who remained with positive cultures at day 60 of ATT exhibited heightened levels of these inflammatory markers compared to those with negative cultures at that time point. Conclusions CRP and Ferritin levels in serum may be useful to identify patients with positive cultures at day 60 of ATT. PMID:28384354

Computer-assisted analysis of cell proliferation markers in oral lesions.

PubMed

Teresa, Debora Barreto; Neves, Karina Antunes; Neto, Carlos Benatti; Fregonezi, Paula Andrea Gabrielli; de Oliveira, Maria Rita Brancini; Zuanon, José Antonio Sampaio; Donadi, Eduardo Antonio; Mendes-Junior, Celso Teixeira; Soares, Christiane Pienna

2007-01-01

Abnormalities in any component of the cell cycle regulatory machine may result in oral cancer, and markers of cell proliferation have been used to determine the prognosis of tumor progression. The aim of this study was to determine whether silver-stained nucleolar organizer region (AgNOR) and Ki-67 measurements could improve the assessment of growth rates in oral lesions. Eighty-three oral biopsies were studied, 20 of which were classified as fibrous inflammatory hyperplasia (FIH), 40 as leukoplakia (LKP) and 23 as oral squamous cell carcinoma (OSCC). Within the LKP group, 22 out of 29 biopsies were diagnosed as non-dysplastic leukoplakia (LK) and 18 as dysplastic leukoplakia (DLK), presenting discrete, moderate and severe dysplasia. Ki-67 immunolabeling of the lesions increased steadily in the following order: FIH, DLK, LK and OSCC, indicating that Ki-67 is a good marker for predicting the proliferative fraction among benign, premalignant and malignant oral lesions. The median values of AgNOR parameters indicate that the morphometric index gives better results regarding the proliferative rate than the numerical one. A series of linear regressions between AgNOR parameters and Ki-67 showed positive associations. We conclude that a combination of Ki-67 and morphometric AgNOR analyses could be used as an aid in the determination of the proliferative status of oral epithelial cells in oral cancer.

Quality of Life in Patients With Advanced Cancer: Differential Association With Performance Status and Systemic Inflammatory Response.

PubMed

Laird, Barry J A; Fallon, Marie; Hjermstad, Marianne J; Tuck, Sharon; Kaasa, Stein; Klepstad, Pål; McMillan, Donald C

2016-08-10

Quality of life is a key component of cancer care; however, the factors that determine quality of life are not well understood. The aim of this study was to examine the relationship between quality of life parameters, performance status (PS), and the systemic inflammatory response in patients with advanced cancer. An international biobank of patients with advanced cancer was analyzed. Quality of life was assessed at a single time point by using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C-30 (EORTC QLQ-C30). PS was assessed by using the Eastern Cooperative Oncology Group (ECOG) classification. Systemic inflammation was assessed by using the modified Glasgow Prognostic Score (mGPS), which combines C-reactive protein and albumin. The relationship between quality of life parameters, ECOG PS, and the mGPS was examined. Data were available for 2,520 patients, and the most common cancers were GI (585 patients [22.2%]) and pulmonary (443 patients [17.6%]). The median survival was 4.25 months (interquartile range, 1.36 to 12.9 months). Increasing mGPS (systemic inflammation) and deteriorating PS were associated with deterioration in quality-of-life parameters (P < .001). Increasing systemic inflammation was associated with deterioration in quality-of-life parameters independent of PS. Systemic inflammation was associated with quality-of-life parameters independent of PS in patients with advanced cancer. Further investigation of these relationships in longitudinal studies and investigations of possible effects of attenuating systemic inflammation are now warranted. © 2016 by American Society of Clinical Oncology.

Importance analysis for Hudson River PCB transport and fate model parameters using robust sensitivity studies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, S.; Toll, J.; Cothern, K.

1995-12-31

The authors have performed robust sensitivity studies of the physico-chemical Hudson River PCB model PCHEPM to identify the parameters and process uncertainties contributing the most to uncertainty in predictions of water column and sediment PCB concentrations, over the time period 1977--1991 in one segment of the lower Hudson River. The term ``robust sensitivity studies`` refers to the use of several sensitivity analysis techniques to obtain a more accurate depiction of the relative importance of different sources of uncertainty. Local sensitivity analysis provided data on the sensitivity of PCB concentration estimates to small perturbations in nominal parameter values. Range sensitivity analysismore » provided information about the magnitude of prediction uncertainty associated with each input uncertainty. Rank correlation analysis indicated which parameters had the most dominant influence on model predictions. Factorial analysis identified important interactions among model parameters. Finally, term analysis looked at the aggregate influence of combinations of parameters representing physico-chemical processes. The authors scored the results of the local and range sensitivity and rank correlation analyses. The authors considered parameters that scored high on two of the three analyses to be important contributors to PCB concentration prediction uncertainty, and treated them probabilistically in simulations. They also treated probabilistically parameters identified in the factorial analysis as interacting with important parameters. The authors used the term analysis to better understand how uncertain parameters were influencing the PCB concentration predictions. The importance analysis allowed us to reduce the number of parameters to be modeled probabilistically from 16 to 5. This reduced the computational complexity of Monte Carlo simulations, and more importantly, provided a more lucid depiction of prediction uncertainty and its causes.« less

Fatigue Life Prediction of Metallic Materials Based on the Combined Nonlinear Ultrasonic Parameter

NASA Astrophysics Data System (ADS)

Zhang, Yuhua; Li, Xinxin; Wu, Zhenyong; Huang, Zhenfeng; Mao, Hanling

2017-08-01

The fatigue life prediction of metallic materials is always a tough problem that needs to be solved in the mechanical engineering field because it is very important for the secure service of mechanical components. In this paper, a combined nonlinear ultrasonic parameter based on the collinear wave mixing technique is applied for fatigue life prediction of a metallic material. Sweep experiments are first conducted to explore the influence of driving frequency on the interaction of two driving signals and the fatigue damage of specimens, and the amplitudes of sidebands at the difference frequency and sum frequency are tracked when the driving frequency changes. Then, collinear wave mixing tests are carried out on a pair of cylindrically notched specimens with different fatigue damage to explore the relationship between the fatigue damage and the relative nonlinear parameters. The experimental results show when the fatigue degree is below 65% the relative nonlinear parameter increases quickly, and the growth rate is approximately 130%. If the fatigue degree is above 65%, the increase in the relative nonlinear parameter is slow, which has a close relationship with the microstructure evolution of specimens. A combined nonlinear ultrasonic parameter is proposed to highlight the relationship of the relative nonlinear parameter and fatigue degree of specimens; the fatigue life prediction model is built based on the relationship, and the prediction error is below 3%, which is below the prediction error based on the relative nonlinear parameters at the difference and sum frequencies. Therefore, the combined nonlinear ultrasonic parameter using the collinear wave mixing method can effectively estimate the fatigue degree of specimens, which provides a fast and convenient method for fatigue life prediction.

Anti-inflammatory, analgesic and anti-pyretic activities of standardized root extract of Jasminum sambac.

PubMed

Sengar, Nidhi; Joshi, Apurva; Prasad, Satyendra K; Hemalatha, S

2015-02-03

The plant Jasminum sambac L. (Oleaceae) is cultivated throughout India. The leaves and roots of the plant are used traditionally in the treatment of inflammation, fever and pain. The leaves of the plant have been reported to posses significant anti-inflammatory and analgesic activities. To scientifically validate anti-inflammatory, analgesic and anti-pyretic activities of roots from Jasminum sambac. Ethanol root extract of Jasminum sambac (EJS) was standardized using HPTLC and was subjected to acute oral toxicity study. Further, analgesic activity of EJS at 100, 200 and 400mg/kg, p.o. was evaluated using writhing test on Swiss albino mice and tail-flick test on Charles Foster albino rats. Anti-inflammatory activity of EJS was assessed by carrageenan-induced rat paw edema, cotton pellet-induced granuloma and Freund׳s adjuvant-induced arthritis models, while antipyretic activity was evaluated using Brewer׳s yeast induced pyrexia. In addition, biochemical parameters such as alkaline phosphatase (ALP), aspartate transaminase (AST), alanine transaminase (ALT), lipid peroxidation (LPO), superoxide dismutase (SOD) and catalase (CAT) in blood serum and edematous tissue of rats exposed to acute (carrageenan) and granulomatous tissue in sub-chronic (cotton pellet granuloma) inflammation models were also evaluated. Phytochemical analysis of EJS revealed the presence of flavonoids, phenols, saponins, tannins and carbohydrates in major quantities, while the quantity of hesperidin in EJS (using HPTLC) was found to be 4.25%w/w. EJS at 400mg/kg, p.o. reduced writhing count up to 49.21%, whereas in tail-flick test, EJS in a dose dependent manner increased latency in flicking tail. EJS at 400mg/kg, p.o. showed significant anti-inflammatory activity after 2nd, 3rd, 4th and 6thh of treatment in carrageenan-induced edema, while a 33.58% inhibition in cotton pellet induced granuloma formation was observed at same dose level. EJS significantly (p<0.001) inhibited adjuvant-induced arthritis and also showed significant antipyretic activity. Further, a significant reversal in alterations of all the biochemical parameters (except ALP) in tissues was also observed. The study confirms the anti-inflammatory, analgesic and antipyretic activity of EJS which may be attributed to the presence of various phytoconstituents quantified especially hesperidin which have already been reported for its significant role in the treatment of inflammation and associated problems. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Effect of correlated observation error on parameters, predictions, and uncertainty

USGS Publications Warehouse

Tiedeman, Claire; Green, Christopher T.

2013-01-01

Correlations among observation errors are typically omitted when calculating observation weights for model calibration by inverse methods. We explore the effects of omitting these correlations on estimates of parameters, predictions, and uncertainties. First, we develop a new analytical expression for the difference in parameter variance estimated with and without error correlations for a simple one-parameter two-observation inverse model. Results indicate that omitting error correlations from both the weight matrix and the variance calculation can either increase or decrease the parameter variance, depending on the values of error correlation (ρ) and the ratio of dimensionless scaled sensitivities (rdss). For small ρ, the difference in variance is always small, but for large ρ, the difference varies widely depending on the sign and magnitude of rdss. Next, we consider a groundwater reactive transport model of denitrification with four parameters and correlated geochemical observation errors that are computed by an error-propagation approach that is new for hydrogeologic studies. We compare parameter estimates, predictions, and uncertainties obtained with and without the error correlations. Omitting the correlations modestly to substantially changes parameter estimates, and causes both increases and decreases of parameter variances, consistent with the analytical expression. Differences in predictions for the models calibrated with and without error correlations can be greater than parameter differences when both are considered relative to their respective confidence intervals. These results indicate that including observation error correlations in weighting for nonlinear regression can have important effects on parameter estimates, predictions, and their respective uncertainties.

Evaluation of neutrophil-lymphocyte ratio, platelet-lymphocyte ratio and red blood cell distribution width-platelet ratio as early predictor of acute pancreatitis in pregnancy.

PubMed

İlhan, Mehmet; İlhan, Gülşah; Gök, Ali Fuat Kaan; Bademler, Süleyman; Verit Atmaca, Fatma; Ertekin, Cemalettin

2016-01-01

Acute pancreatitis (AP) is a state of inflammation. It has been widely known that neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and red blood cell distribution width (RDW) to platelet ratio (RPR) reflect systemic inflammation. The aim of this study is to investigate whether these inflammatory markers could be used as reliable markers in early prediction of AP in pregnancy and if there is a relationship between disease severity and these markers. The study group consisted of 14 patients, who developed AP in ongoing pregnancy, and the control group consisted of 30 healthy pregnant women. NLR, PLR and RPR were calculated for both the groups. NLR was significantly elevated in the AP group when compared with the controls (p = 0.00), but there was no statistically significant difference in terms of PLR and RPR (p > 0.05). ROC curve analysis results for NLR showed that there was a significant prediction power of NLR for AP (R(2) = 0.842; p < 0.001). For NLR parameter, if cut-off value is chosen to be 4.1030, then sensitivity is 71.4% and specificity is 100.0%. There was statistically significant and positive correlation between C-reactive protein (CRP) and glucose with NLR (p = 0.001, p = 0.043). It was seen that Ranson was close to be significant (p = 0.051). NLR might be used as an early marker of AP and may have a role in prediction of disease severity.

Impact of gastrointestinal disease states on oral drug absorption - implications for formulation design - a PEARRL review.

PubMed

Effinger, Angela; O'Driscoll, Caitriona M; McAllister, Mark; Fotaki, Nikoletta

2018-05-16

Drug product performance in patients with gastrointestinal (GI) diseases can be altered compared to healthy subjects due to pathophysiological changes. In this review, relevant differences in patients with inflammatory bowel diseases, coeliac disease, irritable bowel syndrome and short bowel syndrome are discussed and possible in vitro and in silico tools to predict drug product performance in this patient population are assessed. Drug product performance was altered in patients with GI diseases compared to healthy subjects, as assessed in a limited number of studies for some drugs. Underlying causes can be observed pathophysiological alterations such as the differences in GI transit time, the composition of the GI fluids and GI permeability. Additionally, alterations in the abundance of metabolising enzymes and transporter systems were observed. The effect of the GI diseases on each parameter is not always evident as it may depend on the location and the state of the disease. The impact of the pathophysiological change on drug bioavailability depends on the physicochemical characteristics of the drug, the pharmaceutical formulation and drug metabolism. In vitro and in silico methods to predict drug product performance in patients with GI diseases are currently limited but could be a useful tool to improve drug therapy. Development of suitable in vitro dissolution and in silico models for patients with GI diseases can improve their drug therapy. The likeliness of the models to provide accurate predictions depends on the knowledge of pathophysiological alterations, and thus, further assessment of physiological differences is essential. © 2018 Royal Pharmaceutical Society.

Treatment of recurrent Clostridium difficile infection using fecal microbiota transplantation in patients with inflammatory bowel disease.

PubMed

Newman, Krista M; Rank, Kevin M; Vaughn, Byron P; Khoruts, Alexander

2017-05-04

We recently compared results of fecal microbiota transplantation (FMT) in patients with refractory, recurrent Clostridium difficile infection (rCDI), with and without underlying inflammatory bowel disease (IBD). Here we extend this cohort and analyze outcomes in greater detail by subtype of IBD. We find that FMT is generally effective in breaking the cycle of CDI recurrence, but its effects on overall IBD progression are much less predictable. We discuss several challenges intrinsic to this complex clinical situation and outline the next steps that can address these challenges going forward.

Carbohydrate nutrition and inflammatory disease mortality in older adults.

PubMed

Buyken, Anette E; Flood, Victoria; Empson, Marianne; Rochtchina, Elena; Barclay, Alan W; Brand-Miller, Jennie; Mitchell, Paul

2010-09-01

Several studies suggest that carbohydrate nutrition is related to oxidative stress and inflammatory markers. We examined whether dietary glycemic index (GI), dietary fiber, and carbohydrate-containing food groups were associated with the mortality attributable to noncardiovascular, noncancer inflammatory disease in an older Australian cohort. Analysis included 1490 postmenopausal women and 1245 men aged ge 49 y at baseline (1992-1994) from a population-based cohort who completed a validated food-frequency questionnaire. Cox proportional hazards ratios were calculated both for death from diseases in which inflammation or oxidative stress was a predominant contributor and for cardiovascular mortality. Over a 13-y period, 84 women and 86 men died of inflammatory diseases. Women in the highest GI tertile had a 2.9-fold increased risk of inflammatory death compared with women in the lowest GI tertile [multivariate hazard ratio in energy-adjusted tertile 3 (tertile 1 as reference): 2.89; 95% CI: 1.52, 5.51; P for trend: 0.0006, adjusted for age, smoking, diabetes, and alcohol and fiber consumption]. Increasing intakes of foods high in refined sugars or refined starches (P = 0.04) and decreasing intakes of bread and cereals (P = 0.008) or vegetables other than potatoes (P = 0.007) also independently predicted a greater risk, with subjects' GI partly explaining these associations. In men, only an increased consumption of fruit fiber (P = 0.005) and fruit (P = 0.04) conferred an independent decrease in risk of inflammatory death. No associations were observed with cardiovascular mortality. These data provide new epidemiologic evidence of a potentially important link between GI and inflammatory disease mortality among older women.

Tumor necrosis factor-alpha antagonists improve aortic stiffness in patients with inflammatory arthropathies: a controlled study.

PubMed

Angel, Kristin; Provan, Sella Aarrestad; Gulseth, Hanne Løvdahl; Mowinckel, Petter; Kvien, Tore Kristian; Atar, Dan

2010-02-01

The chronic inflammatory state of rheumatoid arthritis and other inflammatory arthropathies, such as ankylosing spondylitis and psoriatic arthritis, contributes to the accelerated atherosclerosis associated with these conditions. This study evaluates the effect of treatment with tumor necrosis factor (TNF)-alpha antagonists on arterial stiffness in patients with inflammatory arthropathies. A total of 60 patients with rheumatoid arthritis, ankylosing spondylitis, or psoriatic arthritis and clinical indication for anti-TNF-alpha therapy were included. Thirty-five patients started with anti-TNF-alpha therapy and were compared with a nontreatment group of 25 patients. Aortic stiffness (aortic pulse wave velocity), augmentation index, and disease activity were assessed at baseline and after 3 months. Aortic pulse wave velocity (mean+/-SD) was reduced in the treatment group but not in the control group (-0.50+/-0.78 m/s versus 0.05+/-0.54 m/s, respectively; P=0.002). Concomitantly, C-reactive protein and the disease activity score were reduced in the treatment group (-9.3+/-20.2 mg/L [P<0.001] and -0.74+/-0.91 [P=0.004]). Augmentation index remained unchanged in both groups (0.1+/-7.1% versus -1.0+/-5.8%, respectively; P=0.53). In a multivariate linear regression model, only treatment with TNF-alpha antagonist and change in mean arterial pressure predicted alterations in aortic pulse wave velocity. In summary, anti-TNF-alpha therapy improved aortic stiffness in patients with inflammatory arthropathies. These findings support the idea that anti-inflammatory treatment has a favorable effect on cardiovascular risk in patients with inflammatory arthropathies.

Exploration of the Anti-Inflammatory Drug Space Through Network Pharmacology: Applications for Drug Repurposing

PubMed Central

de Anda-Jáuregui, Guillermo; Guo, Kai; McGregor, Brett A.; Hur, Junguk

2018-01-01

The quintessential biological response to disease is inflammation. It is a driver and an important element in a wide range of pathological states. Pharmacological management of inflammation is therefore central in the clinical setting. Anti-inflammatory drugs modulate specific molecules involved in the inflammatory response; these drugs are traditionally classified as steroidal and non-steroidal drugs. However, the effects of these drugs are rarely limited to their canonical targets, affecting other molecules and altering biological functions with system-wide effects that can lead to the emergence of secondary therapeutic applications or adverse drug reactions (ADRs). In this study, relationships among anti-inflammatory drugs, functional pathways, and ADRs were explored through network models. We integrated structural drug information, experimental anti-inflammatory drug perturbation gene expression profiles obtained from the Connectivity Map and Library of Integrated Network-Based Cellular Signatures, functional pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome databases, as well as adverse reaction information from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). The network models comprise nodes representing anti-inflammatory drugs, functional pathways, and adverse effects. We identified structural and gene perturbation similarities linking anti-inflammatory drugs. Functional pathways were connected to drugs by implementing Gene Set Enrichment Analysis (GSEA). Drugs and adverse effects were connected based on the proportional reporting ratio (PRR) of an adverse effect in response to a given drug. Through these network models, relationships among anti-inflammatory drugs, their functional effects at the pathway level, and their adverse effects were explored. These networks comprise 70 different anti-inflammatory drugs, 462 functional pathways, and 1,175 ADRs. Network-based properties, such as degree, clustering coefficient, and node strength, were used to identify new therapeutic applications within and beyond the anti-inflammatory context, as well as ADR risk for these drugs, helping to select better repurposing candidates. Based on these parameters, we identified naproxen, meloxicam, etodolac, tenoxicam, flufenamic acid, fenoprofen, and nabumetone as candidates for drug repurposing with lower ADR risk. This network-based analysis pipeline provides a novel way to explore the effects of drugs in a therapeutic space. PMID:29545755

Ginsenoside Rc from Korean Red Ginseng (Panax ginseng C.A. Meyer) Attenuates Inflammatory Symptoms of Gastritis, Hepatitis and Arthritis.

PubMed

Yu, Tao; Rhee, Man Hee; Lee, Jongsung; Kim, Seung Hyung; Yang, Yanyan; Kim, Han Gyung; Kim, Yong; Kim, Chaekyun; Kwak, Yi-Seong; Kim, Jong-Hoon; Cho, Jae Youl

2016-01-01

Korean Red Ginseng (KRG) is an herbal medicine prescribed worldwide that is prepared from Panax ginseng C.A. Meyer (Araliaceae). Out of ginseng's various components, ginsenosides are regarded as the major ingredients, exhibiting anticancer and anti-inflammatory activities. Although recent studies have focused on understanding the anti-inflammatory activities of KRG, compounds that are major anti-inflammatory components, precisely how these can suppress various inflammatory processes has not been fully elucidated yet. In this study, we aimed to identify inhibitory saponins, to evaluate the in vivo efficacy of the saponins, and to understand the inhibitory mechanisms. To do this, we employed in vitro lipopolysaccharide-treated macrophages and in vivo inflammatory mouse conditions, such as collagen (type II)-induced arthritis (CIA), EtOH/HCl-induced gastritis, and lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-triggered hepatitis. Molecular mechanisms were also verified by real-time PCR, immunoblotting analysis, and reporter gene assays. Out of all the ginsenosides, ginsenoside Rc (G-Rc) showed the highest inhibitory activity against the expression of tumor necrosis factor (TNF)-[Formula: see text], interleukin (IL)-1[Formula: see text], and interferons (IFNs). Similarly, this compound attenuated inflammatory symptoms in CIA, EtOH/HCl-mediated gastritis, and LPS/D-galactosamine (D-GalN)-triggered hepatitis without altering toxicological parameters, and without inducing gastric irritation. These anti-inflammatory effects were accompanied by the suppression of TNF-[Formula: see text] and IL-6 production and the induction of anti-inflammatory cytokine IL-10 in mice with CIA. G-Rc also attenuated the increased levels of luciferase activity by IRF-3 and AP-1 but not NF-[Formula: see text]B. In support of this phenomenon, G-Rc reduced TBK1, IRF-3, and ATF2 phosphorylation in the joint and liver tissues of mice with hepatitis. Therefore, our results strongly suggest that G-Rc may be a major component of KRG with useful anti-inflammatory properties due to its suppression of IRF-3 and AP-1 pathways.

Exploration of the Anti-Inflammatory Drug Space Through Network Pharmacology: Applications for Drug Repurposing.

PubMed

de Anda-Jáuregui, Guillermo; Guo, Kai; McGregor, Brett A; Hur, Junguk

2018-01-01

The quintessential biological response to disease is inflammation. It is a driver and an important element in a wide range of pathological states. Pharmacological management of inflammation is therefore central in the clinical setting. Anti-inflammatory drugs modulate specific molecules involved in the inflammatory response; these drugs are traditionally classified as steroidal and non-steroidal drugs. However, the effects of these drugs are rarely limited to their canonical targets, affecting other molecules and altering biological functions with system-wide effects that can lead to the emergence of secondary therapeutic applications or adverse drug reactions (ADRs). In this study, relationships among anti-inflammatory drugs, functional pathways, and ADRs were explored through network models. We integrated structural drug information, experimental anti-inflammatory drug perturbation gene expression profiles obtained from the Connectivity Map and Library of Integrated Network-Based Cellular Signatures, functional pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome databases, as well as adverse reaction information from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). The network models comprise nodes representing anti-inflammatory drugs, functional pathways, and adverse effects. We identified structural and gene perturbation similarities linking anti-inflammatory drugs. Functional pathways were connected to drugs by implementing Gene Set Enrichment Analysis (GSEA). Drugs and adverse effects were connected based on the proportional reporting ratio (PRR) of an adverse effect in response to a given drug. Through these network models, relationships among anti-inflammatory drugs, their functional effects at the pathway level, and their adverse effects were explored. These networks comprise 70 different anti-inflammatory drugs, 462 functional pathways, and 1,175 ADRs. Network-based properties, such as degree, clustering coefficient, and node strength, were used to identify new therapeutic applications within and beyond the anti-inflammatory context, as well as ADR risk for these drugs, helping to select better repurposing candidates. Based on these parameters, we identified naproxen, meloxicam, etodolac, tenoxicam, flufenamic acid, fenoprofen, and nabumetone as candidates for drug repurposing with lower ADR risk. This network-based analysis pipeline provides a novel way to explore the effects of drugs in a therapeutic space.

Treating metabolic syndrome's metaflammation with low level light therapy: preliminary results

NASA Astrophysics Data System (ADS)

Yoshimura, Tania M.; Kato, Ilka T.; Deana, Alessandro M.; Ribeiro, Martha S.

2014-02-01

Metabolic syndrome comprises a constellation of morbidities such as insulin resistance, hyperinsulinemia, atherogenic dyslipidemia, dysglycemia and obesity (especially abdominal). Metabolic alterations are observed in major insulin target organs, increasing the risk of cardiovascular diseases, type-2 diabetes and therefore mortality. Tissue alterations are characterized by immune cells infiltrates (especially activated macrophages). Released inflammatory mediators such as TNF-α induce chronic inflammation in subjects with metabolic syndrome, since inflammatory pathways are activated in the neighboring cells. The intra-abdominal adipose tissue appears to be of particular importance in the onset of the inflammatory state, and strategies contributing to modulate the inflammatory process within this adipose tissue can mitigate the metabolic syndrome consequences. Considering the low level light therapy (LLLT) recognized benefits in inflammatory conditions, we hypothesized this therapeutic approach could promote positive effects in modulating the inflammatory state of metabolic syndrome. That being the scope of this study, male C57BL/6 mice were submitted to a high-fat/high-fructose diet among 8 weeks to induce metabolic syndrome. Animals were then irradiated on the abdominal region during 21 days using an 850 nm LED (6 sessions, 300 seconds per session, 60 mW output power, ~6 J/cm2 fluence, ~19 mW/cm2 fluence rate). Before and during treatment, blood was sampled either from the retroorbital plexus or from tail puncture for glucose, total cholesterol and triglycerides analysis. So far our results indicate no alterations on these metabolic parameters after LLLT. For further investigations, blood was collected for plasma inflammatory cytokine quantification and fresh ex vivo samples of liver and intra-abdominal adipose tissue were harvested for immunohistochemistry purposes.

Gamma-Terpinene Modulates Acute Inflammatory Response in Mice.

PubMed

Ramalho, Theresa Raquel de Oliveira; Oliveira, Maria Talita Pacheco de; Lima, Ana Luisa de Araujo; Bezerra-Santos, Claudio Roberto; Piuvezam, Marcia Regina

2015-09-01

The monoterpene gamma-terpinene is a natural compound present in essential oils of a wide variety of plants, including the Eucalyptus genus, which has been reported to possess anti-inflammatory activity. The goal of this study was to evaluate the effect of gamma-terpinene on several in vivo experimental models of acute inflammation. Swiss mice were pretreated with gamma-terpinene and subjected to protocols of paw edema with different phlogistic agents such as carrageenan, prostaglandin-E2, histamine, or bradykinin. The microvascular permeability was measured by intraperitoneal injection of acetic acid and measuring the amount of protein extravasation. Carrageenan-induced peritonitis was used to analyze the effect of gamma-terpinene on inflammatory cell migration and cytokine production. We also developed an acute lung injury protocol to define the anti-inflammatory effect of gamma-terpinene. Mice pretreated with gamma-terpinene displayed reduced paw edema induced by carrageenan from 1-24 h after challenge. A similar reduction was observed when gamma-terpinene was administered after stimulation with PGE2, bradykinin, and histamine. Treatment with gamma-terpinene also inhibited fluid extravasation in the acetic acid model of microvascular permeability. In a carrageenan-induced peritonitis model, gamma-terpinene treatment reduced neutrophil migration as well as the production of interleukin-1β and tumor necrosis factor-α when compared to nontreated animals, and in the acute lung injury protocol, gamma-terpinene diminished the neutrophil migration into lung tissue independently of the total protein extravasation in the lung. These data demonstrate that, in different models of inflammation, treatment with gamma-terpinene alleviated inflammatory parameters such as edema and pro-inflammatory cytokine production, as well as cell migration into the inflamed site, and that this monoterpene has anti-inflammatory properties. Georg Thieme Verlag KG Stuttgart · New York.

Zinc deficiency induces vascular pro-inflammatory parameters associated with NF-kappaB and PPAR signaling.

PubMed

Shen, Huiyun; Oesterling, Elizabeth; Stromberg, Arnold; Toborek, Michal; MacDonald, Ruth; Hennig, Bernhard

2008-10-01

Marginal intake of dietary zinc can be associated with increased risk of cardiovascular diseases. In the current study we hypothesized that vascular dysfunction and associated inflammatory events are activated during a zinc deficient state. We tested this hypothesis using both vascular endothelial cells and mice lacking the functional LDL-receptor gene. Zinc deficiency increased oxidative stress and NF-kappaB DNA binding activity, and induced COX-2 and E-selectin gene expression, as well as monocyte adhesion in cultured endothelial cells. The NF-kappaB inhibitor CAPE significantly reduced the zinc deficiency-induced COX-2 expression, suggesting regulation through NF-kappaB signaling. PPAR can inhibit NF-kappaB signaling, and our previous data have shown that PPAR transactivation activity requires adequate zinc. Zinc deficiency down-regulated PPARalpha expression in cultured endothelial cells. Furthermore, the PPARgamma agonist rosiglitazone was unable to inhibit the adhesion of monocytes to endothelial cells during zinc deficiency, an event which could be reversed by zinc supplementation. Our in vivo data support the importance of PPAR dysregulation during zinc deficiency. For example, rosiglitazone induced inflammatory genes (e.g., MCP-1) only during zinc deficiency, and adequate zinc was required for rosiglitazone to down-regulate pro-inflammatory markers such as iNOS. In addition, rosiglitazone increased IkappaBalpha protein expression only in zinc adequate mice. Finally, plasma data from LDL-R-deficient mice suggest an overall pro-inflammatory environment during zinc deficiency and support the concept that zinc is required for proper anti-inflammatory or protective functions of PPAR. These studies suggest that zinc nutrition can markedly modulate mechanisms of the pathology of inflammatory diseases such as atherosclerosis.

Does physical exercise reduce excessive daytime sleepiness by improving inflammatory profiles in obstructive sleep apnea patients?

PubMed

Alves, Eduardo da Silva; Ackel-D'Elia, Carolina; Luz, Gabriela Pontes; Cunha, Thays Crosara Abrahão; Carneiro, Gláucia; Tufik, Sergio; Bittencourt, Lia Rita Azeredo; de Mello, Marco Tulio

2013-05-01

Obstructive sleep apnea syndrome (OSAS) is associated with a variety of long-term consequences such as high rates of morbidity and mortality, due to excessive diurnal somnolence as well as cardiovascular and metabolic diseases. Obesity, recurrent episodes of upper airway obstruction, progressive hypoxemia, and sleep fragmentation during sleep cause neural, cardiovascular, and metabolic changes. These changes include activation of peripheral sympathetic nervous system and the hypothalamic-pituitary-adrenal axis, insulin sensitivity, and inflammatory cytokines alterations, which predispose an individual to vascular damage. Previous studies proposed that OSAS modulated the expression and secretion of inflammatory cytokines from fat and other tissues. Independent of obesity, patients with OSAS exhibited elevated levels of C-reactive protein, tumor necrosis factor-α and interleukin-6, which are associated with sleepiness, fatigue, and the development of a variety of metabolic and cardiovascular diseases. OSAS and obesity are strongly associated with each other and share many common pathways that induce chronic inflammation. Previous studies suggested that the protective effect of exercise may be partially attributed to the anti-inflammatory effect of regular exercise, and this effect was observed in obese patients. Although some studies assessed the effects of physical exercise on objective and subjective sleep parameters, the quality of life, and mood in patients with OSAS, no study has evaluated the effects of this treatment on inflammatory profiles. In this review, we cited some studies that directed our opinion to believe that since OSAS causes increased inflammation and has excessive daytime sleepiness as a symptom and being that physical exercise improves inflammatory profiles and possibly OSAS symptoms, it must be that physical exercise improves excessive daytime sleepiness due to its improvement in inflammatory profiles.

Unfavorable inflammatory profile in adults at risk of type 2 diabetes identified by hemoglobin A1c levels according to the American Diabetes Association criteria.

PubMed

Fiorentino, T V; Hribal, M L; Perticone, M; Andreozzi, F; Sciacqua, A; Perticone, F; Sesti, G

2015-04-01

We aimed to evaluate the inflammatory profile of individuals with prediabetes defined by HbA1c levels, according to the new American Diabetes Association criteria, and to determine the ability of HbA1c to identify individuals with subclinical inflammation independently of the contribution of other metabolic parameters such as fasting, 1- or 2-h post-load glucose (PG) levels. High sensitivity C-reactive protein (hsCRP), erythrocyte sedimentation rate (ESR), fibrinogen, white blood cells (WBC) count and complement C3 (C3) were assessed, and oral glucose tolerance test (OGTT) was performed in 711 adults. Subjects were stratified into three groups according to their HbA1c levels. Poor agreement existed between HbA1c and 2-h PG criteria for identification of individuals with prediabetes (κ coefficient = 0.300). As compared with subjects having HbA1c <5.7 % (39 mmol/mol), individuals with prediabetes (HbA1c 5.7-6.4 %, [39-46 mmol/mol]) exhibited a significant increase of the concentration of five inflammatory markers (hsCRP, ESR, fibrinogen, WBC count, C3) as well as of a cluster of inflammatory markers, as measured by an inflammatory score after adjusting for sex, age, smoking, fasting, 1- and 2-h PG levels. In multiple regression models including sex, age, body mass index, smoking habit, fasting, 1- and 2-h PG levels, and HOMA index, HbA1c levels were significant independent contributors to each of the five inflammatory markers examined. These data suggest that HbA1c is a reliable marker of glucose homeostasis, and may identify individuals at increased risk of diabetes with unfavorable inflammatory profile independently from fasting and 2-h PG levels.

Ethnic Variation in Inflammatory Profile in Tuberculosis

PubMed Central

Coussens, Anna K.; Wilkinson, Robert J.; Nikolayevskyy, Vladyslav; Elkington, Paul T.; Hanifa, Yasmeen; Islam, Kamrul; Timms, Peter M.; Bothamley, Graham H.; Claxton, Alleyna P.; Packe, Geoffrey E.; Darmalingam, Mathina; Davidson, Robert N.; Milburn, Heather J.; Baker, Lucy V.; Barker, Richard D.; Drobniewski, Francis A.; Mein, Charles A.; Bhaw-Rosun, Leena; Nuamah, Rosamond A.; Griffiths, Christopher J.; Martineau, Adrian R.

2013-01-01

Distinct phylogenetic lineages of Mycobacterium tuberculosis (MTB) cause disease in patients of particular genetic ancestry, and elicit different patterns of cytokine and chemokine secretion when cultured with human macrophages in vitro. Circulating and antigen-stimulated concentrations of these inflammatory mediators might therefore be expected to vary significantly between tuberculosis patients of different ethnic origin. Studies to characterise such variation, and to determine whether it relates to host or bacillary factors, have not been conducted. We therefore compared circulating and antigen-stimulated concentrations of 43 inflammatory mediators and 14 haematological parameters (inflammatory profile) in 45 pulmonary tuberculosis patients of African ancestry vs. 83 patients of Eurasian ancestry in London, UK, and investigated the influence of bacillary and host genotype on these profiles. Despite having similar demographic and clinical characteristics, patients of differing ancestry exhibited distinct inflammatory profiles at presentation: those of African ancestry had lower neutrophil counts, lower serum concentrations of CCL2, CCL11 and vitamin D binding protein (DBP) but higher serum CCL5 concentrations and higher antigen-stimulated IL-1 receptor antagonist and IL-12 secretion. These differences associated with ethnic variation in host DBP genotype, but not with ethnic variation in MTB strain. Ethnic differences in inflammatory profile became more marked following initiation of antimicrobial therapy, and immunological correlates of speed of elimination of MTB from the sputum differed between patients of African vs. Eurasian ancestry. Our study demonstrates a hitherto unappreciated degree of ethnic heterogeneity in inflammatory profile in tuberculosis patients that associates primarily with ethnic variation in host, rather than bacillary, genotype. Candidate immunodiagnostics and immunological biomarkers of response to antimicrobial therapy should be derived and validated in tuberculosis patients of different ethnic origin. PMID:23853590

The Prognostic Nutritional Index Predicts Survival and Identifies Aggressiveness of Gastric Cancer.

PubMed

Eo, Wan Kyu; Chang, Hye Jung; Suh, Jungho; Ahn, Jin; Shin, Jeong; Hur, Joon-Young; Kim, Gou Young; Lee, Sookyung; Park, Sora; Lee, Sanghun

2015-01-01

Nutritional status has been associated with long-term outcomes in cancer patients. The prognostic nutritional index (PNI) is calculated by serum albumin concentration and absolute lymphocyte count, and it may be a surrogate biomarker for nutritional status and possibly predicts overall survival (OS) of gastric cancer. We evaluated the value of the PNI as a predictor for disease-free survival (DFS) in addition to OS in a cohort of 314 gastric cancer patients who underwent curative surgical resection. There were 77 patients in PNI-low group (PNI ≤ 47.3) and 237 patients in PNI-high group (PNI > 47.3). With a median follow-up of 36.5 mo, 5-yr DFS rates in PNI-low group and PNI-high group were 63.5% and 83.6% and 5-yr OS rates in PNI-low group and PNI-high group were 63.5% and 88.4%, respectively (DFS, P < 0.0001; OS, P < 0.0001). In the multivariate analysis, the only predictors for DFS were PNI, tumor-node-metastasis (TNM) stage, and perineural invasion, whereas the only predictors for OS were PNI, age, TNM stage, and perineural invasion. In addition, the PNI was independent of various inflammatory markers. In conclusion, the PNI is an independent prognostic factor for both DFS and OS, and provides additional prognostic information beyond pathologic parameters.

The contribution of inflammasome components on macrophage response to surface nanotopography and chemistry

NASA Astrophysics Data System (ADS)

Christo, Susan; Bachhuka, Akash; Diener, Kerrilyn R.; Vasilev, Krasimir; Hayball, John D.

2016-05-01

Implantable devices have become an established part of medical practice. However, often a negative inflammatory host response can impede the integration and functionality of the device. In this paper, we interrogate the role of surface nanotopography and chemistry on the potential molecular role of the inflammasome in controlling macrophage responses. To achieve this goal we engineered model substrata having precisely controlled nanotopography of predetermined height and tailored outermost surface chemistry. Bone marrow derived macrophages (BMDM) were harvested from genetically engineered mice deficient in the inflammasome components ASC, NLRP3 and AIM2. These cells were then cultured on these nanoengineered substrata and assessed for their capacity to attach and express pro-inflammatory cytokines. Our data provide evidence that the inflammasome components ASC, NLRP3 and AIM2 play a role in regulating macrophage adhesion and activation in response to surface nanotopography and chemistry. The findings of this paper are important for understanding the inflammatory consequences caused by biomaterials and pave the way to the rational design of future implantable devices having controlled and predictable inflammatory outcomes.

Evaluation of blood neutrophil-lymphocyte ratio and platelet distribution width as inflammatory markers in patients with fibromyalgia.

PubMed

Aktürk, Semra; Büyükavcı, Raikan

2017-08-01

Fibromyalgia syndrome (FMS) is characterized by chronic widespread pain and systemic symptoms. The aetiology and pathogenesis of fibromyalgia are not yet fully understood. Blood neutrophil/lymphocyte ratio (NLR) is a marker of systemic inflammatory response. Platelet distribution width (PDW) and mean platelet volume (MPV) are the determinants of platelet activation and studied as markers in inflammatory diseases. The aim of the present study was to evaluate levels of NLR,PDW and MPV in patients with fibromyalgia. A total of 197 FMS patients and 53 healthy controls are included in the study. Demographic characteristics, erythrocyte sedimentation rate, C-reactive protein, neutrophil, lymphocyte and platelet counts, platelet distribution width and mean platelet volume levels were recorded. In the patient group, the blood NLR and MPV were significantly higher and the PDW was significantly lower compared to the control group. In the roc curve analysis, blood PDW ≥had 90.4% sensitivity and 90% specificity in predicting fibromyalgia. The results of this study suggest NLR and PDW as promising inflammatory markers indicating fibromyalgia and may be beneficial in facilitating the diagnosis of FMS patients.

[Application of basic research to development of diagnostics and therapeutic agents against inflammatory diseases].

PubMed

Izuhara, Kenji; Ohta, Shoichiro; Arima, Kazuhiko; Suzuki, Shoichi; Inamitsu, Masako; Yamamoto, Ken-ichi

2013-10-01

Biomarkers are generally important for the treatment of patients from the points of diagnosis of disease, assessment of cure, assessment of prognosis such as metastasis or recurrence, prevention of disease, and prediction of drug efficacy. Currently it is well accepted that allergic diseases such as bronchial asthma and atopic dermatitis are not single diseases, but syndromes encompassing different diseases entities. Therefore, it is important to cluster allergic disease patients to assess prognosis or the choice of therapeutic drugs, and useful biomarkers are required for these purposes. Periostin, an extracellular matrix protein, has recently emerged as a biomarker useful for clustering asthma patients. We further found that periostin plays an important role in allergic inflammation and based on this finding we are now developing therapeutic agents targeting periostin against allergic diseases. Since periostin is involved in the pathogenesis of various inflammatory diseases in addition to allergic diseases, such diagnostics and therapeutic agents can be applied to many inflammatory diseases. In this article, we describe the history of periostin research and our application of basic research to the development of diagnostics and therapeutic agents against inflammatory diseases.

Discovery of Pyrazolo[4,3-c]quinolines Derivatives as Potential Anti-Inflammatory Agents through Inhibiting of NO Production.

PubMed

Tseng, Chih-Hua; Tung, Chun-Wei; Peng, Shin-I; Chen, Yeh-Long; Tzeng, Cherng-Chyi; Cheng, Chih-Mei

2018-04-28

The synthesis and anti-inflammatory effects of certain pyrazolo[4,3- c ]quinoline derivatives 2a ⁻ 2r are described. The anti-inflammatory activities of these derivatives were evaluated by means of inhibiting nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Among them, 3-amino-4-(4-hydroxyphenylamino)-1 H -pyrazolo[4,3- c ]-quinoline ( 2i ) and 4-(3-amino-1 H -pyrazolo[4,3- c ]quinolin-4-ylamino)benzoic acid ( 2m ) exhibited significant inhibition of LPS-stimulated NO production with a potency approximately equal to that of the positive control, 1400 W. Important structure features were analyzed by quantitative structure⁻activity relationship (QSAR) analysis to give better insights into the structure determinants for predicting the inhibitory effects on the accumulation of nitric oxide for RAW 264.7 cells in response to LPS. In addition, our results indicated that their anti-inflammatory effects involve the inhibition of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) protein expression. Further studies on the structural optimization are ongoing.

[The contribution of inflammatory process in pathogenesis and natural history of atrial fibrillation].

PubMed

Zyśko, Dorota; Gajek, Jacek; Mazurek, Walentyna

2005-02-01

The inflammatory process plays important role in pathogenesis of some cardiovascular diseases. Atrial fibrillation is atrial arrhythmia with rapid, asynchronous activation of atrial myocytes. The inflammatory process can be responsible for atrial electrical and anatomical remodeling and therefore shifts towards arrhythmia persistence. The presence of systemic inflammation may be assessed by means of C-reactive protein (CRP) measurement. Maximal concentration of CRP coincidences with the peak of paroxysmal atrial fibrillation occurrence in patients after cardiac surgery. In patients with sinus rhythm the concentration of CRP is a risk factor for this arrhythmia in long-term follow-up. In patients with atrial fibrillation mean CRP concentration is 2-fold higher comparing to control group. CRP concentration is higher in patients with chronic than paroxysmal form of this arrhythmia. High CRP level predicts worse results of direct current cardioversion and more frequent paroxysms of atrial fibrillation during follow-up. Besides of, the patients with echocardiographic signs of thromboembolic risk have higher CRP levels than control subjects. There is no data about the influence of anti-inflammatory therapy on atrial fibrillation or its recurrences.

Cytokine-induced immune deviation as a therapy for inflammatory autoimmune disease.

PubMed

Racke, M K; Bonomo, A; Scott, D E; Cannella, B; Levine, A; Raine, C S; Shevach, E M; Röcken, M

1994-11-01

The properties and outcome of an immune response are best predicted by the lymphokine phenotype of the responding T cells. Cytokines produced by CD4+ T helper type 1 (Th1) T cells mediate delayed type hypersensitivity (DTH) and inflammatory responses, whereas cytokines produced by Th2 T cells mediate helper T cell functions for antibody production. To determine whether induction of Th2-like cells would modulate an inflammatory response, interleukin 4 (IL-4) was administered to animals with experimental allergic encephalomyelitis (EAE), a prototypic autoimmune disease produced by Th1-like T cells specific for myelin basic protein (MBP). IL-4 treatment resulted in amelioration of clinical disease, the induction of MBP-specific Th2 cells, diminished demyelination, and inhibition of the synthesis of inflammatory cytokines in the central nervous system (CNS). Modulation of an immune response from one dominated by excessive activity of Th1-like T cells to one dominated by the protective cytokines produced by Th2-like T cells may have applicability to the therapy of certain human autoimmune diseases.

[Analysis of risk factors for low bone mineral density in patients with inflammatory bowel disease].

PubMed

Park, Jae Jung; Jung, Sung Ae; Noh, Young Wook; Kang, Min Jung; Jung, Ji Min; Kim, Seong Eun; Jung, Hye Kyung; Shim, Ki Nam; Kim, Tae Hun; Yoo, Kwon; Moon, Il Hwan; Hong, Young Sun

2010-04-01

Several clinical risk factors for low bone mineral density (BMD) in the patients with inflammatory bowel disease (IBD) have been suggested. However, its prevalence and pathophysiology in Korean population have not been fully studied. The aim of this study was to investigate the prevalence and risk factors for low BMD in Korean IBD patient. BMD of the lumbar spine and femur was evaluated using dual-energy X-ray absorptiometry in 30 patients with IBD. Biochemical parameters of bone metabolism, such as serum calcium, phosphorus, osteocalcin, and deoxypyridinoline were measured. The associations between low BMD and clinical parameters such as disease duration, disease activity, drug history, body mass index (BMI), and others were evaluated retrospectively using medical records. Low BMD at the lumbar spine or femur was observed in 63.3% of the patients, and there was no significant difference between the patients with Crohns disease and ulcerative colitis. Clinical and biochemical parameters were irrelevant to BMD. In the patients without glucocorticoid treatment prior to BMD measurement, already 50.0% of patients had low BMD. Low BMD is a common feature in Korean IBD patients, even those who do not use glucocorticoid. The multiple factors may be involved in the pathogenesis of low BMD. Therefore, BMD should be examined in all IBD patients, irrespective of glucocorticoid treatment.

Quantitative contrast-enhanced ultrasound for monitoring vedolizumab therapy in inflammatory bowel disease patients: a pilot study.

PubMed

Goertz, Ruediger S; Klett, Daniel; Wildner, Dane; Atreya, Raja; Neurath, Markus F; Strobel, Deike

2018-01-01

Background Microvascularization of the bowel wall can be visualized and quantified non-invasively by software-assisted analysis of derived time-intensity curves. Purpose To perform software-based quantification of bowel wall perfusion using quantitative contrast-enhanced ultrasound (CEUS) according to clinical response in patients with inflammatory bowel disease treated with vedolizumab. Material and Methods In a prospective study, in 18 out of 34 patients, high-frequency ultrasound of bowel wall thickness using color Doppler flow combined with CEUS was performed at baseline and after 14 weeks of treatment with vedolizumab. Clinical activity scores at week 14 were used to differentiate between responders and non-responders. CEUS parameters were calculated by software analysis of the video loops. Results Nine of 18 patients (11 with Crohn's disease and seven with ulcerative colitis) showed response to treatment with vedolizumab. Overall, the responder group showed a significant decrease in the semi-quantitative color Doppler vascularization score. Amplitude-derived CEUS parameters of mural microvascularization such as peak enhancement or wash-in rate decreased in responders, in contrast with non-responders. Time-derived parameters remained stable or increased during treatment in all patients. Conclusion Analysis of bowel microvascularization by CEUS shows statistically significant changes in the wash-in-rate related to response of vedolizumab therapy.

Long-term in vivo polychlorinated biphenyl 126 exposure induces oxidative stress and alters proteomic profile on islets of Langerhans

NASA Astrophysics Data System (ADS)

Loiola, Rodrigo Azevedo; Dos Anjos, Fabyana Maria; Shimada, Ana Lúcia; Cruz, Wesley Soares; Drewes, Carine Cristiane; Rodrigues, Stephen Fernandes; Cardozo, Karina Helena Morais; Carvalho, Valdemir Melechco; Pinto, Ernani; Farsky, Sandra Helena

2016-06-01

It has been recently proposed that exposure to polychlorinated biphenyls (PCBs) is a risk factor to type 2 diabetes mellitus (DM2). We investigated this hypothesis using long-term in vivo PCB126 exposure to rats addressing metabolic, cellular and proteomic parameters. Male Wistar rats were exposed to PCB126 (0.1, 1 or 10 μg/kg of body weight/day; for 15 days) or vehicle by intranasal instillation. Systemic alterations were quantified by body weight, insulin and glucose tolerance, and blood biochemical profile. Pancreatic toxicity was measured by inflammatory parameters, cell viability and cycle, free radical generation, and proteomic profile on islets of Langerhans. In vivo PCB126 exposure enhanced the body weight gain, impaired insulin sensitivity, reduced adipose tissue deposit, and elevated serum triglycerides, cholesterol, and insulin levels. Inflammatory parameters in the pancreas and cell morphology, viability and cycle were not altered in islets of Langerhans. Nevertheless, in vivo PCB126 exposure increased free radical generation and modified the expression of proteins related to oxidative stress on islets of Langerhans, which are indicative of early β-cell failure. Data herein obtained show that long-term in vivo PCB126 exposure through intranasal route induced alterations on islets of Langerhans related to early end points of DM2.

The safe use of Doliocarpus dentatus in the gestational period: Absence of changes in maternal reproductive performance, embryo-fetal development and DNA integrity.

PubMed

Ishikawa, Raissa Borges; Vani, Juliana Miron; das Neves, Silvia Cordeiro; Rabacow, Ana Paula Maluf; Kassuya, Cândida Aparecida Leite; Croda, Júlio; Cardoso, Claudia Andrea Lima; Monreal, Antônio Carlos Duenhas Ferreira; Antoniolli, Andreia Conceição Milan Brochado; Cunha-Laura, Andréa Luiza; Oliveira, Rodrigo Juliano

2018-05-10

Doliocarpus dentatus (Dilleniaceae) is commonly used in Brazil for the treatment of inflammatory process pain and urinary retention. Previous studies of our group have demonstrated the anti-inflammatory and antimycobacterial action of the ethanolic extract of Doliocarpus dentatus (EEDd) as well as the safety of its use. we investigated the effects of EEDd on reproductive performance, fetal development and DNA integrity in pregnant female Swiss mice. thirty female Swiss mice were divided into three experimental groups (n = 10): control group treated with 1% tween-80 and EEDd1 and EEDd2 groups treated with EEDd at doses of 100 and 1000 mg/kg, respectively. The treatment occurred by oral gavage throughout the gestational period. At the end of pregnancy, parameters related to reproductive performance, embryofoetal development and DNA integrity was evaluated. both doses of the extract tested did not alter the reproductive parameters, did not present significant differences in the embryofetal development when compared to the control group and also did not induce the formation of micronuclei. the EEDd do not alter the reproductive parameters, embryofetal development and DNA integrity, ensuring its safe use during pregnancy. Copyright © 2018 Elsevier B.V. All rights reserved.

Peroxisome proliferator-activated receptor alpha (PPARalpha) agonists down-regulate alpha2-macroglobulin expression by a PPARalpha-dependent mechanism.

EPA Science Inventory

Peroxisome proliferator-activated receptor alpha (PPARα) regulates transcription of genes involved both in lipid and glucose metabolism as well as inflammation. Fibrates are PPARα ligands used to normalize lipid and glucose parameters and exert anti-inflammatory effects. Fibrates...

Linking physiological parameters to perturbations in the human exposome: Environmental exposures modify blood pressure and lung function via inflammatory cytokine pathway

EPA Science Inventory

Human biomonitoring is an indispensable tool for establishing the systemic effects from external stressors including environmental pollutants, chemicals from consumer products, and pharmaceuticals. This article uses a combination of new results and meta-data from previous work to...

Prediction of gas chromatographic retention indices by the use of radial basis function neural networks.

PubMed

Yao, Xiaojun; Zhang, Xiaoyun; Zhang, Ruisheng; Liu, Mancang; Hu, Zhide; Fan, Botao

2002-05-16

A new method for the prediction of retention indices for a diverse set of compounds from their physicochemical parameters has been proposed. The two used input parameters for representing molecular properties are boiling point and molar volume. Models relating relationships between physicochemical parameters and retention indices of compounds are constructed by means of radial basis function neural networks. To get the best prediction results, some strategies are also employed to optimize the topology and learning parameters of the RBFNNs. For the test set, a predictive correlation coefficient R=0.9910 and root mean squared error of 14.1 are obtained. Results show that radial basis function networks can give satisfactory prediction ability and its optimization is less-time consuming and easy to implement.

Markers of systemic inflammation predict survival in patients with advanced renal cell cancer.

PubMed

Fox, P; Hudson, M; Brown, C; Lord, S; Gebski, V; De Souza, P; Lee, C K

2013-07-09

The host inflammatory response has a vital role in carcinogenesis and tumour progression. We examined the prognostic value of inflammatory markers (albumin, white-cell count and its components, and platelets) in pre-treated patients with advanced renal cell carcinoma (RCC). Using data from a randomised trial, multivariable proportional hazards models were generated to examine the impact of inflammatory markers and established prognostic factors (performance status, calcium, and haemoglobin) on overall survival (OS). We evaluated a new prognostic classification incorporating additional information from inflammatory markers. Of the 416 patients, 362 were included in the analysis. Elevated neutrophil counts, elevated platelet counts, and a high neutrophil-lymphocyte ratio were significant independent predictors for shorter OS in a model with established prognostic factors. The addition of inflammatory markers improves the discriminatory value of the prognostic classification as compared with established factors alone (C-statistic 0.673 vs 0.654, P=0.002 for the difference), with 25.8% (P=0.004) of patients more appropriately classified using the new classification. Markers of systemic inflammation contribute significantly to prognostic classification in addition to established factors for pre-treated patients with advanced RCC. Upon validation of these data in independent studies, stratification of patients using these markers in future clinical trials is recommended.

Mindfulness-Based Stress Reduction training reduces loneliness and pro-inflammatory gene expression in older adults: a small randomized controlled trial.

PubMed

Creswell, J David; Irwin, Michael R; Burklund, Lisa J; Lieberman, Matthew D; Arevalo, Jesusa M G; Ma, Jeffrey; Breen, Elizabeth Crabb; Cole, Steven W

2012-10-01

Lonely older adults have increased expression of pro-inflammatory genes as well as increased risk for morbidity and mortality. Previous behavioral treatments have attempted to reduce loneliness and its concomitant health risks, but have had limited success. The present study tested whether the 8-week Mindfulness-Based Stress Reduction (MBSR) program (compared to a Wait-List control group) reduces loneliness and downregulates loneliness-related pro-inflammatory gene expression in older adults (N = 40). Consistent with study predictions, mixed effect linear models indicated that the MBSR program reduced loneliness, compared to small increases in loneliness in the control group (treatment condition × time interaction: F(1,35) = 7.86, p = .008). Moreover, at baseline, there was an association between reported loneliness and upregulated pro-inflammatory NF-κB-related gene expression in circulating leukocytes, and MBSR downregulated this NF-κB-associated gene expression profile at post-treatment. Finally, there was a trend for MBSR to reduce C Reactive Protein (treatment condition × time interaction: (F(1,33) = 3.39, p = .075). This work provides an initial indication that MBSR may be a novel treatment approach for reducing loneliness and related pro-inflammatory gene expression in older adults. Copyright © 2012 Elsevier Inc. All rights reserved.

Mindfulness-Based Stress Reduction Training Reduces Loneliness and Pro-Inflammatory Gene Expression in Older Adults: A Small Randomized Controlled Trial

PubMed Central

Creswell, J. David; Irwin, Michael R.; Burklund, Lisa J.; Lieberman, Matthew D.; Arevalo, Jesusa M. G.; Ma, Jeffrey; Breen, Elizabeth Crabb; Cole, Steven W.

2013-01-01

Lonely older adults have increased expression of pro-inflammatory genes as well as increased risk for morbidity and mortality. Previous behavioral treatments have attempted to reduce loneliness and its concomitant health risks, but have had limited success. The present study tested whether the 8-week Mindfulness-Based Stress Reduction (MBSR) program (compared to a Wait-List control group) reduces loneliness and downregulates loneliness-related pro-inflammatory gene expression in older adults (N=40). Consistent with study predictions, mixed effect linear models indicated that the MBSR program reduced loneliness, compared to small increases in loneliness in the control group (treatment condition × time interaction: F(1,35)=7.86, p=.008). Moreover, at baseline, there was an association between reported loneliness and upregulated pro-inflammatory NF-κB-related gene expression in circulating leukocytes, and MBSR downregulated this NF-κB-associated gene expression profile at post-treatment. Finally, there was a trend for MBSR to reduce C Reactive Protein (treatment condition × time interaction: (F(1,33)=3.39, p=.075). This work provides an initial indication that MBSR may be a novel treatment approach for reducing loneliness and related pro-inflammatory gene expression in older adults. PMID:22820409

Application of a data assimilation method via an ensemble Kalman filter to reactive urea hydrolysis transport modeling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Juxiu Tong; Bill X. Hu; Hai Huang

2014-03-01

With growing importance of water resources in the world, remediations of anthropogenic contaminations due to reactive solute transport become even more important. A good understanding of reactive rate parameters such as kinetic parameters is the key to accurately predicting reactive solute transport processes and designing corresponding remediation schemes. For modeling reactive solute transport, it is very difficult to estimate chemical reaction rate parameters due to complex processes of chemical reactions and limited available data. To find a method to get the reactive rate parameters for the reactive urea hydrolysis transport modeling and obtain more accurate prediction for the chemical concentrations,more » we developed a data assimilation method based on an ensemble Kalman filter (EnKF) method to calibrate reactive rate parameters for modeling urea hydrolysis transport in a synthetic one-dimensional column at laboratory scale and to update modeling prediction. We applied a constrained EnKF method to pose constraints to the updated reactive rate parameters and the predicted solute concentrations based on their physical meanings after the data assimilation calibration. From the study results we concluded that we could efficiently improve the chemical reactive rate parameters with the data assimilation method via the EnKF, and at the same time we could improve solute concentration prediction. The more data we assimilated, the more accurate the reactive rate parameters and concentration prediction. The filter divergence problem was also solved in this study.« less

Real time identification of the internal combustion engine combustion parameters based on the vibration velocity signal

NASA Astrophysics Data System (ADS)

Zhao, Xiuliang; Cheng, Yong; Wang, Limei; Ji, Shaobo

2017-03-01

Accurate combustion parameters are the foundations of effective closed-loop control of engine combustion process. Some combustion parameters, including the start of combustion, the location of peak pressure, the maximum pressure rise rate and its location, can be identified from the engine block vibration signals. These signals often include non-combustion related contributions, which limit the prompt acquisition of the combustion parameters computationally. The main component in these non-combustion related contributions is considered to be caused by the reciprocating inertia force excitation (RIFE) of engine crank train. A mathematical model is established to describe the response of the RIFE. The parameters of the model are recognized with a pattern recognition algorithm, and the response of the RIFE is predicted and then the related contributions are removed from the measured vibration velocity signals. The combustion parameters are extracted from the feature points of the renovated vibration velocity signals. There are angle deviations between the feature points in the vibration velocity signals and those in the cylinder pressure signals. For the start of combustion, a system bias is adopted to correct the deviation and the error bound of the predicted parameters is within 1.1°. To predict the location of the maximum pressure rise rate and the location of the peak pressure, algorithms based on the proportion of high frequency components in the vibration velocity signals are introduced. Tests results show that the two parameters are able to be predicted within 0.7° and 0.8° error bound respectively. The increase from the knee point preceding the peak value point to the peak value in the vibration velocity signals is used to predict the value of the maximum pressure rise rate. Finally, a monitoring frame work is inferred to realize the combustion parameters prediction. Satisfactory prediction for combustion parameters in successive cycles is achieved, which validates the proposed methods.

Vehicle dynamic prediction systems with on-line identification of vehicle parameters and road conditions.

PubMed

Hsu, Ling-Yuan; Chen, Tsung-Lin

2012-11-13

This paper presents a vehicle dynamics prediction system, which consists of a sensor fusion system and a vehicle parameter identification system. This sensor fusion system can obtain the six degree-of-freedom vehicle dynamics and two road angles without using a vehicle model. The vehicle parameter identification system uses the vehicle dynamics from the sensor fusion system to identify ten vehicle parameters in real time, including vehicle mass, moment of inertial, and road friction coefficients. With above two systems, the future vehicle dynamics is predicted by using a vehicle dynamics model, obtained from the parameter identification system, to propagate with time the current vehicle state values, obtained from the sensor fusion system. Comparing with most existing literatures in this field, the proposed approach improves the prediction accuracy both by incorporating more vehicle dynamics to the prediction system and by on-line identification to minimize the vehicle modeling errors. Simulation results show that the proposed method successfully predicts the vehicle dynamics in a left-hand turn event and a rollover event. The prediction inaccuracy is 0.51% in a left-hand turn event and 27.3% in a rollover event.

Vehicle Dynamic Prediction Systems with On-Line Identification of Vehicle Parameters and Road Conditions

PubMed Central

Hsu, Ling-Yuan; Chen, Tsung-Lin

2012-01-01

This paper presents a vehicle dynamics prediction system, which consists of a sensor fusion system and a vehicle parameter identification system. This sensor fusion system can obtain the six degree-of-freedom vehicle dynamics and two road angles without using a vehicle model. The vehicle parameter identification system uses the vehicle dynamics from the sensor fusion system to identify ten vehicle parameters in real time, including vehicle mass, moment of inertial, and road friction coefficients. With above two systems, the future vehicle dynamics is predicted by using a vehicle dynamics model, obtained from the parameter identification system, to propagate with time the current vehicle state values, obtained from the sensor fusion system. Comparing with most existing literatures in this field, the proposed approach improves the prediction accuracy both by incorporating more vehicle dynamics to the prediction system and by on-line identification to minimize the vehicle modeling errors. Simulation results show that the proposed method successfully predicts the vehicle dynamics in a left-hand turn event and a rollover event. The prediction inaccuracy is 0.51% in a left-hand turn event and 27.3% in a rollover event. PMID:23202231

Population-based study of blood biomarkers in prediction of sub-acute recurrent stroke

PubMed Central

Segal, Helen C; Burgess, Annette I; Poole, Debbie L; Mehta, Ziyah; Silver, Louise E; Rothwell, Peter M

2017-01-01

Background and purpose Risk of recurrent stroke is high in the first few weeks after TIA or stroke and clinic risk prediction tools have only limited accuracy, particularly after the hyper-acute phase. Previous studies of the predictive value of biomarkers have been small, been done in selected populations and have not concentrated on the acute phase or on intensively treated populations. We aimed to determine the predictive value of a panel of blood biomarkers in intensively treated patients early after TIA and stroke. Methods We studied 14 blood biomarkers related to inflammation, thrombosis, atherogenesis and cardiac or neuronal cell damage in early TIA or ischaemic stroke in a population-based study (Oxford Vascular Study). Biomarker levels were related to 90-day risk of recurrent stroke as Hazard Ratio (95%CI) per decile increase, adjusted for age and sex. Results Among 1292 eligible patients there were 53 recurrent ischaemic strokes within 90 days. There were moderate correlations (r>0.40; p<0001) between the inflammatory biomarkers and between the cell damage and thrombotic subsets. However, associations with risk of early recurrent stroke were weak, with significant associations limited to Interleukin-6 (HR=1.12, 1.01-1.24; p=0.035) and C-reactive protein (1.16, 1.02-1.30; p=0.019). When stratified by type of presenting event, P-selectin predicted stroke after TIA (1.31, 1.03-1.66; p=0.028) and C-reactive protein predicted stroke after stroke (1.16, 1.01-1.34; p=0.042). These associations remained after fully adjusting for other vascular risk factors. Conclusion In the largest study to date, we found very limited predictive utility for early recurrent stroke for a panel of inflammatory, thrombotic and cell damage biomarkers. PMID:25158774

A computer-based matrix for rapid calculation of pulmonary hemodynamic parameters in congenital heart disease

PubMed Central

Lopes, Antonio Augusto; dos Anjos Miranda, Rogério; Gonçalves, Rilvani Cavalcante; Thomaz, Ana Maria

2009-01-01

BACKGROUND: In patients with congenital heart disease undergoing cardiac catheterization for hemodynamic purposes, parameter estimation by the indirect Fick method using a single predicted value of oxygen consumption has been a matter of criticism. OBJECTIVE: We developed a computer-based routine for rapid estimation of replicate hemodynamic parameters using multiple predicted values of oxygen consumption. MATERIALS AND METHODS: Using Microsoft® Excel facilities, we constructed a matrix containing 5 models (equations) for prediction of oxygen consumption, and all additional formulas needed to obtain replicate estimates of hemodynamic parameters. RESULTS: By entering data from 65 patients with ventricular septal defects, aged 1 month to 8 years, it was possible to obtain multiple predictions for oxygen consumption, with clear between-age groups (P <.001) and between-methods (P <.001) differences. Using these predictions in the individual patient, it was possible to obtain the upper and lower limits of a likely range for any given parameter, which made estimation more realistic. CONCLUSION: The organized matrix allows for rapid obtainment of replicate parameter estimates, without error due to exhaustive calculations. PMID:19641642

Changes in Pilot Behavior with Predictive System Status Information

NASA Technical Reports Server (NTRS)

Trujillo, Anna C.

1998-01-01

Research has shown a strong pilot preference for predictive information of aircraft system status in the flight deck. However, changes in pilot behavior associated with using this predictive information have not been ascertained. The study described here quantified these changes using three types of predictive information (none, whether a parameter was changing abnormally, and the time for a parameter to reach an alert range) and three initial time intervals until a parameter alert range was reached (ITIs) (1 minute, 5 minutes, and 15 minutes). With predictive information, subjects accomplished most of their tasks before an alert occurred. Subjects organized the time they did their tasks by locus-of-control with no predictive information and for the 1-minute ITI, and by aviatenavigate-communicate for the time for a parameter to reach an alert range and the 15-minute conditions. Overall, predictive information and the longer ITIs moved subjects to performing tasks before the alert actually occurred and had them more mission oriented as indicated by their tasks grouping of aviate-navigate-communicate.

Effect of morphological and functional changes in the secundines on biometric parameters of newborns from dichorionic twin pregnancies.

PubMed

Waszak, Małgorzata; Cieślik, Krystyna; Pietryga, Marek; Lewandowski, Jacek; Chuchracki, Marek; Nowak-Markwitz, Ewa; Bręborowicz, Grzegorz

2016-01-01

The aim of the study was to determine if, and to what extent, structural and functional changes of the secundines influence biometric parameters of neonates from dichorionic twin pregnancies. The study included neonates from dichorionic, diamniotic twin pregnancies, along with their secundines. Based on histopathological examination of the secundines, the mass and dimensions of the placenta, length and condition of the umbilical cord, chorionicity, focal lesions, and microscopic placental abnormalities were determined for 445 pairs of twins. Morphological development of examined twins was characterized on the basis of their six somatic traits, while birth status of the newborns was assessed based on their Apgar scores. Statistical analysis included Student t-tests, Snedecor's F-tests, post-hoc tests, non-parametric chi-squared Pearson's tests, and determination of Spearman coefficients of rank correlation. The lowest values of analyzed somatic traits were observed in twins who had placentas with velamentous or marginal cord insertion. Inflammatory lesions in the placenta and placental abruption turned out to have the greatest impact of all analyzed abnormalities of the secundines. Inflammatory lesions in the placenta were associated with lower values of biometric parameters and a greater likelihood of preterm birth. Neonates with a history of placental abruption were characterized by significantly lower birth weight and smaller chest circumference. Morphological changes in the secundines have a limited impact on biometric parameters of neonates from dichorionic twin pregnancies. In turn, functional changes exert a significant effect and more often contribute to impaired fetal development.

Ghrelin and its Association with Nutritional and Inflammatory Status of Patients on Maintenance Hemodialysis in a South Indian Tertiary Care Hospital

PubMed Central

Vanitha, RN; Kavimani, S; Soundararajan, P; Chamundeeswari, D; Kannan, G; Rengarajan, S

2016-01-01

Background: Malnutrition and inflammation are associated with morbidity and mortality in patients on maintenance hemodialysis (MHD). Ghrelin, an orexigenic peptide hormone, is speculated to be associated with nutritional and inflammatory status in MHD. Aim: To assess the serum total ghrelin levels and its possible relationship with inflammation and nutritional status in patients on MHD. Subjects and Methods: The study was conducted on 90 patients on MHD for 6 months and above (56 males, 34 females, mean age 52.6 [11.7] years; mean dialysis vintage 20.9 [12.1] months) and 70 healthy volunteers as control (5 males, 25 females, mean age 50.6 [9.7] years). Demographics were obtained for the study population, and dialysis-related data were collected for cases. Anthropometry, biochemical parameters, serum total ghrelin and inflammatory markers tumor necrosis factor-alpha (TNF-α), and high-sensitivityC-reactive protein (hsCRP) were assessed for cases and control. Self-reported appetite (five questions of appetite and diet assessment tool) and nutritional status (subjective global assessment-dialysis malnutrition score) were assessed for cases. Results: Ghrelin (242.5 [62.3] pg/mL vs. 80.2 [19.6] pg/mL; P < 0.001), TNF-α (39.8 [15.2] pg/mL vs. 6.5 [1.2] pg/mL; P < 0.001), hsCRP (10.2 [2.8] mg/L vs. 2.7 [0.54] mg/L; P < 0.001) were significantly elevated in cases versus control, anthropometry, and biochemical parameters were significantly decreased in hemodialysis patient. Of 90 cases, (13/90 [14.4%]) were well-nourished, (28/90 [31%]) mild to moderately malnourished, and (49/90 [54.4%]) were moderate to severely malnourished. Appetite was very good for14.4%, good and fair for 47.8%, poor and very poor for 37.8% patients. There was a significant difference in appetite with respect to nutritional status (P < 0.001). Ghrelin had positive correlation with inflammatory markers and negative correlation with nutritional status (P < 0.001). Conclusion: The study identified the association of ghrelin with appetite, nutritional, and inflammatory status of the patients on MHD. PMID:27398245

Humanized Mouse Model of Skin Inflammation Is Characterized by Disturbed Keratinocyte Differentiation and Influx of IL-17A Producing T Cells

PubMed Central

de Oliveira, Vivian L.; Keijsers, Romy R. M. C.; van de Kerkhof, Peter C. M.; Seyger, Marieke M. B.; Fasse, Esther; Svensson, Lars; Latta, Markus; Norsgaard, Hanne; Labuda, Tord; Hupkens, Pieter; van Erp, Piet E. J.; Joosten, Irma; Koenen, Hans J. P. M.

2012-01-01

Humanized mouse models offer a challenging possibility to study human cell function in vivo. In the huPBL-SCID-huSkin allograft model human skin is transplanted onto immunodeficient mice and allowed to heal. Thereafter allogeneic human peripheral blood mononuclear cells are infused intra peritoneally to induce T cell mediated inflammation and microvessel destruction of the human skin. This model has great potential for in vivo study of human immune cells in (skin) inflammatory processes and for preclinical screening of systemically administered immunomodulating agents. Here we studied the inflammatory skin response of human keratinocytes and human T cells and the concomitant systemic human T cell response. As new findings in the inflamed human skin of the huPBL-SCID-huSkin model we here identified: 1. Parameters of dermal pathology that enable precise quantification of the local skin inflammatory response exemplified by acanthosis, increased expression of human β-defensin-2, Elafin, K16, Ki67 and reduced expression of K10 by microscopy and immunohistochemistry. 2. Induction of human cytokines and chemokines using quantitative real-time PCR. 3. Influx of inflammation associated IL-17A-producing human CD4+ and CD8+ T cells as well as immunoregulatory CD4+Foxp3+ cells using immunohistochemistry and -fluorescence, suggesting that active immune regulation is taking place locally in the inflamed skin. 4. Systemic responses that revealed activated and proliferating human CD4+ and CD8+ T cells that acquired homing marker expression of CD62L and CLA. Finally, we demonstrated the value of the newly identified parameters by showing significant changes upon systemic treatment with the T cell inhibitory agents cyclosporine-A and rapamycin. In summary, here we equipped the huPBL-SCID-huSkin humanized mouse model with relevant tools not only to quantify the inflammatory dermal response, but also to monitor the peripheral immune status. This combined approach will gain our understanding of the dermal immunopathology in humans and benefit the development of novel therapeutics for controlling inflammatory skin diseases. PMID:23094018

Negative emotions predict elevated interleukin-6 in the United States but not in Japan.

PubMed

Miyamoto, Yuri; Boylan, Jennifer Morozink; Coe, Christopher L; Curhan, Katherine B; Levine, Cynthia S; Markus, Hazel Rose; Park, Jiyoung; Kitayama, Shinobu; Kawakami, Norito; Karasawa, Mayumi; Love, Gayle D; Ryff, Carol D

2013-11-01

Previous studies conducted in Western cultures have shown that negative emotions predict higher levels of pro-inflammatory biomarkers, specifically interleukin-6 (IL-6). This link between negative emotions and IL-6 may be specific to Western cultures where negative emotions are perceived to be problematic and thus may not extend to Eastern cultures where negative emotions are seen as acceptable and normal. Using samples of 1044 American and 382 Japanese middle-aged and older adults, we investigated whether the relationship between negative emotions and IL-6 varies by cultural context. Negative emotions predicted higher IL-6 among American adults, whereas no association was evident among Japanese adults. Furthermore, the interaction between culture and negative emotions remained even after controlling for demographic variables, psychological factors (positive emotions, neuroticism, extraversion), health behaviors (smoking status, alcohol consumption), and health status (chronic conditions, BMI). These findings highlight the role of cultural context in shaping how negative emotions affect inflammatory physiology and underscore the importance of cultural ideas and practices relevant to negative emotions for understanding of the interplay between psychology, physiology, and health. Copyright © 2013 Elsevier Inc. All rights reserved.

The Bi-Directional Prediction of Carbon Fiber Production Using a Combination of Improved Particle Swarm Optimization and Support Vector Machine.

PubMed

Xiao, Chuncai; Hao, Kuangrong; Ding, Yongsheng

2014-12-30

This paper creates a bi-directional prediction model to predict the performance of carbon fiber and the productive parameters based on a support vector machine (SVM) and improved particle swarm optimization (IPSO) algorithm (SVM-IPSO). In the SVM, it is crucial to select the parameters that have an important impact on the performance of prediction. The IPSO is proposed to optimize them, and then the SVM-IPSO model is applied to the bi-directional prediction of carbon fiber production. The predictive accuracy of SVM is mainly dependent on its parameters, and IPSO is thus exploited to seek the optimal parameters for SVM in order to improve its prediction capability. Inspired by a cell communication mechanism, we propose IPSO by incorporating information of the global best solution into the search strategy to improve exploitation, and we employ IPSO to establish the bi-directional prediction model: in the direction of the forward prediction, we consider productive parameters as input and property indexes as output; in the direction of the backward prediction, we consider property indexes as input and productive parameters as output, and in this case, the model becomes a scheme design for novel style carbon fibers. The results from a set of the experimental data show that the proposed model can outperform the radial basis function neural network (RNN), the basic particle swarm optimization (PSO) method and the hybrid approach of genetic algorithm and improved particle swarm optimization (GA-IPSO) method in most of the experiments. In other words, simulation results demonstrate the effectiveness and advantages of the SVM-IPSO model in dealing with the problem of forecasting.

Targeting Siah2 as Novel Therapy for Metastatic Prostate Cancer

DTIC Science & Technology

2015-10-01

metastasis and responses to curcumin 19 Goals: This proposal tests the hypothesis that chemokine biomarkers that predict biochemical recurrence of...prostate cancer regulate metastatic progression of the cancer and curcumin can inhibit metastasis of prostate cancer by antagonizing inflammatory signaling

Anti-inflammatory and antiallergic activity in vivo of lipophilic Isatis tinctoria extracts and tryptanthrin.

PubMed

Recio, María-Carmen; Cerdá-Nicolás, Miguel; Potterat, Olivier; Hamburger, Matthias; Ríos, José-Luis

2006-05-01

The effects of a supercritical CO2 (SFE) extract, a dichloromethane (DCM) extract from Isatis tinctoria leaf and the alkaloidal constituent tryptanthrin were studied in acute and subchronic experimental models of inflammation. The SFE and DCM extracts showed anti-inflammatory activity in the carrageenan-induced acute mouse paw oedema (ED50 values of 78 mg/kg and 165 mg/kg P. O., respectively) and in the acute tetradecanoylphorbol acetate (TPA)-induced mouse ear oedema in oral (62% and 32% oedema reduction at 100 and 125 mg/kg, respectively) and topical application (37% and 33% reduction of oedema at 0.5 mg/ear). In contrast, tryptanthrin showed no significant anti-inflammatory effect. The DCM extract inhibited oedema formation and neutrophil infiltration in subchronic inflammation in mice induced by repeated application of TPA. The extract showed activity after oral and topical administration by reducing the various parameters of the inflammatory response. The DCM extract (1 mg/ear) inhibited the delayed-type hypersensitivity (DTH) reaction induced by application of dinitrofluorobenzene (DNFB) after topical application. The response during the induction phase (24 h) was decreased by 48%, and the inflammatory phase (48 to 96 h) was reduced by 53 to 56%. The extract had no effect in this model when administered orally. The DCM extract (200 mg/kg P. O.) inhibited the acetic acid-induced writhing by 49%.

Lactobacillus casei and Lactobacillus acidophilus regulate inflammatory pathway and improve antioxidant status in collagen-induced arthritic rats.

PubMed

Amdekar, Sarika; Singh, Vinod; Kumar, Avnish; Sharma, Poonam; Singh, Rambir

2013-01-01

In view of well-established immunomodulatory properties of Lactobacillus, present investigation was carried out to evaluate antioxidant and anti-inflammatory potential of Lactobacillus casei and Lactobacillus acidophilus, against inflammatory pathway and oxidative stress developed in an experimental model of arthritis. Collagen-induced arthritis (CIA) model was used. Oral administration of L. casei, L. acidophilus, standard antiarthritic drug indomethacin, and vehicle were started after induced arthritis and continued up to day 28. Interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-1β, IL-17, IL-4, and IL-10 levels were estimated in serum. In parallel, oxidative stress parameters were also measured from synovial effsuate. All rats were graded for arthritis score at the end of each week. L. casei, L. acidophilus, and indomethacin treatment significantly downregulated proinflammatory and upregulated anti-inflammatory cytokines at P<0.0001. They have significantly decreased oxidative stress in synovial effsuate (P<0.0001) and also arthritis score (P<0.05). Protection provided by L. casei and L. acidophilus was more pronounced than that of indomethacin. These lines of evidence suggest that L. casei and L. acidophilus exert potent protective effect against CIA. It further establishes effective anti-inflammatory and antioxidant properties of Lactobacillus. However, additional clinical investigations are needed to prove the efficacy of Lactobacillus in treatment/management of rheumatoid arthritis.

The influence of occupational chronic lead exposure on the levels of selected pro-inflammatory cytokines and angiogenic factors.

PubMed

Machoń-Grecka, A; Dobrakowski, M; Boroń, M; Lisowska, G; Kasperczyk, A; Kasperczyk, S

2017-05-01

The aim of the study was to determine the effect of occupational exposure to lead on the blood levels of pro-inflammatory cytokines and selected factors that influence angiogenesis. The study population was divided into two groups. The first group consisted of 56 male workers chronically exposed to lead. The second group (control) was comprised of 24 male administrative workers. The serum levels of interleukin 1β (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α) were significantly higher in the group of workers chronically exposed to lead compared to control values by 38%, 68%, and 57%, respectively. Similarly, the values of soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) and fibroblast growth factor-basic (FGF-basic) were higher by 19% and 63%, respectively. In the group of workers chronically exposed to lead, there were positive correlations between the levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) and angiogenic factors (VEGF, FGF-basic, sVEGFR-1, and soluble angiopoietin receptor). In the control group, there were no correlations between the levels of the abovementioned parameters. Results of the present study indicate that chronic occupational lead exposure promotes inflammatory processes via induction of pro-inflammatory cytokines, modulates angiogenesis, and elicits interdependencies between the immune response and angiogenic factors.

Synthesis and pharmacological evaluation of polyfunctional benzimidazole-NSAID chimeric molecules combining anti-inflammatory, immunomodulatory and antioxidant activities.

PubMed

Bansal, Yogita; Silakari, Om

2014-11-01

Polyfunctional compounds comprise a novel class of therapeutic agents for treatment of multifactorial diseases. The present study reports a series of benzimidazole-non-steroidal anti-inflammatory drugs (NSAIDs) conjugates (1-10) as novel polyfunctional compounds synthesized in the presence of orthophosphoric acid. The compounds were evaluated for anti-inflammatory (carageenan-induced paw edema model), immunomodulatory (direct haemagglutination test and carbon clearance index models), antioxidant (in vitro and in vivo) and for ulcerogenic effects. Each of the compound has retained the anti-inflammatory activity of the corresponding parent NSAID while exhibiting significantly reduced gastric ulcers. Additionally, the compounds are found to possess potent immunostimulatory and antioxidant activities. The compound 8 was maximally potent (antibody titre value 358.4 ± 140.21, carbon clearance index 0.053 ± 0.002 and antioxidant EC50 value 0.03 ± 0.006). These compounds, exhibiting such multiple pharmacological activities, can be taken as lead for the development of potent drugs for the treatment of chronic multifactorial diseases involving inflammation, immune system modulation and oxidative stress such as cancers. The Lipinski's parameters suggested the compounds to be bear drug like properties.

Hfe Deficiency Impairs Pulmonary Neutrophil Recruitment in Response to Inflammation

PubMed Central

Benesova, Karolina; Vujić Spasić, Maja; Schaefer, Sebastian M.; Stolte, Jens; Baehr-Ivacevic, Tomi; Waldow, Katharina; Zhou, Zhe; Klingmueller, Ursula; Benes, Vladimir; Mall, Marcus A.; Muckenthaler, Martina U.

2012-01-01

Regulation of iron homeostasis and the inflammatory response are tightly linked to protect the host from infection. Here we investigate how imbalanced systemic iron homeostasis in a murine disease model of hereditary hemochromatosis (Hfe−/− mice) affects the inflammatory responses of the lung. We induced acute pulmonary inflammation in Hfe−/− and wild-type mice by intratracheal instillation of 20 µg of lipopolysaccharide (LPS) and analyzed local and systemic inflammatory responses and iron-related parameters. We show that in Hfe−/− mice neutrophil recruitment to the bronchoalveolar space is attenuated compared to wild-type mice although circulating neutrophil numbers in the bloodstream were elevated to similar levels in Hfe−/− and wild-type mice. The underlying molecular mechanisms are likely multifactorial and include elevated systemic iron levels, alveolar macrophage iron deficiency and/or hitherto unexplored functions of Hfe in resident pulmonary cell types. As a consequence, pulmonary cytokine expression is out of balance and neutrophils fail to be recruited efficiently to the bronchoalveolar compartment, a process required to protect the host from infections. In conclusion, our findings suggest a novel role for Hfe and/or imbalanced iron homeostasis in the regulation of the inflammatory response in the lung and hereditary hemochromatosis. PMID:22745741

Blueberry Anthocyanins-Enriched Extracts Attenuate Cyclophosphamide-Induced Cardiac Injury

PubMed Central

Liu, Yunen; Tan, Dehong; Shi, Lin; Liu, Xinwei; Zhang, Yubiao; Tong, Changci; Song, Dequn; Hou, Mingxiao

2015-01-01

We sought to explore the effect of blueberry anthocyanins-enriched extracts (BAE) on cyclophosphamide (CTX)-induced cardiac injury. The rats were divided randomly into five groups including normal control, CTX 100 mg/kg, BAE 80mg/kg, CTX+BAE 20mg/kg and CTX+BAE 80mg/kg groups. The rats in the three BAE-treated groups were administered BAE for four weeks. Seven days after BAE administration, rats in CTX group and two BAE-treated groups were intraperitoneally injected with a single dose of 100 mg/kg CTX. Cardiac injury was assessed using physiological parameters, Echo, morphological staining, real-time PCR and western blot. In addition, cardiotoxicity indices, inflammatory cytokines expression and oxidative stress markers were also detected. Four weeks 20mg/kg and 80mg/kg dose of BAE treatment following CTX exposure attenuated mean arterial blood pressure, heart rate and activities of heart enzymes, improved cardiac dysfunction, left ventricular hypertrophy and fibrosis. Importantly, BAE also attenuated CTX-induced LV leukocyte infiltration and inflammatory cytokines expression, ameliorated oxidative stress as well as cardiomyocyte apoptosis. In conclusion, BAE attenuated the CTX-induced cardiac injury and the protective mechanisms were related closely to the anti-inflammatory, antioxidant and anti-inflammatory characteristics of BAE. PMID:26133371

Acupuncture to Reduce HIV-Associated Inflammation

PubMed Central

Swanson, Barbara; Keithley, Joyce K.; Johnson, Angela; Fogg, Louis; Adeyemi, Oluwatoyin; Sha, Beverly E.; Snell, Kimberly A.

2015-01-01

Background. HIV infection is associated with systemic inflammation that can increase risk for cardiovascular events. Acupuncture has been shown to have immunomodulatory effects and to improve symptoms in persons with inflammatory conditions. Objective. To test the anti-inflammatory effects of an acupuncture protocol that targets the cholinergic anti-inflammatory pathway (CAIP), a neural mechanism whose activation has been shown to reduce the release of proinflammatory cytokines, in persons with HIV-associated inflammation. Design, Setting, Participants, and Interventions. Double-blind, placebo-controlled clinical trial conducted in an outpatient clinic located in a medically underserved urban neighborhood. Twenty-five clinically-stable HIV-infected persons on antiretroviral therapy were randomized to receive once weekly CAIP-based acupuncture or sham acupuncture. Main Outcome Measures. Outcomes included plasma concentrations of high sensitivity C-reactive protein and D-dimer and fasting lipids. Results. Twenty-five participants completed the protocol (treatment group n = 12, control group n = 13). No adverse events related to the acupuncture protocol were observed. Compared to baseline values, the two groups did not significantly differ in any outcome measures at the end of the acupuncture protocol. Conclusions. CAIP-based acupuncture did not favorably modulate inflammatory or lipid parameters. Additional studies are warranted of CAIP-based protocols of different frequencies/durations. PMID:25922615

Favorable results from the use of herbal and plant products in inflammatory bowel disease: evidence from experimental animal studies

PubMed Central

Triantafillidis, John K.; Triantafyllidi, Aikaterini; Vagianos, Constantinos; Papalois, Apostolos

2016-01-01

The use of herbal therapy for inflammatory bowel disease is increasing worldwide. The aim of this study was to review the available literature on the efficacy of herbal therapy in experimental colitis. All relevant studies published in Medline and Embase up to June 2015 have been reviewed. The results of bowel histology and serum parameters have been recorded. A satisfactory number of published experimental studies, and a quite large one of both herbal and plant products tested in different studies have been reported. The results showed that in the majority of the studies, herbal therapy reduced the inflammatory activity of experimental colitis and diminished the levels of many inflammatory indices, including serum cytokines and indices of oxidative stress. The most promising plant and herbal products were tormentil extracts, wormwoodherb, Aloe vera, germinated barley foodstuff, curcumin, Boswellia serrata, Panax notoginseng, Ixeris dentata, green tea, Cordia dichotoma, Plantago lanceolata, Iridoidglycosides, and mastic gum. Herbal therapies exert their therapeutic benefit via various mechanisms, including immune regulation, anti-oxidant activity, inhibition of leukotriene B4 and nuclear factor-κB, and antiplatelet activity. Large, double-blind clinical studies assessing these natural substances should be urgently conducted. PMID:27366027

Exercise Training Plus Sildenafil Treatment: Role on Autonomic and Inflammatory Markers.

PubMed

Leoni, Luis Antonio B; Fukushima, Andre R; Rocha, Leandro Y; Feriani, Daniele J; Júnior, Hélio José Coelho; Gambassi, Bruno B; Mostarda, Cristiano T; Maifrino, Laura Beatriz Mesiano; Rodrigues, Bruno

2018-06-25

The current study aimed to determine the effects of sildenafil-associated aerobic exercise training (ET) on the physical performance, hemodynamic, autonomic and inflammatory parameters of rats. Male Wistar rats were randomly assigned to: sedentary rats placebo-treated (SP); sedentary rats sildenafil-treated (SS); trained rats placebo-treated (TP); and trained rats sildenafil-treated (TS). Sildenafil treatment consisted of 8 weeks of daily oral gavage (1.5 mg/kg), one hour before the session of ET (60-75% of maximal running speed, 5 days/week, for 8 weeks). After ET period, physical capacity, hemodynamic, autonomic and skeletal muscle inflammatory profile were assessed. Chronic sildenafil treatment causes an additional increase of physical capacity in aerobically trained rats. However, these beneficial effects were accompanied by unwanted alterations, as increased of arterial pressure and peripheral sympathetic modulation, as well as exacerbated inflammatory status on skeletal muscle of rats. Taken together, these data suggest the positive and negative effects of sildenafil chronic administration, associated to aerobic ET, at doses used in clinical practice. This report stresses the importance of paying greater attention to the indiscriminate use of this substance in high-performance sports. © Georg Thieme Verlag KG Stuttgart · New York.

Assessment of adrenocortical reserve capacity and inflammatory parameters in critically ill dogs.

PubMed

Csöndes, Judit; Fábián, Ibolya; Szabó, Bernadett; Máthé, Ákos; Vajdovich, Péter

2017-12-01

Inflammatory markers and adrenocorticotropic hormone (ACTH) stimulation test results may help us recognise critically ill dogs with poor disease outcome. Systemic inflammatory response syndrome (SIRS) criteria, the fast version of the Acute Patient Physiologic and Laboratory Evaluation Score (APPLE fast ), complete blood count, albumin and C-reactive protein (CRP) levels, baseline and stimulated cortisol levels and Δcortisol value were recorded in 50 client-owned dogs admitted to the Small Animal Hospital of the University of Veterinary Medicine Budapest with various inflammatory or neoplastic conditions. Increasing APPLE fast score was associated with a decreasing chance of survival (P = 0.0420). The Δcortisol value was significantly higher in SIRS dogs than in non-SIRS dogs (mean ± SD Δcortisol SIRS : 342.5 ± 273.96; mean ± SD Δcortisol non-SIRS : 175.3 ± 150.35; P = 0.0443). Elevated baseline or stimulated cortisol levels were associated with a higher chance of non-survival (P = 0.0135 and P = 0.0311, respectively). These data indicate that pathologically higher baseline and stimulated cortisol levels represent an exaggerated stress response in critically ill dogs, which is negatively associated with survival.

Using radiance predicted by the P3 approximation in a spherical geometry to predict tissue optical properties

NASA Astrophysics Data System (ADS)

Dickey, Dwayne J.; Moore, Ronald B.; Tulip, John

2001-01-01

For photodynamic therapy of solid tumors, such as prostatic carcinoma, to be achieved, an accurate model to predict tissue parameters and light dose must be found. Presently, most analytical light dosimetry models are fluence based and are not clinically viable for tissue characterization. Other methods of predicting optical properties, such as Monet Carlo, are accurate but far too time consuming for clinical application. However, radiance predicted by the P3-Approximation, an anaylitical solution to the transport equation, may be a viable and accurate alternative. The P3-Approximation accurately predicts optical parameters in intralipid/methylene blue based phantoms in a spherical geometry. The optical parameters furnished by the radiance, when introduced into fluence predicted by both P3- Approximation and Grosjean Theory, correlate well with experimental data. The P3-Approximation also predicts the optical properties of prostate tissue, agreeing with documented optical parameters. The P3-Approximation could be the clinical tool necessary to facilitate PDT of solid tumors because of the limited number of invasive measurements required and the speed in which accurate calculations can be performed.

Association of Inflammation With Loss Of Ability to Walk 400 Meters: Longitudinal Findings From the Inchianti Study

PubMed Central

Vasunilashorn, Sarinnapha; Ferrucci, Luigi; Crimmins, Eileen M.; Bandinelli, Stefania; Guralnik, Jack M.; Patel, Kushang V.

2013-01-01

Objectives To examine relationships between eight markers of inflammation (interleukin [IL]-6, IL-6 receptor [R], C-reactive protein [CRP], tumor necrosis factor [TNF]-α, TNF receptor 1[R1], TNFR2, IL-1 receptor antagonist, IL-18) and incident loss of ability to walk 400 m. Design Prospective cohort study. Setting Older adults enrolled in the InvecchiareInChianti Study. Participants One thousand six community-dwelling participants aged 65+. Measurements The eight inflammatory markers were measured at baseline, and an inflammation score was calculated based on the number of inflammatory markers for which the participant was in the highest quartile. Incidence of mobility disability was determined among participants able to walk 400 m at baseline. Logistic regression models were used to determine whether each of the inflammatory markers and the inflammation score predicts loss of the ability to walk 400 m at six-year follow-up. Results After adjusting for covariates, individuals with aTNFR1 level in each of the top 3 quartiles (Q2, 3, 4) were more likely to be unable to walk 400 m at follow-up compared to those with TNFR1 levels in Q1. When adjusting for the same covariates, participants with an inflammation score of 3 or 4 were more likely to become unable to complete the 400 m walk at follow-up compared to participants with a score of 0. Conclusion These results bring additional evidence to the notion that inflammation is implicated in the mechanisms that cause incident mobility disability and suggest that a combined measure of inflammatory markers may improve our prediction of functional prognosis. PMID:24083386

Association of inflammation with loss of ability to walk 400 meters: longitudinal findings from the Invecchiare in Chianti Study.

PubMed

Vasunilashorn, Sarinnapha; Ferrucci, Luigi; Crimmins, Eileen M; Bandinelli, Stefania; Guralnik, Jack M; Patel, Kushang V

2013-10-01

To examine relationships between eight markers of inflammation (interleukin (IL)-6, IL-6 receptor (R), C-reactive protein (CRP), tumor necrosis factor (TNF)-alpha, TNF receptor 1 (R1), TNFR2, IL-1 receptor antagonist, IL-18) and incident loss of ability to walk 400 m. Prospective cohort study. Older adults enrolled in the Invecchiare in Chianti Study. Community-dwelling participants aged 65 and older (N = 1,006). The eight inflammatory markers were measured at baseline, and an inflammation score was calculated based on the number of inflammatory markers for which the participant was in the highest quartile. Incidence of mobility disability was determined in participants able to walk 400 m at baseline. Logistic regression models were used to determine whether each of the inflammatory markers and the inflammation score predicted loss of the ability to walk 400 m at 6-year follow-up. After adjusting for covariates, individuals with a TNFR1 level in each of the highest three quartiles (Q2, 3, 4) were more likely to be unable to walk 400 m at follow-up than those with TNFR1 levels in Q1. When adjusting for the same covariates, participants with an inflammation score of 3 or 4 were more likely to become unable to walk 400 m at follow-up than participants with a score of 0. These results provide additional evidence that inflammation is a factor in the mechanisms that cause incident mobility disability and suggest that a combined measure of inflammatory markers may improve prediction of functional prognosis. © 2013, Copyright the Authors Journal compilation © 2013, The American Geriatrics Society.

Increased extracellular heat shock protein 90α in severe sepsis and SIRS associated with multiple organ failure and related to acute inflammatory-metabolic stress response in children.

PubMed

Fitrolaki, Michaela-Diana; Dimitriou, Helen; Venihaki, Maria; Katrinaki, Marianna; Ilia, Stavroula; Briassoulis, George

2016-08-01

Mammalian heat-shock-protein (HSP) 90α rapidly responses to environmental insults. We examined the hypothesis that not only serum HSP72 but also HSP90α is increased in the systemic inflammatory response syndrome (SIRS), severe-sepsis (SS), and/or sepsis (S) compared to healthy children (H); we assessed HSP90α relation to (a) multiple organ system failure (MOSF) and (b) inflammatory-metabolic response and severity of illness.A total of 65 children with S, SS, or SIRS and 25 H were included. ELISA was used to evaluate extracellular HSP90α and HSP72, chemiluminescence interleukins (ILs), flow-cytometry neutrophil-CD64 (nCD64)-expression.HSP90α, along with HSP72, were dramatically increased among MOSF patients. Patients in septic groups and SIRS had elevated HSP90α compared to H (P < 0.01). HSP90α was independently related to predicted death rate and severity of illness; positively to HSP72, nCD64, ILs, length of stay, days on ventilator, and fever; negatively to HDL and LDL (P < 0.05). The HSP72 was increased in SS/S and related negatively to HDL and LDL (P < 0.05).Serum HSP90α is markedly elevated in children with severe sepsis and is associated with MOSF. Better than the HSP72, also increased in SS, SIRS, and MOSF, HSP90α is related to the inflammatory stress, fever, outcome endpoints, and predicted mortality and inversely related to the low-LDL/low-HDL stress metabolic pattern.

Independent prognostic value of eosinophil and mast cell infiltration in colorectal cancer tissue.

PubMed

Nielsen, H J; Hansen, U; Christensen, I J; Reimert, C M; Brünner, N; Moesgaard, F

1999-12-01

Overall peritumoural inflammatory cell infiltration is a prognostic variable in solid tumours, but the survival-related impact of the individual cell types within the infiltrate has still not been fully evaluated and compared with the conventional disease classification. In the present study, the prognostic value of individual white cell counts in the peritumoural inflammatory infiltrate in colorectal cancer was assessed. Intra-operative tumour tissue samples from 584 patients undergoing elective surgery for colorectal cancer were included. None of the patients received pre- or post-operative adjuvant chemotherapy. Tissue blocks were cut from the periphery of the tumours and embedded in paraffin. All blocks included both tumour tissue and normal bowel tissue. Serial sections of 4 microm were analysed for tumour tissue inflammatory cell infiltration using a computer- and video-assisted microscope, which allowed semi-automated quantification of cells within a fixed area. Total white cells and individual counts of eosinophils, neutrophils, mast cells, lymphocytes, and plasma cells were evaluated in every tumour specimen. Stratification into four groups with similar numbers of events was used to dichotomize the cell counts with respect to survival. The median observation period was 61 (49-75) months. In a multivariate analysis including Dukes' stage, gender, age, peri-operative blood transfusion, tumour location, and counts of specific inflammatory cells, only advanced Dukes' stage ( p< 0.0001), high age ( p=0.0003), and tumour location in the rectum predicted poor survival, while high counts of eosinophils ( p=0.006) and mast cells ( p=0.02) predicted good survival. Tumour-associated eosinophilia and mastocytosis appear to be independent prognostic variables in colorectal cancer. Future studies should investigate the potential biological role of tumour tissue eosinophils and mast cells in the modulation of tumour growth. Copyright 1999 John Wiley & Sons, Ltd.

Predictors for hospitalization and outpatient visits in patients with inflammatory bowel disease: results from the Swiss Inflammatory Bowel Disease Cohort Study.

PubMed

Sulz, Michael C; Siebert, Uwe; Arvandi, Marjan; Gothe, Raffaella M; Wurm, Johannes; von Känel, Roland; Vavricka, Stephan R; Meyenberger, Christa; Sagmeister, Markus

2013-07-01

Patients with inflammatory bowel disease (IBD) have a high resource consumption, with considerable costs for the healthcare system. In a system with sparse resources, treatment is influenced not only by clinical judgement but also by resource consumption. We aimed to determine the resource consumption of IBD patients and to identify its significant predictors. Data from the prospective Swiss Inflammatory Bowel Disease Cohort Study were analysed for the resource consumption endpoints hospitalization and outpatient consultations at enrolment [1187 patients; 41.1% ulcerative colitis (UC), 58.9% Crohn's disease (CD)] and at 1-year follow-up (794 patients). Predictors of interest were chosen through an expert panel and a review of the relevant literature. Logistic regressions were used for binary endpoints, and negative binomial regressions and zero-inflated Poisson regressions were used for count data. For CD, fistula, use of biologics and disease activity were significant predictors for hospitalization days (all P-values <0.001); age, sex, steroid therapy and biologics were significant predictors for the number of outpatient visits (P=0.0368, 0.023, 0.0002, 0.0003, respectively). For UC, biologics, C-reactive protein, smoke quitters, age and sex were significantly predictive for hospitalization days (P=0.0167, 0.0003, 0.0003, 0.0076 and 0.0175 respectively); disease activity and immunosuppressive therapy predicted the number of outpatient visits (P=0.0009 and 0.0017, respectively). The results of multivariate regressions are shown in detail. Several highly significant clinical predictors for resource consumption in IBD were identified that might be considered in medical decision-making. In terms of resource consumption and its predictors, CD and UC show a different behaviour.

Increased extracellular heat shock protein 90α in severe sepsis and SIRS associated with multiple organ failure and related to acute inflammatory-metabolic stress response in children

PubMed Central

Fitrolaki, Michaela-Diana; Dimitriou, Helen; Venihaki, Maria; Katrinaki, Marianna; Ilia, Stavroula; Briassoulis, George

2016-01-01

Abstract Mammalian heat-shock-protein (HSP) 90α rapidly responses to environmental insults. We examined the hypothesis that not only serum HSP72 but also HSP90α is increased in the systemic inflammatory response syndrome (SIRS), severe-sepsis (SS), and/or sepsis (S) compared to healthy children (H); we assessed HSP90α relation to (a) multiple organ system failure (MOSF) and (b) inflammatory-metabolic response and severity of illness. A total of 65 children with S, SS, or SIRS and 25 H were included. ELISA was used to evaluate extracellular HSP90α and HSP72, chemiluminescence interleukins (ILs), flow-cytometry neutrophil-CD64 (nCD64)-expression. HSP90α, along with HSP72, were dramatically increased among MOSF patients. Patients in septic groups and SIRS had elevated HSP90α compared to H (P < 0.01). HSP90α was independently related to predicted death rate and severity of illness; positively to HSP72, nCD64, ILs, length of stay, days on ventilator, and fever; negatively to HDL and LDL (P < 0.05). The HSP72 was increased in SS/S and related negatively to HDL and LDL (P < 0.05). Serum HSP90α is markedly elevated in children with severe sepsis and is associated with MOSF. Better than the HSP72, also increased in SS, SIRS, and MOSF, HSP90α is related to the inflammatory stress, fever, outcome endpoints, and predicted mortality and inversely related to the low-LDL/low-HDL stress metabolic pattern. PMID:27583886

Investigating the Relationships Between Alcohol Consumption, Cannabis Use, and Circulating Cytokines: A Preliminary Analysis.

PubMed

Karoly, Hollis C; Bidwell, L Cinnamon; Mueller, Raeghan L; Hutchison, Kent E

2018-03-01

In recent years, human and animal studies have converged to support altered inflammatory signaling as a molecular mechanism underlying the pathophysiology of alcohol use disorders (AUDs). Alcohol binds to receptors on immune cells, triggering signaling pathways that produce pro-inflammatory cytokines. Chronic inflammation is associated with tissue damage, which may contribute to negative effects of AUD. Conversely, cannabis is associated with decreased inflammatory signaling, and animal studies suggest that cannabinoids may impact alcohol-induced inflammation. Thus, the impact of cannabis on inflammation in AUDs in humans warrants examination. We explored the relationship between self-reported alcohol and cannabis use and circulating levels of the pro-inflammatory cytokines interleukin 6 (IL-6), IL-8, and IL-1β in the blood. Among 66 regular drinkers (mean age = 30.08), we examined circulating cytokines and administered questionnaires assessing alcohol consumption and days of cannabis use over the past 90 days. We examined whether alcohol consumption, cannabis use, and gender were associated with changes in circulating cytokines, and whether there was a significant interaction between alcohol and cannabis use predicting blood levels of circulating cytokines. A positive association between alcohol and IL-6 emerged. We also observed a negative association between cannabis and IL-1β. Follow-up moderation analyses indicated a cannabis by alcohol interaction predicting circulating IL-6, such that cannabis nonusers showed a stronger relationship between alcohol and IL-6 compared to cannabis users. These preliminary findings suggest that cannabinoid compounds may serve to mitigate inflammation associated with alcohol use. In addition, the present results provide data to inform future investigations, with the goal of ultimately leveraging knowledge of the role of inflammation in AUDs to develop more effective treatments focused on novel immune targets. Copyright © 2017 by the Research Society on Alcoholism.

Attempted validation of the NUn score and inflammatory markers as predictors of esophageal anastomotic leak and major complications.

PubMed

Findlay, J M; Tilson, R C; Harikrishnan, A; Sgromo, B; Marshall, R E K; Maynard, N D; Gillies, R S; Middleton, M R

2015-10-01

The ability to predict complications following esophagectomy/extended total gastrectomy would be of great clinical value. A recent study demonstrated significant correlations between anastomotic leak (AL) and numerical values of C-reactive protein (CRP), white cell count (WCC) and albumin measured on postoperative day (POD) 4. A predictive model comprising all three (NUn score >10) was found to be highly sensitive and discriminant in predicting AL and complications. We attempted a retrospective validation in our center. Data were collected on all resections performed during a 5-year period (April 2008-2013) using prospectively maintained databases. Our biochemistry laboratory uses a maximum CRP value (156 mg/L), unlike that of the original study; otherwise all variables and outcome measures were comparable. Analysis was performed for all patients with complete blood results on POD4. Three hundred twenty-six patients underwent resection, of which 248 had POD4 bloods. There were 21 AL overall (6.44%); 16 among those with complete POD4 blood results (6.45%). There were 8 (2.45%) in-hospital deaths; 7 (2.82%) in those with POD4 results. No parameters were associated with AL or complication severity on univariate analysis. WCC was associated with AL in multivariate binary logistic regression with albumin and CRP (OR 1.23 [95% CI 1.03-1.47]; P = 0.021). When a binary variable of CRP ≥ 156 mg/L was used rather than an absolute value, no factors were significant. Mean NUn was 8.30 for AL, compared with 8.40 for non-AL (P = 0.710 independent t-test). NUn > 10 predicted 0 of 16 leaks (sensitivity 0.00%, specificity 94.4%, receiver operator curve [ROC] area under the curve [AUC] 0.485; P = 0.843). NUn > 7.65 was 93% sensitive and 21.6% specific. ROC for WCC alone was comparable with NUn (AUC 0.641 [0.504-0.779]; P = 0.059; WCC > 6.89 93.8% sensitive, 20.7% specific; WCC > 15 6.3% sensitive and 97% specific). There were no associations between any parameters and other complications. In a comparable cohort with the original study, we demonstrated a similar multivariate association between WCC alone on POD4 and subsequent demonstration of AL, but not albumin or CRP (measured up to 156 mg/L). The NUn score overall (calculated with this caveat) and a threshold of 10 was not found to have clinical utility in predicting AL or complications. © 2014 International Society for Diseases of the Esophagus.

Hypothalamic digoxin, hemispheric chemical dominance, and inflammatory bowel disease.

PubMed

Kurup, Ravi Kumar; Kurup, Parameswara Achutha

2003-09-01

The isoprenoid pathway produces three key metabolites--endogenous digoxin, dolichol, and ubiquinone. It was considered pertinent to assess the pathway in inflammatory bowel disease (ulcerative colitis and regional ileitis). Since endogenous digoxin can regulate neurotransmitter transport, the pathway and the related cascade were also assessed in individuals with differing hemispheric dominance to find out the role of hemispheric dominance in its pathogenesis. All the patients with inflammatory bowel disease were right-handed/left hemispheric dominant by the dichotic listening test. The following parameters were measured in patients with inflammatory bowel disease and in individuals with differing hemispheric dominance: (1) plasma HMG CoA reductase, digoxin, dolichol, ubiquinone, and magnesium levels; (2) tryptophan/tyrosine catabolic patterns; (3) free-radical metabolism; (4) glycoconjugate metabolism; and (5) membrane composition and RBC membrane Na+-K+ ATPase activity. Statistical analysis was done by ANOVA. In patients with inflammatory bowel disease there was elevated digoxin synthesis, increased dolichol and glycoconjugate levels, and low ubiquinone and elevated free radical levels. There was also an increase in tryptophan catabolites and a reduction in tyrosine catabolites. There was an increase in cholesterol:phospholipid ratio and a reduction in glycoconjugate level of RBC membrane in these groups of patients. Inflammatory bowel disease is associated with an upregulated isoprenoid pathway and elevated digoxin secretion from the hypothalamus. This can contribute to immune activation, defective glycoprotein bowel antigen presentation, and autoimmunity and a schizophreniform psychosis important in its pathogenesis. The biochemical patterns obtained in inflammatory bowel disease is similar to those obtained in left-handed/right hemispheric dominant individuals by the dichotic listening test. But all the patients with peptic ulcer disease were right-handed/left hemispheric dominant by the dichotic listening test. Hemispheric chemical dominance has no correlation with handedness or the dichotic listening test. Inflammatory bowel disease occurs in right hemispheric chemically dominant individuals and is a reflection of altered brain function.

Prevalence of inflammatory bowel disease among coeliac disease patients in a Hungarian coeliac centre.

PubMed

Kocsis, Dorottya; Tóth, Zsuzsanna; Csontos, Ágnes A; Miheller, Pál; Pák, Péter; Herszényi, László; Tóth, Miklós; Tulassay, Zsolt; Juhász, Márk

2015-10-19

Celiac disease, Crohn disease and ulcerative colitis are inflammatory disorders of the gastrointestinal tract with some common genetic, immunological and environmental factors involved in their pathogenesis. Several research shown that patients with celiac disease have increased risk of developing inflammatory bowel disease when compared with that of the general population. The aim of this study is to determine the prevalence of inflammatory bowel disease in our celiac patient cohort over a 15-year-long study period. To diagnose celiac disease, serological tests were used, and duodenal biopsy samples were taken to determine the degree of mucosal injury. To set up the diagnosis of inflammatory bowel disease, clinical parameters, imaging techniques, colonoscopy histology were applied. DEXA for measuring bone mineral density was performed on every patient. In our material, 8/245 (3,2 %) coeliac disease patients presented inflammatory bowel disease (four males, mean age 37, range 22-67), 6/8 Crohn's disease, and 2/8 ulcerative colitis. In 7/8 patients the diagnosis of coeliac disease was made first and inflammatory bowel disease was identified during follow-up. The average time period during the set-up of the two diagnosis was 10,7 years. Coeliac disease serology was positive in all cases. The distribution of histology results according to Marsh classification: 1/8 M1, 2/8 M2, 3/8 M3a, 2/8 M3b. The distribution according to the Montreal classification: 4/6 Crohn's disease patients are B1, 2/6 Crohn's disease patients are B2, 2/2 ulcerative colitis patients are S2. Normal bone mineral density was detected in 2/8 case, osteopenia in 4/8 and osteoporosis in 2/8 patients. Within our cohort of patients with coeliac disease, inflammatory bowel disease was significantly more common (3,2 %) than in the general population.

Deciphering the complexity of acute inflammation using mathematical models.

PubMed

Vodovotz, Yoram

2006-01-01

Various stresses elicit an acute, complex inflammatory response, leading to healing but sometimes also to organ dysfunction and death. We constructed both equation-based models (EBM) and agent-based models (ABM) of various degrees of granularity--which encompass the dynamics of relevant cells, cytokines, and the resulting global tissue dysfunction--in order to begin to unravel these inflammatory interactions. The EBMs describe and predict various features of septic shock and trauma/hemorrhage (including the response to anthrax, preconditioning phenomena, and irreversible hemorrhage) and were used to simulate anti-inflammatory strategies in clinical trials. The ABMs that describe the interrelationship between inflammation and wound healing yielded insights into intestinal healing in necrotizing enterocolitis, vocal fold healing during phonotrauma, and skin healing in the setting of diabetic foot ulcers. Modeling may help in understanding the complex interactions among the components of inflammation and response to stress, and therefore aid in the development of novel therapies and diagnostics.