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Sample records for experimental sepsis models

  1. Experimental models of sepsis and septic shock: an overview

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    Garrido Alejandra G.

    2004-01-01

    Full Text Available Sepsis remains a major cause of morbidity and mortality in surgical patients and trauma victims, mainly due to sepsis-induced multiple organ dysfunction. In contrast to preclinical studies, most clinical trials of promising new treatment strategies for sepsis have fails to demonstrate efficacy. Although many reasons could account for this discrepancy, the misinterpretation of preclinical data obtained from experimental studies, and especially the use of animal models that do not adequately mimic human sepsis may have been contributing factors. In this review, the benefits and limitations of various animal models of sepsis are discussed to clarify the extend to which findings are relevant to human sepsis, particularly with respect to the subsequent design and execution of clinical trials. Such models include intravascular infusion of endotoxin or live bacteria, bacterial peritonitis, cecal ligation and perforation, soft tissue infection, pneumonia or meningitis models, using different animal species including rats, mice, rabbits, dogs, pigs, sheep and nonhuman primates. Despite several limitations, animal models remain essential in the development of all new therapies for sepsis and septic shock, because they provide fundamental information about the pharmacokinetics, toxicity, and mechanism of drug action that cannot be duplicated by other methods. New therapeutic agents should be studies in infection models, even after the initiation of the septic process. Furthermore, debility conditions need to be reproduced to avoid the exclusive use of healthy animals, which often do not represent the human septic patient.

  2. Experimental sepsis impairs humoral memory in mice.

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    Christian Pötschke

    Full Text Available Patients with sepsis are often immune suppressed, and experimental mouse models of sepsis also display this feature. However, acute sepsis in mice is also characterized by a generalized B cell activation and plasma cell differentiation, resulting in a marked increase in serum antibody concentration. Its effects on humoral memory are not clearly defined. We measured the effects of experimental sepsis on long-term immunological memory for a defined antigen: we induced colon ascendens stent peritonitis (CASP 8 weeks after 2 rounds of immunization with ovalbumin. Four weeks later, the antigen-specific bone marrow plasma cell count had doubled in immunized non-septic animals, but remained unchanged in immunized septic animals. Sepsis also caused a decrease in antigen-specific serum antibody concentration. We conclude that sepsis weakens humoral memory by impeding the antigen-specific plasma cell pool's development, which is not complete 8 weeks after secondary immunization.

  3. A model-specific role of microRNA-223 as a mediator of kidney injury during experimental sepsis.

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    Colbert, James F; Ford, Joshay A; Haeger, Sarah M; Yang, Yimu; Dailey, Kyrie L; Allison, Kristen C; Neudecker, Viola; Evans, Christopher M; Richardson, Vanessa L; Brodsky, Kelley S; Faubel, Sarah; Eltzschig, Holger K; Schmidt, Eric P; Ginde, Adit A

    2017-08-01

    Sepsis outcomes are heavily dependent on the development of septic organ injury, but no interventions exist to interrupt or reverse this process. microRNA-223 (miR-223) is known to be involved in both inflammatory gene regulation and host-pathogen interactions key to the pathogenesis of sepsis. The goal of this study was to determine the role of miR-223 as a mediator of septic kidney injury. Using miR-223 knockout mice and multiple models of experimental sepsis, we found that miR-223 differentially influences acute kidney injury (AKI) based on the model used. In the absence of miR-223, mice demonstrated exaggerated AKI in sterile models of sepsis (LPS injection) and attenuated AKI in a live-infection model of sepsis (cecal ligation and puncture). We demonstrated that miR-223 expression is induced in kidney homogenate after cecal ligation and puncture, but not after LPS or fecal slurry injection. We investigated additional potential mechanistic explanations including differences in peritoneal bacterial clearance and host stool virulence. Our findings highlight the complex role of miR-223 in the pathogenesis of septic kidney injury, as well as the importance of differences in experimental sepsis models and their consequent translational applicability. Copyright © 2017 the American Physiological Society.

  4. Premise for Standardized Sepsis Models.

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    Remick, Daniel G; Ayala, Alfred; Chaudry, Irshad; Coopersmith, Craig M; Deutschman, Clifford; Hellman, Judith; Moldawer, Lyle; Osuchowski, Marcin

    2018-06-05

    Sepsis morbidity and mortality exacts a toll on patients and contributes significantly to healthcare costs. Preclinical models of sepsis have been used to study disease pathogenesis and test new therapies, but divergent outcomes have been observed with the same treatment even when using the same sepsis model. Other disorders such as diabetes, cancer, malaria, obesity and cardiovascular diseases have used standardized, preclinical models that allow laboratories to compare results. Standardized models accelerate the pace of research and such models have been used to test new therapies or changes in treatment guidelines. The National Institutes of Health (NIH) mandated that investigators increase data reproducibility and the rigor of scientific experiments and has also issued research funding announcements about the development and refinement of standardized models. Our premise is that refinement and standardization of preclinical sepsis models may accelerate the development and testing of potential therapeutics for human sepsis, as has been the case with preclinical models for other disorders. As a first step towards creating standardized models, we suggest 1) standardizing the technical standards of the widely used cecal ligation and puncture model and 2) creating a list of appropriate organ injury and immune dysfunction parameters. Standardized sepsis models could enhance reproducibility and allow comparison of results between laboratories and may accelerate our understanding of the pathogenesis of sepsis.

  5. Effects of gamma oryzanol on factors of oxidative stress and sepsis-induced lung injury in experimental animal model

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    Elmira Zolali

    2015-12-01

    Full Text Available Objective (s: There is corroborating evidence to substantiate redox imbalance and oxidative stress in sepsis that finally leads to organ damage or even death. Gamma oryzanol (GO is one of the major bioactive components in rice bran has been considered to function as an antioxidant. The present study was carried out to evaluate the antioxidant activity of gamma oryzanol in vitro and its efficacy in sepsis. Materials and Methods: To induce sepsis, cecal ligation and puncture (CLP method was performed on the rats. A study group of forty male Wistar rats were divided into the following groups: sham group; CLP group; 50 mg/kg GO- treated CLP group and 100 mg/kg GO- treated CLP group. GO was administered with an oral gavage 2 hr prior to inducing sepsis. Tissue and blood samples were collected 12 hr after CLP to prepare tissue sections for histopathological study and assay the oxidative stress biomarkers including: SOD (Superoxide Dismutase, TAC (total antioxidant capacity, MDA (Malondialdehyde, MPO (Myeloperoxidase and PAI-1 (Plasminogen Activator Inhibitor-1. Data are given as mean ± SD. The ANOVA with Tukey post hoc test was used to determine the differences between groups and P Results: TAC level increased in GO- treated CLP groups (P

  6. Sepsis

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    ... mild sepsis, but the mortality rate for septic shock is nearly 50 percent. Also, an episode of severe sepsis may ... of Nondiscrimination Advertising Mayo Clinic is a not-for-profit organization ...

  7. Glial cell-derived neurotrophic factor alleviates sepsis-induced neuromuscular dysfunction by decreasing the expression of γ- and α7-nicotinic acetylcholine receptors in an experimental rat model of neuromyopathy.

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    Wang, Xin; Min, Su; Xie, Fei; Yang, Jun; Li, Liang; Chen, Jingyuan

    2018-02-05

    Sepsis-induced neuromuscular dysfunction results from up-regulation of the expression of γ- and α7-nicotinic acetylcholine receptors (nAChR). Although glial cell derived neurotrophic factor (GDNF) has been implicated in repairing and supporting neurons, little is known about the effects of GDNF on demyelination of nerves in sepsis. In this study, we tested the hypothesis that GDNF could alleviate sepsis-induced neuromuscular dysfunction by decreasing the expression of γ- and α7-nAChR in an experimental rat model of neuromyopathy. Rats were randomly divided into a sham group and a sepsis group. Levels of inflammatory factors, muscle function, and nicotinic acetylcholine receptors were tested in rats after cecal ligation and puncture (CLP). At 24 h after CLP, GDNF was injected around the sciatic nerve of sepsis rats, cytokines were detected by enzyme-linked immunosorbent assay (ELISA), and immunofluorescence staining was used to detect the expression of nAChRs. GDNF and its downstream effector (Erk1/2 and GFR-α), neuregulin-1 (NRG-1) and γ- and α7-nAChR were measured using Western blot analysis. The expression of GDNF reached a minimum at 24 h after CLP. Compared with the sham group, the release of cytokines and the expression of γ- and α7-nAChR were significantly increased in the sepsis group. The administration of GDNF significantly alleviated sepsis-induced neuromuscular dysfunction, as well as reducing the expression of γ- and α7-nAChR. In addition, the expression of Erk1/2, GFR-α, NRG-1 were significantly increased after GDNF treatment. GDNF administration may improve patient outcomes by reducing the demyelination of nerves and the expression of γ- and α7-nAChR. Copyright © 2018. Published by Elsevier Inc.

  8. Sepsis

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    Perner, Anders; Gordon, Anthony C; De Backer, Daniel

    2016-01-01

    Sepsis is a major growing global burden and a major challenge to intensive care clinicians, researchers, guideline committee members and policy makers, because of its high and increasing incidence and great pathophysiological, molecular, genetic and clinical complexity. In spite of recent progress......, short-term mortality remains high and there is growing evidence of long-term morbidity and increased long-term mortality in survivors of sepsis both in developed and developing countries. Further improvement in the care of patients with sepsis will impact upon global health. In this narrative review...... and subsequent outcomes are to be improved in patients with sepsis....

  9. Sepsis progression and outcome: a dynamical model

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    Gessler Damian DG

    2006-02-01

    Full Text Available Abstract Background Sepsis (bloodstream infection is the leading cause of death in non-surgical intensive care units. It is diagnosed in 750,000 US patients per annum, and has high mortality. Current understanding of sepsis is predominately observational and correlational, with only a partial and incomplete understanding of the physiological dynamics underlying the syndrome. There exists a need for dynamical models of sepsis progression, based upon basic physiologic principles, which could eventually guide hourly treatment decisions. Results We present an initial mathematical model of sepsis, based on metabolic rate theory that links basic vascular and immunological dynamics. The model includes the rate of vascular circulation, a surrogate for the metabolic rate that is mechanistically associated with disease progression. We use the mass-specific rate of blood circulation (SRBC, a correlate of the body mass index, to build a differential equation model of circulation, infection, organ damage, and recovery. This introduces a vascular component into an infectious disease model that describes the interaction between a pathogen and the adaptive immune system. Conclusion The model predicts that deviations from normal SRBC correlate with disease progression and adverse outcome. We compare the predictions with population mortality data from cardiovascular disease and cancer and show that deviations from normal SRBC correlate with higher mortality rates.

  10. Metabolomics with Nuclear Magnetic Resonance Spectroscopy in a Drosophila melanogaster Model of Surviving Sepsis

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    Bakalov, Veli; Amathieu, Roland; Triba, Mohamed N.; Clément, Marie-Jeanne; Reyes Uribe, Laura; Le Moyec, Laurence; Kaynar, Ata Murat

    2016-01-01

    Patients surviving sepsis demonstrate sustained inflammation, which has been associated with long-term complications. One of the main mechanisms behind sustained inflammation is a metabolic switch in parenchymal and immune cells, thus understanding metabolic alterations after sepsis may provide important insights to the pathophysiology of sepsis recovery. In this study, we explored metabolomics in a novel Drosophila melanogaster model of surviving sepsis using Nuclear Magnetic Resonance (NMR), to determine metabolite profiles. We used a model of percutaneous infection in Drosophila melanogaster to mimic sepsis. We had three experimental groups: sepsis survivors (infected with Staphylococcus aureus and treated with oral linezolid), sham (pricked with an aseptic needle), and unmanipulated (positive control). We performed metabolic measurements seven days after sepsis. We then implemented metabolites detected in NMR spectra into the MetExplore web server in order to identify the metabolic pathway alterations in sepsis surviving Drosophila. Our NMR metabolomic approach in a Drosophila model of recovery from sepsis clearly distinguished between all three groups and showed two different metabolomic signatures of inflammation. Sham flies had decreased levels of maltose, alanine, and glutamine, while their level of choline was increased. Sepsis survivors had a metabolic signature characterized by decreased glucose, maltose, tyrosine, beta-alanine, acetate, glutamine, and succinate. PMID:28009836

  11. Brain infection following experimental Staphylococcus aureus sepsis in pigs

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    Astrup, Lærke Boye; Iburg, Tine Moesgaard; Nielsen, Ole Lerberg

    2010-01-01

    Introduction: Sepsis is a major problem in humans and both the incidence and mortality is increasing. Multiple microabcesses can be found in the brain of septic patients. Staphylococcus aureus is one of the most common causes of sepsis and brain abscesses. S. aureus is also a frequent cause...... of spontaneous porcine pyemia including endocarditis and associated brain lesions. We present a porcine model of haematogenous S. aureus induced brain infection. Materials and Methods: Twelve pigs received an intravenous injection of S. aureus of 108 CFU/kg body weight once at 0h or twice at 0h and 12h. Four...... pigs were kept as controls. The pigs were euthanized in groups of four at either 6, 12, 24 or 48 h post infection. The brain was collected from all the animals and examined histologically. Results: All the inoculated pigs developed sepsis and 7 out of 12 animals had microabscesses in the prosencephalon...

  12. Increase in seizure susceptibility in sepsis like condition explained by spiking cytokines and altered adhesion molecules level with impaired blood brain barrier integrity in experimental model of rats treated with lipopolysaccharides.

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    Sewal, Rakesh K; Modi, Manish; Saikia, Uma Nahar; Chakrabarti, Amitava; Medhi, Bikash

    2017-09-01

    Epilepsy is a neurological disorder characterized by recurrent unprovoked seizures. Sepsis is a condition which initiates a cascade of a surge of inflammatory mediators. Interplay between seizures and inflammation other than of brain origin is yet to be explored. The present study was designed to evaluate the seizure susceptibility in experimental models of lipopolysaccharide (LPS) induced sepsis. Experimental sepsis was induced using lipopolysaccharides in Wistar rats. Valproic acid, dexametasone were given to two different groups of animals along with LPS. Two groups of animals were subjected to administration of vehicle and LPS respectively with no other treatment. 24h later, animals were subjected to seizures by using either maximal electro shock or pentylenetetrazole. Seizures related parameters, oxidative stress and TNF-α, IL-6, IL-1β, ICAM-1, ICAM-2, VCAM-1, MMP-9 level in serum and brain samples were evaluated. Histopathological and blood brain barrier permeability studies were conducted. Seizures were decreased in valproic acid treated animals. Reduced oxidative stress was seen in dexamethasone plus valproic acid treated groups as compared to LPS alone treated group. TNF-α, IL-6, IL-1β, ICAM-1, VCAM-1, MMP-9 levels were found increased in LPS treated animals whereas a reverse observation was noted for ICAM-2 level in brain and serum. Histopathological findings confirmed the successful establishment of sepsis like state in animals. Blood brain barrier permeability was found increased in LPS treated groups of animals. Seizure susceptibility may escalate during the sepsis like inflammatory conditions and curbing the inflammatory state might reverse the phenomenon. Copyright © 2017. Published by Elsevier B.V.

  13. Virulence genes and subclone status as markers of experimental virulence in a murine sepsis model among Escherichia coli sequence type 131 clinical isolates from Spain.

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    Irene Merino

    Full Text Available To assess experimental virulence among sequence type 131 (ST131 Escherichia coli bloodstream isolates in relation to virulence genotype and subclone.We analysed 48 Spanish ST131 bloodstream isolates (2010 by PCR for ST131 subclone status (H30Rx, H30 non-Rx, or non-H30, virulence genes (VGs, and O-type. Then we compared these traits with virulence in a murine sepsis model, as measured by illness severity score (ISS and rapid lethality (mean ISS ≥ 4.Of the 48 study isolates, 65% were H30Rx, 21% H30 non-Rx, and 15% non-H30; 44% produced ESBLs, 98% were O25b, and 83% qualified as extraintestinal pathogenic E. coli (ExPEC. Of 49 VGs, ibeA and iss were associated significantly with non-H30 isolates, and sat, iha and malX with H30 isolates. Median VG scores differed by subclone, i.e., 12 (H30Rx, 10 (H30 non-Rx, and 11 (non-H30 (p < 0.01. Nearly 80% of isolates represented a described virotype. In mice, H30Rx and non-H30 isolates were more virulent than H30 non-Rx isolates (according to ISS [p = 0.03] and rapid lethality [p = 0.03], as were ExPEC isolates compared with non-ExPEC isolates (median ISS, 4.3 vs. 2.7: p = 0.03. In contrast, most individual VGs, VG scores, VG profiles, and virotypes were not associated with mouse virulence.ST131 subclone and ExPEC status, but not individual VGs, VG scores or profiles, or virotypes, predicted mouse virulence. Given the lower virulence of non-Rx H30 isolates, hypervirulence probably cannot explain the ST131-H30 clade's epidemic emergence.

  14. Dexmedetomidine attenuates the microcirculatory derangements evoked by experimental sepsis.

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    Miranda, Marcos L; Balarini, Michelle M; Bouskela, Eliete

    2015-03-01

    Dexmedetomidine, an α-2 adrenergic receptor agonist, has already been used in septic patients although few studies have examined its effects on microcirculatory dysfunction, which may play an important role in perpetuating sepsis syndrome. Therefore, the authors have designed a controlled experimental study to characterize the microcirculatory effects of dexmedetomidine in an endotoxemia rodent model that allows in vivo studies of microcirculation. After skinfold chamber implantation, 49 golden Syrian hamsters were randomly allocated in five groups: (1) control animals; (2) nonendotoxemic animals treated with saline; (3) nonendotoxemic animals treated with dexmedetomidine (5.0 μg kg h); (4) endotoxemic (lipopolysaccharide 1.0 mg/kg) animals treated with saline; and (5) endotoxemic animals treated with dexmedetomidine. Intravital microscopy of skinfold chamber preparations allowed quantitative analysis of microvascular variables and venular leukocyte rolling and adhesion. Mean arterial blood pressure, heart rate, arterial blood gases, and lactate concentrations were also documented. Lipopolysaccharide administration increased leukocyte rolling and adhesion and decreased capillary perfusion. Dexmedetomidine significantly attenuated these responses: compared with endotoxemic animals treated with saline, those treated with dexmedetomidine had less leukocyte rolling (11.8 ± 7.2% vs. 24.3 ± 15.0%; P the end of the experiment. Dexmedetomidine decreased lipopolysaccharide-induced leukocyte-endothelial interactions in the hamster skinfold chamber microcirculation. This was accompanied by a significant attenuation of capillary perfusion deficits, suggesting that dexmedetomidine yields beneficial effects on endotoxemic animals' microcirculation.

  15. Sepsis

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    Perner, Anders; Rhodes, Andrew; Venkatesh, Bala

    2017-01-01

    Because of its high incidence and clinical complexity, sepsis is a major challenge to clinicians and researchers and a global burden to healthcare systems and society. Despite recent progress, short- and long-term morbidity, mortality and costs remain high in both developed and developing countri...

  16. Ensemble models of neutrophil trafficking in severe sepsis.

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    Sang Ok Song

    Full Text Available A hallmark of severe sepsis is systemic inflammation which activates leukocytes and can result in their misdirection. This leads to both impaired migration to the locus of infection and increased infiltration into healthy tissues. In order to better understand the pathophysiologic mechanisms involved, we developed a coarse-grained phenomenological model of the acute inflammatory response in CLP (cecal ligation and puncture-induced sepsis in rats. This model incorporates distinct neutrophil kinetic responses to the inflammatory stimulus and the dynamic interactions between components of a compartmentalized inflammatory response. Ensembles of model parameter sets consistent with experimental observations were statistically generated using a Markov-Chain Monte Carlo sampling. Prediction uncertainty in the model states was quantified over the resulting ensemble parameter sets. Forward simulation of the parameter ensembles successfully captured experimental features and predicted that systemically activated circulating neutrophils display impaired migration to the tissue and neutrophil sequestration in the lung, consequently contributing to tissue damage and mortality. Principal component and multiple regression analyses of the parameter ensembles estimated from survivor and non-survivor cohorts provide insight into pathologic mechanisms dictating outcome in sepsis. Furthermore, the model was extended to incorporate hypothetical mechanisms by which immune modulation using extracorporeal blood purification results in improved outcome in septic rats. Simulations identified a sub-population (about 18% of the treated population that benefited from blood purification. Survivors displayed enhanced neutrophil migration to tissue and reduced sequestration of lung neutrophils, contributing to improved outcome. The model ensemble presented herein provides a platform for generating and testing hypotheses in silico, as well as motivating further experimental

  17. Comparison of Cox and Gray's survival models in severe sepsis

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    Kasal, Jan; Andersen, Zorana Jovanovic; Clermont, Gilles

    2004-01-01

    Although survival is traditionally modeled using Cox proportional hazards modeling, this approach may be inappropriate in sepsis, in which the proportional hazards assumption does not hold. Newer, more flexible models, such as Gray's model, may be more appropriate....

  18. The New York Sepsis Severity Score: Development of a Risk-Adjusted Severity Model for Sepsis.

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    Phillips, Gary S; Osborn, Tiffany M; Terry, Kathleen M; Gesten, Foster; Levy, Mitchell M; Lemeshow, Stanley

    2018-05-01

    In accordance with Rory's Regulations, hospitals across New York State developed and implemented protocols for sepsis recognition and treatment to reduce variations in evidence informed care and preventable mortality. The New York Department of Health sought to develop a risk assessment model for accurate and standardized hospital mortality comparisons of adult septic patients across institutions using case-mix adjustment. Retrospective evaluation of prospectively collected data. Data from 43,204 severe sepsis and septic shock patients from 179 hospitals across New York State were evaluated. Prospective data were submitted to a database from January 1, 2015, to December 31, 2015. None. Maximum likelihood logistic regression was used to estimate model coefficients used in the New York State risk model. The mortality probability was estimated using a logistic regression model. Variables to be included in the model were determined as part of the model-building process. Interactions between variables were included if they made clinical sense and if their p values were less than 0.05. Model development used a random sample of 90% of available patients and was validated using the remaining 10%. Hosmer-Lemeshow goodness of fit p values were considerably greater than 0.05, suggesting good calibration. Areas under the receiver operator curve in the developmental and validation subsets were 0.770 (95% CI, 0.765-0.775) and 0.773 (95% CI, 0.758-0.787), respectively, indicating good discrimination. Development and validation datasets had similar distributions of estimated mortality probabilities. Mortality increased with rising age, comorbidities, and lactate. The New York Sepsis Severity Score accurately estimated the probability of hospital mortality in severe sepsis and septic shock patients. It performed well with respect to calibration and discrimination. This sepsis-specific model provides an accurate, comprehensive method for standardized mortality comparison of adult

  19. A Neutrophil Phenotype Model for Extracorporeal Treatment of Sepsis.

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    Alexander D Malkin

    2015-10-01

    Full Text Available Neutrophils play a central role in eliminating bacterial pathogens, but may also contribute to end-organ damage in sepsis. Interleukin-8 (IL-8, a key modulator of neutrophil function, signals through neutrophil specific surface receptors CXCR-1 and CXCR-2. In this study a mechanistic computational model was used to evaluate and deploy an extracorporeal sepsis treatment which modulates CXCR-1/2 levels. First, a simplified mechanistic computational model of IL-8 mediated activation of CXCR-1/2 receptors was developed, containing 16 ODEs and 43 parameters. Receptor level dynamics and systemic parameters were coupled with multiple neutrophil phenotypes to generate dynamic populations of activated neutrophils which reduce pathogen load, and/or primed neutrophils which cause adverse tissue damage when misdirected. The mathematical model was calibrated using experimental data from baboons administered a two-hour infusion of E coli and followed for a maximum of 28 days. Ensembles of parameters were generated using a Bayesian parallel tempering approach to produce model fits that could recreate experimental outcomes. Stepwise logistic regression identified seven model parameters as key determinants of mortality. Sensitivity analysis showed that parameters controlling the level of killer cell neutrophils affected the overall systemic damage of individuals. To evaluate rescue strategies and provide probabilistic predictions of their impact on mortality, time of onset, duration, and capture efficacy of an extracorporeal device that modulated neutrophil phenotype were explored. Our findings suggest that interventions aiming to modulate phenotypic composition are time sensitive. When introduced between 3-6 hours of infection for a 72 hour duration, the survivor population increased from 31% to 40-80%. Treatment efficacy quickly diminishes if not introduced within 15 hours of infection. Significant harm is possible with treatment durations ranging from 5

  20. A novel natural compound from garlic (Allium sativum L.) with therapeutic effects against experimental polymicrobial sepsis.

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    Lee, Sung Kyun; Park, Yoo Jung; Ko, Min Jung; Wang, Ziyu; Lee, Ha Young; Choi, Young Whan; Bae, Yoe-Sik

    2015-08-28

    Sepsis is a serious, life-threatening, infectious disease. In this study, we demonstrate that sucrose methyl 3-formyl-4-methylpentanoate (SMFM), a novel natural compound isolated from garlic (Allium sativum L.), markedly enhances survival rates by inhibiting lung inflammation in a cecal ligation and puncture (CLP) experimental polymicrobial sepsis model. SMFM strongly reduced bacterial colony units from peritoneal fluid in CLP mice by stimulating the generation of reactive oxygen species. Lymphocyte apoptosis in spleens from CLP mice was also markedly decreased by SMFM administration. SMFM also significantly inhibited the production of proinflammatory cytokines, such as TNF-α, interleukin-1β (IL-1β) and IL-6, in CLP mice. Lipopolysaccharide-stimulated production of TNF-α and IL-6 were also strongly inhibited by SMFM in mouse bone marrow-derived macrophages. Taken together, our results indicate that SMFM has therapeutic effects against polymicrobial sepsis that are mediated by enhanced microbial killing and blockage of cytokine storm. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Inoculum effect on the efficacies of amoxicillin-clavulanate, piperacillin-tazobactam, and imipenem against extended-spectrum β-lactamase (ESBL)-producing and non-ESBL-producing Escherichia coli in an experimental murine sepsis model.

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    Docobo-Pérez, F; López-Cerero, L; López-Rojas, R; Egea, P; Domínguez-Herrera, J; Rodríguez-Baño, J; Pascual, A; Pachón, J

    2013-05-01

    Escherichia coli is commonly involved in infections with a heavy bacterial burden. Piperacillin-tazobactam and carbapenems are among the recommended empirical treatments for health care-associated complicated intra-abdominal infections. In contrast to amoxicillin-clavulanate, both have reduced in vitro activity in the presence of high concentrations of extended-spectrum β-lactamase (ESBL)-producing and non-ESBL-producing E. coli bacteria. Our goal was to compare the efficacy of these antimicrobials against different concentrations of two clinical E. coli strains, one an ESBL-producer and the other a non-ESBL-producer, in a murine sepsis model. An experimental sepsis model {~5.5 log10 CFU/g [low inoculum concentration (LI)] or ~7.5 log(10) CFU/g [high inoculum concentration (HI)]} using E. coli strains ATCC 25922 (non-ESBL producer) and Ec1062 (CTX-M-14 producer), which are susceptible to the three antimicrobials, was used. Amoxicillin-clavulanate (50/12.5 mg/kg given intramuscularly [i.m.]), piperacillin-tazobactam (25/3.125 mg/kg given intraperitoneally [i.p.]), and imipenem (30 mg/kg i.m.) were used. Piperacillin-tazobactam and imipenem reduced spleen ATCC 25922 strain concentrations (-2.53 and -2.14 log10 CFU/g [P imipenem, and amoxicillin-clavulanate, respectively, although imipenem and amoxicillin-clavulanate were more efficacious than piperacillin-tazobactam). An adapted imipenem treatment (based on the time for which the serum drug concentration remained above the MIC obtained with a HI of the ATCC 25922 strain) improved its efficacy to -1.67 log10 CFU/g (P imipenem treatment of infections caused by ESBL- and non-ESBL-producing E. coli strains in patients with therapeutic failure with piperacillin-tazobactam.

  2. Blockade of Thrombopoietin Reduces Organ Damage in Experimental Endotoxemia and Polymicrobial Sepsis.

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    Cuccurullo, Alessandra; Greco, Elisabetta; Lupia, Enrico; De Giuli, Paolo; Bosco, Ornella; Martin-Conte, Erica; Spatola, Tiziana; Turco, Emilia; Montrucchio, Giuseppe

    2016-01-01

    Thrombopoietin (TPO), a growth factor primarily involved in thrombopoiesis may also have a role in the pathophysiology of sepsis. In patients with sepsis, indeed, TPO levels are markedly increased, with disease severity being the major independent determinant of TPO concentrations. Moreover, TPO increases and correlates with ex vivo indices of platelet activation in patients with burn injury upon sepsis development, and may contribute to depress cardiac contractility in septic shock. Still, the role of TPO in sepsis pathophysiology remains controversial, given the protective role of TPO in other experimental disease models, for instance in doxorubicin-induced cardiotoxicity and myocardial ischemia/reperfusion injury. The aim of our study was to define the contribution of TPO in the development of organ damage induced by endotoxemia or sepsis, and to investigate the effects of inhibiting TPO in these conditions. We synthesized a chimeric protein able to inhibit TPO, mTPOR-MBP, and studied its effect in two murine experimental models, acute endotoxemia and cecal ligation and puncture (CLP) model. In both models, TPO levels markedly increased, from 289.80±27.87 pg/mL to 465.60±45.92 pg/mL at 3 hours in the LPS model (P<0.01), and from 265.00±26.02 pg/mL to 373.70±26.20 pg/mL in the CLP model (P<0.05), respectively. Paralleling TPO levels, also platelet-monocyte aggregates increased, from 32.86±2.48% to 46.13±1.39% at 3 hours in the LPS model (P<0.01), and from 43.68±1.69% to 56.52±4.66% in the CLP model (P<0.05). Blockade of TPO by mTPOR-MBP administration reduced histological damage in target organs, namely lung, liver, and gut. In particular, neutrophil infiltration and lung septal thickening were reduced from a score of 1.86±0.34 to 0.60±0.27 (P<0.01) and from 1.43±0.37 to 0.40±0.16 (P<0.05), respectively, in the LPS model at 3 hours, and from a score of 1.75±0.37 to 0.38±0.18 (P<0.01) and from 1.25±0.31 to 0.13±0.13 (P<0.001), respectively, in the

  3. Blockade of Thrombopoietin Reduces Organ Damage in Experimental Endotoxemia and Polymicrobial Sepsis.

    Directory of Open Access Journals (Sweden)

    Alessandra Cuccurullo

    Full Text Available Thrombopoietin (TPO, a growth factor primarily involved in thrombopoiesis may also have a role in the pathophysiology of sepsis. In patients with sepsis, indeed, TPO levels are markedly increased, with disease severity being the major independent determinant of TPO concentrations. Moreover, TPO increases and correlates with ex vivo indices of platelet activation in patients with burn injury upon sepsis development, and may contribute to depress cardiac contractility in septic shock. Still, the role of TPO in sepsis pathophysiology remains controversial, given the protective role of TPO in other experimental disease models, for instance in doxorubicin-induced cardiotoxicity and myocardial ischemia/reperfusion injury. The aim of our study was to define the contribution of TPO in the development of organ damage induced by endotoxemia or sepsis, and to investigate the effects of inhibiting TPO in these conditions.We synthesized a chimeric protein able to inhibit TPO, mTPOR-MBP, and studied its effect in two murine experimental models, acute endotoxemia and cecal ligation and puncture (CLP model.In both models, TPO levels markedly increased, from 289.80±27.87 pg/mL to 465.60±45.92 pg/mL at 3 hours in the LPS model (P<0.01, and from 265.00±26.02 pg/mL to 373.70±26.20 pg/mL in the CLP model (P<0.05, respectively. Paralleling TPO levels, also platelet-monocyte aggregates increased, from 32.86±2.48% to 46.13±1.39% at 3 hours in the LPS model (P<0.01, and from 43.68±1.69% to 56.52±4.66% in the CLP model (P<0.05. Blockade of TPO by mTPOR-MBP administration reduced histological damage in target organs, namely lung, liver, and gut. In particular, neutrophil infiltration and lung septal thickening were reduced from a score of 1.86±0.34 to 0.60±0.27 (P<0.01 and from 1.43±0.37 to 0.40±0.16 (P<0.05, respectively, in the LPS model at 3 hours, and from a score of 1.75±0.37 to 0.38±0.18 (P<0.01 and from 1.25±0.31 to 0.13±0.13 (P<0.001, respectively

  4. Increased NTPDase Activity in Lymphocytes during Experimental Sepsis

    Science.gov (United States)

    Bertoncheli, Claudia de Mello; Zimmermann, Carine Eloise Prestes; Jaques, Jeandre Augusto dos Santos; Leal, Cláudio Alberto Martins; Ruchel, Jader Betsch; Rocha, Bruna Cipolatto; Pinheiro, Kelly de Vargas; Souza, Viviane do Carmo Gonçalves; Stainki, Daniel Roulim; Luz, Sônia Cristina Almeida; Schetinger, Maria Rosa Chitolina; Leal, Daniela Bitencourt Rosa

    2012-01-01

    We investigated in rats induced to sepsis the activity of ectonucleoside triphosphate diphosphohydrolase (NTPDase; CD39; E.C. 3.6.1.5), an enzyme involved in the modulation of immune responses. After 12 hours of surgery, lymphocytes were isolated from blood and NTPDase activity was determined. It was also performed the histology of kidney, liver, and lung. The results demonstrated an increase in the hydrolysis of adenosine-5′-triphosphate (ATP) (P 0.05). Histological analysis showed several morphological changes in the septic group, such as vascular congestion, necrosis, and infiltration of mononuclear cells. It is known that the intracellular milieu contains much more ATP nucleotides than the extracellular. In this context, the increased ATPasic activity was probably induced as a dynamic response to clean up the elevated ATP levels resulting from cellular death. PMID:22645477

  5. The German Quality Network Sepsis: study protocol for the evaluation of a quality collaborative on decreasing sepsis-related mortality in a quasi-experimental difference-in-differences design.

    Science.gov (United States)

    Schwarzkopf, Daniel; Rüddel, Hendrik; Gründling, Matthias; Putensen, Christian; Reinhart, Konrad

    2018-01-18

    While sepsis-related mortality decreased substantially in other developed countries, mortality of severe sepsis remained as high as 44% in Germany. A recent German cluster randomized trial was not able to improve guideline adherence and decrease sepsis-related mortality within the participating hospitals, partly based on lacking support by hospital management and lacking resources for documentation of prospective data. Thus, more pragmatic approaches are needed to improve quality of sepsis care in Germany. The primary objective of the study is to decrease sepsis-related hospital mortality within a quality collaborative relying on claims data. The German Quality Network Sepsis (GQNS) is a quality collaborative involving 75 hospitals. This study protocol describes the conduction and evaluation of the start-up period of the GQNS running from March 2016 to August 2018. Democratic structures assure participatory action, a study coordination bureau provides central support and resources, and local interdisciplinary quality improvement teams implement changes within the participating hospitals. Quarterly quality reports focusing on risk-adjusted hospital mortality in cases with sepsis based on claims data are provided. Hospitals committed to publish their individual risk-adjusted mortality compared to the German average. A complex risk-model is used to control for differences in patient-related risk factors. Hospitals are encouraged to implement a bundle of interventions, e.g., interdisciplinary case analyses, external peer-reviews, hospital-wide staff education, and implementation of rapid response teams. The effectiveness of the GQNS is evaluated in a quasi-experimental difference-in-differences design by comparing the change of hospital mortality of cases with sepsis with organ dysfunction from a retrospective baseline period (January 2014 to December 2015) and the intervention period (April 2016 to March 2018) between the participating hospitals and all other German

  6. IRAK-M regulates chromatin remodeling in lung macrophages during experimental sepsis.

    Directory of Open Access Journals (Sweden)

    Kenneth Lyn-Kew

    2010-06-01

    Full Text Available Sepsis results in a profound state of immunosuppression, which is temporally associated with impaired leukocyte function. The mechanism of leukocyte reprogramming in sepsis is incompletely understood. In this study, we explored mechanisms contributing to dysregulated inflammatory cytokine expression by pulmonary macrophages during experimental sepsis. Pulmonary macrophages (PM recovered from the lungs of mice undergoing cecal ligation and puncture (CLP display transiently reduced expression of some, but not all innate genes in response to LPS. Impaired expression of TNF-alpha and iNOS was associated with reduced acetylation and methylation of specific histones (AcH4 and H3K4me3 and reduced binding of RNA polymerase II to the promoters of these genes. Transient impairment in LPS-induced cytokine responses in septic PM temporally correlated with induction of IRAK-M mRNA and protein, which occurred in a MyD88-dependent fashion. PM isolated from IRAK-M(-/- mice were largely refractory to CLP-induced impairment in cytokine expression, chromatin remodeling, recruitment of RNA polymerase II, and induction of histone deacetylase-2 observed during sepsis. Our findings indicate that systemic sepsis induces epigenetic silencing of cytokine gene expression in lung macrophages, and IRAK-M appears to be a critical mediator of this response.

  7. Efficacy of Enrofloxacin in a Mouse Model of Sepsis

    OpenAIRE

    Slate, Andrea R; Bandyopadhyay, Sheila; Francis, Kevin P; Papich, Mark G; Karolewski, Brian; Hod, Eldad A; Prestia, Kevin A

    2014-01-01

    We examined the efficacy of enrofloxacin administered by 2 different routes in a mouse model of sepsis. Male CD1 mice were infected with a bioluminescent strain of enteropathogenic Escherichia coli and treated with enrofloxacin either by injection or in drinking water. Peak serum levels were evaluated by using HPLC. Mice were monitored for signs of clinical disease, and infections were monitored by using bioluminescence imaging. Serum levels of enrofloxacin and the active metabolite ciproflox...

  8. An Interpretable Machine Learning Model for Accurate Prediction of Sepsis in the ICU.

    Science.gov (United States)

    Nemati, Shamim; Holder, Andre; Razmi, Fereshteh; Stanley, Matthew D; Clifford, Gari D; Buchman, Timothy G

    2018-04-01

    clinical utility of the proposed sepsis prediction model.

  9. Systemic and regional hemodynamic effects of enalaprilat infusion in experimental normotensive sepsis

    Directory of Open Access Journals (Sweden)

    L. Rahal

    Full Text Available Angiotensin-converting enzyme inhibitors have been shown to improve splanchnic perfusion in distinct shock states. We hypothesized that enalaprilat potentiates the benefits of early fluid resuscitation in severe experimental sepsis, particularly in the splanchnic region. Anesthetized and mechanically ventilated mongrel dogs received an intravenous infusion of live Escherichia coli over a period of 30 min. Thereafter, two interventions were performed: fluid infusion (normal saline, 32 mL/kg over 30 min and enalaprilat infusion (0.02 mg kg-1 min-1 for 60 min in randomized groups. The following groups were studied: controls (fluid infusion, N = 4, E1 (enalaprilat infusion followed by fluid infusion, N = 5 and E2 (fluid infusion followed by enalaprilat infusion, N = 5. All animals were observed for a 120 min after bacterial infusion. Mean arterial pressure, cardiac output (CO, portal vein blood flow (PVBF, systemic and regional oxygen-derived variables, and lactate levels were measured. Rapid and progressive reductions in CO and PVBF were induced by the infusion of live bacteria, while minor changes were observed in mean arterial pressure. Systemic and regional territories showed a significant increase in oxygen extraction and lactate levels. Widening venous-arterial and portal-arterial pCO2 gradients were also detected. Fluid replacement promoted transient benefits in CO and PVBF. Enalaprilat after fluid resuscitation did not affect systemic or regional hemodynamic variables. We conclude that in this model of normotensive sepsis inhibition of angiotensin-converting enzyme did not interfere with the course of systemic or regional hemodynamic and oxygen-derived variables.

  10. Regulation of IL-17 family members by adrenal hormones during experimental sepsis in mice.

    Science.gov (United States)

    Bosmann, Markus; Meta, Fabien; Ruemmler, Robert; Haggadone, Mikel D; Sarma, J Vidya; Zetoune, Firas S; Ward, Peter A

    2013-04-01

    Severe sepsis is a life-threatening disease that causes major morbidity and mortality. Catecholamines and glucocorticoids often have been used for the treatment of sepsis. Several recent studies have suggested a potential role of IL-17 during the development and progression of sepsis in small animal models. In this study, the cross-talk of catecholamines and glucocorticoids with members of the IL-17 family was investigated during sepsis in C57BL/6 mice. The concentrations in plasma of IL-17A, IL-17F, and the IL-17AF heterodimer all were increased greatly in mice after endotoxemia or cecal ligation and puncture as compared with sham mice. Surprisingly, when compared with IL-17A (487 pg/mL), the concentrations of IL-17F (2361 pg/mL) and the heterodimer, IL-17AF (5116 pg/mL), were much higher 12 hours after endotoxemia. After surgical removal of the adrenal glands, mice had much higher mortality after endotoxemia or cecal ligation and puncture. The absence of endogenous adrenal gland hormones (cortical and medullary) was associated with 3- to 10-fold higher concentrations of IL-17A, IL-17F, IL-17AF, and IL-23. The addition of adrenaline, noradrenaline, hydrocortisone, or dexamethasone to lipopolysaccharide-activated peritoneal macrophages dose-dependently suppressed the expression and release of IL-17s. The production of IL-17s required activation of c-Jun-N-terminal kinase, which was antagonized by both catecholamines and glucocorticoids. These data provide novel insights into the molecular mechanisms of immune modulation by catecholamines and glucocorticoids during acute inflammation. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  11. Xylitol-supplemented nutrition enhances bacterial killing and prolongs survival of rats in experimental pneumococcal sepsis

    Science.gov (United States)

    Renko, Marjo; Valkonen, Päivi; Tapiainen, Terhi; Kontiokari, Tero; Mattila, Pauli; Knuuttila, Matti; Svanberg, Martti; Leinonen, Maija; Karttunen, Riitta; Uhari, Matti

    2008-01-01

    Background Xylitol has antiadhesive effects on Streptococcus pneumoniae and inhibits its growth, and has also been found to be effective in preventing acute otitis media and has been used in intensive care as a valuable source of energy. Results We evaluated the oxidative burst of neutrophils in rats fed with and without xylitol. The mean increase in the percentage of activated neutrophils from the baseline was higher in the xylitol-exposed group than in the control group (58.1% vs 51.4%, P = 0.03 for the difference) and the mean induced increase in the median strength of the burst per neutrophil was similarly higher in the xylitol group (159.6 vs 140.3, P = 0.04). In two pneumococcal sepsis experiments rats were fed either a basal powder diet (control group) or the same diet supplemented with 10% or 20% xylitol and infected with an intraperitoneal inoculation of S. pneumoniae after two weeks. The mean survival time was 48 hours in the xylitol groups and 34 hours in the control groups (P Xylitol has beneficial effects on both the oxidative killing of bacteria in neutrophilic leucocytes and on the survival of rats with experimental pneumococcal sepsis. PMID:18334022

  12. Frontline Science: HMGB1 induces neutrophil dysfunction in experimental sepsis and in patients who survive septic shock.

    Science.gov (United States)

    Grégoire, Murielle; Tadié, Jean-Marc; Uhel, Fabrice; Gacouin, Arnaud; Piau, Caroline; Bone, Nathaniel; Le Tulzo, Yves; Abraham, Edward; Tarte, Karin; Zmijewski, Jaroslaw W

    2017-06-01

    Sepsis is accompanied by the initial activation of proinflammatory pathways and long-lasting immunosuppression that appears to contribute to late-occurring mortality. Although high-mobility group box 1 (HMGB1) is involved in many aspects of inflammation, its role in sepsis-induced immune suppression remains unclear. In this study, we examined HMGB1's contribution to neutrophil NADPH oxidase activity dysfunction and associated neutrophil-dependent bacterial clearance in mice subjected to sepsis and in patients who survive septic shock. Using a murine model of polymicrobial septic peritonitis, we demonstrated that treatment with anti-HMGB1 Ab significantly diminished sepsis-induced dysfunction of neutrophil NADPH oxidase activity. In a subsequent set of experiments, we found that blocking HMGB1 preserved the ability of neutrophils from patients recovering from septic shock to activate NADPH oxidase. Taken together, our data suggest that HMGB1 accumulation in the late phase of sepsis plays a specific role in the development of postsepsis immunosuppression and specifically affects neutrophil-dependent antibacterial defense mechanisms. Thus, blocking HMGB1 may be a promising therapeutic intervention to diminish the adverse effects of sepsis-induced immunosuppression. © Society for Leukocyte Biology.

  13. Efficacy of enrofloxacin in a mouse model of sepsis.

    Science.gov (United States)

    Slate, Andrea R; Bandyopadhyay, Sheila; Francis, Kevin P; Papich, Mark G; Karolewski, Brian; Hod, Eldad A; Prestia, Kevin A

    2014-07-01

    We examined the efficacy of enrofloxacin administered by 2 different routes in a mouse model of sepsis. Male CD1 mice were infected with a bioluminescent strain of enteropathogenic Escherichia coli and treated with enrofloxacin either by injection or in drinking water. Peak serum levels were evaluated by using HPLC. Mice were monitored for signs of clinical disease, and infections were monitored by using bioluminescence imaging. Serum levels of enrofloxacin and the active metabolite ciprofloxacin were greater in the group treated by injection than in controls or the groups treated by administration in drinking water. Survival of the group treated with enrofloxacin injection was greater than that of controls and groups treated with enrofloxacin in the drinking water. Bioluminescence in the group treated with enrofloxacin injection was less than that in the groups treated with oral administration at 12 h and in the groups treated orally and the control group at 16 h. According to these findings, we recommend the use of injectable enrofloxacin at 5 mg/kg SC for mice with systemic infections.

  14. Antithrombin III in animal models of sepsis and organ failure.

    Science.gov (United States)

    Dickneite, G

    1998-01-01

    Antithrombin III (AT III) is the physiological inhibitor of thrombin and other serine proteases of the clotting cascade. In the development of sepsis, septic shock and organ failure, the plasma levels of AT III decrease considerably, suggesting the concept of a substitution therapy with the inhibitor. A decrease of AT III plasma levels might also be associated with other pathological disorders like trauma, burns, pancreatitis or preclampsia. Activation of coagulation and consumption of AT III is the consequence of a generalized inflammation called SIRS (systemic inflammatory response syndrome). The clotting cascade is also frequently activated after organ transplantation, especially if organs are grafted between different species (xenotransplantation). During the past years AT III has been investigated in numerous corresponding disease models in different animal species which will be reviewed here. The bulk of evidence suggests, that AT III substitution reduces morbidity and mortality in the diseased animals. While gaining more experience with AT III, the concept of substitution therapy to maximal baseline plasma levels (100%) appears to become insufficient. Evidence from clinical and preclinical studies now suggests to adjust the AT III plasma levels to about 200%, i.e., doubling the normal value. During the last few years several authors proposed that AT III might not only be an anti-thrombotic agent, but to have in addition an anti-inflammatory effect.

  15. Sepsis Alert - a triage model that reduces time to antibiotics and length of hospital stay.

    Science.gov (United States)

    Rosenqvist, Mari; Fagerstrand, Emma; Lanbeck, Peter; Melander, Olle; Åkesson, Per

    2017-07-01

    To study if a modified triage system at an Emergency Department (ED) combined with educational efforts resulted in reduced time to antibiotics and decreased length of hospital stay (LOS) for patients with severe infection. A retrospective, observational study comparing patients before and after the start of a new triage model at the ED of a University Hospital. After the implementation of the model, patients with fever and abnormal vital signs were triaged into a designated sepsis line (Sepsis Alert) for rapid evaluation by the attending physician supported by a infectious diseases (IDs) specialist. Also, all ED staff participated in a designated sepsis education before Sepsis Alert was introduced. Medical records were evaluated for patients during a 3-month period after the triage system was started in 2012, and also during the corresponding months in 2010 and 2014. A total of 1837 patients presented with abnormal vital signs. Of these, 221 patients presented with fever and thus at risk of having severe sepsis. Among patients triaged according to the new model, median time to antibiotics was 58.5 at startup and 24.5 minutes at follow-up two years later. This was significantly less than for patients treated before the new model, 190 minutes. Also, median LOS was significantly decreased after introduction of the new triage model, from nine to seven days. A triage model at the ED with special attention to severe sepsis patients, led to sustained improvements of time to antibiotic treatment and LOS.

  16. Modelling severe Staphylococcus aureus sepsis in conscious pigs: are implications for animal welfare justified?

    DEFF Research Database (Denmark)

    Olsen, Helle G; Kjelgaard-Hansen, Mads; Tveden-Nyborg, Pernille

    2016-01-01

    A porcine model of haematogenous Staphylococcus aureus sepsis has previously been established in our research group. In these studies, pigs developed severe sepsis including liver dysfunction during a 48 h study period. As pigs were awake during the study, animal welfare was challenged by the sev......A porcine model of haematogenous Staphylococcus aureus sepsis has previously been established in our research group. In these studies, pigs developed severe sepsis including liver dysfunction during a 48 h study period. As pigs were awake during the study, animal welfare was challenged....... Prior to euthanasia, a galactose elimination capacity test was performed to assess liver function. Pigs were euthanised 48 h post inoculation for necropsy and histopathological evaluation. While infusion times of 6.66 min, and higher, did not induce liver dysfunction (n = 3), the infusion time of 3......, according to humane endpoints. A usable balance between scientific purpose and animal welfare could not be achieved, and we therefore find it hard to justify further use of this conscious porcine sepsis model. In order to make a model of translational relevance for human sepsis, we suggest that future model...

  17. Glucocorticoid resistance as a major drive in sepsis pathology.

    Science.gov (United States)

    Dendoncker, Karen; Libert, Claude

    2017-06-01

    Sepsis is an acute systemic inflammatory disease. Glucocorticoids (GCs), which function by binding to the GC receptor GR have very powerful anti-inflammatory activities, yet they are hardly useful in sepsis. We can thus consider sepsis as a GC resistant disease. We here review the literature which has investigated this GC resistance, and summarize the mechanisms of GC resistance that have been observed in other diseases and in experimental models. We also discuss the importance of GC resistance in sepsis, in terms of the contribution of this phenomenon to the pathogenesis of sepsis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Development and validation of a mortality risk model for pediatric sepsis

    Science.gov (United States)

    Chen, Mengshi; Lu, Xiulan; Hu, Li; Liu, Pingping; Zhao, Wenjiao; Yan, Haipeng; Tang, Liang; Zhu, Yimin; Xiao, Zhenghui; Chen, Lizhang; Tan, Hongzhuan

    2017-01-01

    Abstract Pediatric sepsis is a burdensome public health problem. Assessing the mortality risk of pediatric sepsis patients, offering effective treatment guidance, and improving prognosis to reduce mortality rates, are crucial. We extracted data derived from electronic medical records of pediatric sepsis patients that were collected during the first 24 hours after admission to the pediatric intensive care unit (PICU) of the Hunan Children's hospital from January 2012 to June 2014. A total of 788 children were randomly divided into a training (592, 75%) and validation group (196, 25%). The risk factors for mortality among these patients were identified by conducting multivariate logistic regression in the training group. Based on the established logistic regression equation, the logit probabilities for all patients (in both groups) were calculated to verify the model's internal and external validities. According to the training group, 6 variables (brain natriuretic peptide, albumin, total bilirubin, D-dimer, lactate levels, and mechanical ventilation in 24 hours) were included in the final logistic regression model. The areas under the curves of the model were 0.854 (0.826, 0.881) and 0.844 (0.816, 0.873) in the training and validation groups, respectively. The Mortality Risk Model for Pediatric Sepsis we established in this study showed acceptable accuracy to predict the mortality risk in pediatric sepsis patients. PMID:28514310

  19. Simvastatin Treatment Improves Survival in a Murine Model of Burn Sepsis

    Science.gov (United States)

    Beffa, David C; Fischman, Alan J.; Fagan, Shawn P.; Hamrahi, Victoria F.; Kaneki, Masao; Yu, Yong-Ming; Tompkins, Ronald G.; Carter, Edward A.

    2014-01-01

    Infection is the most common and most serious complication of a major burn injury related to burn size. Despite improvements in antimicrobial therapies sepsis still accounts for 50–60% of deaths in burn patients. Given the acute onset and unpredictable nature of sepsis, primary prevention was rarely attempted in its management. However, recent studies have demonstrated that statin treatment can decrease mortality is a murine model of sepsis by preservation of cardiac function and reversal of inflammatory alterations. In addition, it has been shown that treatment with statins is associated with reduced incidence of sepsis in human patients. In the current study groups of CD1 male mice (n=12) were anesthetized and subjected to a dorsal 30% TBSA scald burn injury. Starting 2 hours post burn, the animals were divided into a treatment group receiving 0.2 µ/g simvastatin or a sham group receiving placebo. Simvastatin and placebo were administered by intraperitoneal injection with two dosing regimens; once daily and every 12 hours. On Post burn day 7 cecal ligation and puncture with a 21-gauge needle was performed under ketamine/xylazine anesthesia and the two different dosing schedules were continued. A simvastatin dose dependant improvement in survival was observed in the burn sepsis model. PMID:21145172

  20. Cutting Edge: 2B4-Mediated Coinhibition of CD4+ T Cells Underlies Mortality in Experimental Sepsis.

    Science.gov (United States)

    Chen, Ching-Wen; Mittal, Rohit; Klingensmith, Nathan J; Burd, Eileen M; Terhorst, Cox; Martin, Greg S; Coopersmith, Craig M; Ford, Mandy L

    2017-09-15

    Sepsis is a leading cause of death in the United States, but the mechanisms underlying sepsis-induced immune dysregulation remain poorly understood. 2B4 (CD244, SLAM4) is a cosignaling molecule expressed predominantly on NK cells and memory CD8 + T cells that has been shown to regulate T cell function in models of viral infection and autoimmunity. In this article, we show that 2B4 signaling mediates sepsis lymphocyte dysfunction and mortality. 2B4 expression is increased on CD4 + T cells in septic animals and human patients at early time points. Importantly, genetic loss or pharmacologic inhibition of 2B4 significantly increased survival in a murine cecal ligation and puncture model. Further, CD4-specific conditional knockouts showed that 2B4 functions on CD4 + T cell populations in a cell-intrinsic manner and modulates adaptive and innate immune responses during sepsis. Our results illuminate a novel role for 2B4 coinhibitory signaling on CD4 + T cells in mediating immune dysregulation. Copyright © 2017 by The American Association of Immunologists, Inc.

  1. Dynamics of hepatic gene expression and serum cytokine profiles in single and double-hit burn and sepsis animal models

    Directory of Open Access Journals (Sweden)

    Rohit Rao

    2015-06-01

    Full Text Available We simulate the pathophysiology of severe burn trauma and burn-induced sepsis, using rat models of experimental burn injury and cecal ligation and puncture (CLP either individually (singe-hit model or in combination (double-hit model. The experimental burn injury simulates a systemic but sterile pro-inflammatory response, while the CLP simulates the effect of polymicrobial sepsis. Given the liver׳s central role in mediating the host immune response and onset of hypermetabolism after burn injury, elucidating the alterations in hepatic gene expression in response to injury can lead to a better understanding of the regulation of the inflammatory response, whereas circulating cytokine protein expression, reflects key systemic inflammatory mediators. In this article, we present both the hepatic gene expression and circulating cytokine/chemokine protein expression data for the above-mentioned experimental model to gain insights into the temporal dynamics of the inflammatory and hypermetabolic response following burn and septic injury. This data article supports results discussed in research articles (Yang et al., 2012 [1,4]; Mattick et al. 2012, 2013 [2,3]; Nguyen et al., 2014 [5]; Orman et al., 2011, 2012 [6–8].

  2. Evaluating the effects of protective ventilation on organ-specific cytokine production in porcine experimental postoperative sepsis.

    Science.gov (United States)

    Sperber, Jesper; Lipcsey, Miklós; Larsson, Anders; Larsson, Anders; Sjölin, Jan; Castegren, Markus

    2015-05-10

    Protective ventilation with lower tidal volume (VT) and higher positive end-expiratory pressure (PEEP) reduces the negative additive effects of mechanical ventilation during systemic inflammatory response syndrome. We hypothesised that protective ventilation during surgery would affect the organ-specific immune response in an experimental animal model of endotoxin-induced sepsis-like syndrome. 30 pigs were laparotomised for 2 hours (h), after which a continuous endotoxin infusion was started at 0.25 micrograms × kg(-1) × h(-1) for 5 h. Catheters were placed in the carotid artery, hepatic vein, portal vein and jugular bulb. Animals were randomised to two protective ventilation groups (n = 10 each): one group was ventilated with VT 6 mL × kg(-1) during the whole experiment while the other group was ventilated during the surgical phase with VT of 10 mL × kg(-1). In both groups PEEP was 5 cmH2O during surgery and increased to 10 cmH2O at the start of endotoxin infusion. A control group (n = 10) was ventilated with VT of 10 mL × kg(-1) and PEEP 5 cm H20 throughout the experiment. In four sample locations we a) simultaneously compared cytokine levels, b) studied the effect of protective ventilation initiated before and during endotoxemia and c) evaluated protective ventilation on organ-specific cytokine levels. TNF-alpha levels were highest in the hepatic vein, IL-6 levels highest in the artery and jugular bulb and IL-10 levels lowest in the artery. Protective ventilation initiated before and during endotoxemia did not differ in organ-specific cytokine levels. Protective ventilation led to lower levels of TNF-alpha in the hepatic vein compared with the control group, whereas no significant differences were seen in the artery, portal vein or jugular bulb. Variation between organs in cytokine output was observed during experimental sepsis. We see no implication from cytokine levels for initiating protective ventilation before endotoxemia. However, during endotoxemia

  3. Interleukin-30 (IL27p28) alleviates experimental sepsis by modulating cytokine profile in NKT cells.

    Science.gov (United States)

    Yan, Jun; Mitra, Abhisek; Hu, Jiemiao; Cutrera, Jeffery J; Xia, Xueqing; Doetschman, Thomas; Gagea, Mihai; Mishra, Lopa; Li, Shulin

    2016-05-01

    Sepsis is an acute systemic inflammatory response to infection associated with high patient mortality (28-40%). We hypothesized that interleukin (IL)-30, a novel cytokine protecting mice against liver injury resulting from inflammation, would generate a protective effect against systemic inflammation and sepsis-induced death. Sepsis was induced by lipopolysaccharide (LPS) or cecal ligation and puncture (CLP). The inhibitory effects of IL-30 on septic inflammation and associated therapeutic effects were determined in wild-type, IL30 (p28)(-/-), IL10(-/-), and CD1d(-/-) mice. Mice treated with pIL30 gene therapy or recombinant IL-30 protein (rIL30) were protected from LPS-induced septic shock or CLP-induced polymicrobial sepsis and showed markedly less liver damage and lymphocyte apoptosis than control septic mice. The resulting reduction in mortality was mediated through attenuation of the systemic pro-inflammatory response and augmentation of bacterial clearance. Mice lacking IL-30 were more sensitive to LPS-induced sepsis. Natural killer-like T cells (NKT) produced much higher levels of IL-10 and lower levels of interferon-gamma and tumor necrosis factor-alpha in IL-30-treated septic mice than in control septic mice. Likewise, deficiency in IL-10 or NKT cells abolished the protective role of IL-30 against sepsis. Furthermore, IL-30 induced IL-10 production in purified and LPS-stimulated NKT cells. Blocking IL-6R or gp130 inhibited IL-30 mediated IL-10 production. IL-30 is important in modulating production of NKT cytokines and subsequent NKT cell-mediated immune regulation of other cells. Therefore, IL-30 has a role in prevention and treatment of sepsis via modulation of cytokine production by NKT. Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  4. Chronic Porcine Two-Hit Model with Hemorrhagic Shock and textitPseudomonas aeruginosa Sepsis

    OpenAIRE

    Eissner, B.;Matz, K.;Smorodchenko, A.;Röschmann, A.;Specht, B. U. v.

    2016-01-01

    Background: Sepsis is still a major cause of death despite well-developed therapeutical strategies such as antibiotics and supportive medication. The aim of this study was to characterize the long-term effects of a two-hit porcine sepsis model with a hemorrhagic shock as ‘first hit’ followed by a Pseudomonas aeruginosa infusion as ‘second hit’. Materials and Methods: Twelve juvenile healthy pigs were anesthetized and hemodynamically monitored. The two-hit group (n = 6) underwent a hemorrhagic...

  5. Effect of selective inhibition of renal inducible nitric oxide synthase on renal blood flow and function in experimental hyperdynamic sepsis.

    Science.gov (United States)

    Ishikawa, Ken; Calzavacca, Paolo; Bellomo, Rinaldo; Bailey, Michael; May, Clive N

    2012-08-01

    Nitric oxide plays an important role in the control of renal blood flow and renal function. In sepsis, increased levels of inducible nitric oxide synthase produce excessive nitric oxide, which may contribute to the development of acute kidney injury. We, therefore, examined the effects of intrarenal infusion of selective inducible nitric oxide synthase inhibitors in a large animal model of hyperdynamic sepsis in which acute kidney injury occurs in the presence of increased renal blood flow. Prospective crossover randomized controlled interventional studies. University-affiliated research institute. Twelve unilaterally nephrectomized Merino ewes. Infusion of a selective (1400W) and a partially selective inducible nitric oxide synthase inhibitor (aminoguanidine) into the renal artery for 2 hrs after the induction of sepsis, and comparison with a nonselective inhibitor (Nω-nitro-L-arginine methyl ester). In sheep with nonhypotensive hyperdynamic sepsis, creatinine clearance halved (32 to 16 mL/min, ratio [95% confidence interval] 0.51 [0.28-0.92]) despite increased renal blood flow (241 to 343 mL/min, difference [95% confidence interval] 102 [78-126]). Infusion of 1400W did not change renal blood flow, urine output, or creatinine clearance, whereas infusion of Nω-nitro-L-arginine methyl ester and a high dose of aminoguanidine normalized renal blood flow, but did not alter creatinine clearance. In hyperdynamic sepsis, intrarenal infusion of a highly selective inducible nitric oxide synthase inhibitor did not reduce the elevated renal blood flow or improve renal function. In contrast, renal blood flow was reduced by infusion of a nonselective NOS inhibitor or a high dose of a partially selective inducible nitric oxide synthase inhibitor. The renal vasodilatation in septic acute kidney injury may be due to nitric oxide derived from the endothelial and neural isoforms of nitric oxide synthase, but their blockade did not restore renal function.

  6. Effect of chronic ethanol consumption in female rats subjected to experimental sepsis

    Energy Technology Data Exchange (ETDEWEB)

    Castro, C.L. [Programa de Pós-Graduação em Patologia, Universidade Federal Fluminense, Niterói, RJ (Brazil); Aguiar-Nemer, A.S. [Departamento de Nutrição, Instituto de Ciências Biológicas, Universidade Federal de Juiz de Fora, Juiz de Fora, MG (Brazil); Castro-Faria-Neto, H.C. [Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, RJ (Brazil); Barros, F.R. [Programa de Pós-Graduação em Patologia, Universidade Federal Fluminense, Niterói, RJ (Brazil); Rocha, E.M.S. [Departamento de Microbiologia e Parasitologia, Universidade Federal Fluminense, Niterói, RJ (Brazil); Silva-Fonseca, V.A. [Departamento de Fisiologia e Farmacologia, Universidade Federal Fluminense, Niterói, RJ (Brazil)

    2013-12-10

    The objective of this research was to evaluate the interference of ethanol consumption by female rats with cytokines involved in the sepsis process and its correlation with mortality, the main outcome of sepsis. Female Wistar rats in estrus phase were evaluated in three experiments. Experiment 1 (n=40) was performed to determine survival rates. Experiment 2 (n=69) was designed for biochemical analysis, measurement of cytokine and estrogen levels before and after sepsis, and experiment 3 (n=10) was performed to evaluate bacterial growth by colony counts of peritoneal fluid. In all experiments, treated animals were exposed to a 10% ethanol/water solution (v/v) as the single drinking source, while untreated animals were given tap water. After 4 weeks, sepsis was induced in the rats by ip injection of feces. In experiment 1, mortality in ethanol-exposed animals was delayed compared with those that drank water (48 h; P=0.0001). Experiment 2 showed increased tumor necrosis factor alpha (TNF-α) and decreased interleukin-6 (IL-6) and macrophage migration inhibitory factor in septic animals exposed to ethanol compared to septic animals not exposed. Sepsis also increased TNF-α and IL-6 levels in both ethanol- and water-exposed groups. Biochemical analysis showed higher creatinine, alanine aminotransferase and aspartate aminotransferase and decreased glucose levels in septic animals that were exposed to ethanol. In experiment 3, septic animals exposed to ethanol showed decreased numbers of colony-forming units than septic animals exposed to water. These results suggest that ethanol consumption delays the mortality of female rats in estrus phase after sepsis induction. Female characteristics, most probably sex hormones, may be involved in cytokine expression.

  7. Effect of chronic ethanol consumption in female rats subjected to experimental sepsis

    International Nuclear Information System (INIS)

    Castro, C.L.; Aguiar-Nemer, A.S.; Castro-Faria-Neto, H.C.; Barros, F.R.; Rocha, E.M.S.; Silva-Fonseca, V.A.

    2013-01-01

    The objective of this research was to evaluate the interference of ethanol consumption by female rats with cytokines involved in the sepsis process and its correlation with mortality, the main outcome of sepsis. Female Wistar rats in estrus phase were evaluated in three experiments. Experiment 1 (n=40) was performed to determine survival rates. Experiment 2 (n=69) was designed for biochemical analysis, measurement of cytokine and estrogen levels before and after sepsis, and experiment 3 (n=10) was performed to evaluate bacterial growth by colony counts of peritoneal fluid. In all experiments, treated animals were exposed to a 10% ethanol/water solution (v/v) as the single drinking source, while untreated animals were given tap water. After 4 weeks, sepsis was induced in the rats by ip injection of feces. In experiment 1, mortality in ethanol-exposed animals was delayed compared with those that drank water (48 h; P=0.0001). Experiment 2 showed increased tumor necrosis factor alpha (TNF-α) and decreased interleukin-6 (IL-6) and macrophage migration inhibitory factor in septic animals exposed to ethanol compared to septic animals not exposed. Sepsis also increased TNF-α and IL-6 levels in both ethanol- and water-exposed groups. Biochemical analysis showed higher creatinine, alanine aminotransferase and aspartate aminotransferase and decreased glucose levels in septic animals that were exposed to ethanol. In experiment 3, septic animals exposed to ethanol showed decreased numbers of colony-forming units than septic animals exposed to water. These results suggest that ethanol consumption delays the mortality of female rats in estrus phase after sepsis induction. Female characteristics, most probably sex hormones, may be involved in cytokine expression

  8. Sepsis reconsidered: Identifying novel metrics for behavioral landscape characterization with a high-performance computing implementation of an agent-based model.

    Science.gov (United States)

    Cockrell, Chase; An, Gary

    2017-10-07

    developed two novel methods for characterizing the behavior of a RDS: Probabilistic Basins of Attraction (PBoA) and Stochastic Trajectory Analysis (STA). Computationally generated behavioral landscapes demonstrated attractor structures around stochastic regions of behavior that could be described in a complementary fashion through use of PBoA and STA. The stochasticity of the boundaries of the attractors highlights the challenge for correlative attempts to characterize and classify clinical sepsis. HPC simulations of models like the IIRABM can be used to generate approximations of the behavior space of sepsis to both establish "boundaries of futility" with respect to existing investigatory approaches and apply system engineering principles to investigate the general dynamic properties of sepsis to provide a pathway for developing control strategies. The issues that bedevil the study and treatment of sepsis, namely clinical data sparseness and inadequate experimental sampling of system behavior space, are fundamental to nearly all biomedical research, manifesting in the "Crisis of Reproducibility" at all levels. HPC-augmented simulation-based research offers an investigatory strategy more consistent with that seen in the physical sciences (which combine experiment, theory and simulation), and an opportunity to utilize the leading advances in HPC, namely deep machine learning and evolutionary computing, to form the basis of an iterative scientific process to meet the full promise of Precision Medicine (right drug, right patient, right time). Copyright © 2017. Published by Elsevier Ltd.

  9. Murine Models of Sepsis and Trauma: Can We Bridge the Gap?

    Science.gov (United States)

    Stortz, Julie A; Raymond, Steven L; Mira, Juan C; Moldawer, Lyle L; Mohr, Alicia M; Efron, Philip A

    2017-07-01

    Sepsis and trauma are both leading causes of death in the United States and represent major public health challenges. Murine models have largely been used in sepsis and trauma research to better understand the pathophysiological changes that occur after an insult and to develop potential life-saving therapeutic agents. Mice are favorable subjects for this type of research given the variety of readily available strains including inbred, outbred, and transgenic strains. In addition, they are relatively easy to maintain and have a high fecundity. However, pharmacological therapies demonstrating promise in preclinical mouse models of sepsis and trauma often fail to demonstrate similar efficacy in human clinical trials, prompting considerable criticism surrounding the capacity of murine models to recapitulate complex human diseases like sepsis and traumatic injury. Fundamental differences between the two species include, but are not limited to, the divergence of the transcriptomic response, the mismatch of temporal response patterns, differences in both innate and adaptive immunity, and heterogeneity within the human population in comparison to the homogeneity of highly inbred mouse strains. Given the ongoing controversy, this narrative review aims to not only highlight the historical importance of the mouse as an animal research model but also highlight the current benefits and limitations of the model as it pertains to sepsis and trauma. Lastly, this review will propose future directions that may promote further use of the model. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  10. Changes in ceftriaxone pharmacokinetics/pharmacodynamics during the early phase of sepsis: a prospective, experimental study in the rat

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    Valentina Selmi

    2016-11-01

    Full Text Available Abstract Background Sepsis is characterized by the loss of the perm-selectivity properties of the glomerular filtration barrier (GFB with consequent albuminuria. We examined whether the pharmacokinetics–pharmacodynamics (PK/PD of ceftriaxone (CTX, an extensively protein-bound 3rd generation cephalosporin, is altered during early sepsis and whether an increase in urinary loss of bound-CTX, due to GFB alteration, can occur in this condition. Methods A prospective, experimental, randomized study was carried out in adult male Sprague–Dawley rats. Sepsis was induced by cecal ligation and puncture (CLP. Rats were divided into two groups: Sham-operated and CLP. CTX (100 mg i.p., equivalent to 1 g dose in humans was administered in order to measure plasma and lung CTX concentrations at several time-points: baseline and 1, 2, 4 and 6 h after administration. CTX was measured by High Performance Liquid Chromatography (HPLC. The morphological status of the sialic components of the GFB barrier was assessed by lectin histo-chemistry. Monte Carlo simulation was performed to calculate the probability of target attainment (PTA >90% for 80 and 100% of Tfree > minimum inhibitory concentration (MIC for 80 and 100% of dosing interval. Measurements and main results After CLP, sepsis developed in rats as documented by the growth of polymicrobial flora in the peritoneal fluid (≤1 × 101 CFU in sham rats vs 5 × 104–1 × 105 CFU in CLP rats. CTX plasma concentrations were higher in CLP than in sham rats at 2 and 4 h after administration (difference at 2 h was 47.3, p = 0.012; difference at 4 h was 24.94, p = 0.004, while lung penetration tended to be lower. An increased urinary elimination of protein-bound CTX occurred (553 ± 689 vs 149 ± 128 mg/L, p  90% for 100% of the dosing interval was reached neither for sham nor CLP rats using MIC = 1 mg/L, the clinical breakpoint for Enterobacteriacee. Conclusions Sepsis causes changes in

  11. Local infusion of Staphylococcus aureus into the porcine internal carotid artery as a model of sepsis-related brain abscesses - A pilot study

    DEFF Research Database (Denmark)

    Astrup, Lærke B.; Iburg, Tine M.; Agerholm, Jørgen S.

    2017-01-01

    Brain pathology is an important aspect of human sepsis but is difficult to study in human patients. Th erefore, animal models of sepsis-related brain pathology are needed. As pigs mirror multiple aspects of sepsis-related brain pathology in humans, this makes the pig a potentially suitable model...

  12. Endothelin receptor antagonist attenuates oxidative stress in a neonatal sepsis piglet model.

    Science.gov (United States)

    Goto, Tatenobu; Hussein, Mohamed Hamed; Kato, Shin; Daoud, Ghada Abdel-Hamid; Kato, Takenori; Sugiura, Takahiro; Kakita, Hiroki; Nobata, Masanori; Kamei, Michi; Mizuno, Haruo; Imai, Masaki; Ito, Tetsuya; Kato, Ineko; Suzuki, Satoshi; Okada, Noriko; Togari, Hajime; Okada, Hidechika

    2012-12-01

    Oxidative stress (oxidant-antioxidant imbalance) plays an important role in the pathophysiology of neonatal sepsis. This study evaluated whether an antisense peptide endothelin receptor antagonist, ETR-P1/fl, could attenuate oxidative stress in a neonatal sepsis model. A total of 18 3-d-old piglets were anesthetized and mechanically ventilated. Six piglets received cecal ligation and perforation (CLP group) for induction of sepsis. Six piglets also received continuous infusion (0.05 mg/kg/h) of ETR-P1/fl 30 min after CLP (ETR-P1/fl group). Six piglets received a sham operation. Serum total hydroperoxide (TH), biological antioxidant potentials (BAPs), oxidative stress index (OSI, calculated as TH/BAP), interleukin (IL)-6, serum glutamic oxaloacetic transaminase (GOT), and creatinine were measured before CLP and at 1, 3, and 6 h after CLP. CLP evoked a state of shock resulting in elevated TH, OSI, and IL-6 levels. ETR-P1/fl administration after CLP resulted in lower serum TH at 1 and 3 h after CLP, OSI at 1 and 3 h after CLP, IL-6 at 1 and 3 h after CLP, and GOT at 3 and 6 h after CLP as compared with the CLP group. ETR-P1/fl treatment significantly attenuated the elevation of serum oxidative stress markers (TH and OSI), IL-6, and GOT in a progressive neonatal sepsis CLP model.

  13. Dynamic cerebral autoregulation to induced blood pressure changes in human experimental and clinical sepsis

    DEFF Research Database (Denmark)

    Berg, Ronan M G; Plovsing, Ronni R; Bailey, Damian M

    2016-01-01

    (-1) ; P = 0·91 versus baseline; P = 0·14 versus LPS]. While our findings support the concept that dynamic cerebral autoregulation is enhanced during the very early stages of sepsis, they remain inconclusive with regard to more advanced stages of disease, because thigh-cuff deflation failed to induce...... (Ps...

  14. Pharmacologic studies on ET-26 hydrochloride in a rat model of lipopolysaccharide-induced sepsis.

    Science.gov (United States)

    Wang, Bin; Jiang, Junli; Yang, Jun; Chen, Jun; Zhu, Zhaoqiong; Liu, Jin; Zhang, Wensheng

    2017-11-15

    ET-26 hydrochloride (ET-26 HCl) is a promising sedation-hypnotic compound with stable hemodynamic features that elicits virtually no adrenocortical suppression. However, whether it preserves better pharmacologic characteristics in a rat model of sepsis is not known. This study compared the survival rate, levels of corticosterone and pro-inflammatory cytokines, and histologic injury in the lungs and kidneys of rats suffering from sepsis treated with ET-26 HCl, etomidate, or normal saline (NS). Rats were given lipopolysaccharide (1mg/kg body weight, i.v.) to establish a sepsis model. Thirty minutes after lipopolysaccharide administration, ET-26 HCl, etomidate or NS were given as a bolus injection at equivalent doses. Plasma levels of corticosterone, interleukin-1β, interleukin-6, interleukin-10, and tumor necrosis factor-α were measured 1, 2, 4, 6 and 24h after administration. Histologic injury was observed at the time of death or 24h after drug administration. The survival rate for rats in the etomidate, ET-26 HCl and NS groups was 40%, 90% and 90%, respectively. Corticosterone concentrations in the etomidate group were lower than those in the other groups 1h after administration of hypnotic compounds. Concentrations of pro-inflammatory cytokines in the ET-26 HCl group and NS group were not significantly different, but were significantly lower than those in the etomidate group. The injury scores of kidneys and lungs in the etomidate group were higher than those in ET-26 HCl and NS groups. ET-26 HCl showed virtually no suppression of corticosterone synthesis, lower concentrations of pro-inflammatory cytokines, higher survival rate, and less organ injury in rats suffering from sepsis compared with the etomidate group. It may be safer to induce anesthesia using ET-26 HCl, rather than etomidate, in patients suffering from sepsis. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Mycobacterium tuberculosis PPE18 Protein Reduces Inflammation and Increases Survival in Animal Model of Sepsis.

    Science.gov (United States)

    Ahmed, Asma; Dolasia, Komal; Mukhopadhyay, Sangita

    2018-04-18

    Mycobacterium tuberculosis PPE18 is a member of the PPE family. Previous studies have shown that recombinant PPE18 (rPPE18) protein binds to TLR2 and triggers a signaling cascade which reduces levels of TNF-α and IL-12, and increases IL-10 in macrophages. Because TNF-α is a major mediator of the pathophysiology of sepsis and blocking inflammation is a possible line of therapy in such circumstances, we tested the efficacy of rPPE18 in reducing symptoms of sepsis in a mouse model of Escherichia coli- induced septic peritonitis. rPPE18 significantly decreased levels of serum TNF-α, IL-1β, IL-6, and IL-12 and reduced organ damage in mice injected i.p. with high doses of E. coli Peritoneal cells isolated from rPPE18-treated mice had characteristics of M2 macrophages which are protective in excessive inflammation. Additionally, rPPE18 inhibited disseminated intravascular coagulation, which can cause organ damage resulting in death. rPPE18 was able to reduce sepsis-induced mortality when given prophylactically or therapeutically. Additionally, in a mouse model of cecal ligation and puncture-induced sepsis, rPPE18 reduced TNF-α, alanine transaminase, and creatinine, attenuated organ damage, prevented depletion of monocytes and lymphocytes, and improved survival. Our studies show that rPPE18 has potent anti-inflammatory properties and can serve as a novel therapeutic to control sepsis. Copyright © 2018 by The American Association of Immunologists, Inc.

  16. Effects of Ecballium elaterium on brain in a rat model of sepsis-associated encephalopathy

    Science.gov (United States)

    Arslan, Demet; Ekinci, Aysun; Arici, Akgul; Bozdemir, Eda; Akil, Esref; Ozdemir, Hasan Huseyin

    2017-01-01

    ABSTRACT Despite recent advances in antibiotic therapy, sepsis remains a major clinical challenge in intensive care units. Here we examined the anti-inflammatory and antioxidant effects of Ecballium elaterium (EE) on brain, and explored its therapeutic potential in an animal model of sepsis-associated encephalopathy (SAE) [induced by cecal ligation and puncture (CLP)]. Thirty rats were divided into three groups of 10 each: control, sepsis, and treatment. Rats were subjected to CLP except for the control group, which underwent laparatomy only. The treatment group received 2.5 mg/kg EE while the sepsis group was administered by saline. Twenty-four hours after laparotomy, animals were sacrificied and the brains were removed. Brain homogenates were prepared to assess interleukin 1beta (IL-1β), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), total antioxidant capacity (TAC), and total oxidant status (TOS). Brain tissue sections were stained by hematoxylin and eosin (H&E) to semi-quantitatively examine the histopathologic changes such as neuron degeneration, pericellular/perivascular edema and inflammatory cell infiltration in the cerebral cortex. We found a statistically significant reduction in brain tissue homogenate levels of TNF-α 59.5 ± 8.4/50.2 ± 6.2 (p = 0.007) and TOS 99.3 ± 16.9/82.3 ± 7.8 (p = 0.01) in rats treated with EE; although interleukin 6 levels were increased in the treatment group compared to the sepsis group, this was not statistically significant. Neuronal damage (p = 0.00), pericellular/perivascular edema and inflammatory cell infiltration (p = 0.001) were also significantly lower in the treatment group compared to those in the sepsis group. These data suggest that Ecballium elaterium contains some components that exert protective effects against SAE in part by attenuating accumulation of proinflammatory cytokines, which may be important contributors to its anti-inflammatory effects during sepsis. PMID:28859554

  17. CXCR4 blockade decreases CD4+ T cell exhaustion and improves survival in a murine model of polymicrobial sepsis.

    Science.gov (United States)

    Ramonell, Kimberly M; Zhang, Wenxiao; Hadley, Annette; Chen, Ching-Wen; Fay, Katherine T; Lyons, John D; Klingensmith, Nathan J; McConnell, Kevin W; Coopersmith, Craig M; Ford, Mandy L

    2017-01-01

    Sepsis is a dysregulated systemic response to infection involving many inflammatory pathways and the induction of counter-regulatory anti-inflammatory processes that results in a state of immune incompetence and can lead to multi-organ failure. CXCR4 is a chemokine receptor that, following ligation by CXCL12, directs cells to bone marrow niches and also plays an important role in T cell cosignaling and formation of the immunological synapse. Here, we investigated the expression and function of CXCR4 in a murine model of polymicrobial sepsis. Results indicate that CXCR4 is selectively upregulated on naïve CD4+ and CD8+ T cells and CD4+ central memory T cells following the induction of sepsis, and that CXCR4 antagonism resulted in a significant decrease in sepsis-induced mortality. We probed the mechanistic basis for these findings and found that CXCR4 antagonism significantly increased the number of peripheral CD4+ and CD8+ T cells following sepsis. Moreover, mice treated with the CXCR4 antagonist contained fewer PD-1+ LAG-3+ 2B4+ cells, suggesting that blockade of CXCR4 mitigates CD4+ T cell exhaustion during sepsis. Taken together, these results characterize CXCR4 as an important pathway that modulates immune dysfunction and mortality following sepsis, which may hold promise as a target for future therapeutic intervention in septic patients.

  18. CXCR4 blockade decreases CD4+ T cell exhaustion and improves survival in a murine model of polymicrobial sepsis.

    Directory of Open Access Journals (Sweden)

    Kimberly M Ramonell

    Full Text Available Sepsis is a dysregulated systemic response to infection involving many inflammatory pathways and the induction of counter-regulatory anti-inflammatory processes that results in a state of immune incompetence and can lead to multi-organ failure. CXCR4 is a chemokine receptor that, following ligation by CXCL12, directs cells to bone marrow niches and also plays an important role in T cell cosignaling and formation of the immunological synapse. Here, we investigated the expression and function of CXCR4 in a murine model of polymicrobial sepsis. Results indicate that CXCR4 is selectively upregulated on naïve CD4+ and CD8+ T cells and CD4+ central memory T cells following the induction of sepsis, and that CXCR4 antagonism resulted in a significant decrease in sepsis-induced mortality. We probed the mechanistic basis for these findings and found that CXCR4 antagonism significantly increased the number of peripheral CD4+ and CD8+ T cells following sepsis. Moreover, mice treated with the CXCR4 antagonist contained fewer PD-1+ LAG-3+ 2B4+ cells, suggesting that blockade of CXCR4 mitigates CD4+ T cell exhaustion during sepsis. Taken together, these results characterize CXCR4 as an important pathway that modulates immune dysfunction and mortality following sepsis, which may hold promise as a target for future therapeutic intervention in septic patients.

  19. The Effects of Dexmedetomidine on Secondary Acute Lung and Kidney Injuries in the Rat Model of Intra-Abdominal Sepsis

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    Uğur Koca

    2013-01-01

    Full Text Available In the present study, the effects of dexmedetomidine on secondary lung and kidney injuries were studied in the rat model of intra-abdominal sepsis by immunohistological and biochemical examinations. We measured serum creatinine, kidney tissue malondialdehide and plasma neutrophil gelatinase-associated lipocalin levels. In order to evaluate tissue injury we determined kidney tissue mononuclear cell infiltration score, alveolar macrophage count, histological kidney and lung injury scores and kidney and lung tissue immunoreactivity scores. We demonstrated that dexmedetomidine attenuates sepsis-induced lung and kidney injuries and apoptosis in the rat model of sepsis. There is still need for comparative studies in order to determine the effects of dexmedetomidine on organ functions in early human sepsis.

  20. Combined treatment with atorvastatin and imipenem improves survival and vascular functions in mouse model of sepsis.

    Science.gov (United States)

    Choudhury, Soumen; Kannan, Kandasamy; Pule Addison, M; Darzi, Sazad A; Singh, Vishakha; Singh, Thakur Uttam; Thangamalai, Ramasamy; Dash, Jeevan Ranjan; Parida, Subhashree; Debroy, Biplab; Paul, Avishek; Mishra, Santosh Kumar

    2015-08-01

    We have recently reported that pre-treatment, but not the post-treatment with atorvastatin showed survival benefit and improved hemodynamic functions in cecal ligation and puncture (CLP) model of sepsis in mice. Here we examined whether combined treatment with atorvastatin and imipenem after onset of sepsis can prolong survival and improve vascular functions. At 6 and 18h after sepsis induction, treatment with atorvastatin plus imipenem, atorvastatin or imipenem alone or placebo was initiated. Ex vivo experiments were done on mouse aorta to examine the vascular reactivity to nor-adrenaline and acetylcholine and mRNA expressions of α1D AR, GRK2 and eNOS. Atorvastatin plus imipenem extended the survival time to 56.00±4.62h from 20.00±1.66h observed in CLP mice. The survival time with atorvastatin or imipenem alone was 20.50±1.89h and 27.00±4.09h, respectively. The combined treatment reversed the hyporeactivity to nor-adrenaline through preservation of α1D AR mRNA/protein expression and reversal of α1D AR desensitization mediated by GRK2/Gβγ pathway. The treatment also restored endothelium-dependent relaxation to ACh through restoration of aortic eNOS mRNA expression and NO availability. In conclusion, combined treatment with atorvastatin and imipenem exhibited survival benefit and improved vascular functions in septic mice. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Regulation of Akt-mTOR, ubiquitin-proteasome and autophagy-lysosome pathways in locomotor and respiratory muscles during experimental sepsis in mice.

    Science.gov (United States)

    Morel, Jérome; Palao, Jean-Charles; Castells, Josiane; Desgeorges, Marine; Busso, Thierry; Molliex, Serge; Jahnke, Vanessa; Del Carmine, Peggy; Gondin, Julien; Arnould, David; Durieux, Anne Cécile; Freyssenet, Damien

    2017-09-07

    Sepsis induced loss of muscle mass and function contributes to promote physical inactivity and disability in patients. In this experimental study, mice were sacrificed 1, 4, or 7 days after cecal ligation and puncture (CLP) or sham surgery. When compared with diaphragm, locomotor muscles were more prone to sepsis-induced muscle mass loss. This could be attributed to a greater activation of ubiquitin-proteasome system and an increased myostatin expression. Thus, this study strongly suggests that the contractile activity pattern of diaphragm muscle confers resistance to atrophy compared to the locomotor gastrocnemius muscle. These data also suggest that a strategy aimed at preventing the activation of catabolic pathways and preserving spontaneous activity would be of interest for the treatment of patients with sepsis-induced neuromyopathy.

  2. Examining the controllability of sepsis using genetic algorithms on an agent-based model of systemic inflammation.

    Directory of Open Access Journals (Sweden)

    Robert Chase Cockrell

    2018-02-01

    Full Text Available Sepsis, a manifestation of the body's inflammatory response to injury and infection, has a mortality rate of between 28%-50% and affects approximately 1 million patients annually in the United States. Currently, there are no therapies targeting the cellular/molecular processes driving sepsis that have demonstrated the ability to control this disease process in the clinical setting. We propose that this is in great part due to the considerable heterogeneity of the clinical trajectories that constitute clinical "sepsis," and that determining how this system can be controlled back into a state of health requires the application of concepts drawn from the field of dynamical systems. In this work, we consider the human immune system to be a random dynamical system, and investigate its potential controllability using an agent-based model of the innate immune response (the Innate Immune Response ABM or IIRABM as a surrogate, proxy system. Simulation experiments with the IIRABM provide an explanation as to why single/limited cytokine perturbations at a single, or small number of, time points is unlikely to significantly improve the mortality rate of sepsis. We then use genetic algorithms (GA to explore and characterize multi-targeted control strategies for the random dynamical immune system that guide it from a persistent, non-recovering inflammatory state (functionally equivalent to the clinical states of systemic inflammatory response syndrome (SIRS or sepsis to a state of health. We train the GA on a single parameter set with multiple stochastic replicates, and show that while the calculated results show good generalizability, more advanced strategies are needed to achieve the goal of adaptive personalized medicine. This work evaluating the extent of interventions needed to control a simplified surrogate model of sepsis provides insight into the scope of the clinical challenge, and can serve as a guide on the path towards true "precision control" of

  3. Examining the controllability of sepsis using genetic algorithms on an agent-based model of systemic inflammation.

    Science.gov (United States)

    Cockrell, Robert Chase; An, Gary

    2018-02-01

    Sepsis, a manifestation of the body's inflammatory response to injury and infection, has a mortality rate of between 28%-50% and affects approximately 1 million patients annually in the United States. Currently, there are no therapies targeting the cellular/molecular processes driving sepsis that have demonstrated the ability to control this disease process in the clinical setting. We propose that this is in great part due to the considerable heterogeneity of the clinical trajectories that constitute clinical "sepsis," and that determining how this system can be controlled back into a state of health requires the application of concepts drawn from the field of dynamical systems. In this work, we consider the human immune system to be a random dynamical system, and investigate its potential controllability using an agent-based model of the innate immune response (the Innate Immune Response ABM or IIRABM) as a surrogate, proxy system. Simulation experiments with the IIRABM provide an explanation as to why single/limited cytokine perturbations at a single, or small number of, time points is unlikely to significantly improve the mortality rate of sepsis. We then use genetic algorithms (GA) to explore and characterize multi-targeted control strategies for the random dynamical immune system that guide it from a persistent, non-recovering inflammatory state (functionally equivalent to the clinical states of systemic inflammatory response syndrome (SIRS) or sepsis) to a state of health. We train the GA on a single parameter set with multiple stochastic replicates, and show that while the calculated results show good generalizability, more advanced strategies are needed to achieve the goal of adaptive personalized medicine. This work evaluating the extent of interventions needed to control a simplified surrogate model of sepsis provides insight into the scope of the clinical challenge, and can serve as a guide on the path towards true "precision control" of sepsis.

  4. Study on the protective effect of ethyl pyruvate on mouse models of sepsis-induced lung injury

    International Nuclear Information System (INIS)

    Ti Dongdong; Deng Zihui; Xue Hui; Wang Luhuan; Lin Ji; Yan Guangtao

    2008-01-01

    Objective: To investigate the protective role of ethyl pyruvate on mouse models of lung injury from sepsis. Methods: Mouse sepsis models were established by cecal ligation-perforation. Four enzyme parameters related to synthesis of free radicals in lung homogenized fluids namely malonaldehyde (MDA), pyruvate acid, lactic acid and total anti-oxidative capacity (TAOC) were determined with spectrophotometry, and serum leptin levels were detected with radioimmunoassay at 3, 6, 9, 12h after operation in these models. Half of the models were treated with intraperitoneal injection of ethyl pyruvate (EP) (75mg/kg). Results: In the models treated with ethyl pyruvate injection, the activity of malonaldehyde, pyruvate acid, lactic acid and total anti-oxidative capacity were affected to certain extent, at some time frames but the results were not unanimously inhibitive or promotive. Serum leptin levels in EP injection models at 6h and 12h after sepsis were significantly higher than those in non-treated models. Conclusion: Ethyl pyruvate perhaps exerted its protective effect on sepsis-induced lung injury through increase of leptin levels in the models. (authors)

  5. In vivo characterization of neutrophil extracellular traps in various organs of a murine sepsis model.

    Directory of Open Access Journals (Sweden)

    Koji Tanaka

    Full Text Available Neutrophil extracellular traps (NETs represent extracellular microbial trapping and killing. Recently, it has been implicated in thrombogenesis, autoimmune disease, and cancer progression. The aim of this study was to characterize NETs in various organs of a murine sepsis model in vivo and to investigate their associations with platelets, leukocytes, or vascular endothelium. NETs were classified as two distinct forms; cell-free NETs that were released away from neutrophils and anchored NETs that were anchored to neutrophils. Circulating cell-free NETs were characterized as fragmented or cotton-like structures, while anchored NETs were characterized as linear, reticular, membranous, or spot-like structures. In septic mice, both anchored and cell-free NETs were significantly increased in postcapillary venules of the cecum and hepatic sinusoids with increased leukocyte-endothelial interactions. NETs were also observed in both alveolar space and pulmonary capillaries of the lung. The interactions of NETs with platelet aggregates, leukocyte-platelet aggregates or vascular endothelium of arterioles and venules were observed in the microcirculation of septic mice. Microvessel occlusions which may be caused by platelet aggregates or leukocyte-platelet aggregates and heterogeneously decreased blood flow were also observed in septic mice. NETs appeared to be associated with the formation of platelet aggregates or leukocyte-platelet aggregates. These observational findings may suggest the adverse effect of intravascular NETs on the host during a sepsis.

  6. Alcohol acute intoxication before sepsis impairs the wound healing of intestinal anastomosis: rat model of the abdominal trauma patient

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    Morais Pedro

    2012-08-01

    Full Text Available Abstract Introduction Most trauma patients are drunk at the time of injury. Up to 2% of traumatized patients develop sepsis, which considerably increases their mortality. Inadequate wound healing of the colonic repair can lead to postoperative complications such as leakage and sepsis. Objective To assess the effects of acute alcohol intoxication on colonic anastomosis wound healing in septic rats. Methods Thirty six Wistar rats were allocated into two groups: S (induction of sepsis and AS (alcohol intake before sepsis induction. A colonic anastomosis was performed in all groups. After 1, 3 or 7 days the animals were killed. Weight variations, mortality rate, histopathology and tensile breaking strength of the colonic anastomosis were evaluated. Results There was an overall mortality of 4 animals (11.1%, three in the group AS (16.6% and one in the S group (5.5%. Weight loss occurred in all groups. The colon anastomosis of the AS group didn’t gain strength from the first to the seventh postoperative day. On the histopathological analysis there were no differences in the deposition of collagen or fibroblasts between the groups AS and S. Conclusion Alcohol intake increased the mortality rate three times in septic animals. Acute alcohol intoxication delays the acquisition of tensile strength of colonic anastomosis in septic rats. Therefore, acute alcohol intoxication before sepsis leads to worse prognosis in animal models of the abdominal trauma patients.

  7. Effects of volume resuscitation on the microcirculation in animal models of lipopolysaccharide sepsis: a systematic review

    OpenAIRE

    Obonyo, Nchafatso G.; Fanning, Jonathon P.; Ng, Angela S. Y.; Pimenta, Leticia P.; Shekar, Kiran; Platts, David G.; Maitland, Kathryn; Fraser, John F.

    2016-01-01

    Background Recent research has identified an increased rate of mortality associated with fluid bolus therapy for severe sepsis and septic shock, but the mechanisms are still not well understood. Fluid resuscitation therapy administered for sepsis and septic shock targets restoration of the macro-circulation, but the pathogenesis of sepsis is complex and includes microcirculatory dysfunction. Objective The objective of the study is to systematically review data comparing the effects of differe...

  8. A fragment of the alarmin prothymosin α as a novel biomarker in murine models of bacteria-induced sepsis.

    Science.gov (United States)

    Samara, Pinelopi; Miriagou, Vivi; Zachariadis, Michael; Mavrofrydi, Olga; Promponas, Vasilis J; Dedos, Skarlatos G; Papazafiri, Panagiota; Kalbacher, Hubert; Voelter, Wolfgang; Tsitsilonis, Ourania

    2017-07-25

    Sepsis is a life-threatening condition that requires urgent care. Thus, the identification of specific and sensitive biomarkers for its early diagnosis and management are of clinical importance. The alarmin prothymosin alpha (proTα) and its decapeptide proTα(100-109) are immunostimulatory peptides related to cell death. In this study, we generated bacterial models of sepsis in mice using two Klebsiella pneumoniae strains (L-78 and ATCC 43816) and monitored sepsis progression using proTα(100-109) as a biomarker. Serum concentration of proTα(100-109) gradually increased as sepsis progressed in mice infected with L-78, a strain which, unlike ATCC 43816, was phagocytosed by monocytes/macrophages. Analysis of splenocytes from L-78-infected animals revealed that post-infection spleen monocytes/macrophages were gradually driven to caspase-3-mediated apoptosis. These results were verified in vitro in L-78-infected human monocytes/macrophages. Efficient phagocytosis of L-78 by monocytes stimulated their apoptosis and the concentration of proTα(100-109) in culture supernatants increased. Human macrophages strongly phagocytosed L-78, but resisted cell death. This is the first report suggesting that high levels of proTα(100-109) correlate, both in vitro and in vivo, with increased percentages of cell apoptosis. Moreover, we showed that low levels of proTα(100-109) early post-infection likely correlate with sepsis resolution and thus, the decapeptide could eventually serve as an early surrogate biomarker for predicting bacteria-induced sepsis outcome.

  9. Possible Causes of Ileal Injury in Two Models of Microbial Sepsis and Protective Effect of Phytic Acid

    Directory of Open Access Journals (Sweden)

    Rasha Rashad Ahmed

    2010-03-01

    Full Text Available Background: Sepsis related-multiple organ dysfunction is associatedwith ileum injury. We aimed to determine the causes ofileal injury in two models of microbial sepsis resulted from infectionwith Aeromonas hydrophila or its endotoxin. We alsoevaluated the protective effect of phytic acid.Methods: Thin sections of ileum from 60 Swiss male mice incontrol, bacteria-infected or lipopolysaccharides (LPS andbacteria-infected or LPS-infected co-administered with phyticacid were subjected to histopathological and TdT-mediateddUTP nick-end labeling (TUNEL assay for apoptotic cellsdetection while ultra thin sections were stained with uranylacetate and lead citrate for cytological changes examination.Also, ileum images were exposed to the image analysis softwareto determine some related morphometric measures.Results: Necrosis and apoptosis were observed in ileum injuryin both examined sepsis models. The ileum injury was moresevere in LPS model. Phytic acid showed the ability to attenuateileum injury in Aeromonas hydrophila and its endotoxinmodels of sepsis after four weeks administration where itssupplementation significantly minimized the histopathologicaland cytological complications and morphometric alterationsresulted from the injury.Conclusion: The protective effects of phytic acid may becaused by increased mucous secretion, decreased apoptoticindex, attenuating the inflammatory and lymphocytic cellscount or increasing the renewal of the crypt cells and villousepithelial cells proliferation.

  10. Glutamine reduces myocardial cell apoptosis in a rat model of sepsis by promoting expression of heat shock protein 90.

    Science.gov (United States)

    Li, Wanxia; Tao, Shaoyu; Wu, Qinghua; Wu, Tao; Tao, Ran; Fan, Jun

    2017-12-01

    Myocardial cell injury and cardiac myocyte apoptosis are associated with sepsis. Glutamine (Gln) has been reported to repair myocardial cell injury. The aim of this study was to explore the role of Gln on cardiac myocytes in a cecal ligation and puncture (CLP) model of sepsis in Wistar rats. Following induction of sepsis in a CLP rat model, viral encoding heat shock protein 90 (Hsp90) gene and Hsp90dsDNA were designed to express and knockdown Hsp90, respectively. Rat cardiac tissues were examined histologically, and apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling staining. The expression of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein, Hsp90, p53 upregulated modulator of apoptosis, and p53 was measured by western blotting and real-time polymerase chain reaction. Caspase-3, caspase-8, and caspase-9 were detected by enzyme-linked immunosorbent assay. Rat cardiac myocyte damage induced by CLP was reduced by Gln treatment and Hsp90 overexpression, and these changes were reversed by Hsp90 knockdown. Bcl-2 expression, Bcl-2-associated X protein, p53, p53 upregulated modulator of apoptosis, caspase-8, caspase-9, and caspase-3 activities were significantly upregulated in the CLP model, which were reduced by Gln treatment and Hsp90 overexpression. Gln reduced apoptosis of cardiac myocytes in a rat model of sepsis, by promoting Hsp90 expression. Further studies are needed to determine the possible therapeutic action of Gln in sepsis in human tissue. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Antibody to endotoxin core glycolipid reverses reticuloendothelial system depression in an animal model of severe sepsis and surgical injury

    Energy Technology Data Exchange (ETDEWEB)

    Aldridge, M.C.; Chadwick, S.J.; Cheslyn-Curtis, S.; Rapson, N.; Dudley, H.A.

    1987-10-01

    To study the effect of severe sepsis on the function of the reticuloendothelial system (RES) we have measured the clearance kinetics and organ distribution of both low-dose technetium tin colloid (TTC) and /sup 75/selenomethionine-labelled E. coli in rabbits 24 hours after either sham laparotomy or appendix devascularization. Sepsis resulted in similar delayed blood clearance and reduced liver (Kupffer cell) uptake of both TTC and E. coli. To investigate the ability of polyclonal antibody to E. coli-J-5 (core glycolipid) to improve RES function in the same model of sepsis, further animals were pretreated with either core glycolipid antibody or control serum (10 ml IV) 2 hours before induction of sepsis. TTC clearance kinetics were determined 24 hours later. Antibody pretreated animals showed: a reduced incidence of bacteremia; normalization of the rate of blood clearance and liver uptake of TTC; and a 'rebound' increase in splenic uptake of TTC. We conclude that antibody to E. coli-J-5 enhances bacterial clearance by the RES.

  12. Antibody to endotoxin core glycolipid reverses reticuloendothelial system depression in an animal model of severe sepsis and surgical injury

    International Nuclear Information System (INIS)

    Aldridge, M.C.; Chadwick, S.J.; Cheslyn-Curtis, S.; Rapson, N.; Dudley, H.A.

    1987-01-01

    To study the effect of severe sepsis on the function of the reticuloendothelial system (RES) we have measured the clearance kinetics and organ distribution of both low-dose technetium tin colloid (TTC) and 75 selenomethionine-labelled E. coli in rabbits 24 hours after either sham laparotomy or appendix devascularization. Sepsis resulted in similar delayed blood clearance and reduced liver (Kupffer cell) uptake of both TTC and E. coli. To investigate the ability of polyclonal antibody to E. coli-J-5 (core glycolipid) to improve RES function in the same model of sepsis, further animals were pretreated with either core glycolipid antibody or control serum (10 ml IV) 2 hours before induction of sepsis. TTC clearance kinetics were determined 24 hours later. Antibody pretreated animals showed: a reduced incidence of bacteremia; normalization of the rate of blood clearance and liver uptake of TTC; and a 'rebound' increase in splenic uptake of TTC. We conclude that antibody to E. coli-J-5 enhances bacterial clearance by the RES

  13. Prophylactic Antioxidant Potential of Gallic Acid in Murine Model of Sepsis

    OpenAIRE

    Maurya, Harikesh; Mangal, Vaishali; Gandhi, Sanjay; Prabhu, Kathiresan; Ponnudurai, Kathiresan

    2014-01-01

    Present study is to investigate the effect of Gallic acid pretreatment on survival of septic animals and oxidative stress in different organs like lungs, liver, kidney, spleen, and vascular dysfunction of mice. Sepsis was induced by cecal ligation and puncture (CLP) in healthy adult male albino mice (25–30 g) and was divided into 3 groups each consisting of 6 animals, that is, sham-operated (SO group (Group I), SO + sepsis (Group II), and Gallic acid + sepsis (Group III)). Group III animals w...

  14. Sepsis (For Parents)

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Sepsis KidsHealth / For Parents / Sepsis What's in this article? ... When to Call the Doctor Print What Is Sepsis? Sepsis is when the immune system responds to ...

  15. Hepatoprotective effects of {gamma}-irradiated caraway essential oils in experimental sepsis

    Energy Technology Data Exchange (ETDEWEB)

    Fatemi, F. [Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, P.O. Box, 14115-111, Tehran (Iran, Islamic Republic of); Allameh, A. [Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, P.O. Box, 14115-111, Tehran (Iran, Islamic Republic of)], E-mail: allameha@modares.ac.ir; Khalafi, H. [Radiation Application Research School, Nuclear Science and Technology Research Institute, Tehran (Iran, Islamic Republic of); Ashrafihelan, J. [Department of Pathobiology, Faculty of Veterinary Medicine, University of Tabriz, Tabriz (Iran, Islamic Republic of)

    2010-02-15

    Irradiation is an important method of processing herbal drugs, while our understanding of the effects of {gamma}-irradiation on pharmacological properties of seed products such as caraway essential oils is however still very limited. In this study, caraway seeds were irradiated at dose levels of 0, 10 and 25 kGy. After extracting the essential oils, the effects of fresh and {gamma}-irradiated caraway oils (100 mg/kg b.w) on preventing septic-related oxidative liver injury induced by cecal ligation and puncture (CLP) model were investigated by measuring oxidative stress parameters in the liver. CLP operation caused a marked increase in myeloperoxidase (MPO) activity which was readily reversed in rats treated with fresh and irradiated caraway oils. Likewise, thiobarbituric acid reactive substances (TBARS) level in the liver was compensated in rats treated with the fresh and irradiated caraway oils. Moreover, liver GSH which was initially depleted due to CLP was recovered by essential oil treatments. The protective role of oils was further confirmed by showing that liver function tests (ALT/AST) as well as histopathological changes following CLP operation were recovered in rats treated with oils from either fresh or irradiated caraway seeds. These data may suggest that {gamma}-irradiation to caraway seeds at 10 and 25 kGy has no influence on the antioxidative properties of caraway essential oils.

  16. Hepatoprotective effects of γ-irradiated caraway essential oils in experimental sepsis

    International Nuclear Information System (INIS)

    Fatemi, F.; Allameh, A.; Khalafi, H.; Ashrafihelan, J.

    2010-01-01

    Irradiation is an important method of processing herbal drugs, while our understanding of the effects of γ-irradiation on pharmacological properties of seed products such as caraway essential oils is however still very limited. In this study, caraway seeds were irradiated at dose levels of 0, 10 and 25 kGy. After extracting the essential oils, the effects of fresh and γ-irradiated caraway oils (100 mg/kg b.w) on preventing septic-related oxidative liver injury induced by cecal ligation and puncture (CLP) model were investigated by measuring oxidative stress parameters in the liver. CLP operation caused a marked increase in myeloperoxidase (MPO) activity which was readily reversed in rats treated with fresh and irradiated caraway oils. Likewise, thiobarbituric acid reactive substances (TBARS) level in the liver was compensated in rats treated with the fresh and irradiated caraway oils. Moreover, liver GSH which was initially depleted due to CLP was recovered by essential oil treatments. The protective role of oils was further confirmed by showing that liver function tests (ALT/AST) as well as histopathological changes following CLP operation were recovered in rats treated with oils from either fresh or irradiated caraway seeds. These data may suggest that γ-irradiation to caraway seeds at 10 and 25 kGy has no influence on the antioxidative properties of caraway essential oils.

  17. Histone deacetylase inhibitor treatment attenuates coagulation imbalance in a lethal murine model of sepsis

    DEFF Research Database (Denmark)

    Zhao, Ting; Li, Yongqing; Liu, Baoling

    2014-01-01

    BACKGROUND: Sepsis has a profound impact on the inflammatory and hemostatic systems. In addition to systemic inflammation, it can produce disseminated intravascular coagulation, microvascular thrombosis, consumptive coagulopathy, and multiple organ failure. We have shown that treatment with suber...

  18. The effect of E coli virulence on bacterial translocation and systemic sepsis in the neonatal rabbit model.

    Science.gov (United States)

    Jackson, R J; Smith, S D; Wadowsky, R M; DePudyt, L; Rowe, M I

    1991-04-01

    In the surgical neonate, three factors that promote bacterial translocation and systemic infection are: (1) intestinal bacterial colonization and overgrowth; (2) compromised host defenses; and (3) disruption of the mucosal epithelial barrier. The newborn rabbit provides an excellent model to study these factors. Like the human, there is early closure of the gut mucosa to macromolecules, and nutrition can be maintained by breast or formula feeding. This study examines translocation and systemic sepsis after colonization with virulent K1 and avirulent K100 strains of Escherichia coli. New Zealand white rabbit pups (2 to 5 days old) were studied. The gastrointestinal tracts of 12 were colonized with K1 E coli; 14 were colonized with K100 E coli; 12 control animals were not inoculated. Mesenteric lymph node (MLN), liver, spleen, and colon homogenate were cultured 72 hours postinoculation. No bacteria were isolated from the colons of all but one control animal. Translocation or systemic sepsis did not occur. Translocation to the MLN was significantly increased (P less than .03) in K1 (50%) and K100 (36%) groups compared with controls (0%). Translocation to liver and spleen (systemic sepsis) was significantly increased (P less than .03) in K1 animals (67%) compared with K100 (0%) or controls (0%). Colonization by both strains of E coli led to translocation to the MLN, but only K1 E coli caused systemic sepsis. This suggests that although colonization by E coli in the newborn leads to translocation to the MLN, progression to systemic sepsis is the result of characteristics of the bacteria and/or neonatal host responses.

  19. The effect of pomegranate extract on survival and peritoneal bacterial load in cecal ligation and perforation model of sepsis in rats

    Directory of Open Access Journals (Sweden)

    Sanaz Tavasoli

    2014-01-01

    Conclusions: Our study demonstrates for the first time that pomegranate extract could increase mortality rate via increasing peritoneal cavity bacterial load, in CLP sepsis model. More studies to assess mechanisms of this effect are warranted.

  20. Differential regulation of the PGC family of genes in a mouse model of Staphylococcus aureus sepsis.

    Directory of Open Access Journals (Sweden)

    Timothy E Sweeney

    2010-07-01

    Full Text Available The PGC family of transcriptional co-activators (PGC-1alpha [Ppargc1a], PGC-1beta [Ppargc1b], and PRC [Pprc] coordinates the upregulation of mitochondrial biogenesis, and Ppargc1a is known to be activated in response to mitochondrial damage in sepsis. Therefore, we postulated that the PGC family is regulated by the innate immune system. We investigated whether mitochondrial biogenesis and PGC gene expression are disrupted in an established model of Staphylococcus aureus sepsis both in mice with impaired innate immune function (TLR2-/- and TLR4-/- and in wild-type controls. We found an early up-regulation of Ppargc1a and Ppargc1b post-infection (at 6 h in WT mice, but the expression of both genes was concordantly dysregulated in TLR2-/- mice (no increase at 6 h and in TLR4-/- mice (amplified at 6 h. However, the third family member, PRC, was regulated differently, and its expression increased significantly at 24 h in all three mouse strains (WT, TLR2-/-, and TLR4-/-. In silico analyses showed that Ppargc1a and Ppargc1b share binding sites for microRNA mmu-mir-202-3p. Thus, miRNA-mediated post-transcriptional mRNA degradation could account for the failure to increase the expression of both genes in TLR2-/- mice. The expression of mmu-mir-202-3p was measured by real-time PCR and found to be significantly increased in TLR2-/- but not in WT or TLR4-/- mice. In addition, it was found that mir-202-3p functionally decreases Ppargc1a mRNA in vitro. Thus, both innate immune signaling through the TLRs and mir-202-3p-mediated mRNA degradation are implicated in the co-regulation of Ppargc1a and Ppargc1b during inflammation. Moreover, the identification of mir-202-3p as a potential factor for Ppargc1a and Ppargc1b repression in acute inflammation may open new avenues for mitochondrial research and, potentially, therapy.

  1. Lactobacillus rhamnosus L34 Attenuates Gut Translocation-Induced Bacterial Sepsis in Murine Models of Leaky Gut.

    Science.gov (United States)

    Panpetch, Wimonrat; Chancharoenthana, Wiwat; Bootdee, Kanthika; Nilgate, Sumanee; Finkelman, Malcolm; Tumwasorn, Somying; Leelahavanichkul, Asada

    2018-01-01

    Gastrointestinal (GI) bacterial translocation in sepsis is well known, but the role of Lactobacillus species probiotics is still controversial. We evaluated the therapeutic effects of Lactobacillus rhamnosus L34 in a new sepsis model of oral administration of pathogenic bacteria with GI leakage induced by either an antibiotic cocktail (ATB) and/or dextran sulfate sodium (DSS). GI leakage with ATB, DSS, and DSS plus ATB (DSS+ATB) was demonstrated by fluorescein isothiocyanate (FITC)-dextran translocation to the circulation. The administration of pathogenic bacteria, either Klebsiella pneumoniae or Salmonella enterica serovar Typhimurium, enhanced translocation. Bacteremia was demonstrated within 24 h in 50 to 88% of mice with GI leakage plus the administration of pathogenic bacteria but not with GI leakage induction alone or bacterial gavage alone. Salmonella bacteremia was found in only 16 to 29% and 0% of mice with Salmonella and Klebsiella administrations, respectively. Klebsiella bacteremia was demonstrated in 25 to 33% and 10 to 16% of mice with Klebsiella and Salmonella administrations, respectively. Lactobacillus rhamnosus L34 attenuated GI leakage in these models, as shown by the reductions of FITC-dextran gut translocation, serum interleukin-6 (IL-6) levels, bacteremia, and sepsis mortality. The reduction in the amount of fecal Salmonella bacteria with Lactobacillus treatment was demonstrated. In addition, an anti-inflammatory effect of the conditioned medium from Lactobacillus rhamnosus L34 was also demonstrated by the attenuation of cytokine production in colonic epithelial cells in vitro In conclusion, Lactobacillus rhamnosus L34 attenuated the severity of symptoms in a murine sepsis model induced by GI leakage and the administration of pathogenic bacteria. Copyright © 2017 American Society for Microbiology.

  2. Prophylactic Antioxidant Potential of Gallic Acid in Murine Model of Sepsis

    Science.gov (United States)

    Maurya, Harikesh; Mangal, Vaishali; Gandhi, Sanjay; Prabhu, Kathiresan; Ponnudurai, Kathiresan

    2014-01-01

    Present study is to investigate the effect of Gallic acid pretreatment on survival of septic animals and oxidative stress in different organs like lungs, liver, kidney, spleen, and vascular dysfunction of mice. Sepsis was induced by cecal ligation and puncture (CLP) in healthy adult male albino mice (25–30 g) and was divided into 3 groups each consisting of 6 animals, that is, sham-operated (SO group (Group I), SO + sepsis (Group II), and Gallic acid + sepsis (Group III)). Group III animals were pretreated with Gallic acid at the dose rate of 20 mg/kg body weight for 2 days before induction of sepsis. Animals were sacrificed on 8th day and the tissue samples were obtained for further investigation on lipid peroxidation (LPO), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GSH). Gallic acid pretreatment significant (P Gallic acid pretreated mice showed significant improvement in SOD activity of kidney and spleen when compared to septic mice. Finally, the beneficial effects of Gallic acid pretreatment in sepsis are evident from the observations that Gallic acid partially restored SOD and catalase activity and completely reversed lipid peroxidation. Further studies are required to find out the possible mechanisms underlying the beneficial effects of Gallic acid on large population. PMID:25018890

  3. The SUCCESS model for laboratory performance and execution of rapid molecular diagnostics in patients with sepsis.

    Science.gov (United States)

    Dekmezian, Mhair; Beal, Stacy G; Damashek, Mary Jane; Benavides, Raul; Dhiman, Neelam

    2015-04-01

    Successful performance and execution of rapid diagnostics in a clinical laboratory hinges heavily on careful validation, accurate and timely communication of results, and real-time quality monitoring. Laboratories must develop strategies to integrate diagnostics with stewardship and evidence-based clinical practice guidelines. We present a collaborative SUCCESS model for execution and monitoring of rapid sepsis diagnostics to facilitate timely treatment. Six months after execution of the Verigene Gram-Positive Blood Culture (BC-GP) and the AdvanDx PNA-FISH assays, data were collected on 579 and 28 episodes of bacteremia and fungemia, respectively. Clinical testing was executed using a SUCCESS model comprising the following components: stewardship, utilization of resources, core strategies, concierge services, education, support, and surveillance. Stewardship needs were identified by evaluating the specialty services benefiting from new testing. Utilization of resources was optimized by reviewing current treatment strategies and antibiogram and formulary options. Core strategies consisted of input from infectious disease leadership, pharmacy, and laboratory staff. Concierge services included automated Micro-eUpdate and physician-friendly actionable reports. Education modules were user-specific, and support was provided through a dedicated 24/7 microbiology hotline. Surveillance was performed by daily audit by the director. Using the SUCCESS model, the turnaround time for the detailed report with actionable guidelines to the physician was ∼3 hours from the time of culture positivity. The overall correlation between rapid methods and culture was 94% (546/579). Discrepant results were predominantly contaminants such as a coagulase-negative staphylococci or viridans streptococci in mixed cultures. SUCCESS is a cost-effective and easily adaptable model for clinical laboratories with limited stewardship resources.

  4. Anatomo-radiological correlation using 18-FDG-PET in abdominal sepsis model in rats: A preliminary study

    Energy Technology Data Exchange (ETDEWEB)

    Azevedo, Italo Medeiros; Carvalho, Marilia Daniela Ferreira; Nascimento, Rafael Pereira; Macedo, Robson; Aquino, Monica Raquel de Souza; Medeiros, Aldo Cunha, E-mail: cirurgex.ufrn@gmail.com [Universidade Federal do Rio Grande do Norte (UFRN), Natal (Brazil)

    2017-03-15

    Purpose: To examine a correlation of micro-PET images with photographic images of the digestive organs in abdominal sepsis model. Methods: Male Wistar rats weighing 265±18g were used. Abdominal sepsis was induced by ligature and cecal puncture. Micro-PET Images from abdominal cavity septic foci were obtained using 18-Fluoro-deoxyglucose, looking for a correlation with photographic images of abdominal cavity organs. Pearson's correlation test was used. Results: The mean standard uptake values (SUV) and lesion areas were 2.58±0.63SUVbwg/ml and 546.87±300.95mm{sup 2} , respectively. There was a strong positive correlation between the two variables (r=0.863, p=0.137), which resulted in a coefficient of determination r{sup 2} ≅0.75, meaning that 75% of SUV variation is explained by the lesion areas of digestive organs. Conclusion: Micro-PET allows high throughput assessment of lesion count and volume in pre-clinical rat model of CPL abdominal sepsis. (author)

  5. Omega-9 Oleic Acid Induces Fatty Acid Oxidation and Decreases Organ Dysfunction and Mortality in Experimental Sepsis.

    Directory of Open Access Journals (Sweden)

    Cassiano Felippe Gonçalves-de-Albuquerque

    Full Text Available Sepsis is characterized by inflammatory and metabolic alterations, which lead to massive cytokine production, oxidative stress and organ dysfunction. In severe systemic inflammatory response syndrome, plasma non-esterified fatty acids (NEFA are increased. Several NEFA are deleterious to cells, activate Toll-like receptors and inhibit Na+/K+-ATPase, causing lung injury. A Mediterranean diet rich in olive oil is beneficial. The main component of olive oil is omega-9 oleic acid (OA, a monounsaturated fatty acid (MUFA. We analyzed the effect of OA supplementation on sepsis. OA ameliorated clinical symptoms, increased the survival rate, prevented liver and kidney injury and decreased NEFA plasma levels in mice subjected to cecal ligation and puncture (CLP. OA did not alter food intake and weight gain but diminished reactive oxygen species (ROS production and NEFA plasma levels. Carnitine palmitoyltransferase IA (CPT1A mRNA levels were increased, while uncoupling protein 2 (UCP2 liver expression was enhanced in mice treated with OA. OA also inhibited the decrease in 5' AMP-activated protein kinase (AMPK expression and increased the enzyme expression in the liver of OA-treated mice compared to septic animals. We showed that OA pretreatment decreased NEFA concentration and increased CPT1A and UCP2 and AMPK levels, decreasing ROS production. We suggest that OA has a beneficial role in sepsis by decreasing metabolic dysfunction, supporting the benefits of diets high in monounsaturated fatty acids (MUFA.

  6. Kaempferol attenuates acute lung injury in caecal ligation and puncture model of sepsis in mice.

    Science.gov (United States)

    Rabha, Dipankar Jyoti; Singh, Thakur Uttam; Rungsung, Soya; Kumar, Tarun; Parida, Subhashree; Lingaraju, Madhu Cholenahalli; Paul, Avishek; Sahoo, Monalisa; Kumar, Dinesh

    2018-03-01

    Kaempferol is a flavonoid and important part of the diet. Kaempferol has shown antioxidant, antiinflammatory and antidiabetic activities in various studies. However, protective potential of kaempferol in acute lung injury induced by sepsis and its mechanism remains unclear. The present study was undertaken to evaluate the effect of kaempferol in sepsis-induced acute lung injury in mice and its possible mechanism of action. Acute lung injury was induced by CLP surgery in mice. Kaempferol (100 mg/kg bw) was administered orally one hour before caecal ligation and puncture surgery in mice. Mice were divided into four groups sham, KEM+sham, sepsis (CLP), and KEM+sepsis. Assessment of lung injury was done by estimation of protein content in lung tissue, lung edema, proinflammatory cytokines in plasma and lung tissue, oxidative stress, antioxidant enzymes, nitrite production, and histopathology. Kaempferol pretreated mice showed significant (P Kaempferol pretreatment showed reduction in cytokines IL-6, IL-1β, and TNF-α in plasma as well as in lung tissue in comparison with septic mice without pretreatment. Pretreatment with kaempferol did not show any reduction in MDA level in comparison with septic mice. Antioxidant enzymes SOD and catalase and nonenzymatic antioxidant GSH activities were also increased with kaempferol pretreatment in septic mice. Further, kaempferol pretreatment reduced the lung tissue nitrite level (P Kaempferol pretreatment did not decrease bacterial load in septic mice. Mice pretreated with kaempferol followed by sepsis showed lesser infiltration of cells and more arranged alveolar structure in histopathological analysis. The study suggests that kaempferol showed attenuation in sepsis-induced acute lung injury in mice through suppression of oxidative stress, iNOS, and ICAM-1 pathways.

  7. The anti-inflammatory effect of the synthetic antimicrobial peptide 19-2.5 in a murine sepsis model: a prospective randomized study

    Science.gov (United States)

    2013-01-01

    Introduction Increasing rates of multi-resistant bacteria are a major problem in the treatment of critically ill patients. Furthermore, conventional antibiotics lead to the release of bacterial derived membrane parts initiating pro-inflammatory cascades with potential harm to the patient. Antimicrobial peptides (AMP) may kill bacteria without releasing pro-inflammatory factors. Thus, we compared three newly developed synthetic anti-lipopolysaccharide peptides (SALPs) with a broader range of efficacy to suppress cytokine release in plasma and CD14 mRNA expression in organ tissue in a murine, polymicrobial sepsis model. Methods A randomized, experimental trial was conducted in an animal research facility. Male NMRI mice (n = 90; 8- to 12-weeks old) were randomized to the following six groups: (i) sham operation and parenteral vehicle (NaCl 0.9%) administration (sham); (ii) cecal ligation and puncture (CLP) and vehicle infusion (sepsis-control), (iii) CLP and polymyxin B infusion (polyB), or (iv to vi) CLP and infusion of three different synthetic antimicrobial peptides Peptide 19-2.5 (Pep2.5), Peptide 19-4 (Pep4) or Peptide 19-8 (Pep8). All animals underwent arterial and venous catheterization for hemodynamic monitoring 48 hours prior to CLP or sham-operation. Physical appearance and behavior (activity), plasma cytokine levels, and CD14 mRNA expression in heart, lung, liver, spleen and kidney tissue were determined 24 hours after CLP or sham operation. Results Only Pep2.5 significantly enhanced the activity after CLP, whereas none of the therapeutic regimens elevated the mean arterial pressure or heart rate. The strongly elevated IL-6, IL-10 and monocyte chemoattractant protein serum levels in septic animals were significantly reduced after Pep2.5 administration (P < 0.001, P < 0.001, and P < 0.001, respectively). Similarly, Pep2.5 significantly reduced the sepsis-induced CD14 mRNA expression in heart (P = 0.003), lung (P = 0.008), and spleen tissue (P = 0.009) but

  8. Gas tonometry for evaluation of gastrointestinal mucosal perfusion: experimental and clinical sepsis¹. part 2 Tonometria a gás para a avaliação da perfusão da mucosa gastrointestinal: sepse clínica e experimental. Parte 2

    Directory of Open Access Journals (Sweden)

    Eliezer Silva

    2002-09-01

    Full Text Available Substantial clinical and animal evidences indicate that the mesenteric circulatory bed, particularly the gut mucosa, is highly vulnerable to reductions in oxygen supply and prone to early injury in the course of hemodynamic changes induced by sepsis and septic shock. Gut hypoxia or ischemia is one possible contributing factor to gastrointestinal tract barrier dysfunction that may be associated with the development of systemic inflammatory response and multiple organ dysfunction syndrome, the principal cause of death after sepsis. Monitoring gut perfusion during experimental and clinical sepsis may provide valuable insights over new interventions and therapies highly needed to reduce multiple organ dysfunction and sepsis-related morbidity and mortality. We present our experience with gas tonometry as a monitor of the adequacy of gastrointestinal mucosal perfusion in experimental models sepsis and with the use of vasoactive agents for hemodynamic management in patients with septic shock.Evidências clínicas e experimentais substanciais indicam que o território circulatório mesentérico, principalmente na mucosa intestinal, é altamente vulnerável a redução na oferta de oxigênio e predisposto a lesão precoce na presença de alterações hemodinâmicas induzidas pela sepse e choque séptico. A hipóxia ou isquemia intestinal é um dos possíveis mecanismos contribuintes para a disfunção da barreira gastrointestinal que pode estar associada com o desenvolvimento da resposta inflamatória sistêmica e com a síndrome da disfunção de múltiplos órgãos, a principal causa comum de morte na sepse. Monitorar a perfusão intestinal na sepse experimental e clínica pode fornecer dados valiosos quanto a novas intervenções e tratamentos altamente necessários para reduzir disfunção de múltiplos órgãos e mortalidade extremamente elevadas na sepse. Apresentamos nossa experiência com a tonometria a gás como monitor da adequação da perfus

  9. Benznidazole, the trypanocidal drug used for Chagas disease, induces hepatic NRF2 activation and attenuates the inflammatory response in a murine model of sepsis

    International Nuclear Information System (INIS)

    Lambertucci, Flavia; Motiño, Omar; Villar, Silvina; Rigalli, Juan Pablo; Luján Alvarez, María de; Catania, Viviana A; Martín-Sanz, Paloma; Carnovale, Cristina Ester; Quiroga, Ariel Darío; Francés, Daniel Eleazar; Ronco, María Teresa

    2017-01-01

    Molecular mechanisms on sepsis progression are linked to the imbalance between reactive oxygen species (ROS) production and cellular antioxidant capacity. Previous studies demonstrated that benznidazole (BZL), known for its antiparasitic action on Trypanosoma cruzi, has immunomodulatory effects, increasing survival in C57BL/6 mice in a model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). The mechanism by which BZL inhibits inflammatory response in sepsis is poorly understood. Also, our group recently reported that BZL is able to activate the nuclear factor erytroide-derived 2-Like 2 (NRF2) in vitro. The aim of the present work was to delineate the beneficial role of BZL during sepsis, analyzing its effects on the cellular redox status and the possible link to the innate immunity receptor TLR4. Specifically, we analyzed the effect of BZL on Nrf2 regulation and TLR4 expression in liver of mice 24 hours post-CLP. BZL was able to induce NRF2 nuclear protein localization in CLP mice. Also, we found that protein kinase C (PKC) is involved in the NRF2 nuclear accumulation and induction of its target genes. In addition, BZL prompted a reduction in hepatic CLP-induced TLR4 protein membrane localization, evidencing its immunomodulatory effects. Together, our results demonstrate that BZL induces hepatic NRF2 activation with the concomitant increase in the antioxidant defenses, and the attenuation of inflammatory response, in part, by inhibiting TLR4 expression in a murine model of sepsis. - Highlights: • BZL improves survival rate after polymicrobial sepsis • BZL enhances hepatic NRF2 nuclear accumulation in a model of sepsis, in part, by a mechanism dependent on PKC activation • BZL-enhanced NRF2 induction regulates antioxidant enzymes and increases antioxidant cellular defenses in sepsis • BZL blocks liver ROS production and ROS-induced TLR4 plasma membrane expression in septic mice

  10. Benznidazole, the trypanocidal drug used for Chagas disease, induces hepatic NRF2 activation and attenuates the inflammatory response in a murine model of sepsis

    Energy Technology Data Exchange (ETDEWEB)

    Lambertucci, Flavia [Instituto de Fisiología Experimental (IFISE-CONICET), Suipacha 570, 2000 Rosario (Argentina); Motiño, Omar [Instituto de Investigaciones Biomédicas Alberto Sols, CSIC-UAM, Arturo Duperier 4, 28029 Madrid (Spain); Villar, Silvina [Instituto de Inmunología, Facultad de Ciencias Médicas, UNR, Suipacha 531, 2000 Rosario (Argentina); Rigalli, Juan Pablo; Luján Alvarez, María de; Catania, Viviana A [Instituto de Fisiología Experimental (IFISE-CONICET), Suipacha 570, 2000 Rosario (Argentina); Martín-Sanz, Paloma [Instituto de Investigaciones Biomédicas Alberto Sols, CSIC-UAM, Arturo Duperier 4, 28029 Madrid (Spain); Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Monforte de Lemos 3-5, 28029 Madrid (Spain); Carnovale, Cristina Ester; Quiroga, Ariel Darío; Francés, Daniel Eleazar [Instituto de Fisiología Experimental (IFISE-CONICET), Suipacha 570, 2000 Rosario (Argentina); Ronco, María Teresa, E-mail: ronco@ifise-conicet.gov.ar [Instituto de Fisiología Experimental (IFISE-CONICET), Suipacha 570, 2000 Rosario (Argentina)

    2017-01-15

    Molecular mechanisms on sepsis progression are linked to the imbalance between reactive oxygen species (ROS) production and cellular antioxidant capacity. Previous studies demonstrated that benznidazole (BZL), known for its antiparasitic action on Trypanosoma cruzi, has immunomodulatory effects, increasing survival in C57BL/6 mice in a model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). The mechanism by which BZL inhibits inflammatory response in sepsis is poorly understood. Also, our group recently reported that BZL is able to activate the nuclear factor erytroide-derived 2-Like 2 (NRF2) in vitro. The aim of the present work was to delineate the beneficial role of BZL during sepsis, analyzing its effects on the cellular redox status and the possible link to the innate immunity receptor TLR4. Specifically, we analyzed the effect of BZL on Nrf2 regulation and TLR4 expression in liver of mice 24 hours post-CLP. BZL was able to induce NRF2 nuclear protein localization in CLP mice. Also, we found that protein kinase C (PKC) is involved in the NRF2 nuclear accumulation and induction of its target genes. In addition, BZL prompted a reduction in hepatic CLP-induced TLR4 protein membrane localization, evidencing its immunomodulatory effects. Together, our results demonstrate that BZL induces hepatic NRF2 activation with the concomitant increase in the antioxidant defenses, and the attenuation of inflammatory response, in part, by inhibiting TLR4 expression in a murine model of sepsis. - Highlights: • BZL improves survival rate after polymicrobial sepsis • BZL enhances hepatic NRF2 nuclear accumulation in a model of sepsis, in part, by a mechanism dependent on PKC activation • BZL-enhanced NRF2 induction regulates antioxidant enzymes and increases antioxidant cellular defenses in sepsis • BZL blocks liver ROS production and ROS-induced TLR4 plasma membrane expression in septic mice.

  11. Antioxidant protection of statins in acute kidney injury induced by sepsis

    Directory of Open Access Journals (Sweden)

    Franciele do Nascimento Santos

    2014-10-01

    Full Text Available Objective Evaluating the effect of preconditioning with simvastatin in acute kidney injury induced by sepsis. Method Male adult Wistar rats were divided into the following groups: SHAM (control; SHAM+Statin (0.5 mg/kg simvastatin, orally; Sepsis (cecal puncture ligation – CPL; Sepsis+Statin. Physiological parameters, peritoneal fluid culture, renal function, oxidative metabolites, severity of acute kidney injury and animal survival were evaluated. Results The treatment with simvastatin in induced sepsis showed elevation of creatinine clearance with attenuation of generation of oxidative metabolites, lower severity of acute kidney injury and reduced mortality. Conclusion This investigation confirmed the renoprotection with antioxidant principle of the simvastatin in acute kidney injury induced by sepsis in an experimental model.

  12. Effects of Ecballium elaterium on brain in a rat model of sepsis ...

    African Journals Online (AJOL)

    Demet Arslan

    2017-08-31

    Aug 31, 2017 ... cytokines, which may be important contributors to its anti-inflammatory effects during sepsis. ARTICLE HISTORY. Received 18 February ... effects and to determine if EE has neuroprotective potential during SAE. 2. ..... EE fruit contains black seeds and a liquid juice. EE extract is made from this juice, which is ...

  13. Prophylactic Antioxidant Potential of Gallic Acid in Murine Model of Sepsis

    Directory of Open Access Journals (Sweden)

    Harikesh Maurya

    2014-01-01

    healthy adult male albino mice (25–30 g and was divided into 3 groups each consisting of 6 animals, that is, sham-operated (SO group (Group I, SO + sepsis (Group II, and Gallic acid + sepsis (Group III. Group III animals were pretreated with Gallic acid at the dose rate of 20 mg/kg body weight for 2 days before induction of sepsis. Animals were sacrificed on 8th day and the tissue samples were obtained for further investigation on lipid peroxidation (LPO, malondialdehyde (MDA, superoxide dismutase (SOD, catalase (CAT, and glutathione reductase (GSH. Gallic acid pretreatment significant (P<0.05 reduces kidney, spleen, liver, and lungs’ malondialdehyde level in septic mice. However, it fails to improve reduced glutathione level in all given organs, while, Gallic acid pretreated mice showed significant improvement in SOD activity of kidney and spleen when compared to septic mice. Finally, the beneficial effects of Gallic acid pretreatment in sepsis are evident from the observations that Gallic acid partially restored SOD and catalase activity and completely reversed lipid peroxidation. Further studies are required to find out the possible mechanisms underlying the beneficial effects of Gallic acid on large population.

  14. Decreased intracellular [Ca2+ ] coincides with reduced expression of Dhprα1s, RyR1, and diaphragmatic dysfunction in a rat model of sepsis.

    Science.gov (United States)

    Wang, Meng-Meng; Hao, Li-Ying; Guo, Feng; Zhong, Bin; Zhong, Xiao-Mei; Yuan, Jing; Hao, Yi-Fei; Zhao, Shuang; Sun, Xue-Fei; Lei, Ming; Jiao, Guang-Yu

    2017-12-01

    Sepsis can cause decreased diaphragmatic contractility. Intracellular calcium as a second messenger is central to diaphragmatic contractility. However, changes in intracellular calcium concentration ([Ca 2+ ]) and the distribution and co-localization of relevant calcium channels [dihydropyridine receptors, (DHPRα1s) and ryanodine receptors (RyR1)] remain unclear during sepsis. In this study we investigated the effect of changed intracellular [Ca 2+ ] and expression and distribution of DHPRα1s and RyR1 on diaphragm function during sepsis. We measured diaphragm contractility and isolated diaphragm muscle cells in a rat model of sepsis. The distribution and co-localization of DHPRα1s and RyR1 were determined using immunohistochemistry and immunofluorescence, whereas intracellular [Ca 2+ ] was measured by confocal microscopy and fluorescence spectrophotometry. Septic rat diaphragm contractility, expression of DHPRα1s and RyR1, and intracellular [Ca 2+ ] were significantly decreased in the rat sepsis model compared with controls. Decreased intracellular [Ca 2+ ] coincides with diaphragmatic contractility and decreased expression of DHPRα1s and RyR1 in sepsis. Muscle Nerve 56: 1128-1136, 2017. © 2017 Wiley Periodicals, Inc.

  15. Experimental Object-Oriented Modelling

    DEFF Research Database (Denmark)

    Hansen, Klaus Marius

    through, e.g., technical prototyping and active user involvement. We introduce and examine “experimental object-oriented modelling” as the intersection of these practices. The contributions of this thesis are expected to be within three perspectives on models and modelling in experimental system...... development: Grounding We develop an empirically based conceptualization of modelling and use of models in system development projects characterized by a high degree of uncertainty in requirements and point to implications for tools and techniques for modelling in such a setting. Techniques We introduce......This thesis examines object-oriented modelling in experimental system development. Object-oriented modelling aims at representing concepts and phenomena of a problem domain in terms of classes and objects. Experimental system development seeks active experimentation in a system development project...

  16. Preclinical models of shock and sepsis: what can they tell us?

    NARCIS (Netherlands)

    Marshall, John C.; Deitch, Edwin; Moldawer, Lyle L.; Opal, Steven; Redl, Heinz; van der Poll, Tom

    2005-01-01

    The goal of translational research is to transform biologic knowledge into new treatments for human disease. Although preclinical models replicate some of the features of the disease process modeled, they invariably fail to reproduce the complexity of human illness, and by their very experimental

  17. Conserved Bacterial-Binding Peptides of the Scavenger-Like Human Lymphocyte Receptor CD6 Protect From Mouse Experimental Sepsis

    Directory of Open Access Journals (Sweden)

    Mario Martínez-Florensa

    2018-04-01

    Full Text Available Sepsis is an unmet clinical need constituting one of the most important causes of death worldwide, a fact aggravated by the appearance of multidrug resistant strains due to indiscriminate use of antibiotics. Host innate immune receptors involved in pathogen-associated molecular patterns (PAMPs recognition represent a source of broad-spectrum therapies alternative or adjunctive to antibiotics. Among the few members of the ancient and highly conserved scavenger receptor cysteine-rich superfamily (SRCR-SF sharing bacterial-binding properties there is CD6, a lymphocyte-specific surface receptor. Here, we analyze the bacterial-binding properties of three conserved short peptides (11-mer mapping at extracellular SRCR domains of human CD6 (CD6.PD1, GTVEVRLEASW; CD6.PD2 GRVEMLEHGEW; and CD6.PD3, GQVEVHFRGVW. All peptides show high binding affinity for PAMPs from Gram-negative (lipopolysaccharide; Kd from 3.5 to 3,000 nM and Gram-positive (lipoteichoic acid; Kd from 36 to 680 nM bacteria. The CD6.PD3 peptide possesses broad bacterial-agglutination properties and improved survival of mice undergoing polymicrobial sepsis in a dose- and time-dependent manner. Accordingly, CD6.PD3 triggers a decrease in serum levels of both pro-inflammatory cytokines and bacterial load. Interestingly, CD6.PD3 shows additive survival effects on septic mice when combined with Imipenem/Cilastatin. These results illustrate the therapeutic potential of peptides retaining the bacterial-binding properties of native CD6.

  18. Sepsis: Multiple Abnormalities, Heterogeneous Responses, and Evolving Understanding

    Science.gov (United States)

    Iskander, Kendra N.; Osuchowski, Marcin F.; Stearns-Kurosawa, Deborah J.; Kurosawa, Shinichiro; Stepien, David; Valentine, Catherine

    2013-01-01

    Sepsis represents the host's systemic inflammatory response to a severe infection. It causes substantial human morbidity resulting in hundreds of thousands of deaths each year. Despite decades of intense research, the basic mechanisms still remain elusive. In either experimental animal models of sepsis or human patients, there are substantial physiological changes, many of which may result in subsequent organ injury. Variations in age, gender, and medical comorbidities including diabetes and renal failure create additional complexity that influence the outcomes in septic patients. Specific system-based alterations, such as the coagulopathy observed in sepsis, offer both potential insight and possible therapeutic targets. Intracellular stress induces changes in the endoplasmic reticulum yielding misfolded proteins that contribute to the underlying pathophysiological changes. With these multiple changes it is difficult to precisely classify an individual's response in sepsis as proinflammatory or immunosuppressed. This heterogeneity also may explain why most therapeutic interventions have not improved survival. Given the complexity of sepsis, biomarkers and mathematical models offer potential guidance once they have been carefully validated. This review discusses each of these important factors to provide a framework for understanding the complex and current challenges of managing the septic patient. Clinical trial failures and the therapeutic interventions that have proven successful are also discussed. PMID:23899564

  19. Neonatal sepsis

    Directory of Open Access Journals (Sweden)

    Angelica Dessì

    2014-06-01

    Full Text Available In this paper on neonatal sepsis, after a short presentation of etiopathogenesis and physiopathology, we will briefly present the clinical picture, the diagnosis and the therapy. Concerning diagnosis, we will focus our attention on procalcitonin (PCT, serum amyloid A (SAA, presepsin (sCD14 and metabolomics. Three practical tables complete the review. Proceedings of the International Course on Perinatal Pathology (part of the 10th International Workshop on Neonatology · October 22nd-25th, 2014 · Cagliari (Italy · October 25th, 2014 · The role of the clinical pathological dialogue in problem solving Guest Editors: Gavino Faa, Vassilios Fanos, Peter Van Eyken

  20. The effects of colloids or crystalloids on acute respiratory distress syndrome in swine (Sus scrofa models with severe sepsis: analysis on extravascular lung water, IL-8, and VCAM-1

    Directory of Open Access Journals (Sweden)

    Rismala Dewi

    2016-04-01

    Full Text Available Background: Acute respiratory distress syndrome (ARDS is a fatal complication of severe sepsis. Due to its higher molecular weight, the use of colloids in fluid resuscitation may be associated with fewer cases of ARDS compared to crystalloids. Extravascular lung water (EVLW elevation and levels of interleukin-8 (IL-8 and vascular cell adhesion molecule-1 (VCAM-1 have been studied as indicators playing a role in the pathogenesis of ARDS. The aim of the study was to determine the effects of colloid or crystalloid on the incidence of ARDS, elevation of EVLW, and levels of IL-8 and VCAM-1, in swine models with severe sepsis.Methods: This was a randomized trial conducted at the Laboratory of Experimental Surgery, School of Veterinary Medicine, IPB, using 22 healthy swine models with a body weight of 8 to 12 kg. Subjects were randomly allocated to receive either colloid or crystalloid fluid resuscitation. After administration of endotoxin, clinical signs of ARDS, EVLW, IL-8, and VCAM-1 were monitored during sepsis, severe sepsis, and one- and three hours after fluid resuscitation. Analysis of data using the Wilcoxon test , Kolmogorov-Smirnov test, Mann-Whitney test, unpaired t test.Results: Mild ARDS was more prevalent in the colloid group, while moderate ARDS was more frequent in the crystalloid group. EVLW elevation was lower in the colloid compared to the crystalloid group. There was no significant difference in IL-8 and VCAM-1 levels between the two groups.Conclusion: The use of colloids in fluid resuscitation does not decrease the probability of ARDS events compared to crystalloids. Compared to crystalloids, colloids are associated with a lower increase in EVLWI, but not with IL-8 or VCAM-1 levels.

  1. Early Hepatic Dysfunction in a Large Animal Model of Nonhypotensive Sepsis

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    Stephen Sullivan

    1991-01-01

    Full Text Available Sepsis was induced in 12 sheep by cecal devascularization and perforation. Intravenous crystalloid was administered to maintain th e pulmonary capillary wedge pressure at preseptic levels. By 24 h there was a significant drop in albumin and alkaline phosphatase with increases in aspartate aminotransferase (AST, lactate dehydrogenase and bilirubin. By 48 h the alkaline phosphatase had returned to presepsis levels, the bilirubin continued to rise, the AST and lactate dehydrogenase had plateaued while the alhumin remained low. These biochemical alterations were confirmed by examining data from 25 sheer used in similar sepsis experiments. These data revealed that marked elevations in AST were associated with a higher central venous pressure and worse renal impairment, but there was no relationship with any other hemodynamic parameter, PO2, pH or serum lactate. Histologically these biochemical alterations were associated with extensive microvesicular fatty change at 24 h and centrilobular necrosis at 48 h. Electron microscopy revealed mitochondrial degeneration, hyperplasia of the smooth endoplasmic reticulum and intracellular cholestasis.

  2. Sepsis is a preventable public health problem.

    Science.gov (United States)

    Kempker, Jordan A; Wang, Henry E; Martin, Greg S

    2018-05-06

    There is a paradigm shift happening for sepsis. Sepsis is no longer solely conceptualized as problem of individual patients treated in emergency departments and intensive care units but also as one that is addressed as public health issue with population- and systems-based solutions. We offer a conceptual framework for sepsis as a public health problem by adapting the traditional model of primary, secondary, and tertiary prevention.

  3. Influence of endotoxin-induced sepsis on the requirements of propofol-fentanyl infusion rate in pigs

    DEFF Research Database (Denmark)

    Bollen, Peter; Nielsen, Bjørn J; Toft, Palle

    2007-01-01

    Endotoxin-induced sepsis in pigs is a recognized experimental model for the study of human septic shock. Generally, pigs are brought into general anaesthesia before sepsis is induced. It is our experience that drug dosages of propofol and fentanyl need to be reduced during endotoxin-induced sepsis......, in order to prevent respiratory and cardiovascular depression, but the scientific evidence for this observation is lacking. Therefore, we measured the consumption of propofol and fentanyl at equal level of anaesthesia in pigs with (n = 5) and without (n = 5) endotoxin-induced sepsis, using the cerebral...... state index (CSI) as measure of anaesthetic depth. Infusion rates of propofol (P endotoxin-induced sepsis had an infusion rate of 2.2 mg/kg/hr (S.D. 0.5) for propofol and 12 microg/kg/hr (S.D. 2) for fentanyl, whereas...

  4. Complement Factor B is the Downstream Effector of Toll-Like Receptors and Plays an Important Role in a Mouse Model of Severe Sepsis

    Science.gov (United States)

    Zou, Lin; Feng, Yan; Li, Yan; Zhang, Ming; Chen, Chan; Cai, Jiayan; Gong, Yu; Wang, Larry; Thurman, Joshua M.; Wu, Xiaobo; Atkinson, John P.; Chao, Wei

    2013-01-01

    Severe sepsis involves massive activation of the innate immune system and leads to high mortality. Previous studies have demonstrated that various types of Toll-like receptors (TLRs) mediate a systemic inflammatory response and contribute to organ injury and mortality in animal models of severe sepsis. However, the downstream mechanisms responsible for TLR-mediated septic injury are poorly understood. Here, we show that activation of TLR2, TLR3 and TLR4 markedly enhanced complement factor B (cfB) synthesis and release by macrophages and cardiac cells. Polymicrobial sepsis, created by cecal ligation and puncture (CLP) in a mouse model, augmented cfB levels in the serum, peritoneal cavity and major organs including the kidney and heart. CLP also led to the alternative pathway (AP) activation, C3 fragment deposition in the kidney and heart, and cfB-dependent C3dg elevation. Bacteria isolated from septic mice activated the serum AP via a factor D-dependent manner. MyD88 deletion attenuated cfB/C3 up-regulation as well as cleavage induced by polymicrobial infection. Importantly, during sepsis, absence of cfB conferred a protective effect with improved survival and cardiac function, and markedly attenuated acute kidney injury. cfB deletion also led to increased neutrophil migratory function during the early phase of sepsis, decreased local and systemic bacterial load, attenuated cytokine production and reduced neutrophil reactive oxygen species production. Together, our data indicate that cfB acts as a downstream effector of TLR signaling and plays a critical role in the pathogenesis of severe bacterial sepsis. PMID:24154627

  5. Attenuation of sepsis-induced rat liver injury by epigallocatechin ...

    African Journals Online (AJOL)

    rat model of sepsis established by cercal ligation and puncture (CLP). Methods: Male Wistar ... capacity, resulting in excessive oxidants in cells. [6]. ... Care (NIH publication no. 85-23 ..... estimates of severe sepsis in United States emergency.

  6. Sepsis Strengthens Antagonistic Actions of Neostigmine on Rocuronium in a Rat Model of Cecal Ligation and Puncture

    Science.gov (United States)

    Wu, Jin; Jin, Tian; Wang, Hong; Li, Shi-Tong

    2016-01-01

    Background: The antagonistic actions of anticholinesterase drugs on non-depolarizing muscle relaxants are theoretically related to the activity of acetylcholinesterase (AChE) in the neuromuscular junction (NMJ). However, till date the changes of AChE activity in the NMJ during sepsis have not been directly investigated. We aimed to investigate the effects of sepsis on the antagonistic actions of neostigmine on rocuronium (Roc) and the underlying changes of AChE activity in the NMJ in a rat model of cecal ligation and puncture (CLP). Methods: A total of 28 male adult Sprague-Dawley rats were randomized to undergo a sham surgery (the sham group, n = 12) or CLP (the septic group, n = 16). After 24 h, the time-response curves of the antagonistic actions of 0.1 or 0.5 μmol/L of neostigmine on Roc (10 μmol/L)-depressed diaphragm twitch tension were measured. Meanwhile, the activity of AChE in the NMJ was detected using a modified Karnovsky and Roots method. The mRNA levels of the primary transcript and the type T transcript of AChE (AChET) in the diaphragm were determined by real-time reverse transcription-polymerase chain reaction. Results: Four of 16 rats in the septic group died within 24 h. The time-response curves of both two concentrations of neostigmine in the septic group showed significant upward shifts from those in the sham group (P < 0.001 for 0.1 μmol/L; P = 0.009 for 0.5 μmol/L). Meanwhile, the average optical density of AChE in the NMJ in the septic group was significantly lower than that in the sham group (0.517 ± 0.045 vs. 1.047 ± 0.087, P < 0.001). The AChE and AChET mRNA expression levels in the septic group were significantly lower than those in the sham group (P = 0.002 for AChE; P = 0.001 for AChET). Conclusions: Sepsis strengthened the antagonistic actions of neostigmine on Roc-depressed twitch tension of the diaphragm by inhibiting the activity of AChE in the NMJ. The reduced content of AChE might be one of the possible causes of the

  7. PEMFC modeling and experimental validation

    Energy Technology Data Exchange (ETDEWEB)

    Vargas, J.V.C. [Federal University of Parana (UFPR), Curitiba, PR (Brazil). Dept. of Mechanical Engineering], E-mail: jvargas@demec.ufpr.br; Ordonez, J.C.; Martins, L.S. [Florida State University, Tallahassee, FL (United States). Center for Advanced Power Systems], Emails: ordonez@caps.fsu.edu, martins@caps.fsu.edu

    2009-07-01

    In this paper, a simplified and comprehensive PEMFC mathematical model introduced in previous studies is experimentally validated. Numerical results are obtained for an existing set of commercial unit PEM fuel cells. The model accounts for pressure drops in the gas channels, and for temperature gradients with respect to space in the flow direction, that are investigated by direct infrared imaging, showing that even at low current operation such gradients are present in fuel cell operation, and therefore should be considered by a PEMFC model, since large coolant flow rates are limited due to induced high pressure drops in the cooling channels. The computed polarization and power curves are directly compared to the experimentally measured ones with good qualitative and quantitative agreement. The combination of accuracy and low computational time allow for the future utilization of the model as a reliable tool for PEMFC simulation, control, design and optimization purposes. (author)

  8. Mesenchymal stem cells cannot affect mRNA expression of toll-like receptors in different tissues during sepsis.

    Science.gov (United States)

    Pedrazza, Leonardo; Pereira, Talita Carneiro Brandão; Abujamra, Ana Lucia; Nunes, Fernanda Bordignon; Bogo, Maurício Reis; de Oliveira, Jarbas Rodrigues

    2017-07-01

    Experimental animal models and human clinical studies support a crucial role for TLRs in infectious diseases. The aim of this study was to test the ability of MSCs, which have immunomodulatory effects, of altering the mRNA expression of toll-like receptors during a experimental model of sepsis in different tissues. Three experimental groups (male C57BL/6 mice) were formed for the test: control group, untreated septic group and septic group treated with MSCs (1 × 10 6 cells/animal). Lungs, cortex, kidney, liver and colon tissue were dissected after 12 h of sepsis induction and TLR2/3/4/9 mRNA were evaluated by RT-qPCR. We observed a decrease of TLR2 and 9 mRNA expression in the liver of the sepsis group, while TLR3 was decreased in the lung and liver. No change was found between the sepsis group and the sepsis + MSC group. In this model of experimental sepsis the MSCs were unable to modify the mRNA expression of the different toll-like receptors evaluated.

  9. Experimental Modeling of Dynamic Systems

    DEFF Research Database (Denmark)

    Knudsen, Morten Haack

    2006-01-01

    An engineering course, Simulation and Experimental Modeling, has been developed that is based on a method for direct estimation of physical parameters in dynamic systems. Compared with classical system identification, the method appears to be easier to understand, apply, and combine with physical...

  10. A risk-model for hospital mortality among patients with severe sepsis or septic shock based on German national administrative claims data.

    Science.gov (United States)

    Schwarzkopf, Daniel; Fleischmann-Struzek, Carolin; Rüddel, Hendrik; Reinhart, Konrad; Thomas-Rüddel, Daniel O

    2018-01-01

    Sepsis is a major cause of preventable deaths in hospitals. Feasible and valid methods for comparing quality of sepsis care between hospitals are needed. The aim of this study was to develop a risk-adjustment model suitable for comparing sepsis-related mortality between German hospitals. We developed a risk-model using national German claims data. Since these data are available with a time-lag of 1.5 years only, the stability of the model across time was investigated. The model was derived from inpatient cases with severe sepsis or septic shock treated in 2013 using logistic regression with backward selection and generalized estimating equations to correct for clustering. It was validated among cases treated in 2015. Finally, the model development was repeated in 2015. To investigate secular changes, the risk-adjusted trajectory of mortality across the years 2010-2015 was analyzed. The 2013 deviation sample consisted of 113,750 cases; the 2015 validation sample consisted of 134,851 cases. The model developed in 2013 showed good validity regarding discrimination (AUC = 0.74), calibration (observed mortality in 1st and 10th risk-decile: 11%-78%), and fit (R2 = 0.16). Validity remained stable when the model was applied to 2015 (AUC = 0.74, 1st and 10th risk-decile: 10%-77%, R2 = 0.17). There was no indication of overfitting of the model. The final model developed in year 2015 contained 40 risk-factors. Between 2010 and 2015 hospital mortality in sepsis decreased from 48% to 42%. Adjusted for risk-factors the trajectory of decrease was still significant. The risk-model shows good predictive validity and stability across time. The model is suitable to be used as an external algorithm for comparing risk-adjusted sepsis mortality among German hospitals or regions based on administrative claims data, but secular changes need to be taken into account when interpreting risk-adjusted mortality.

  11. A collaborative quality improvement model and electronic community of practice to support sepsis management in emergency departments: investigating care harmonization for provincial knowledge translation.

    Science.gov (United States)

    Ho, Kendall; Marsden, Julian; Jarvis-Selinger, Sandra; Novak Lauscher, Helen; Kamal, Noreen; Stenstrom, Rob; Sweet, David; Goldman, Ran D; Innes, Grant

    2012-07-12

    Emergency medicine departments within several organizations are now advocating the adoption of early intervention guidelines for patients with the signs and symptoms of sepsis. This proposed research will lead to a comprehensive understanding of how diverse emergency department (ED) sites across British Columbia (BC), Canada, engage in a quality improvement collaborative to lead to improvements in time-based process measures and clinical outcomes for septic patients in EDs. To address the challenge of sepsis management, in 2007, the BC Ministry of Health began working with emergency health professionals, including health administrators, to establish a provincial ED collaborative: Evidence to Excellence (E2E). The E2E initiative employs the Institute for Healthcare Improvement (IHI) model and is supported by a Web-based community of practice (CoP) in emergency medicine. It aims to (1) support clinicians in accessing and applying evidence to clinical practice in emergency medicine, (2) support system change and clinical process improvement, and (3) develop resources and strategies to facilitate knowledge translation and process improvement. Improving sepsis management is one of the central foci of the E2E initiative. The primary purpose of our research is to investigate whether the application of sepsis management protocols leads to improved time-based process measures and clinical outcomes for patients presenting to EDs with sepsis. Also, we seek to investigate the implementation of sepsis protocols among different EDs. For example: (1) How can sepsis protocols be harmonized among different EDs? (2) What are health professionals' perspectives on interprofessional collaboration with various EDs? and (3) What are the factors affecting the level of success among EDs? Lastly, working in collaboration with the BC Ministry of Health as our policy-maker partner, the research will investigate how the demonstrated efficacy of this research can be applied on a provincial and

  12. The release of endotoxin, TNF and IL-6 during the antibiotic treatment of experimental Gram-negative sepsis

    NARCIS (Netherlands)

    Dofferhoff, A.S.M.; Potthoff, H.; Bom, V.J.J.; Bartels, H.L.; De Vries-Hospers, H.G.; Bijzet, J.; Weits, J.; Buurman, W.; Bleichrodt, R.P.

    1995-01-01

    To evaluate the role of different antibiotics in the release of endotoxin and the production of tumor necrosis factor-α (TNF) and interleukin 6 (IL-6) during the treatment of experimental Escherichia coli septical peritonitis, we obtained serial blood samples from septic rats treated with placebo,

  13. Intestine-Specific Mttp Deletion Decreases Mortality and Prevents Sepsis-Induced Intestinal Injury in a Murine Model of Pseudomonas aeruginosa Pneumonia

    Science.gov (United States)

    Dominguez, Jessica A.; Xie, Yan; Dunne, W. Michael; Yoseph, Benyam P.; Burd, Eileen M.; Coopersmith, Craig M.; Davidson, Nicholas O.

    2012-01-01

    Background The small intestine plays a crucial role in the pathophysiology of sepsis and has been referred to as the “motor” of the systemic inflammatory response. One proposed mechanism is that toxic gut-derived lipid factors, transported in mesenteric lymph, induce systemic injury and distant organ failure. However, the pathways involved are yet to be defined and the role of intestinal chylomicron assembly and secretion in transporting these lipid factors is unknown. Here we studied the outcome of sepsis in mice with conditional, intestine-specific deletion of microsomal triglyceride transfer protein (Mttp-IKO), which exhibit a block in chylomicron assembly together with lipid malabsorption. Methodology/Principal Findings Mttp-IKO mice and controls underwent intratracheal injection with either Pseudomonas aeruginosa or sterile saline. Mttp-IKO mice exhibited decreased seven-day mortality, with 0/20 (0%) dying compared to 5/17 (29%) control mice (p<0.05). This survival advantage in Mttp-IKO mice, however, was not associated with improvements in pulmonary bacterial clearance or neutrophil infiltration. Rather, Mttp-IKO mice exhibited protection against sepsis-associated decreases in villus length and intestinal proliferation and were also protected against increased intestinal apoptosis, both central features in control septic mice. Serum IL-6 levels, a major predictor of mortality in human and mouse models of sepsis, were elevated 8-fold in septic control mice but remained unaltered in septic Mttp-IKO mice. Serum high density lipoprotein (HDL) levels were reduced in septic control mice but were increased in septic Mttp-IKO mice. The decreased levels of HDL were associated with decreased hepatic expression of apolipoprotein A1 in septic control mice. Conclusions/Significance These studies suggest that strategies directed at blocking intestinal chylomicron secretion may attenuate the progression and improve the outcome of sepsis through effects mediated by

  14. Intestine-specific Mttp deletion decreases mortality and prevents sepsis-induced intestinal injury in a murine model of Pseudomonas aeruginosa pneumonia.

    Directory of Open Access Journals (Sweden)

    Jessica A Dominguez

    Full Text Available The small intestine plays a crucial role in the pathophysiology of sepsis and has been referred to as the "motor" of the systemic inflammatory response. One proposed mechanism is that toxic gut-derived lipid factors, transported in mesenteric lymph, induce systemic injury and distant organ failure. However, the pathways involved are yet to be defined and the role of intestinal chylomicron assembly and secretion in transporting these lipid factors is unknown. Here we studied the outcome of sepsis in mice with conditional, intestine-specific deletion of microsomal triglyceride transfer protein (Mttp-IKO, which exhibit a block in chylomicron assembly together with lipid malabsorption.Mttp-IKO mice and controls underwent intratracheal injection with either Pseudomonas aeruginosa or sterile saline. Mttp-IKO mice exhibited decreased seven-day mortality, with 0/20 (0% dying compared to 5/17 (29% control mice (p<0.05. This survival advantage in Mttp-IKO mice, however, was not associated with improvements in pulmonary bacterial clearance or neutrophil infiltration. Rather, Mttp-IKO mice exhibited protection against sepsis-associated decreases in villus length and intestinal proliferation and were also protected against increased intestinal apoptosis, both central features in control septic mice. Serum IL-6 levels, a major predictor of mortality in human and mouse models of sepsis, were elevated 8-fold in septic control mice but remained unaltered in septic Mttp-IKO mice. Serum high density lipoprotein (HDL levels were reduced in septic control mice but were increased in septic Mttp-IKO mice. The decreased levels of HDL were associated with decreased hepatic expression of apolipoprotein A1 in septic control mice.These studies suggest that strategies directed at blocking intestinal chylomicron secretion may attenuate the progression and improve the outcome of sepsis through effects mediated by metabolic and physiological adaptations in both intestinal and

  15. [Factors affecting in-hospital mortality in patients with sepsis: Development of a risk-adjusted model based on administrative data from German hospitals].

    Science.gov (United States)

    König, Volker; Kolzter, Olaf; Albuszies, Gerd; Thölen, Frank

    2018-05-01

    Inpatient administrative data from hospitals is already used nationally and internationally in many areas of internal and public quality assurance in healthcare. For sepsis as the principal condition, only a few published approaches are available for Germany. The aim of this investigation is to identify factors influencing hospital mortality by employing appropriate analytical methods in order to improve the internal quality management of sepsis. The analysis was based on data from 754,727 DRG cases of the CLINOTEL hospital network charged in 2015. The association then included 45 hospitals of all supply levels with the exception of university hospitals (range of beds: 100 to 1,172 per hospital). Cases of sepsis were identified via the ICD codes of their principal diagnosis. Multiple logistic regression analysis was used to determine the factors influencing in-hospital lethality for this population. The model was developed using sociodemographic and other potential variables that could be derived from the DRG data set, and taking into account current literature data. The model obtained was validated with inpatient administrative data of 2016 (51 hospitals, 850,776 DRG cases). Following the definition of the inclusion criteria, 5,608 cases of sepsis (2016: 6,384 cases) were identified in 2015. A total of 12 significant and, over both years, stable factors were identified, including age, severity of sepsis, reason for hospital admission and various comorbidities. The AUC value of the model, as a measure of predictability, is above 0.8 (H-L test p>0.05, R 2 value=0.27), which is an excellent result. The CLINOTEL model of risk adjustment for in-hospital lethality can be used to determine the mortality probability of patients with sepsis as principal diagnosis with a very high degree of accuracy, taking into account the case mix. Further studies are needed to confirm whether the model presented here will prove its value in the internal quality assurance of hospitals

  16. Gas tonometry for evaluation of gastrointestinal mucosal perfusion: experimental models of trauma, shock and complex surgical maneuvers - Part 1

    Directory of Open Access Journals (Sweden)

    Figueiredo Luiz Francisco Poli de

    2002-01-01

    Full Text Available Substantial clinical and animal evidences indicate that the mesenteric circulatory bed, particularly the gut mucosa, is highly vulnerable to reductions in oxygen supply and prone to early injury in the course of hemodynamic changes induced by trauma, shock, sepsis and several complex surgical maneuvers. Gut hypoxia or ischemia is one possible contributing factor to gastrointestinal tract barrier dysfunction that may be associated with the development of systemic inflammatory response and multiple organ dysfunction syndrome, a common cause of death after trauma, sepsis or major surgeries. Monitoring gut perfusion during experiments may provide valuable insights over new interventions and therapies highly needed to reduce trauma and sepsis-related morbidity and mortality. We present our experience with gas tonometry as a monitor of the adequacy of gastrointestinal mucosal perfusion in clinical and experimental models of trauma, shock and surgical maneuvers associated with abrupt hemodynamic changes, such as aortic occlusion and hepatic vascular exclusion. Next issue we will be presenting our experience with gas tonometry in experimental and clinical sepsis.

  17. A novel model to study neonatal Escherichia coli sepsis and the effect of treatment on the human immune system using humanized mice.

    Science.gov (United States)

    Schlieckau, Florian; Schulz, Daniela; Fill Malfertheiner, Sara; Entleutner, Kathrin; Seelbach-Goebel, Birgit; Ernst, Wolfgang

    2018-04-19

    Neonatal sepsis is a serious threat especially for preterm infants. As existing in vitro and in vivo models have limitations, we generated a novel neonatal sepsis model using humanized mice and tested the effect of Betamethasone and Indomethacin which are used in the clinic in case of premature birth. Humanized mice were infected with Escherichia coli (E. coli). Subsequently, the effect of the infection itself, and treatment with Betamethasone and Indomethacin on survival, recovery, bacterial burden, leukocyte populations, and cytokine production, was analyzed. The human immune system in the animals responded with leukocyte trafficking to the site of infection and granulopoiesis in the bone marrow. Treatment with Indomethacin had no pronounced effect on the immune system or bacterial burden. Betamethasone induced a decline of splenocytes. The human immune system in humanized mice responds to the infection, making them a suitable model to study neonatal E. coli sepsis and the immune response of the neonatal immune system. Treatment with Betamethasone could have potential negative long-term effects for the immune system of the child. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. S-thanatin functionalized liposome potentially targeting on Klebsiella pneumoniae and its application in sepsis mouse model

    Directory of Open Access Journals (Sweden)

    Xiaobo eFan

    2015-10-01

    Full Text Available S-thanatin (Ts was a short antimicrobial peptide with selective antibacterial activity. In this study, we aimed to design a drug carrier with specific bacterial targeting potential. The positively charged Ts was modified onto the liposome surface by linking Ts to the constituent lipids via a PEG linker. The benefits of this design were evaluated by preparing a series of liposomes and comparing their biological effects in vitro and in vivo. The particle size and Zeta potential of the constructed liposomes were measured with a Zetasizer Nano ZS system and a confocal laser scanning microscope (CLSM. The in vitro drug delivery potential was evaluated by measuring the cellular uptake of encapsulated levofloxacin using HPLC. Ts-linked liposome or its conjugates with quantum dots favored bacterial cells, and increased the bacterial uptake of levofloxacin. In antimicrobial assays, the Ts and levofloxacin combination showed a synergistic effect, and Ts-LPs-LEV exhibited excellent activity against the quality control stain Klebsiella pneumoniae ATCC 700603 and restored the susceptibility of multidrug-resistant K. pneumoniae clinical isolates to levofloxacin in vitro. Furthermore, Ts-LPs-LEV markedly reduced the lethality rate of the septic shock and resulted in rapid bacterial clearance in mouse models receiving clinical MDR isolates. These results suggest that the Ts-functionalized liposome may be a promising antibiotic delivery system for clinical infectious disorders caused by MDR bacteria, in particular the sepsis related diseases.

  19. Experimental models of developmental hypothyroidism.

    Science.gov (United States)

    Argumedo, G S; Sanz, C R; Olguín, H J

    2012-02-01

    Hypothyroidism is a systemic disease resulting from either thyroid gland's anatomical and functional absence or lack of hypophyseal stimulation, both of which can lead to deficiency in thyroid hormone (TH) production. TH is essential for human and animal development, growth, and function of multiple organs. Children with deficient TH can develop alterations in central nervous system (CNS), striated muscle, bone tissue, liver, bone marrow, and cardiorespiratory system. Among the clinical outlook are signs like breathing difficulty, cardiac insufficiency, dysphagia, and repeated bronchial aspiration, constipation, muscle weakness, cognitive alterations, cochlear dysfunction, reduced height, defects in temperature regulation, anaemia, jaundice, susceptibility to infection, and others. Experimental and clinical studies have shown that TH is very essential for normal brain development. Other research work based on mice pointed out that a reduced level of TH in pregnant mother leads to congenital hypothyroidism in animal models and it is associated with mental retardation, deep neurologic deficiency that impacts on cognitive, learning, and memory functions. The principal experimental model studies that have focused on hypothyroidism are reviewed in this study. This is important on considering the fact that almost all animal species require thyroid hormones for their metabolism. © Georg Thieme Verlag KG Stuttgart · New York.

  20. Glucocorticosteroids for sepsis

    DEFF Research Database (Denmark)

    Volbeda, M; Wetterslev, J; Gluud, C

    2015-01-01

    INTRODUCTION: Glucocorticosteroids (steroids) are widely used for sepsis patients. However, the potential benefits and harms of both high and low dose steroids remain unclear. A systematic review of randomised clinical trials with meta-analysis and trial sequential analysis (TSA) might shed light...... for sepsis patients (systemic inflammatory response syndrome, sepsis, severe sepsis or septic shock) aged >18 years. Cochrane Central Register of Controlled Trials (CENTRAL), PubMed/Medline, Embase, Web of Science and Cinahl were searched until 18 February 2015. No language restrictions were applied. Primary......-adjusted CI 0.7-1.48). The effects did not vary according to the degree of sepsis. TSA showed that many more randomised patients are needed before definitive conclusions may be drawn. CONCLUSION: Evidence to support or negate the use of steroids in any dose in sepsis patients is lacking. The results...

  1. Atrofia mucosa/translocação bacteriana na sepse experimental em ratos Wistar Mucosal atrophy/bacterial translocation in experimental sepsis in Wistar rats

    Directory of Open Access Journals (Sweden)

    Armando José d'Acampora

    2004-10-01

    jejunum were processed histologically for morphometric measure of the total thickness of the jejujum's wall in comparison to the thickness of the mucosa + submucosa layer. RESULTS: In blood culture, there was growth of Pseudomonas aeruginosa and Escherichia coli in 90% and 52,5% of the animals, respectively. In the peritoneal culture, there was growth of P aeruginosa, E.coli and Klebsiella sp in 87,5%, 85% and 5% of the animals. About the histological analysis and the thickness of the mucosa + submucosa's layer, there was not significant alteration. CONCLUSION: Acute sepsis did not develop any thickness alteration in the small intestine's mucosa layer. Bacterial translocation can not be a direct consequence produced by mucosal intestinal injury.

  2. Autophagy Primes Neutrophils for Neutrophil Extracellular Trap Formation during Sepsis.

    Science.gov (United States)

    Park, So Young; Shrestha, Sanjeeb; Youn, Young-Jin; Kim, Jun-Kyu; Kim, Shin-Yeong; Kim, Hyun Jung; Park, So-Hee; Ahn, Won-Gyun; Kim, Shin; Lee, Myung Goo; Jung, Ki-Suck; Park, Yong Bum; Mo, Eun-Kyung; Ko, Yousang; Lee, Suh-Young; Koh, Younsuck; Park, Myung Jae; Song, Dong-Keun; Hong, Chang-Won

    2017-09-01

    Neutrophils are key effectors in the host's immune response to sepsis. Excessive stimulation or dysregulated neutrophil functions are believed to be responsible for sepsis pathogenesis. However, the mechanisms regulating functional plasticity of neutrophils during sepsis have not been fully determined. We investigated the role of autophagy in neutrophil functions during sepsis in patients with community-acquired pneumonia. Neutrophils were isolated from patients with sepsis and stimulated with phorbol 12-myristate 13-acetate (PMA). The levels of reactive oxygen species generation, neutrophil extracellular trap (NET) formation, and granule release, and the autophagic status were evaluated. The effect of neutrophil autophagy augmentation was further evaluated in a mouse model of sepsis. Neutrophils isolated from patients who survived sepsis showed an increase in autophagy induction, and were primed for NET formation in response to subsequent PMA stimulation. In contrast, neutrophils isolated from patients who did not survive sepsis showed dysregulated autophagy and a decreased response to PMA stimulation. The induction of autophagy primed healthy neutrophils for NET formation and vice versa. In a mouse model of sepsis, the augmentation of autophagy improved survival via a NET-dependent mechanism. These results indicate that neutrophil autophagy primes neutrophils for increased NET formation, which is important for proper neutrophil effector functions during sepsis. Our study provides important insights into the role of autophagy in neutrophils during sepsis.

  3. The aPC treatment improves microcirculation in severe sepsis/septic shock syndrome

    NARCIS (Netherlands)

    Donati, Abele; Damiani, Elisa; Botticelli, Laura; Adrario, Erica; Lombrano, Maria Rita; Domizi, Roberta; Marini, Benedetto; van Teeffelen, Jurgen W. G. E.; Carletti, Paola; Girardis, Massimo; Pelaia, Paolo; Ince, Can

    2013-01-01

    The role of recombinant activated protein C (aPC) during sepsis is still controversial. It showed anti-inflammatory effect and improved the microvascular perfusion in experimental models of septic shock. The present study was aimed at testing the hypothesis that recombinant aPC therapy improves the

  4. Experimental models of liver fibrosis.

    Science.gov (United States)

    Yanguas, Sara Crespo; Cogliati, Bruno; Willebrords, Joost; Maes, Michaël; Colle, Isabelle; van den Bossche, Bert; de Oliveira, Claudia Pinto Marques Souza; Andraus, Wellington; Alves, Venâncio Avancini Ferreira; Leclercq, Isabelle; Vinken, Mathieu

    2016-05-01

    Hepatic fibrosis is a wound healing response to insults and as such affects the entire world population. In industrialized countries, the main causes of liver fibrosis include alcohol abuse, chronic hepatitis virus infection and non-alcoholic steatohepatitis. A central event in liver fibrosis is the activation of hepatic stellate cells, which is triggered by a plethora of signaling pathways. Liver fibrosis can progress into more severe stages, known as cirrhosis, when liver acini are substituted by nodules, and further to hepatocellular carcinoma. Considerable efforts are currently devoted to liver fibrosis research, not only with the goal of further elucidating the molecular mechanisms that drive this disease, but equally in view of establishing effective diagnostic and therapeutic strategies. The present paper provides a state-of-the-art overview of in vivo and in vitro models used in the field of experimental liver fibrosis research.

  5. Intervention of Dietary Dipeptide Gamma-l-Glutamyl-l-Valine (γ-EV) Ameliorates Inflammatory Response in a Mouse Model of LPS-Induced Sepsis.

    Science.gov (United States)

    Chee, MacKenzie E; Majumder, Kaustav; Mine, Yoshinori

    2017-07-26

    Sepsis, the systemic inflammatory response syndrome (SIRS) with infection is one of the leading causes of death in critically ill patients in the developed world due to the lack of effective antisepsis treatments. This study examined the efficacy of dietary dipeptide gamma-l-glutamyl-l-valine (γ-EV), which was characterized previously as an anti-inflammatory peptide, in an LPS-induced mouse model of sepsis. BALB/c mice were administered γ-EV via oral gavage followed by an intraperitoneal injection of LPS to induce sepsis. The γ-EV exhibited antisepsis activity by reducing the expression of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β in plasma and small intestine. γ-EV also reduced the phosphorylation of the signaling proteins JNK and IκBα. We concluded that γ-EV could possess an antisepsis effect against bacterial infection in intestine. This study proposes a signaling mechanism whereby the calcium-sensing receptor (CaSR) allosterically activated by γ-EV stimulates the interaction of β-arrestin2 with the TIR(TLR/IL-1R) signaling proteins TRAF6, TAB1, and IκBα to suppress inflammatory signaling.

  6. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).

    Science.gov (United States)

    Singer, Mervyn; Deutschman, Clifford S; Seymour, Christopher Warren; Shankar-Hari, Manu; Annane, Djillali; Bauer, Michael; Bellomo, Rinaldo; Bernard, Gordon R; Chiche, Jean-Daniel; Coopersmith, Craig M; Hotchkiss, Richard S; Levy, Mitchell M; Marshall, John C; Martin, Greg S; Opal, Steven M; Rubenfeld, Gordon D; van der Poll, Tom; Vincent, Jean-Louis; Angus, Derek C

    2016-02-23

    Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination. To evaluate and, as needed, update definitions for sepsis and septic shock. A task force (n = 19) with expertise in sepsis pathobiology, clinical trials, and epidemiology was convened by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. Definitions and clinical criteria were generated through meetings, Delphi processes, analysis of electronic health record databases, and voting, followed by circulation to international professional societies, requesting peer review and endorsement (by 31 societies listed in the Acknowledgment). Limitations of previous definitions included an excessive focus on inflammation, the misleading model that sepsis follows a continuum through severe sepsis to shock, and inadequate specificity and sensitivity of the systemic inflammatory response syndrome (SIRS) criteria. Multiple definitions and terminologies are currently in use for sepsis, septic shock, and organ dysfunction, leading to discrepancies in reported incidence and observed mortality. The task force concluded the term severe sepsis was redundant. Sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. For clinical operationalization, organ dysfunction can be represented by an increase in the Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score of 2 points or more, which is associated with an in-hospital mortality greater than 10%. Septic shock should be defined as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone. Patients with septic shock

  7. Sepsis Strengthens Antagonistic Actions of Neostigmine on Rocuronium in a Rat Model of Cecal Ligation and Puncture

    Directory of Open Access Journals (Sweden)

    Jin Wu

    2016-01-01

    Conclusions: Sepsis strengthened the antagonistic actions of neostigmine on Roc-depressed twitch tension of the diaphragm by inhibiting the activity of AChE in the NMJ. The reduced content of AChE might be one of the possible causes of the decreased AChE activity in the NMJ.

  8. Clinical management of sepsis.

    Science.gov (United States)

    Lam, S M; Lau, A Cw; Lam, R Pk; Yan, W W

    2017-06-01

    Sepsis is a common cause of hospital admission worldwide and contributes significantly to morbidity and mortality. The definition of sepsis has evolved from the 1991 American College of Chest Physicians/Society of Critical Care Medicine definition based on the criteria of systemic inflammatory response syndrome, to the 2016 Sepsis-3 definition that incorporates the Sequential Organ Failure Assessment score. The landmark trial on protocolised early goal-directed therapy was published in 2001, but three subsequent multicentre randomised controlled trials (ProCESS, ARISE, and ProMISe) in 2014-2015 did not confirm a survival benefit with protocolised care. Over the years, there has been considerable improvement in sepsis outcome and management that hinges on early detection; timely source control; prompt, appropriate, and correctly dosed antibiotics; aggressive fluid resuscitation; and shock reversal. These are all directed by repeated bedside assessment. This article summarises recent developments and landmark trials that should guide current sepsis management.

  9. Novel biomarkers for sepsis

    DEFF Research Database (Denmark)

    Larsen, Frederik Fruergaard; Petersen, J Asger

    2017-01-01

    BACKGROUND: Sepsis is a prevalent condition among hospitalized patients that carries a high risk of morbidity and mortality. Rapid recognition of sepsis as the cause of deterioration is desirable, so effective treatment can be initiated rapidly. Traditionally, diagnosis was based on presence of two...... or more positive SIRS criteria due to infection. However, recently published sepsis-3 criteria put more emphasis on organ dysfunction caused by infection in the definition of sepsis. Regardless of this, no gold standard for diagnosis exist, and clinicians still rely on a number of traditional and novel...... biomarkers to discriminate between patients with and without infection, as the cause of deterioration. METHOD: Narrative review of current literature. RESULTS: A number of the most promising biomarkers for diagnoses and prognostication of sepsis are presented. CONCLUSION: Procalcitonin, presepsin, CD64, su...

  10. Survival benefits of remote ischemic conditioning in sepsis.

    Science.gov (United States)

    Joseph, Bellal; Khalil, Mazhar; Hashmi, Ammar; Hecker, Louise; Kulvatunyou, Narong; Tang, Andrew; Friese, Randall S; Rhee, Peter

    2017-06-01

    Sepsis remains the leading cause of death in the surgical intensive care unit. Prior studies have demonstrated a survival benefit of remote ischemic conditioning (RIC) in many disease states. The aim of this study was to determine the effects of RIC on survival in sepsis in an animal model and to assess alterations in inflammatory biochemical profiles. We hypothesized that RIC alters inflammatory biochemical profiles resulting in decreased mortality in a septic mouse model. Eight to 12 week C57BL/6 mice received intra-peritoneal injection of 12.5-mg/kg lipopolysaccharide (LPS). Septic animals in the experimental group underwent RIC at 0, 2, and 6 h after LPS by surgical exploration and alternate clamping of the femoral artery. Six 4-min cycles of ischemia-reperfusion were performed. Primary outcome was survival at 5-d after LPS injection. Secondary outcome was to assess the following serum cytokine levels: interferon-γ (IFN-γ), interleukin (IL)-10, IL-1β, and tumor necrosis factoralpha (TNFα) at the baseline before LPS injection, 0 hour after LPS injection, and at 2, 4, 24 hours after induction of sepsis (RIC was performed at 2 h after LPS injection). Kaplan-Meier survival analysis and log-rank test were used. ANOVA test was used to compare cytokine measurements. We performed experiments on 44 mice: 14 sham and 30 RIC mice (10 at each time point). Overall survival was higher in the experimental group compared to the sham group (57% versus 21%; P = 0.02), with the highest survival rate observed in the 2-hour post-RIC group (70%). On Kaplan-Meier analysis, 2-h post-RIC group had increased survival at 5 days after LPS (P = 0.04) with hazard ratio of 0.3 (95% confidence interval = 0.09-0.98). In the RIC group, serum concentrations of IFN-γ, IL-10, IL-1β, and TNFα peaked at 2 h after LPS and then decreased significantly over 24 hours (P sepsis and has the potential for implementation in the clinical practice. Early implementation of RIC may play an

  11. Biomarkers of sepsis

    Science.gov (United States)

    2013-01-01

    Sepsis is an unusual systemic reaction to what is sometimes an otherwise ordinary infection, and it probably represents a pattern of response by the immune system to injury. A hyper-inflammatory response is followed by an immunosuppressive phase during which multiple organ dysfunction is present and the patient is susceptible to nosocomial infection. Biomarkers to diagnose sepsis may allow early intervention which, although primarily supportive, can reduce the risk of death. Although lactate is currently the most commonly used biomarker to identify sepsis, other biomarkers may help to enhance lactate’s effectiveness; these include markers of the hyper-inflammatory phase of sepsis, such as pro-inflammatory cytokines and chemokines; proteins such as C-reactive protein and procalcitonin which are synthesized in response to infection and inflammation; and markers of neutrophil and monocyte activation. Recently, markers of the immunosuppressive phase of sepsis, such as anti-inflammatory cytokines, and alterations of the cell surface markers of monocytes and lymphocytes have been examined. Combinations of pro- and anti-inflammatory biomarkers in a multi-marker panel may help identify patients who are developing severe sepsis before organ dysfunction has advanced too far. Combined with innovative approaches to treatment that target the immunosuppressive phase, these biomarkers may help to reduce the mortality rate associated with severe sepsis which, despite advances in supportive measures, remains high. PMID:23480440

  12. Sepsis and septic shock

    Science.gov (United States)

    Hotchkiss, Richard S.; Moldawer, Lyle L.; Opal, Steven M.; Reinhart, Konrad; Turnbull, Isaiah R.; Vincent, Jean-Louis

    2017-01-01

    For more than two decades, sepsis was defined as a microbial infection that produces fever (or hypothermia), tachycardia, tachypnoea and blood leukocyte changes. Sepsis is now increasingly being considered a dysregulated systemic inflammatory and immune response to microbial invasion that produces organ injury for which mortality rates are declining to 15–25%. Septic shock remains defined as sepsis with hyperlactataemia and concurrent hypotension requiring vasopressor therapy, with in-hospital mortality rates approaching 30–50%. With earlier recognition and more compliance to best practices, sepsis has become less of an immediate life-threatening disorder and more of a long-term chronic critical illness, often associated with prolonged inflammation, immune suppression, organ injury and lean tissue wasting. Furthermore, patients who survive sepsis have continuing risk of mortality after discharge, as well as long-term cognitive and functional deficits. Earlier recognition and improved implementation of best practices have reduced in-hospital mortality, but results from the use of immunomodulatory agents to date have been disappointing. Similarly, no biomarker can definitely diagnose sepsis or predict its clinical outcome. Because of its complexity, improvements in sepsis outcomes are likely to continue to be slow and incremental. PMID:28117397

  13. Sepsis: from bench to bedside

    Directory of Open Access Journals (Sweden)

    Eliézer Silva

    2008-01-01

    Full Text Available Sepsis is a syndrome related to severe infections. It is defined as the systemic host response to microorganisms in previously sterile tissues and is characterized by end-organ dysfunction away from the primary site of infection. The normal host response to infection is complex and aims to identify and control pathogen invasion, as well as to start immediate tissue repair. Both the cellular and humoral immune systems are activated, giving rise to both anti-inflammatory and proinflammatory responses. The chain of events that leads to sepsis is derived from the exacerbation of these mechanisms, promoting massive liberation of mediators and the progression of multiple organ dysfunction. Despite increasing knowledge about the pathophysiological pathways and processes involved in sepsis, morbidity and mortality remain unacceptably high. A large number of immunomodulatory agents have been studied in experimental and clinical settings in an attempt to find an efficacious anti-inflammatory drug that reduces mortality. Even though preclinical results had been promising, the vast majority of these trials actually showed little success in reducing the overwhelmingly high mortality rate of septic shock patients as compared with that of other critically ill intensive care unit patients. Clinical management usually begins with prompt recognition, determination of the probable infection site, early administration of antibiotics, and resuscitation protocols based on "early-goal" directed therapy. In this review, we address the research efforts that have been targeting risk factor identification, including genetics, pathophysiological mechanisms and strategies to recognize and treat these patients as early as possible.

  14. New biomarkers for sepsis

    Directory of Open Access Journals (Sweden)

    Li-xin XIE

    2013-01-01

    Full Text Available There is a higher sepsis rate in the intensive care unit (ICU patients, which is one of the most important causes for patient death, but the sepsis lacks specific clinical manifestations. Exploring sensitive and specific molecular markers for infection that accurately reflect infection severity and prognosis is very clinically important. In this article, based on our previous study, we introduce some new biomarkers with high sensitivity and specificity for the diagnosis and predicting the prognosis and severity of sepsis. Increase of serum soluble(s triggering receptor expressed on myeloid cells-1 (sTREM-1 suggests a poor prognosis of septic patients, and changes of locus rs2234237 of sTREM-1 may be the one of important mechanisms. Additionally, urine sTREM-1 can provide an early warning of possible secondary acute kidney injury (AKI in sepsis patients. Serum sCD163 level was found to be a more important factor than procalcitonin (PCT and C-reactive protein (CRP in prognosis of sepsis, especially severe sepsis. Moreover, urine sCD163 also shows excellent performance in the diagnosis of sepsis and sepsis-associated AKI. Circulating microRNAs, such as miR-150, miR-297, miR-574-5p, miR -146a , miR-223, miR -15a and miR-16, also play important roles in the evaluation of status of septic patients. In the foreseeable future, newly-emerging technologies, including proteomics, metabonomics and trans-omics, may exert profound effects on the discovery of valuable biomarkers for sepsis.

  15. EXPERIMENTAL MEASUREMENT, ANALYSIS AND MODELLING ...

    African Journals Online (AJOL)

    30 juin 2010 ... We obtain a good agreement between the resolution of the nonlinear equation of heat and the results obtained by the experimentation. . Keywords: Emissivity, Température, optimal Linearisation, finite elements. 1. ..... basse température, Rapport de Stage de D.E.A, Université Paris 12 – Val de Marne.

  16. Increased plasma zonulin in patients with sepsis.

    Science.gov (United States)

    Klaus, Daniel A; Motal, Michael C; Burger-Klepp, Ursula; Marschalek, Corinna; Schmidt, Elisabeth M; Lebherz-Eichinger, Diana; Krenn, Claus G; Roth, Georg A

    2013-01-01

    Zonulin is a eukaryotic protein structurally similar to Vibrio cholerae's zonula occludens toxin. It plays an important role in the opening of small intestine tight junctions. The loss of gut wall integrity during sepsis might be pivotal and has been described in various experimental as well as human studies. Increased levels of zonulin could be demonstrated in diseases associated with increased intestinal inflammation, such as celiac disease and type 1 diabetes. We therefore investigated the role of plasma levels of zonulin in patients with sepsis as a non-invasive marker of gut wall integrity. Plasma level of zonulin was measured in 25 patients with sepsis, severe sepsis or septic shock according to ACCP/SCCM criteria at the first day of diagnosed sepsis. 18 non-septic post-surgical ICU-patients and 20 healthy volunteers served as control. Plasma levels were determined by using commercially available ELISA kit. Data are given as median and interquartile range (IQR). Significantly higher plasma concentration of zonulin were found in the sepsis group: 6.61 ng/mL (IQR 3.51-9.46), as compared to the to the post-surgical control group: 3.40 ng/mL (IQR 2.14-5.70) (P = 0.025), as well as to the healthy group: 3.55 ng/mL (IQR 3.14-4.14) (P = 0.008). We were able demonstrate elevated levels of plasma zonulin, a potential marker of intestinal permeability in septic patients. Increased zonulin may serve as an additional mechanism for the observed increased intestinal permeability during sepsis and SIRS.

  17. Diagnosis and management of sepsis

    Science.gov (United States)

    Arifin

    2018-03-01

    Sepsis is the life-threatening condition with organ dysfunction caused by dysregulated host response to the infection. Septic shock is part of sepsis where circulatory abnormalities and cellular metabolism occur. Sepsis and septic shock are still a problem in the world, where one in four people with sepsis will die. As well as any trauma case, acute myocardial infarction, or stroke, early identification and appropriate treatment of sepsis immediately after sepsis will improve the prognosis of the patient. Comprehensive management of septic patients is required, ranging from infection controls that include antibiotic administration and infection source control as well as hemodynamic stabilization that included fluid resuscitation and vasoactive drug delivery.

  18. Diverse and Tissue Specific Mitochondrial Respiratory Response in A Mouse Model of Sepsis-Induced Multiple Organ Failure

    DEFF Research Database (Denmark)

    Karlsson, Michael; Hara, Naomi; Morata, Saori

    2016-01-01

    control ratio was also significantly increased. Maximal Protonophore-induced respiratory (uncoupled) capacity was similar between the two treatment groups.The present study suggests a diverse and tissue specific mitochondrial respiratory response to sepsis. The brain displayed an early impaired...... C57BL/6 mice were analyzed at either 6 hours or 24 hours. ROS-production was simultaneously measured in brain samples using fluorometry.Septic brain tissue exhibited an early increased uncoupling of respiration. Temporal changes between the two time points were diminutive and no difference in ROS...

  19. Baicalin improves survival in a murine model of polymicrobial sepsis via suppressing inflammatory response and lymphocyte apoptosis.

    Directory of Open Access Journals (Sweden)

    Jiali Zhu

    Full Text Available BACKGROUND: An imbalance between overwhelming inflammation and lymphocyte apoptosis is the main cause of high mortality in patients with sepsis. Baicalin, the main active ingredient of the Scutellaria root, exerts anti-inflammatory, anti-apoptotic, and even antibacterial properties in inflammatory and infectious diseases. However, the therapeutic effect of baicalin on polymicrobial sepsis remains unknown. METHODOLOGY/PRINCIPAL FINDINGS: Polymicrobial sepsis was induced by cecal ligation and puncture (CLP in C57BL/6 mice. Mice were infused with baicalin intraperitoneally at 1 h, 6 h and 12 h after CLP. Survival rates were assessed over the subsequent 8 days. Bacterial burdens in blood and peritoneal cavity were calculated to assess the bacterial clearance. Neutrophil count in peritoneal lavage fluid was also calculated. Injuries to the lung and liver were detected by hematoxylin and eosin staining. Levels of cytokines, including tumor necrosis factor (TNF-alpha, interleukin (IL-6, IL-10 and IL-17, in blood and peritoneum were measured by enzyme-linked immunosorbent assay. Adaptive immune function was assessed by apoptosis of lymphocytes in the thymus and counts of different cell types in the spleen. Baicalin significantly enhanced bacterial clearance and improved survival of septic mice. The number of neutrophils in peritoneal lavage fluid was reduced by baicalin. Less neutrophil infiltration of the lung and liver in baicalin-treated mice was associated with attenuated injuries to these organs. Baicalin significantly reduced the levels of proinflammatory cytokines but increased the level of anti-inflammatory cytokine in blood and peritoneum. Apoptosis of CD3(+ T cell was inhibited in the thymus. The numbers of CD4(+, CD8(+ T lymphocytes and dendritic cells (DCs were higher, while the number of CD4(+CD25(+ regulatory T cells was lower in the baicalin group compared with the CLP group. CONCLUSIONS/SIGNIFICANCE: Baicalin improves survival of mice

  20. Mechanisms of Intestinal Barrier Dysfunction in Sepsis.

    Science.gov (United States)

    Yoseph, Benyam P; Klingensmith, Nathan J; Liang, Zhe; Breed, Elise R; Burd, Eileen M; Mittal, Rohit; Dominguez, Jessica A; Petrie, Benjamin; Ford, Mandy L; Coopersmith, Craig M

    2016-07-01

    Intestinal barrier dysfunction is thought to contribute to the development of multiple organ dysfunction syndrome in sepsis. Although there are similarities in clinical course following sepsis, there are significant differences in the host response depending on the initiating organism and time course of the disease, and pathways of gut injury vary widely in different preclinical models of sepsis. The purpose of this study was to determine whether the timecourse and mechanisms of intestinal barrier dysfunction are similar in disparate mouse models of sepsis with similar mortalities. FVB/N mice were randomized to receive cecal ligation and puncture (CLP) or sham laparotomy, and permeability was measured to fluoresceinisothiocyanate conjugated-dextran (FD-4) six to 48 h later. Intestinal permeability was elevated following CLP at all timepoints measured, peaking at 6 to 12 h. Tight junction proteins claudin 1, 2, 3, 4, 5, 7, 8, 13, and 15, Junctional Adhesion Molecule-A (JAM-A), occludin, and ZO-1 were than assayed by Western blot, real-time polymerase chain reaction, and immunohistochemistry 12 h after CLP to determine potential mechanisms underlying increases in intestinal permeability. Claudin 2 and JAM-A were increased by sepsis, whereas claudin-5 and occludin were decreased by sepsis. All other tight junction proteins were unchanged. A further timecourse experiment demonstrated that alterations in claudin-2 and occludin were detectable as early as 1 h after the onset of sepsis. Similar experiments were then performed in a different group of mice subjected to Pseudomonas aeruginosa pneumonia. Mice with pneumonia had an increase in intestinal permeability similar in timecourse and magnitude to that seen in CLP. Similar changes in tight junction proteins were seen in both models of sepsis although mice subjected to pneumonia also had a marked decrease in ZO-1 not seen in CLP. These results indicate that two disparate, clinically relevant models of sepsis

  1. Experimental models of acute infection and Toll-like receptor driven septic shock.

    Science.gov (United States)

    Ferstl, Ruth; Spiller, Stephan; Fichte, Sylvia; Dreher, Stefan; Kirschning, Carsten J

    2009-01-01

    Mainly Gram-negative and Gram-positive bacterial infections, but also other infections such as with fungal or viral pathogens, can cause the life-threatening clinical condition of septic shock. Transgression of the host immune response from a local level limited to the pathogen's place of entry to the systemic level is recognised as a major mode of action leading to sepsis. This view has been established upon demonstration of the capacity of specific pathogen-associated molecular patterns (PAMPs) to elicit symptoms of septic shock upon systemic administration. Immune stimulatory PAMPs are agonists of soluble, cytoplasmic, as well as/or cell membrane-anchored and/or -spanning pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs). However, reflection of pathogen-host crosstalk triggering sepsis pathogenesis upon an infection by a host response to challenge with an isolated PAMP is incomplete. Therefore, an experimental model more reflective of pathogen-host interaction requires experimental host confrontation with a specific pathogen in its viable form resulting in a collective stimulation of a variety of specific PRRs. This chapter describes methods to analyse innate pathogen sensing by the host on both a cellular and systemic level.

  2. Developing Phenomena Models from Experimental Data

    DEFF Research Database (Denmark)

    Kristensen, Niels Rode; Madsen, Henrik; Jørgensen, Sten Bay

    2003-01-01

    A systematic approach for developing phenomena models from experimental data is presented. The approach is based on integrated application of stochastic differential equation (SDE) modelling and multivariate nonparametric regression, and it is shown how these techniques can be used to uncover...... unknown functionality behind various phenomena in first engineering principles models using experimental data. The proposed modelling approach has significant application potential, e.g. for determining unknown reaction kinetics in both chemical and biological processes. To illustrate the performance...... of the approach, a case study is presented, which shows how an appropriate phenomena model for the growth rate of biomass in a fed-batch bioreactor can be inferred from data....

  3. Developing Phenomena Models from Experimental Data

    DEFF Research Database (Denmark)

    A systematic approach for developing phenomena models from experimental data is presented. The approach is based on integrated application of stochastic differential equation (SDE) modelling and multivariate nonparametric regression, and it is shown how these techniques can be used to uncover...... unknown functionality behind various phenomena in first engineering principles models using experimental data. The proposed modelling approach has significant application potential, e.g. for determining unknown reaction kinetics in both chemical and biological processes. To illustrate the performance...... of the approach, a case study is presented, which shows how an appropriate phenomena model for the growth rate of biomass in a fed-batch bioreactor can be inferred from data....

  4. Experimental models of demyelination and remyelination.

    Science.gov (United States)

    Torre-Fuentes, L; Moreno-Jiménez, L; Pytel, V; Matías-Guiu, J A; Gómez-Pinedo, U; Matías-Guiu, J

    2017-08-29

    Experimental animal models constitute a useful tool to deepen our knowledge of central nervous system disorders. In the case of multiple sclerosis, however, there is no such specific model able to provide an overview of the disease; multiple models covering the different pathophysiological features of the disease are therefore necessary. We reviewed the different in vitro and in vivo experimental models used in multiple sclerosis research. Concerning in vitro models, we analysed cell cultures and slice models. As for in vivo models, we examined such models of autoimmunity and inflammation as experimental allergic encephalitis in different animals and virus-induced demyelinating diseases. Furthermore, we analysed models of demyelination and remyelination, including chemical lesions caused by cuprizone, lysolecithin, and ethidium bromide; zebrafish; and transgenic models. Experimental models provide a deeper understanding of the different pathogenic mechanisms involved in multiple sclerosis. Choosing one model or another depends on the specific aims of the study. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  5. Thrombocytopenia impairs host defense in gram-negative pneumonia-derived sepsis in mice

    NARCIS (Netherlands)

    de Stoppelaar, Sacha F.; van 't Veer, Cornelis; Claushuis, Theodora A. M.; Albersen, Bregje J. A.; Roelofs, Joris J. T. H.; van der Poll, Tom

    2014-01-01

    Thrombocytopenia is a common finding in sepsis and associated with a worse outcome. We used a mouse model of pneumonia-derived sepsis caused by the human pathogen Klebsiella pneumoniae to study the role of platelets in host response to sepsis. Platelet counts (PCs) were reduced to less than a median

  6. Improving the physiological realism of experimental models.

    Science.gov (United States)

    Vinnakota, Kalyan C; Cha, Chae Y; Rorsman, Patrik; Balaban, Robert S; La Gerche, Andre; Wade-Martins, Richard; Beard, Daniel A; Jeneson, Jeroen A L

    2016-04-06

    The Virtual Physiological Human (VPH) project aims to develop integrative, explanatory and predictive computational models (C-Models) as numerical investigational tools to study disease, identify and design effective therapies and provide an in silico platform for drug screening. Ultimately, these models rely on the analysis and integration of experimental data. As such, the success of VPH depends on the availability of physiologically realistic experimental models (E-Models) of human organ function that can be parametrized to test the numerical models. Here, the current state of suitable E-models, ranging from in vitro non-human cell organelles to in vivo human organ systems, is discussed. Specifically, challenges and recent progress in improving the physiological realism of E-models that may benefit the VPH project are highlighted and discussed using examples from the field of research on cardiovascular disease, musculoskeletal disorders, diabetes and Parkinson's disease.

  7. Sepsis and Septic Shock Strategies.

    Science.gov (United States)

    Armstrong, Bracken A; Betzold, Richard D; May, Addison K

    2017-12-01

    Three therapeutic principles most substantially improve organ dysfunction and survival in sepsis: early, appropriate antimicrobial therapy; restoration of adequate cellular perfusion; timely source control. The new definitions of sepsis and septic shock reflect the inadequate sensitivity, specify, and lack of prognostication of systemic inflammatory response syndrome criteria. Sequential (sepsis-related) organ failure assessment more effectively prognosticates in sepsis and critical illness. Inadequate cellular perfusion accelerates injury and reestablishing perfusion limits injury. Multiple organ systems are affected by sepsis and septic shock and an evidence-based multipronged approach to systems-based therapy in critical illness results in improve outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. MICRONUTRIENT THERAPY FOR SEPSIS

    Directory of Open Access Journals (Sweden)

    Agung Prasetiyo

    2015-05-01

    Full Text Available Micronutrients are nutrients which are needed by the body to perform the function of body. The amounts is less than 100% μg per day and consist of vitamins and minerals. It cannot be synthesized in the body. Research in the US mentioned that the rate prevalence of sepsis is tended to be increased 8.7 % annually. In sepsis, nutrition is one of the important component which could drive the success treatment. Micronutrient, especially a vitamin which is soluble in fats, it would be toxic if the number exceed the capability of body to receive it. Although there are guidance and mutual agreement about sepsis using, it still need to concern on micronutrient which potentially giving bad effect. In sepsis case, micronutrients also determine the success of treatment due to redistribution of vitamin and trace element from circulation to the tissue which involved in the proteins formation and immune system. The conclusions of the latest 7 experiments and 4 random controlled studies of multi-centre support the micronutrients supplementation because it can decrease mortality rate. However, it still need to be aware to the toxicity of fat soluble micronutrient if the doses are excessive.

  9. Approach to neonatal sepsis

    Directory of Open Access Journals (Sweden)

    Shankar Narayan

    2015-01-01

    The treatment includes supportive care along with administration of appropriate antibiotics. Adjuvant treatment includes IVIG, GCSF, exchange transfusion and pentoxifylline administration. This paper aims to present an algorithmic approach to neonatal sepsis to expedite the diagnosis along with providing appropriate and adequate treatment.

  10. Nitrogenoxid og sepsis

    DEFF Research Database (Denmark)

    El-Haj, Lama; Bestle, Morten Heiberg

    2018-01-01

    The main purpose of this study is to review the function of nitric oxide during sepsis and septic shock. Futhermore, the study reviews the various physiological functions of nitric oxide in the human body, and how these functions can and have been used clinically. Nitric oxide plays an important ...

  11. Sepsis Associated Encephalopathy

    Directory of Open Access Journals (Sweden)

    Neera Chaudhry

    2014-01-01

    Full Text Available Sepsis associated encephalopathy (SAE is a common but poorly understood neurological complication of sepsis. It is characterized by diffuse brain dysfunction secondary to infection elsewhere in the body without overt CNS infection. The pathophysiology of SAE is complex and multifactorial including a number of intertwined mechanisms such as vascular damage, endothelial activation, breakdown of the blood brain barrier, altered brain signaling, brain inflammation, and apoptosis. Clinical presentation of SAE may range from mild symptoms such as malaise and concentration deficits to deep coma. The evaluation of cognitive dysfunction is made difficult by the absence of any specific investigations or biomarkers and the common use of sedation in critically ill patients. SAE thus remains diagnosis of exclusion which can only be made after ruling out other causes of altered mentation in a febrile, critically ill patient by appropriate investigations. In spite of high mortality rate, management of SAE is limited to treatment of the underlying infection and symptomatic treatment for delirium and seizures. It is important to be aware of this condition because SAE may present in early stages of sepsis, even before the diagnostic criteria for sepsis can be met. This review discusses the diagnostic approach to patients with SAE along with its epidemiology, pathophysiology, clinical presentation, and differential diagnosis.

  12. Understanding Leadership: An Experimental-Experiential Model

    Science.gov (United States)

    Hole, George T.

    2014-01-01

    Books about leadership are dangerous to readers who fantasize about being leaders or apply leadership ideas as if they were proven formulas. As an antidote, I offer an experimental framework in which any leadership-management model can be tested to gain experiential understanding of the model. As a result one can gain reality-based insights about…

  13. Beneficial antimicrobial effect of the addition of an aminoglycoside to a β-lactam antibiotic in an E. coli porcine intensive care severe sepsis model.

    Science.gov (United States)

    Skorup, Paul; Maudsdotter, Lisa; Lipcsey, Miklós; Castegren, Markus; Larsson, Anders; Jonsson, Ann-Beth; Sjölin, Jan

    2014-01-01

    This study aimed to determine whether the addition of an aminoglycoside to a ß-lactam antibiotic increases the antimicrobial effect during the early phase of Gram-negative severe sepsis/septic shock. A porcine model was selected that considered each animal's individual blood bactericidal capacity. Escherichia coli, susceptible to both antibiotics, was given to healthy pigs intravenously during 3 h. At 2 h, the animals were randomized to a 20-min infusion with either cefuroxime alone (n = 9), a combination of cefuroxime+tobramycin (n = 9), or saline (control, n = 9). Blood samples were collected hourly for cultures and quantitative polymerase chain reaction (PCR). Bacterial growth in the organs after 6 h was chosen as the primary endpoint. A blood sample was obtained at baseline before start of bacterial infusion for ex vivo investigation of the blood bactericidal capacity. At 1 h after the administration of the antibiotics, a second blood sample was taken for ex vivo investigation of the antibiotic-induced blood killing activity. All animals developed severe sepsis/septic shock. Blood cultures and PCR rapidly became negative after completed bacterial infusion. Antibiotic-induced blood killing activity was significantly greater in the combination group than in the cefuroxime group (pantibiotic groups compared with the controls (pantibiotic groups. Bacterial growth in the liver was significantly less in the combination group than in the cefuroxime group (pantibiotic-induced blood killing activity and less bacteria in the liver than cefuroxime alone. Individual blood bactericidal capacity may have a significant effect on antimicrobial outcome.

  14. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)

    Science.gov (United States)

    Singer, Mervyn; Deutschman, Clifford S.; Seymour, Christopher Warren; Shankar-Hari, Manu; Annane, Djillali; Bauer, Michael; Bellomo, Rinaldo; Bernard, Gordon R.; Chiche, Jean-Daniel; Coopersmith, Craig M.; Hotchkiss, Richard S.; Levy, Mitchell M.; Marshall, John C.; Martin, Greg S.; Opal, Steven M.; Rubenfeld, Gordon D.; van der Poll, Tom; Vincent, Jean-Louis; Angus, Derek C.

    2016-01-01

    IMPORTANCE Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination. OBJECTIVE To evaluate and, as needed, update definitions for sepsis and septic shock. PROCESS A task force (n = 19) with expertise in sepsis pathobiology, clinical trials, and epidemiology was convened by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. Definitions and clinical criteria were generated through meetings, Delphi processes, analysis of electronic health record databases, and voting, followed by circulation to international professional societies, requesting peer review and endorsement (by 31 societies listed in the Acknowledgment). KEY FINDINGS FROMEVIDENCE SYNTHESIS Limitations of previous definitions included an excessive focus on inflammation, the misleading model that sepsis follows a continuum through severe sepsis to shock, and inadequate specificity and sensitivity of the systemic inflammatory response syndrome (SIRS) criteria. Multiple definitions and terminologies are currently in use for sepsis, septic shock, and organ dysfunction, leading to discrepancies in reported incidence and observed mortality. The task force concluded the term severe sepsis was redundant. RECOMMENDATIONS Sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. For clinical operationalization, organ dysfunction can be represented by an increase in the Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score of 2 points or more, which is associated with an in-hospital mortality greater than 10%. Septic shock should be defined as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a

  15. EXPERIMENTAL MODEL OF THE PRIMARY MALE HYPOGONADISM

    Directory of Open Access Journals (Sweden)

    P. A. Kulikova

    2014-01-01

    Full Text Available Background: Development of the new methods of treatment of primary male hypogonadism is an urgent medical problem. Its solution requires a suitable experimental model of the disease. Aim: The creation of new experimental model of primary male hypogonadism. Materials and methods: The study was conducted on the male Wistar rats, hypogonadism was modeled by temporary ligation of the distal part of the spermatic cord. Results: It was shown that three-day ligation of the spermatic cord led to persistent disturbance of the testosterone-producing and reproductive functions. These manifestations were reversible at shorter duration of the exposure. Conclusion: The created model of primary male hypogonadism is characterized by the persistent testosterone-producing and reproductive functions disturbance, technical availability, non-toxicity to the other organs and systems. Availability of the model provides new opportunities for the development of approaches to treating diseases of the reproductive organs in men.

  16. Modeling of Experimental Adsorption Isotherm Data

    Directory of Open Access Journals (Sweden)

    Xunjun Chen

    2015-01-01

    Full Text Available Adsorption is considered to be one of the most effective technologies widely used in global environmental protection areas. Modeling of experimental adsorption isotherm data is an essential way for predicting the mechanisms of adsorption, which will lead to an improvement in the area of adsorption science. In this paper, we employed three isotherm models, namely: Langmuir, Freundlich, and Dubinin-Radushkevich to correlate four sets of experimental adsorption isotherm data, which were obtained by batch tests in lab. The linearized and non-linearized isotherm models were compared and discussed. In order to determine the best fit isotherm model, the correlation coefficient (r2 and standard errors (S.E. for each parameter were used to evaluate the data. The modeling results showed that non-linear Langmuir model could fit the data better than others, with relatively higher r2 values and smaller S.E. The linear Langmuir model had the highest value of r2, however, the maximum adsorption capacities estimated from linear Langmuir model were deviated from the experimental data.

  17. Surviving Sepsis Campaign

    DEFF Research Database (Denmark)

    Rhodes, Andrew; Evans, Laura E; Alhazzani, Waleed

    2017-01-01

    OBJECTIVE: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012." DESIGN: A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings...... (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups......, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low...

  18. Surviving Sepsis Campaign

    DEFF Research Database (Denmark)

    Rhodes, Andrew; Evans, Laura E; Alhazzani, Waleed

    2017-01-01

    OBJECTIVE: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012". DESIGN: A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings...... (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups......, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low...

  19. Assessment of Clinical Criteria for Sepsis

    Science.gov (United States)

    Seymour, Christopher W.; Liu, Vincent X.; Iwashyna, Theodore J.; Brunkhorst, Frank M.; Rea, Thomas D.; Scherag, André; Rubenfeld, Gordon; Kahn, Jeremy M.; Shankar-Hari, Manu; Singer, Mervyn; Deutschman, Clifford S.; Escobar, Gabriel J.; Angus, Derek C.

    2016-01-01

    IMPORTANCE The Third International Consensus Definitions Task Force defined sepsis as “life-threatening organ dysfunction due to a dysregulated host response to infection.” The performance of clinical criteria for this sepsis definition is unknown. OBJECTIVE To evaluate the validity of clinical criteria to identify patients with suspected infection who are at risk of sepsis. DESIGN, SETTINGS, AND POPULATION Among 1.3 million electronic health record encounters from January 1, 2010, to December 31, 2012, at 12 hospitals in southwestern Pennsylvania, we identified those with suspected infection in whom to compare criteria. Confirmatory analyses were performed in 4 data sets of 706 399 out-of-hospital and hospital encounters at 165 US and non-US hospitals ranging from January 1, 2008, until December 31, 2013. EXPOSURES Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score, systemic inflammatory response syndrome (SIRS) criteria, Logistic Organ Dysfunction System (LODS) score, and a new model derived using multivariable logistic regression in a split sample, the quick Sequential [Sepsis-related] Organ Failure Assessment (qSOFA) score (range, 0–3 points, with 1 point each for systolic hypotension [≤100 mm Hg], tachypnea [≥22/min], or altered mentation). MAIN OUTCOMES AND MEASURES For construct validity, pairwise agreement was assessed. For predictive validity, the discrimination for outcomes (primary: in-hospital mortality; secondary: in-hospital mortality or intensive care unit [ICU] length of stay ≥3 days) more common in sepsis than uncomplicated infection was determined. Results were expressed as the fold change in outcome over deciles of baseline risk of death and area under the receiver operating characteristic curve (AUROC). RESULTS In the primary cohort, 148 907 encounters had suspected infection (n = 74 453 derivation; n = 74 454 validation), of whom 6347 (4%) died. Among ICU encounters in the validation cohort (n = 7932 with suspected

  20. Hemorrhoids: an experimental model in monkeys

    Directory of Open Access Journals (Sweden)

    Plapler Hélio

    2006-01-01

    Full Text Available PURPOSE: Hemorrhoids are a matter of concern due to a painful outcome. We describe a simple, easy and reliable experimental model to produce hemorrhoids in monkeys. METHODS: 14 monkeys (Cebus apella were used. After general anesthesia, hemorrhoids were induced by ligation of the inferior hemorrhoidal vein, which is very alike to humans. The vein was located through a perianal incision, dissected and ligated with a 3-0 vicryl. The skin was sutured with a 4-0 catgut thread. Animals were kept in appropriate cages and evaluated daily. RESULTS: Nine days later there were hemorrhoidal piles in the anus in fifty percent (50% of the animals. Outcome was unremarkable. There was no bleeding and all animals showed no signs of pain or suffering. CONCLUSION: This is an affordable and reliable experimental model to induce hemorrhoids for experimental studies.

  1. Progranulin Plays a Central Role in Host Defense during Sepsis by Promoting Macrophage Recruitment.

    Science.gov (United States)

    Song, Zhixin; Zhang, Xuemei; Zhang, Liping; Xu, Fang; Tao, Xintong; Zhang, Hua; Lin, Xue; Kang, Lihua; Xiang, Yu; Lai, Xaiofei; Zhang, Qun; Huang, Kun; Dai, Yubing; Yin, Yibing; Cao, Ju

    2016-11-15

    Progranulin, a widely expressed protein, has multiple physiological functions. The functional role of progranulin in the host response to sepsis remains unknown. To assess the role of progranulin in the host response to sepsis. Effects of progranulin on host response to sepsis were determined. Progranulin concentrations were significantly elevated in adult (n = 74) and pediatric (n = 26) patients with sepsis relative to corresponding healthy adult (n = 36) and pediatric (n = 17) control subjects, respectively. By using a low-lethality model of nonsevere sepsis, we observed that progranulin deficiency not only increased mortality but also decreased bacterial clearance during sepsis. The decreased host defense to sepsis in progranulin-deficient mice was associated with reduced macrophage recruitment, with correspondingly impaired chemokine CC receptor ligand 2 (CCL2) production in peritoneal lavages during the early phase of sepsis. Progranulin derived from hematopoietic cells contributed to host defense in sepsis. Therapeutic administration of recombinant progranulin not only rescued impaired host defense in progranulin-deficient mice after nonsevere sepsis but also protected wild-type mice against a high-lethality model of severe sepsis. Progranulin-mediated protection against sepsis was closely linked to improved peritoneal macrophage recruitment. In addition, CCL2 treatment of progranulin-deficient mice improved survival and decreased peritoneal bacterial loads during sepsis, at least in part through promotion of peritoneal macrophage recruitment. This proof-of-concept study supports a central role of progranulin-dependent macrophage recruitment in host defense to sepsis, opening new opportunities to host-directed therapeutic strategy that manipulate host immune response in the treatment of sepsis.

  2. Optimal Experimental Design for Model Discrimination

    Science.gov (United States)

    Myung, Jay I.; Pitt, Mark A.

    2009-01-01

    Models of a psychological process can be difficult to discriminate experimentally because it is not easy to determine the values of the critical design variables (e.g., presentation schedule, stimulus structure) that will be most informative in differentiating them. Recent developments in sampling-based search methods in statistics make it…

  3. Macrophages and Uveitis in Experimental Animal Models

    Directory of Open Access Journals (Sweden)

    Salvador Mérida

    2015-01-01

    Full Text Available Resident and infiltrated macrophages play relevant roles in uveitis as effectors of innate immunity and inductors of acquired immunity. They are major effectors of tissue damage in uveitis and are also considered to be potent antigen-presenting cells. In the last few years, experimental animal models of uveitis have enabled us to enhance our understanding of the leading role of macrophages in eye inflammation processes, including macrophage polarization in experimental autoimmune uveoretinitis and the major role of Toll-like receptor 4 in endotoxin-induced uveitis. This improved knowledge should guide advantageous iterative research to establish mechanisms and possible therapeutic targets for human uveitis resolution.

  4. Electrochemical desalination of bricks - Experimental and modeling

    DEFF Research Database (Denmark)

    Skibsted, Gry; Ottosen, Lisbeth M.; Jensen, Pernille Erland

    2015-01-01

    Chlorides, nitrates and sulfates play an important role in the salt-decay of porous materials in buildings and monuments. Electrochemical desalination is a technology able to remove salts from such porous materials in order to stop or prevent the decay. In this paper, experimental and numerical......-contaminated bricks with respect to the monovalent ions is discussed. Comparison between the experimental and the simulation results showed that the proposed numerical model is able to predict electrochemical desalination treatments with remarkable accuracy, and it can be used as a predictive tool...

  5. Unrevealing culture-negative severe sepsis

    OpenAIRE

    de Prost, Nicolas; Razazi, Keyvan; Brun-Buisson, Christian

    2013-01-01

    Sepsis involves a wide array of sources and microorganisms, only a fraction of which are microbiologically documented. Culture-negative sepsis poses special diagnostic challenges to both clinicians and microbiologists and further questions the validity of sepsis definitions.

  6. Diagnosis trajectories of prior multi-morbidity predict sepsis mortality

    DEFF Research Database (Denmark)

    Beck, Mette Kristina; Jensen, Anders Boeck; Nielsen, Annelaura Bach

    2016-01-01

    Sepsis affects millions of people every year, many of whom will die. In contrast to current survival prediction models for sepsis patients that primarily are based on data from within-admission clinical measurements (e.g. vital parameters and blood values), we aim for using the full disease histo...... of disease history to scoring based on within-admission clinical measurements emphasizing the value of long term data in novel patient scores that combine the two types of data.......Sepsis affects millions of people every year, many of whom will die. In contrast to current survival prediction models for sepsis patients that primarily are based on data from within-admission clinical measurements (e.g. vital parameters and blood values), we aim for using the full disease history...... recurrent trajectories of time-ordered co-morbidities had significantly increased sepsis mortality compared to those who did not follow a trajectory. We identified trajectories which significantly altered sepsis mortality, and found three major starting points in a combined temporal sepsis network: Alcohol...

  7. Irradiation Design for an Experimental Murine Model

    International Nuclear Information System (INIS)

    Ballesteros-Zebadua, P.; Moreno-Jimenez, S.; Suarez-Campos, J. E.; Celis, M. A.; Larraga-Gutierrez, J. M.; Garcia-Garduno, O. A.; Rubio-Osornio, M. C.; Custodio-Ramirez, V.; Paz, C.

    2010-01-01

    In radiotherapy and stereotactic radiosurgery, small animal experimental models are frequently used, since there are still a lot of unsolved questions about the biological and biochemical effects of ionizing radiation. This work presents a method for small-animal brain radiotherapy compatible with a dedicated 6MV Linac. This rodent model is focused on the research of the inflammatory effects produced by ionizing radiation in the brain. In this work comparisons between Pencil Beam and Monte Carlo techniques, were used in order to evaluate accuracy of the calculated dose using a commercial planning system. Challenges in this murine model are discussed.

  8. Huntington disease: Experimental models and therapeutic perspectives

    International Nuclear Information System (INIS)

    Serrano Sanchez, Teresa; Blanco Lezcano, Lisette; Garcia Minet, Rocio; Alberti Amador, Esteban; Diaz Armesto, Ivan and others

    2011-01-01

    Huntington's disease (HD) is a degenerative dysfunction of hereditary origin. Up to date there is not, an effective treatment to the disease which having lapsed 15 or 20 years advances inexorably, in a slow form, toward the total inability or death. This paper reviews the clinical and morphological characteristics of Huntington's disease as well as the experimental models more commonly used to study this disease, having as source the articles indexed in Medline data base, published in the last 20 years. Advantages and disadvantages of all experimental models to reproduce the disease as well as the perspectives to therapeutic assay have been also considered. the consent of outline reported about the toxic models, those induced by neurotoxins such as quinolinic acid, appears to be the most appropriate to reproduce the neuropathologic characteristic of the disease, an genetic models contributing with more evidence to the knowledge of the disease etiology. Numerous treatments ameliorate clinical manifestations, but none of them has been able to stop or diminish the affectations derived from neuronal loss. At present time it is possible to reproduce, at least partially, the characteristics of the disease in experimentation animals that allow therapy evaluation in HD. from the treatment view point, the more promissory seems to be transplantation of no neuronal cells, taking into account ethical issues and factibility. On the other hand the new technology of interference RNA emerges as a potential therapeutic tool for treatment in HD, and to respond basic questions on the development of the disease.

  9. Adjustment model of thermoluminescence experimental data

    International Nuclear Information System (INIS)

    Moreno y Moreno, A.; Moreno B, A.

    2002-01-01

    This model adjusts the experimental results for thermoluminescence according to the equation: I (T) = I (a i * exp (-1/b i * (T-C i )) where: a i , b i , c i are the i-Th peak adjusted to a gaussian curve. The adjustments of the curve can be operated manual or analytically using the macro function and the solver.xla complement installed previously in the computational system. In this work it is shown: 1. The information of experimental data from a LiF curve obtained from the Physics Institute of UNAM which the data adjustment model is operated in the macro type. 2. A LiF curve of four peaks obtained from Harshaw information simulated in Microsoft Excel, discussed in previous works, as a reference not in macro. (Author)

  10. Construction and management of ARDS/sepsis registry with REDCap.

    Science.gov (United States)

    Pang, Xiaoqing; Kozlowski, Natascha; Wu, Sulong; Jiang, Mei; Huang, Yongbo; Mao, Pu; Liu, Xiaoqing; He, Weiqun; Huang, Chaoyi; Li, Yimin; Zhang, Haibo

    2014-09-01

    The study aimed to construct and manage an acute respiratory distress syndrome (ARDS)/sepsis registry that can be used for data warehousing and clinical research. The workflow methodology and software solution of research electronic data capture (REDCap) was used to construct the ARDS/sepsis registry. Clinical data from ARDS and sepsis patients registered to the intensive care unit (ICU) of our hospital formed the registry. These data were converted to the electronic case report form (eCRF) format used in REDCap by trained medical staff. Data validation, quality control, and database management were conducted to ensure data integrity. The clinical data of 67 patients registered to the ICU between June 2013 and December 2013 were analyzed. Of the 67 patients, 45 (67.2%) were classified as sepsis, 14 (20.9%) as ARDS, and eight (11.9%) as sepsis-associated ARDS. The patients' information, comprising demographic characteristics, medical history, clinical interventions, daily assessment, clinical outcome, and follow-up data, was properly managed and safely stored in the ARDS/sepsis registry. Data efficiency was guaranteed by performing data collection and data entry twice weekly and every two weeks, respectively. The ARDS/sepsis database that we constructed and manage with REDCap in the ICU can provide a solid foundation for translational research on the clinical data of interest, and a model for development of other medical registries in the future.

  11. Inibição da atividade da citrato sintase cerebral em um modelo animal de sepse Inhibition of brain citrate synthase activity in an animal model of sepsis

    Directory of Open Access Journals (Sweden)

    Giselli Scaini

    2011-06-01

    fisiopatologia desta doença.OBJECTIVE: An extensive body of evidence from experimental studies indicates that sepsis is associated with increased reactive oxygen species production, depletion of antioxidants, and accumulation of markers of oxidative stress. Moreover, mitochondrial dysfunction has been implicated in the pathogenesis of multiple organ dysfunction syndrome (MODS. Citrate synthase is an enzyme localized in the mitochondrial matrix and an important component of the Krebs cycle; consequently, citrate synthase has been used as a quantitative enzyme marker for the presence of intact mitochondria. Thus, we investigated citrate synthase activity in the brains of rats submitted to a cecal ligation puncture model of sepsis. METHODS: At several times points (3, 6, 12, 24 and 48 hours after the cecal ligation puncture operation, six rats were killed by decapitation. Their brains were removed, and the hippocampus, striatum, cerebellum, cerebral cortex and prefrontal cortex were dissected and used to determine citrate synthase activity. RESULTS: We found that citrate synthase activity in the prefrontal cortex was inhibited 12, 24 and 48 hours after cecal ligation puncture. In the cerebral cortex, citrate synthase activity was inhibited 3, 12, 24 and 48 hours after cecal ligation puncture. Citrate synthase was not affected in the hippocampus, striatum or cerebellum up to 48 hours after cecal ligation puncture. CONCLUSION: Considering that energy impairment due to mitochondrial dysfunction in sepsis has been well described and that oxidative stress plays a crucial role in sepsis development, we believe that energy impairment may also be involved in these processes. If citrate synthase inhibition also occurs in a sepsis model, it is tempting to speculate that a reduction in brain metabolism may be related to the pathophysiology of this disease.

  12. Endotoxin dosage in sepsis

    Directory of Open Access Journals (Sweden)

    Vincenzo Rondinelli

    2012-03-01

    Full Text Available Introduction. Endotoxin, a component of the cell wall of Gram-negative bacteria is a major contributor to the pathogenesis of septic shock and multiple organ failure (MOF. Its entry into the bloodstream stimulates monocytes/macrophages which once activated produce and release cytokines, nitric oxide and other mediators that induce systemic inflammation, endothelial damage, organ dysfunction, hypotension (shock and MOF.The aim of this study is to evaluate the usefulness of a quantitative test for the dosage of endotoxin to determine the risk of severe Gram-negative sepsis. Materials and methods. In the period January 2009 - June 2011 we performed 897 tests for 765 patients, mostly coming from the emergency room and intensive care, of which 328 (43% women (mean age 53 and 437 (57% male (mean age 49. Fifty-nine patients, no statistically significant difference in sex, were monitored by an average of two determinations of EA.All patients had procalcitonin values significantly altered.The kit used was EAA (Endotoxin Activity Assay Estor Company, Milan, which has three ranges of endotoxin activity (EA: low risk of sepsis if <0.40 units, medium if between 0.40 and 0.59; high if 0.60. Results. 78 out of 765 patients (10% had a low risk, 447 (58% a medium risk and 240 (32% a high risk.The dosage of EA, combined with that of procalcitonin, has allowed a more targeted antibiotic therapy. Six patients in serious clinical conditions were treated by direct hemoperfusion with Toraymyxin, a device comprising a housing containing a fiber polypropylene and polystyrene with surface-bound polymyxin B, an antibiotic that removes bacterial endotoxins from the blood. Conclusions.The test is useful in risk stratification as well as Gram negative sepsis, to set and monitor targeted therapies, also based on the neutralization of endotoxin.

  13. Experimental tests of proton spin models

    International Nuclear Information System (INIS)

    Ramsey, G.P.; Argonne National Lab., IL

    1989-01-01

    We have developed models for the spin-weighted quark and gluon distribution in a longitudinally polarized proton. The model parameters are determined from current algebra sum rules and polarized deep-inelastic scattering data. A number of different scenarios are presented for the fraction of spin carried the constituent parton distributions. A possible long-range experimental program is suggested for measuring various hard scattering processes using polarized lepton and proton beams. With the knowledge gained from these experiments, we can begin to understand the parton contributions to the proton spin. 28 refs., 5 figs

  14. Experimental In Vivo Models of Candidiasis

    Directory of Open Access Journals (Sweden)

    Esther Segal

    2018-02-01

    Full Text Available Candidiasis is a multifaceted fungal disease including mucosal-cutaneous, visceral, and disseminated infections caused by yeast species of the genus Candida. Candida infections are among the most common human mycoses. Candida species are the third to fourth most common isolates from bloodstream infections in neutropenic or immunocompromised hospitalized patients. The mucosal-cutaneous forms—particularly vaginal infections—have a high prevalence. Vaginitis caused by Candida species is the second most common vaginal infection. Hence, candidiasis is a major subject for research, including experimental in vivo models to study pathogenesis, prevention, or therapy of the disease. The following review article will focus on various experimental in vivo models in different laboratory animals, such as mammals (mice, rats, rabbits, the fruit fly–Drosophila melanogaster, the larvae of the moth Galleria mellonella, or the free-living nematode Caenorhabditis elegans. The review will describe the induction of the different clinical forms of candidiasis in the various models and the validity of such models in mimicking the human clinical situations. The use of such models for the assessment of antifungal drugs, evaluation of potential vaccines to protect before candidiasis, exploration of Candida virulence factors, and comparison of pathogenicity of different Candida species will be included in the review. All of the above will be reported as based on published studies of numerous investigators as well as on the research of the author and his group.

  15. Experimental modeling of eddy current inspection capabilities

    International Nuclear Information System (INIS)

    Junker, W.R.; Clark, W.G.

    1984-01-01

    This chapter examines the experimental modeling of eddy current inspection capabilities based upon the use of liquid mercury samples designed to represent metal components containing discontinuities. A brief summary of past work with mercury modeling and a detailed discussion of recent experiments designed to further evaluate the technique are presented. The main disadvantages of the mercury modeling concept are that mercury is toxic and must be handled carefully, liquid mercury can only be used to represent nonferromagnetic materials, and wetting and meniscus problems can distort the effective size of artificial discontinuities. Artificial discontinuities placed in a liquid mercury sample can be used to represent discontinuities in solid metallic structures. Discontinuity size and type cannot be characterized from phase angle and signal amplitude data developed with a surface scanning, pancake-type eddy current probe. It is concluded that the mercury model approach can greatly enhance the overall understanding and applicability of eddy current inspection techniques

  16. Endometriose: modelo experimental em ratas Endometriosis: experimental model in rats

    Directory of Open Access Journals (Sweden)

    Eduardo Schor

    1999-06-01

    Full Text Available Objetivo: divulgar a metodologia da indução de endometriose experimental em animais de laboratório. Método: utilizamos ratas albinas, virgens, adultas de aproximadamente três meses de idade, que foram inicialmente anestesiadas pelo éter etílico. Aberta a cavidade abdominal, identificamos os cornos uterinos e retiramos um fragmento de aproximadamente 4 cm do corno uterino direito. Esse fragmento foi mergulhado em solução fisiológica e sob lupa estereoscópica foi separado o endométrio do miométrio e feitos retângulos de aproximadamente 4 por 5 mm. Esses foram fixados por meio de fio de sutura, sobre vasos sangüíneos visíveis a olho nu, na parede lateral do abdômen, tomando-se sempre o cuidado de manter a porção do endométrio livre voltada para a luz da cavidade abdominal. Após 21 dias os animais foram novamente operados para verificarmos o tamanho dos implantes e para retirada do endométrio ectópico para análise histológica. Resultados: macroscopicamente observamos crescimento significativo dos implantes endometriais. Ao exame microscópico pudemos observar a presença de epitélio glandular e estroma semelhantes ao do endométrio tópico. Conclusões: o modelo utilizado reproduz a doença, em ratas, sendo método auxiliar de valia para estudar esta afecção, principalmente a ação de medicamentos sobre esses implantes.Purpose: to demonstrate the experimental endometriosis induction in animals. Method: we used adult female Wistar rats weighing 200 - 250 g anesthetized with ethyl ether to open the abdominal cavity. After identifying the uterine horns, we removed an approximately 4 cm fragment from the right uterine horn. This fragment was placed in physiological saline and, with the aid of a stereoscopic magnifying glass, the endometrium was separated from the myometrium and cut into rectangles of approximately 4 x 5 mm. These rectangles were fastened to the lateral abdominal wall near great blood vessels, taking care

  17. Detoxification in Abdominal Sepsis

    Directory of Open Access Journals (Sweden)

    A. F. Potapov

    2005-01-01

    Full Text Available Objective. To comparatively analyze the efficiency of methods for extracorporeal detoxification (ED of the body in abdominal sepsis (AS and to choose the optimum detoxifying methods in relation to the level of endotoxicosis.Material and methods. 56 patients (41 males and 15 females; mean age 39.4±12.2 years with surgical abdominal infection of various genesis, complicated by the development of sepsis whose treatment included ED methods, were examined. The level of intoxication and the efficiency of detoxification were evaluated by general clinical and biochemical blood parameters, the leukocytic intoxication index, the levels of low and medium molecular-weight substances in the body’s media. Hemosorption, plasmapheresis, hemodialysis, hemodiafiltration, and hemofiltration were used for detoxification.Results. Surgical abdominal infection is accompanied by endotoxemia that has no clear nosological specificity, but it depends on the pattern of a clinical course of the disease and is most pronounced in the septic syndrome. In AS, 80.4% of the patients are observed to have an irreversible decompensation phase and a terminal degree of endotoxicosis, which require detoxification. The use of different ED methods according to the level of intoxication may reduce the level of endotoxicosis and yield a persistent beneficial effect in 85.2% of cases of its application. Conclusion. Filtration and dialysis techniques (hemodialysis, hemofiltration, and hemodiafiltration are the methods of choice in AS. Hemosorption and plasmapheresis may be recommended for use at the early stages of endotoxicosis development and in preserved renal excretory function.

  18. Experimental animal modelling for TB vaccine development

    Directory of Open Access Journals (Sweden)

    Pere-Joan Cardona

    2017-03-01

    Full Text Available Research for a novel vaccine to prevent tuberculosis is an urgent medical need. The current vaccine, BCG, has demonstrated a non-homogenous efficacy in humans, but still is the gold standard to be improved upon. In general, the main indicator for testing the potency of new candidates in animal models is the reduction of the bacillary load in the lungs at the acute phase of the infection. Usually, this reduction is similar to that induced by BCG, although in some cases a weak but significant improvement can be detected, but none of candidates are able to prevent establishment of infection. The main characteristics of several laboratory animals are reviewed, reflecting that none are able to simulate the whole characteristics of human tuberculosis. As, so far, no surrogate of protection has been found, it is important to test new candidates in several models in order to generate convincing evidence of efficacy that might be better than that of BCG in humans. It is also important to investigate the use of “in silico” and “ex vivo” models to better understand experimental data and also to try to replace, or at least reduce and refine experimental models in animals.

  19. Models for Experimental High Density Housing

    Science.gov (United States)

    Bradecki, Tomasz; Swoboda, Julia; Nowak, Katarzyna; Dziechciarz, Klaudia

    2017-10-01

    The article presents the effects of research on models of high density housing. The authors present urban projects for experimental high density housing estates. The design was based on research performed on 38 examples of similar housing in Poland that have been built after 2003. Some of the case studies show extreme density and that inspired the researchers to test individual virtual solutions that would answer the question: How far can we push the limits? The experimental housing projects show strengths and weaknesses of design driven only by such indexes as FAR (floor attenuation ratio - housing density) and DPH (dwellings per hectare). Although such projects are implemented, the authors believe that there are reasons for limits since high index values may be in contradiction to the optimum character of housing environment. Virtual models on virtual plots presented by the authors were oriented toward maximising the DPH index and DAI (dwellings area index) which is very often the main driver for developers. The authors also raise the question of sustainability of such solutions. The research was carried out in the URBAN model research group (Gliwice, Poland) that consists of academic researchers and architecture students. The models reflect architectural and urban regulations that are valid in Poland. Conclusions might be helpful for urban planners, urban designers, developers, architects and architecture students.

  20. Experimental data and dose-response models

    International Nuclear Information System (INIS)

    Ullrich, R.L.

    1985-01-01

    Dose-response relationships for radiation carcinogenesis have been of interest to biologists, modelers, and statisticians for many years. Despite his interest there are few instances in which there are sufficient experimental data to allow the fitting of various dose-response models. In those experimental systems for which data are available the dose-response curves for tumor induction for the various systems cannot be described by a single model. Dose-response models which have been observed following acute exposures to gamma rays include threshold, quadratic, and linear models. Data on sex, age, and environmental influences of dose suggest a strong role of host factors on the dose response. With decreasing dose rate the effectiveness of gamma ray irradiation tends to decrease in essentially every instance. In those cases in which the high dose rate dose response could be described by a quadratic model, the effect of dose rate is consistent with predictions based on radiation effects on the induction of initial events. Whether the underlying reasons for the observed dose-rate effect is a result of effects on the induction of initial events or is due to effects on the subsequent steps in the carcinogenic process is unknown. Information on the dose response for tumor induction for high LET (linear energy transfer) radiations such as neutrons is even more limited. The observed dose and dose rate data for tumor induction following neutron exposure are complex and do not appear to be consistent with predictions based on models for the induction of initial events

  1. Surface physics theoretical models and experimental methods

    CERN Document Server

    Mamonova, Marina V; Prudnikova, I A

    2016-01-01

    The demands of production, such as thin films in microelectronics, rely on consideration of factors influencing the interaction of dissimilar materials that make contact with their surfaces. Bond formation between surface layers of dissimilar condensed solids-termed adhesion-depends on the nature of the contacting bodies. Thus, it is necessary to determine the characteristics of adhesion interaction of different materials from both applied and fundamental perspectives of surface phenomena. Given the difficulty in obtaining reliable experimental values of the adhesion strength of coatings, the theoretical approach to determining adhesion characteristics becomes more important. Surface Physics: Theoretical Models and Experimental Methods presents straightforward and efficient approaches and methods developed by the authors that enable the calculation of surface and adhesion characteristics for a wide range of materials: metals, alloys, semiconductors, and complex compounds. The authors compare results from the ...

  2. Role of C5 Activation Products in Sepsis

    Directory of Open Access Journals (Sweden)

    Peter A. Ward

    2010-01-01

    Full Text Available Complement activation products are known to be generated in the setting of both experimental and human sepsis. C5 activation products (C5a anaphylatoxin and the membrane attack complex [MAC] C5b-9 are generated during sepsis following infusion of endotoxin, or after cecal ligation and puncture (CLP, which produces polymicrobial sepsis. C5a reacts with its receptors C5aR and C5L2 in a manner that creates the “cytokine storm”, and is associated with development of multiorgan failure (MOF. A number of other complications arising from the interaction of C5a with its receptors include apoptosis of lymphoid cells, loss of innate immune functions of neutrophils (PMNs, polymorphonuclear leukocytes, cardiomyopathy, disseminated intravascular coagulation, and complications associated with MOF. Neutralization of C5a in vivo or absence/blockade of C5a receptors greatly reduces the adverse events in the setting of sepsis, markedly attenuates MOF, and greatly improves survival. Regarding the possible role of C5b-9 in sepsis, the literature is conflicting. Some studies suggest that C5b-9 is protective, while other studies suggest the contrary. Clearly, in human sepsis, C5a and its receptors may be logical targets for interception.

  3. Melatonin suppresses markers of inflammation and oxidative damage in a human daytime endotoxemia model

    DEFF Research Database (Denmark)

    Alamili, Mahdi; Bendtzen, Klaus; Lykkesfeldt, Jens

    2014-01-01

    Melatonin used as an exogenous drug has been documented to have potent antioxidant and anti-inflammatory effects in animal model. We aimed to examine the effect of melatonin in an experimental human sepsis model....

  4. Superficial tension: experimental model with simple materials

    Directory of Open Access Journals (Sweden)

    Tintori Ferreira, María Alejandra

    2012-09-01

    Full Text Available In this work appears a didactic offer based on an experimental activity using materials of very low cost, orientated to achieving that the student understand and interpret the phenomenon of superficial tension together with the importance of the modeling in sciences. It has as principal aim of education bring the student over to the mechanics of the static fluids and the intermolecular forces, combining scientific contents with questions near to the student what provides an additional motivation to the reflection of the scientific investigation.

  5. Experimental model of bladder instability in rabbits

    Directory of Open Access Journals (Sweden)

    Balasteghin K.T.

    2003-01-01

    Full Text Available OBJECTIVE: Propose a new experimental model of bladder instability in rabbits after partial bladder obstruction. MATERIALS AND METHODS: Thirty North Folk male rabbits, weighting 1,700 to 2,820 g (mean: 2,162 g were studied. The animals were distributed in 2 experimental groups, formed by 15 rabbits each: Group 1 - clinical control. In this group there was no surgical intervention; Group 2 - bladder outlet obstruction. In this group, after anesthetizing the animal, urethral cannulation with Foley catheter 10F was performed and then an adjustable plastic bracelet was passed around the bladder neck. It was then adjusted in order to not constrict the urethra. The following parameters were studied in M1 - pre-operative period; M2 - 4 weeks post-operatively moments: 1- urine culture; 2- cystometric study; 3- serum creatinine and BUN. RESULTS: Bladder weight was 2.5 times larger in the group with obstruction than in the control group. Cystometric evaluation showed a significant increase in maximal vesical volume in the final moment at Group G2. However, there was no statistically significant difference among the groups studied. There was no statistically significant difference between maximal detrusor pressure and vesical compliance in the different moments or in the studied groups. There was an absence of uninhibited detrusor contractions in all the animals in group 1, and involuntary contractions were detected in 93% of group 2 animals. There was no significant variation in BUN and serum creatinine either among the groups or in the same group. CONCLUSIONS: We observed in the group with obstruction a bladder weight 2.5 higher than normal bladders. We detected involuntary contractions in 93% of the animals in group 2, establishing this experimental model as appropriate to secondary bladder instability and partial bladder outlet obstruction.

  6. Sepsis por shigella flexneri

    Directory of Open Access Journals (Sweden)

    César Cabrera C

    2005-04-01

    Full Text Available Se presenta un caso raro de sepsis por Shigella flexneri en una paciente de 45 años de edad quien estando hospitalizada para el estudio de un tumor cerebral, requirió el uso de manitol y dosis altas de corticoides; luego de ello presenta deposiciones líquidas con moco y sangre, desarrolla síndrome de respuesta inflamatoria sistémica, luego se aísla Shigella flexneri en el hemocultivo; recibió tratamiento antibiótico con ciprofloxacina. Se describen las características del caso y se comenta de acuerdo con la revisión de literatura.

  7. Moraxella catarrhalis sepsis

    Directory of Open Access Journals (Sweden)

    Paola Gualdi

    2008-06-01

    Full Text Available Moraxella catarrhalis is a Gram-negative aerobic diplococcus, commensal of the oro-pharingeal cavity, actually playing an emerging role in the upper respiratory tract infections together with Streptococcus pneumoniae and Haemophilus influenzae. This study reports the case of a twoyearold child who was admitted into hospital with fever, headache and vomit. The chest radiograph showed signs of basal lung involvementmaking the clinical suspicion of bacterial infectionlikely. From blood culture a Moraxella catarrhalis strain was isolated. In young children M. catarrhalis is known to cause otitis media and sinusitis, but only rarely bacteremia. In this case the child showed a clinical picture of lung infection and consequent sepsis due to M. catarrhalis.

  8. Experimental Oral Candidiasis in Animal Models

    Science.gov (United States)

    Samaranayake, Yuthika H.; Samaranayake, Lakshman P.

    2001-01-01

    Oral candidiasis is as much the final outcome of the vulnerability of the host as of the virulence of the invading organism. We review here the extensive literature on animal experiments mainly appertaining to the host predisposing factors that initiate and perpetuate these infections. The monkey, rat, and mouse are the choice models for investigating oral candidiasis, but comparisons between the same or different models appear difficult, because of variables such as the study design, the number of animals used, their diet, the differences in Candida strains, and the duration of the studies. These variables notwithstanding, the following could be concluded. (i) The primate model is ideal for investigating Candida-associated denture stomatitis since both erythematous and pseudomembranous lesions have been produced in monkeys with prosthetic plates; they are, however, expensive and difficult to obtain and maintain. (ii) The rat model (both Sprague-Dawley and Wistar) is well proven for observing chronic oral candidal colonization and infection, due to the ease of breeding and handling and their ready availability. (iii) Mice are similar, but in addition there are well characterized variants simulating immunologic and genetic abnormalities (e.g., athymic, euthymic, murine-acquired immune deficiency syndrome, and severe combined immunodeficient models) and hence are used for short-term studies relating the host immune response and oral candidiasis. Nonetheless, an ideal, relatively inexpensive model representative of the human oral environment in ecological and microbiological terms is yet to be described. Until such a model is developed, researchers should pay attention to standardization of the experimental protocols described here to obtain broadly comparable and meaningful data. PMID:11292645

  9. Experimental models of chronic subdural hematoma.

    Science.gov (United States)

    D'Abbondanza, Josephine A; Loch Macdonald, R

    2014-02-01

    Chronic subdural hematoma (CSDH) is a common neurosurgical problem. Most studies of pathogenesis and treatment involve humans. Advances in understanding of human diseases may be made using animal models. We reviewed all animal models of CSDH and report here their results, conclusions and limitations in order to set a baseline upon which further advanced experimental work related to this disease can be made. PubMed, Medline, Embase and ISI Web of Knowledge were searched with no time limits using the keyword 'chronic subdural hematoma' and MeSH term 'hematoma, subdural, chronic'. The authors reviewed all papers written related to this disease and selected all publications involving animals. There were no other restrictions. The findings and conclusions of the papers are summarized here. No formal analysis was done because of the variation in species used, methods for induction of CSDH, times of assessment and reporting of results. Attempts to create CSDH have been made in mice, rats, cats, dogs and monkeys. Methods include injection or surgical implantation of clotted blood or various other blood products and mixtures into the potential subdural space or the subcutaneous space. No intracranial model produced a progressively expanding CSDH. Transient hematoma expansion with liquification could be produced by subcutaneous injections in some models. Spontaneous subdural blood collections were found after creation of hydrocephalus in mice by systemic injection of the neurotoxin, 6-aminonicotinamide. The histology of the hematoma membranes in several models resembles the appearance in humans. None of the models has been replicated since its first description. We did not find a report of a reproducible, well-described animal model of human CSDH.

  10. Experimental and theoretical requirements for fuel modelling

    International Nuclear Information System (INIS)

    Gatesoupe, J.P.

    1979-01-01

    From a scientific point of view it may be considered that any event in the life of a fuel pin under irradiation should be perfectly well understood and foreseen from that deterministic point of view, the whole behaviour of the pin maybe analysed and dismantled with a specific function for every component part and each component part related to one basic phenomenon which can be independently studied on pure physical grounds. When extracted from the code structure the subroutine is studied for itself by specialists who try to keep as close as possible to the physics involved in the phenomenon; that often leads to an impressive luxury in details and a subsequent need for many unavailable input data. It might seem more secure to follow that approach since it tries to be firmly based on theoretical grounds. One should think so if the phenomenological situation in the pin were less complex than it is. The codes would not be adequate for off-normal operating conditions since for the accidental transient conditions the key-phenomena would not be the same as for steady-state or slow transient conditions. The orientation given to fuel modelling is based on our two main technological constraints which are: no fuel melting; no cladding failure; no excessive cladding deformation. In this context, the only relevant models are those which have a significant influence on the maximum temperatures in the fuel or on the cladding damage hence the selection between key models and irrelevant models which will next be done. A rather pragmatic view is kept on codification with a special focus on a few determinant aspects of fuel behaviour and no attention to models which are nothing but decorative. Fuel modeling is merely considered as a link between experimental knowledge; it serves as a guide for further improvements in fuel design and as so happens to be quite useful. On this basis the main lacks in of fuel behaviour is described. These are mainly concerning: thermal transfer through

  11. Experimental study and modelling of transient boiling

    International Nuclear Information System (INIS)

    Baudin, Nicolas

    2015-01-01

    A failure in the control system of the power of a nuclear reactor can lead to a Reactivity Initiated Accident in a nuclear power plant. Then, a power peak occurs in some fuel rods, high enough to lead to the coolant film boiling. It leads to an important increase of the temperature of the rod. The possible risk of the clad failure is a matter of interest for the Institut de Radioprotection et de Securite Nucleaire. The transient boiling heat transfer is not yet understood and modelled. An experimental set-up has been built at the Institut de Mecanique des Fluides de Toulouse (IMFT). Subcooled HFE-7000 flows vertically upward in a semi annulus test section. The inner half cylinder simulates the clad and is made of a stainless steel foil, heated by Joule effect. Its temperature is measured by an infrared camera, coupled with a high speed camera for the visualization of the flow topology. The whole boiling curve is studied in steady state and transient regimes: convection, onset of boiling, nucleate boiling, critical heat flux, film boiling and rewetting. The steady state heat transfers are well modelled by literature correlations. Models are suggested for the transient heat flux: the convection and nucleate boiling evolutions are self-similar during a power step. This observation allows to model more complex evolutions, as temperature ramps. The transient Hsu model well represents the onset of nucleate boiling. When the intensity of the power step increases, the film boiling begins at the same temperature but with an increasing heat flux. For power ramps, the critical heat flux decreases while the corresponding temperature increases with the heating rate. When the wall is heated, the film boiling heat transfer is higher than in steady state but it is not understood. A two-fluid model well simulates the cooling film boiling and the rewetting. (author)

  12. Radiologic findings of neonatal sepsis

    International Nuclear Information System (INIS)

    Kim, Sam Soo; Han, Dae Hee; Choi, Guk Myeong; Jung, Hye Won; Yoon, Hye Kyung; Han, Bokyung Kim; Lee, Nam Yong

    1997-01-01

    To review the simple radiographic and sonographic findings in infants with neonatal sepsis. We retrospectively analyzed simple chest and abdominal radiographs, and brain sonograms in 36 newborn infants (preterm : term=23 :13). With neonatal sepsis diagnosed by blood culture and clinical manifestations. Pulmonary parenchymal infiltrate excluding respiratory distress syndrome and pulmonary edema or atelectasis was found in 22 infants (61%). Paralytic ileus, hepatosplenomegaly, and necrotizing enterocolitis were present in 18(50%), 9(25%), and 1(3%) infants, respectively, while skeletal changes suggesting osteomyelitis were found in three. Brain sonography was performed in 29 infants and in four, abnormalities were seen ; these comprised three germinal matrix hemorrhages and one intraparenchymal hemorrhage. In six patients(17%) radiologic examinations revealed no abnormality. In patients with neonatal sepsis, pulmonary infiltrates and paralytic ileus were common abnormalities. Although these were nonspecific, radiologic findings may be used to supplement clinical and laboratory findings in diagnosing neonatal sepsis and planning its treatment

  13. Radiologic findings of neonatal sepsis

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sam Soo; Han, Dae Hee; Choi, Guk Myeong; Jung, Hye Won [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of); Yoon, Hye Kyung; Han, Bokyung Kim; Lee, Nam Yong [Sansung Medical Center, Seoul (Korea, Republic of)

    1997-06-01

    To review the simple radiographic and sonographic findings in infants with neonatal sepsis. We retrospectively analyzed simple chest and abdominal radiographs, and brain sonograms in 36 newborn infants (preterm : term=23 :13). With neonatal sepsis diagnosed by blood culture and clinical manifestations. Pulmonary parenchymal infiltrate excluding respiratory distress syndrome and pulmonary edema or atelectasis was found in 22 infants (61%). Paralytic ileus, hepatosplenomegaly, and necrotizing enterocolitis were present in 18(50%), 9(25%), and 1(3%) infants, respectively, while skeletal changes suggesting osteomyelitis were found in three. Brain sonography was performed in 29 infants and in four, abnormalities were seen ; these comprised three germinal matrix hemorrhages and one intraparenchymal hemorrhage. In six patients(17%) radiologic examinations revealed no abnormality. In patients with neonatal sepsis, pulmonary infiltrates and paralytic ileus were common abnormalities. Although these were nonspecific, radiologic findings may be used to supplement clinical and laboratory findings in diagnosing neonatal sepsis and planning its treatment.

  14. Prognostic Implications of Serum Lipid Metabolism over Time during Sepsis

    Directory of Open Access Journals (Sweden)

    Sang Hoon Lee

    2015-01-01

    Full Text Available Background. Despite extensive research and an improved standard of care, sepsis remains a disorder with a high mortality rate. Sepsis is accompanied by severe metabolic alterations. Methods. We evaluated 117 patients with sepsis (severe sepsis [n=19] and septic shock [n=98] who were admitted to the intensive care unit. Serum cholesterol, triglyceride (TG, high-density lipoprotein (HDL, low-density lipoprotein (LDL, free fatty acid (FFA, and apolipoprotein (Apo A-I levels were measured on days 0, 1, 3, and 7. Results. Nonsurvivors had low levels of cholesterol, TG, HDL, LDL, and Apo A-I on days 0, 1, 3, and 7. In a linear mixed model analysis, the variations in TG, LDL, FFA, and Apo A-I levels over time differed significantly between the groups (p=0.043, p=0.020, p=0.005, and p=0.015, resp.. According to multivariate analysis, TG levels and SOFA scores were associated with mortality on days 0 and 1 (p=0.018 and p=0.008, resp.. Conclusions. Our study illustrated that TG levels are associated with mortality in patients with sepsis. This may be attributable to alterations in serum lipid metabolism during sepsis, thus modulating the host response to inflammation in critically ill patients.

  15. Experimental models of autoimmune inflammatory ocular diseases

    Directory of Open Access Journals (Sweden)

    Fabio Gasparin

    2012-04-01

    Full Text Available Ocular inflammation is one of the leading causes of blindness and loss of vision. Human uveitis is a complex and heterogeneous group of diseases characterized by inflammation of intraocular tissues. The eye may be the only organ involved, or uveitis may be part of a systemic disease. A significant number of cases are of unknown etiology and are labeled idiopathic. Animal models have been developed to the study of the physiopathogenesis of autoimmune uveitis due to the difficulty in obtaining human eye inflamed tissues for experiments. Most of those models are induced by injection of specific photoreceptors proteins (e.g., S-antigen, interphotoreceptor retinoid-binding protein, rhodopsin, recoverin, phosducin. Non-retinal antigens, including melanin-associated proteins and myelin basic protein, are also good inducers of uveitis in animals. Understanding the basic mechanisms and pathogenesis of autoimmune ocular diseases are essential for the development of new treatment approaches and therapeutic agents. The present review describes the main experimental models of autoimmune ocular inflammatory diseases.

  16. Modeling a nuclear reactor for experimental purposes

    International Nuclear Information System (INIS)

    Berta, V.T.

    1980-01-01

    The Loss-of-Fluid Test (LOFT) Facility is a scale model of a commercial PWR and is as fully functional and operational as the generic commercial counterpart. LOFT was designed and built for experimental purposes as part of the overall NRC reactor safety research program. The purpose of LOFT is to assess the capability of reactor safety systems to perform their intended functions during occurrences of off-normal conditions in a commercial nuclear reactor. Off-normal conditions arising from large and small break loss-of-coolant accidents (LOCA), operational transients, and anticipated transients without scram (ATWS) were to be investigated. This paper describes the LOFT model of the generic PWR and summarizes the experiments that have been conducted in the context of the significant findings involving the complex transient thermal-hydraulics and the consequent effects on the commercial reactor analytical licensing techniques. Through these techniques the validity of the LOFT model as a scaled counterpart of the generic PWR is shown

  17. Aspectos histomorfológicos e respiratórios em modelo de lesão pulmonar aguda por sepse em ratos tratados com pentoxifilina Histomorphologic and respiratory aspects of acute lung injury in rats induced by experimental sepsis and under pentoxifylline treatment

    Directory of Open Access Journals (Sweden)

    Wagner Rogerio Souza de Oliveira

    2009-01-01

    Full Text Available OBJETIVO: Analisar as alterações histomorfológicas e respiratórias em modelo de lesão pulmonar aguda por sepse em ratos tratados com pentoxifilina. MÉTODOS: Foram utilizados 15 ratos adultos distribuídos em três grupos (n=5, por grupo, assim constituídos: GC - receberam apenas ventilação mecânica; GS - Animais sépticos tratados com solução salina e mecanicamente ventilados; GS+PTX - Animais sépticos, com infusão de pentoxifilina e mecanicamente ventilados. Todos os animais foram ventilados por um período de 180 minutos. Ao final deste período, foram avaliadas variáveis gasométricas (gasometria arterial, gravimétricas (relação peso úmido/peso seco, concentração de proteínas totais no lavado broncoalveolar e histomorfométricas (espessura dos septos alveolares. Os dados obtidos foram submetidos a análise estatística (P OBJECTIVE: Respiratory repercussion on acute lung injury in a model of induced sepsis intraperitoneally. METHODS: Fifteen animals taken at random were submitted to adult male Wistar rats. The rats were randomly divided into 3 groups (n=15: Group C - control group received only mechanical ventilation; Group S - rats received live Escherichia coli (E. coli intraperitoneally (septic and after 6 hours they were treated with normal saline infusion and ventilated with a low tidal volume. Group S+PTX - rats received live Escherichia coli intraperitoneally (septic and after 6 hours they were treated with pentoxifylline (PTX infusion and ventilated with a low tidal volume. All animals were ventilated during 180 minutes. We analyzed the arterial blood gases, gravimetric indices and histomorphometric analysis. RESULTS: Blood gases, wet to dry ratios, and total protein concentrations in the bronchoalveolar lavage were analyzed in all experimental groups. In the end of the experiment the partial pressure of oxygen was higher in the GS+PTX (460,0 ± 38,2 mmHg compared with GS (336,0 ± 14,6 mmHg. Pentoxifylline with

  18. Experimental models for Murray’s law

    Science.gov (United States)

    Akita, Dai; Kunita, Itsuki; Fricker, Mark D.; Kuroda, Shigeru; Sato, Katsuhiko; Nakagaki, Toshiyuki

    2017-01-01

    Transport networks are ubiquitous in multicellular organisms and include leaf veins, fungal mycelia and blood vessels. While transport of materials and signals through the network plays a crucial role in maintaining the living system, the transport capacity of the network can best be understood in terms of hydrodynamics. We report here that plasmodium from the large, single-celled amoeboid Physarum was able to construct a hydrodynamically optimized vein-network when evacuating biomass from confined arenas of various shapes through a narrow exit. Increasingly thick veins developed towards the exit, and the network spanned the arena via repetitive bifurcations to give a branching tree. The Hausdorff distance from all parts of the plasmodium to the vein network was kept low, whilst the hydrodynamic conductivity from distal parts of the network to the exit was equivalent, irrespective of the arena shape. This combination of spatial patterning and differential vein thickening served to evacuate biomass at an equivalent rate across the entire arena. The scaling relationship at the vein branches was determined experimentally to be 2.53-3.29, consistent with predictions from Murray’s law. Furthermore, we show that mathematical models for self-organised, adaptive transport in Physarum simulate the experimental network organisation well if the scaling coefficient of the current-reinforcement rule is set to 3. In simulations, this resulted in rapid development of an optimal network that minimised the combined volume and frictional energy in comparison with other scaling coefficients. This would predict that the boundary shear forces within each vein are constant throughout the network, and would be consistent with a feedback mechanism based on a sensing a threshold shear at the vein wall.

  19. Experimental models for Murray’s law

    International Nuclear Information System (INIS)

    Akita, Dai; Kunita, Itsuki; Fricker, Mark D; Kuroda, Shigeru; Sato, Katsuhiko; Nakagaki, Toshiyuki

    2017-01-01

    Transport networks are ubiquitous in multicellular organisms and include leaf veins, fungal mycelia and blood vessels. While transport of materials and signals through the network plays a crucial role in maintaining the living system, the transport capacity of the network can best be understood in terms of hydrodynamics. We report here that plasmodium from the large, single-celled amoeboid Physarum was able to construct a hydrodynamically optimized vein-network when evacuating biomass from confined arenas of various shapes through a narrow exit. Increasingly thick veins developed towards the exit, and the network spanned the arena via repetitive bifurcations to give a branching tree. The Hausdorff distance from all parts of the plasmodium to the vein network was kept low, whilst the hydrodynamic conductivity from distal parts of the network to the exit was equivalent, irrespective of the arena shape. This combination of spatial patterning and differential vein thickening served to evacuate biomass at an equivalent rate across the entire arena. The scaling relationship at the vein branches was determined experimentally to be 2.53–3.29, consistent with predictions from Murray’s law. Furthermore, we show that mathematical models for self-organised, adaptive transport in Physarum simulate the experimental network organisation well if the scaling coefficient of the current-reinforcement rule is set to 3. In simulations, this resulted in rapid development of an optimal network that minimised the combined volume and frictional energy in comparison with other scaling coefficients. This would predict that the boundary shear forces within each vein are constant throughout the network, and would be consistent with a feedback mechanism based on a sensing a threshold shear at the vein wall. (paper)

  20. [Nutritional support in sepsis].

    Science.gov (United States)

    Ortiz Leyba, C; López Martínez, J; Blesa Malpica, A L

    2005-06-01

    Although it is considered that metabolic and nutritional support must be part of the management of septic patients, it has not been conclusively shown that nutritional support will improve survival or complications from sepsis. Specific data on this issue are scarce since there are few studies that have investigated specialized nutritional support in septic patients. Thus, most of the recommendations are based on outcomes obtained in severely ill patients with different pathologies. It is assumed that nutritional support should be carried out through the enteral route whenever possible, as in other critically ill patients. The energetic waste in these patients is highly variable, although in general terms the hypermetabolic situation may be classified as moderate. An adjustment factor of 1.25-1.30 is recommended for the Harris-Benedict's equation to calculate the caloric intake. Septic patients should receive a hyperproteic intake. The amount of glucose administered should not exceed 70% of non-protein calories, and lipids intake should not exceed 40%. With regards to micronutrients, it is recommended to increase the supply of those with antioxidant properties (vitamin E, carotenes, vitamin C, selenium). There are data to consider that the use of diets enriched with pharmaco-nutrients (both with parenteral and enteral routes) may be beneficial in septic patients, although there is some controversy when interpreting the outcomes.

  1. Standard Model theory calculations and experimental tests

    International Nuclear Information System (INIS)

    Cacciari, M.; Hamel de Monchenault, G.

    2015-01-01

    To present knowledge, all the physics at the Large Hadron Collider (LHC) can be described in the framework of the Standard Model (SM) of particle physics. Indeed the newly discovered Higgs boson with a mass close to 125 GeV seems to confirm the predictions of the SM. Thus, besides looking for direct manifestations of the physics beyond the SM, one of the primary missions of the LHC is to perform ever more stringent tests of the SM. This requires not only improved theoretical developments to produce testable predictions and provide experiments with reliable event generators, but also sophisticated analyses techniques to overcome the formidable experimental environment of the LHC and perform precision measurements. In the first section, we describe the state of the art of the theoretical tools and event generators that are used to provide predictions for the production cross sections of the processes of interest. In section 2, inclusive cross section measurements with jets, leptons and vector bosons are presented. Examples of differential cross sections, charge asymmetries and the study of lepton pairs are proposed in section 3. Finally, in section 4, we report studies on the multiple production of gauge bosons and constraints on anomalous gauge couplings

  2. IVIM: modeling, experimental validation and application to animal models

    International Nuclear Information System (INIS)

    Fournet, Gabrielle

    2016-01-01

    This PhD thesis is centered on the study of the IVIM ('Intravoxel Incoherent Motion') MRI sequence. This sequence allows for the study of the blood microvasculature such as the capillaries, arterioles and venules. To be sensitive only to moving groups of spins, diffusion gradients are added before and after the 180 degrees pulse of a spin echo (SE) sequence. The signal component corresponding to spins diffusing in the tissue can be separated from the one related to spins travelling in the blood vessels which is called the IVIM signal. These two components are weighted by f IVIM which represents the volume fraction of blood inside the tissue. The IVIM signal is usually modelled by a mono-exponential (ME) function and characterized by a pseudo-diffusion coefficient, D*. We propose instead a bi-exponential IVIM model consisting of a slow pool, characterized by F slow and D* slow corresponding to the capillaries as in the ME model, and a fast pool, characterized by F fast and D* fast, related to larger vessels such as medium-size arterioles and venules. This model was validated experimentally and more information was retrieved by comparing the experimental signals to a dictionary of simulated IVIM signals. The influence of the pulse sequence, the repetition time and the diffusion encoding time was also studied. Finally, the IVIM sequence was applied to the study of an animal model of Alzheimer's disease. (author) [fr

  3. Immunosuppression after Sepsis: Systemic Inflammation and Sepsis Induce a Loss of Naïve T-Cells but No Enduring Cell-Autonomous Defects in T-Cell Function

    Science.gov (United States)

    Markwart, Robby; Condotta, Stephanie A.; Requardt, Robert P.; Borken, Farina; Schubert, Katja; Weigel, Cynthia; Bauer, Michael; Griffith, Thomas S.; Förster, Martin; Brunkhorst, Frank M.; Badovinac, Vladimir P.; Rubio, Ignacio

    2014-01-01

    Sepsis describes the life-threatening systemic inflammatory response (SIRS) of an organism to an infection and is the leading cause of mortality on intensive care units (ICU) worldwide. An acute episode of sepsis is characterized by the extensive release of cytokines and other mediators resulting in a dysregulated immune response leading to organ damage and/or death. This initial pro-inflammatory burst often transits into a state of immune suppression characterised by loss of immune cells and T-cell dysfunction at later disease stages in sepsis survivors. However, despite these appreciations, the precise nature of the evoked defect in T-cell immunity in post-acute phases of SIRS remains unknown. Here we present an in-depth functional analysis of T-cell function in post-acute SIRS/sepsis. We document that T-cell function is not compromised on a per cell basis in experimental rodent models of infection-free SIRS (LPS or CpG) or septic peritonitis. Transgenic antigen-specific T-cells feature an unaltered cytokine response if challenged in vivo and ex vivo with cognate antigens. Isolated CD4+/CD8+ T-cells from post-acute septic animals do not exhibit defects in T-cell receptor-mediated activation at the the level of receptor-proximal signalling, activation marker upregulation or expansion. However, SIRS/sepsis induced transient lymphopenia and gave rise to an environment of immune attenuation at post acute disease stages. Thus, systemic inflammation has an acute impact on T-cell numbers and adaptive immunity, but does not cause major cell-autonomous enduring functional defects in T-cells. PMID:25541945

  4. Multi-analytical Approaches Informing the Risk of Sepsis

    Science.gov (United States)

    Gwadry-Sridhar, Femida; Lewden, Benoit; Mequanint, Selam; Bauer, Michael

    Sepsis is a significant cause of mortality and morbidity and is often associated with increased hospital resource utilization, prolonged intensive care unit (ICU) and hospital stay. The economic burden associated with sepsis is huge. With advances in medicine, there are now aggressive goal oriented treatments that can be used to help these patients. If we were able to predict which patients may be at risk for sepsis we could start treatment early and potentially reduce the risk of mortality and morbidity. Analytic methods currently used in clinical research to determine the risk of a patient developing sepsis may be further enhanced by using multi-modal analytic methods that together could be used to provide greater precision. Researchers commonly use univariate and multivariate regressions to develop predictive models. We hypothesized that such models could be enhanced by using multiple analytic methods that together could be used to provide greater insight. In this paper, we analyze data about patients with and without sepsis using a decision tree approach and a cluster analysis approach. A comparison with a regression approach shows strong similarity among variables identified, though not an exact match. We compare the variables identified by the different approaches and draw conclusions about the respective predictive capabilities,while considering their clinical significance.

  5. Biomass thermochemical gasification: Experimental studies and modeling

    Science.gov (United States)

    Kumar, Ajay

    The overall goals of this research were to study the biomass thermochemical gasification using experimental and modeling techniques, and to evaluate the cost of industrial gas production and combined heat and power generation. This dissertation includes an extensive review of progresses in biomass thermochemical gasification. Product gases from biomass gasification can be converted to biopower, biofuels and chemicals. However, for its viable commercial applications, the study summarizes the technical challenges in the gasification and downstream processing of product gas. Corn stover and dried distillers grains with solubles (DDGS), a non-fermentable byproduct of ethanol production, were used as the biomass feedstocks. One of the objectives was to determine selected physical and chemical properties of corn stover related to thermochemical conversion. The parameters of the reaction kinetics for weight loss were obtained. The next objective was to investigate the effects of temperature, steam to biomass ratio and equivalence ratio on gas composition and efficiencies. DDGS gasification was performed on a lab-scale fluidized-bed gasifier with steam and air as fluidizing and oxidizing agents. Increasing the temperature resulted in increases in hydrogen and methane contents and efficiencies. A model was developed to simulate the performance of a lab-scale gasifier using Aspen Plus(TM) software. Mass balance, energy balance and minimization of Gibbs free energy were applied for the gasification to determine the product gas composition. The final objective was to optimize the process by maximizing the net energy efficiency, and to estimate the cost of industrial gas, and combined heat and power (CHP) at a biomass feedrate of 2000 kg/h. The selling price of gas was estimated to be 11.49/GJ for corn stover, and 13.08/GJ for DDGS. For CHP generation, the electrical and net efficiencies were 37 and 86%, respectively for corn stover, and 34 and 78%, respectively for DDGS. For

  6. An Endotoxin Tolerance Signature Predicts Sepsis and Organ Dysfunction at Initial Clinical Presentation

    Directory of Open Access Journals (Sweden)

    Olga M. Pena

    2014-11-01

    Interpretation: Our data support an updated model of sepsis pathogenesis in which endotoxin tolerance-mediated immune dysfunction (cellular reprogramming is present throughout the clinical course of disease and related to disease severity. Thus endotoxin tolerance might offer new insights guiding the development of new therapies and diagnostics for early sepsis.

  7. Injury Based on Its Study in Experimental Models

    Directory of Open Access Journals (Sweden)

    M. Mendes-Braz

    2012-01-01

    Full Text Available The present review focuses on the numerous experimental models used to study the complexity of hepatic ischemia/reperfusion (I/R injury. Although experimental models of hepatic I/R injury represent a compromise between the clinical reality and experimental simplification, the clinical transfer of experimental results is problematic because of anatomical and physiological differences and the inevitable simplification of experimental work. In this review, the strengths and limitations of the various models of hepatic I/R are discussed. Several strategies to protect the liver from I/R injury have been developed in animal models and, some of these, might find their way into clinical practice. We also attempt to highlight the fact that the mechanisms responsible for hepatic I/R injury depend on the experimental model used, and therefore the therapeutic strategies also differ according to the model used. Thus, the choice of model must therefore be adapted to the clinical question being answered.

  8. Prospects of experimentally reachable beyond Standard Model ...

    Indian Academy of Sciences (India)

    2016-01-06

    Jan 6, 2016 ... Since then, the theory has been experimentally verified to a ... Despite the fact that SM has unravelled the gauge origin of fundamental forces and the structure of Universe while successfully confronting numerous ...

  9. What?s New in Paediatric Sepsis

    OpenAIRE

    Farrell, Deborah; Nadel, Simon

    2016-01-01

    Severe sepsis and septic shock remains a leading cause of mortality and morbidity in children. There is ongoing uncertainty regarding the optimal treatment pathways however the initial management of sepsis is crucial. This article is designed to be an informal and personal review of recent developments in paediatric sepsis over the past 3?years.

  10. Role of microRNAs in sepsis.

    Science.gov (United States)

    Kingsley, S Manoj Kumar; Bhat, B Vishnu

    2017-07-01

    MicroRNAs have been found to be of high significance in the regulation of various genes and processes in the body. Sepsis is a serious clinical problem which arises due to the excessive host inflammatory response to infection. The non-specific clinical features and delayed diagnosis of sepsis has been a matter of concern for long time. MicroRNAs could enable better diagnosis of sepsis and help in the identification of the various stages of sepsis. Improved diagnosis may enable quicker and more effective treatment measures. The initial acute and transient phase of sepsis involves excessive secretion of pro-inflammatory cytokines which causes severe damage. MicroRNAs negatively regulate the toll-like receptor signaling pathway and regulate the production of inflammatory cytokines during sepsis. Likewise, microRNAs have shown to regulate the vascular barrier and endothelial function in sepsis. They are also involved in the regulation of the apoptosis, immunosuppression, and organ dysfunction in later stages of sepsis. Their importance at various levels of the pathophysiology of sepsis has been discussed along with the challenges and future perspectives. MicroRNAs could be key players in the diagnosis and staging of sepsis. Their regulation at various stages of sepsis suggests that they may have an important role in altering the outcome associated with sepsis.

  11. Endothelial Progenitor Cell Mobilization in Preterm Infants With Sepsis Is Associated With Improved Survival.

    Science.gov (United States)

    Siavashi, Vahid; Asadian, Simin; Taheri-Asl, Masoud; Keshavarz, Samaneh; Zamani-Ahmadmahmudi, Mohamad; Nassiri, Seyed Mahdi

    2017-10-01

    Microvascular dysfunction plays a key role in the pathology of sepsis, leading to multi-organ failure, and death. Circulating endothelial progenitor cells (cEPCs) are critically involved in the maintenance of the vascular homeostasis in both physiological and pathological contexts. In this study, concentration of cEPCs in preterm infants with sepsis was determined to recognize whether the EPC mobilization would affect the clinical outcome of infantile sepsis. One hundred and thirty-three preterm infants (81 with sepsis and 52 without sepsis) were enrolled in this study. The release of EPCs in circulation was first quantified. Thereafter, these cells were cultivated and biological features of these cells such as, proliferation and colony forming efficiency were analyzed. The levels of chemoattractant cytokines were also measured in infants. In mouse models of sepsis, effects of VEGF and SDF-1 as well as anti-VEGF and anti-SDF-1 were evaluated in order to shed light upon the role which the EPC mobilization plays in the overall survival of septic animals. Circulating EPCs were significantly higher in preterm infants with sepsis than in the non-sepsis group. Serum levels of VEGF, SDF-1, and Angiopoietin-2 were also higher in preterm infants with sepsis than in control non-sepsis. In the animal experiments, injection of VEGF and SDF-1 prompted the mobilization of EPCs, leading to an improvement in survival whereas injection of anti-VEGF and anti-SDF-1 was associated with significant deterioration of survival. Overall, our results demonstrated the beneficial effects of EPC release in preterm infants with sepsis, with increased mobilization of these cells was associated with improved survival. J. Cell. Biochem. 118: 3299-3307, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  12. The podoplanin-CLEC-2 axis inhibits inflammation in sepsis.

    Science.gov (United States)

    Rayes, Julie; Lax, Siân; Wichaiyo, Surasak; Watson, Stephanie K; Di, Ying; Lombard, Stephanie; Grygielska, Beata; Smith, Stuart W; Skordilis, Kassiani; Watson, Steve P

    2017-12-21

    Platelets play a critical role in vascular inflammation through the podoplanin and collagen/fibrin receptors, C-type-lectin-like-2 (CLEC-2) and glycoprotein VI (GPVI), respectively. Both receptors regulate endothelial permeability and prevent peri-vascular bleeding in inflammation. Here we show that platelet-specific deletion of CLEC-2 but not GPVI leads to enhanced systemic inflammation and accelerated organ injury in two mouse models of sepsis-intra-peritoneal lipopolysaccharide and cecal ligation and puncture. CLEC-2 deficiency is associated with reduced numbers of podoplanin-expressing macrophages despite increased cytokine and chemokine levels in the infected peritoneum. Pharmacological inhibition of the interaction between CLEC-2 and podoplanin regulates immune cell infiltration and the inflammatory reaction during sepsis, suggesting that activation of podoplanin underlies the anti-inflammatory action of platelet CLEC-2. We suggest podoplanin-CLEC-2 as a novel anti-inflammatory axis regulating immune cell recruitment and activation in sepsis.

  13. The epidemiology of sepsis in Brazilian intensive care units (the Sepsis PREvalence Assessment Database, SPREAD): an observational study.

    Science.gov (United States)

    Machado, Flavia R; Cavalcanti, Alexandre Biasi; Bozza, Fernando Augusto; Ferreira, Elaine M; Angotti Carrara, Fernanda Sousa; Sousa, Juliana Lubarino; Caixeta, Noemi; Salomao, Reinaldo; Angus, Derek C; Pontes Azevedo, Luciano Cesar

    2017-11-01

    The sepsis burden on acute care services in middle-income countries is a cause for concern. We estimated incidence, prevalence, and mortality of sepsis in adult Brazilian intensive care units (ICUs) and association of ICU organisational factors with outcome. We did a 1-day point prevalence study with follow-up of patients in ICU with sepsis in a nationally representative pseudo-random sample. We produced a sampling frame initially stratified by geographical region. Each stratum was then stratified by hospitals' main source of income (serving general public vs privately insured individuals) and ICU size (ten or fewer beds vs more than ten beds), finally generating 40 strata. In each stratum we selected a random sample of ICUs so as to enrol the total required beds in 1690 Brazilian adult ICUs. We followed up patients until hospital discharge censored at 60 days, estimated incidence from prevalence and length of stay, and generated national estimates. We assessed mortality prognostic factors using random-effects logistic regression models. On Feb 27, 2014, 227 (72%) of 317 ICUs that were randomly selected provided data on 2632 patients, of whom 794 had sepsis (30·2 septic patients per 100 ICU beds, 95% CI 28·4-31·9). The ICU sepsis incidence was 36·3 per 1000 patient-days (95% CI 29·8-44·0) and mortality was observed in 439 (55·7%) of 788 patients (95% CI 52·2-59·2). Low availability of resources (odds ratio [OR] 1·67, 95% CI 1·02-2·75, p=0·045) and adequacy of treatment (OR 0·56, 0·37-0·84, p=0·006) were independently associated with mortality. The projected incidence rate is 290 per 100 000 population (95% CI 237·9-351·2) of adult cases of ICU-treated sepsis per year, which yields about 420 000 cases annually, of whom 230 000 die in hospital. The incidence, prevalence, and mortality of ICU-treated sepsis is high in Brazil. Outcome varies considerably, and is associated with access to adequate resources and treatment. Our results show the

  14. T-cell proliferative responses following sepsis in neonatal rats.

    Science.gov (United States)

    Dallal, Ousama; Ravindranath, Thyyar M; Choudhry, Mashkoor A; Kohn, Annamarie; Muraskas, Jonathan K; Namak, Shahla Y; Alattar, Mohammad H; Sayeed, Mohammed M

    2003-01-01

    Both experimental and clinical evidence suggest a suppression of T-cell function in burn and sepsis. The objective of the present study was to evaluate splenocyte and purified T-cell proliferative response and IL-2 production in septic neonatal rats. We also examined if alterations in T-cell proliferation and IL-2 production in neonatal sepsis is due to elevation in PGE2. PGE2 is known to play a significant role in T-cell suppression during sepsis in adults. Sepsis was induced in 15-day-old neonatal Sprague-Dawley rats by implanting 0.1 cm3 of fecal pellet impregnated with Escherichia coli (50 CFU) and Bacteroides fragilis (10(3) CFU). Animals receiving fecal pellets without the bacteria were designated as sterile. A group of septic and sterile rats were treated with PGE2 synthesis inhibitors, NS398 and resveratrol. These treatments of animals allowed us to evaluate the role of PGE2 in T-cell suppression during neonatal sepsis. Splenocytes as well as purified T cells were prepared and then proliferative response and IL-2 productive capacities were measured. A significant suppression of splenocyte proliferation and IL-2 production was noticed in both sterile and septic animals compared to the T cells from unoperated control rats. In contrast, the proliferation and IL-2 production by nylon wool purified T cells in sterile rats was not significantly different from control rats, whereas, a significant suppression in Con A-mediated T-cell proliferation and IL-2 production noticed in septic rat T cells compared to the sterile and control rat T cells. Such decrease in T-cell proliferation and IL-2 production was accompanied with 20-25% deaths in neonates implanted with septic pellets. No mortality was noted in sterile-implanted neonates. Treatment of animals with COX-1 inhibitor had no effect on T-cell proliferation response in both septic and sterile groups, whereas COX-2 inhibitor abrogated the decrease in T-cell proliferative response in the septic group. The treatment

  15. Toxin Mediates Sepsis Caused by Methicillin-Resistant Staphylococcus epidermidis.

    Directory of Open Access Journals (Sweden)

    Li Qin

    2017-02-01

    Full Text Available Bacterial sepsis is a major killer in hospitalized patients. Coagulase-negative staphylococci (CNS with the leading species Staphylococcus epidermidis are the most frequent causes of nosocomial sepsis, with most infectious isolates being methicillin-resistant. However, which bacterial factors underlie the pathogenesis of CNS sepsis is unknown. While it has been commonly believed that invariant structures on the surface of CNS trigger sepsis by causing an over-reaction of the immune system, we show here that sepsis caused by methicillin-resistant S. epidermidis is to a large extent mediated by the methicillin resistance island-encoded peptide toxin, PSM-mec. PSM-mec contributed to bacterial survival in whole human blood and resistance to neutrophil-mediated killing, and caused significantly increased mortality and cytokine expression in a mouse sepsis model. Furthermore, we show that the PSM-mec peptide itself, rather than the regulatory RNA in which its gene is embedded, is responsible for the observed virulence phenotype. This finding is of particular importance given the contrasting roles of the psm-mec locus that have been reported in S. aureus strains, inasmuch as our findings suggest that the psm-mec locus may exert effects in the background of S. aureus strains that differ from its original role in the CNS environment due to originally "unintended" interferences. Notably, while toxins have never been clearly implied in CNS infections, our tissue culture and mouse infection model data indicate that an important type of infection caused by the predominant CNS species is mediated to a large extent by a toxin. These findings suggest that CNS infections may be amenable to virulence-targeted drug development approaches.

  16. Models of experimental saccular aneurysms of carotid arteries in canine

    International Nuclear Information System (INIS)

    Zhang Haixia; Cheng Yingsheng; Li Minghua

    2006-01-01

    Objective: To study the availability by making experimental saccular aneurysm models of carotid arteries in canine similar to human intracranial aneurysms. Methods: Twenty healthy canines with experimental saccular side-wall aneurysms of carotid arteries were created successfully by surgery. Results: Forty experimental saccular side-wall aneurysms of carotid arteries were created successfully with 36 aneurysms and parent arteries maintaining patency with each other and four spontaneously occluded confirmed by angiography. Model successful rate reached 90%. Conclusions: Experimental saccular side-wall aneurysms of carotid arteries in canines were one of best models created for simulating human intracranial aneurysms. (authors)

  17. S1PR3 Signaling Drives Bacterial Killing and Is Required for Survival in Bacterial Sepsis.

    Science.gov (United States)

    Hou, JinChao; Chen, QiXing; Wu, XiaoLiang; Zhao, DongYan; Reuveni, Hadas; Licht, Tamar; Xu, MengLong; Hu, Hu; Hoeft, Andreas; Ben-Sasson, Shmuel A; Shu, Qiang; Fang, XiangMing

    2017-12-15

    Efficient elimination of pathogenic bacteria is a critical determinant in the outcome of sepsis. Sphingosine-1-phosphate receptor 3 (S1PR3) mediates multiple aspects of the inflammatory response during sepsis, but whether S1PR3 signaling is necessary for eliminating the invading pathogens remains unknown. To investigate the role of S1PR3 in antibacterial immunity during sepsis. Loss- and gain-of-function experiments were performed using cell and murine models. S1PR3 levels were determined in patients with sepsis and healthy volunteers. S1PR3 protein levels were up-regulated in macrophages upon bacterial stimulation. S1pr3 -/- mice showed increased mortality and increased bacterial burden in multiple models of sepsis. The transfer of wild-type bone marrow-derived macrophages rescued S1pr3 -/- mice from lethal sepsis. S1PR3-overexpressing macrophages further ameliorated the mortality rate of sepsis. Loss of S1PR3 led to markedly decreased bacterial killing in macrophages. Enhancing endogenous S1PR3 activity using a peptide agonist potentiated the macrophage bactericidal function and improved survival rates in multiple models of sepsis. Mechanically, the reactive oxygen species levels were decreased and phagosome maturation was delayed in S1pr3 -/- macrophages due to impaired recruitment of vacuolar protein-sorting 34 to the phagosomes. In addition, S1RP3 expression levels were elevated in monocytes from patients with sepsis. Higher levels of monocytic S1PR3 were associated with efficient intracellular bactericidal activity, better immune status, and preferable outcomes. S1PR3 signaling drives bacterial killing and is essential for survival in bacterial sepsis. Interventions targeting S1PR3 signaling could have translational implications for manipulating the innate immune response to combat pathogens.

  18. Chronic Alcohol Ingestion Delays T Cell Activation and Effector Function in Sepsis.

    Directory of Open Access Journals (Sweden)

    Lindsay M Margoles

    Full Text Available Sepsis is the leading cause of death in intensive care units in the US, and it is known that chronic alcohol use is associated with higher incidence of sepsis, longer ICU stays, and higher mortality from sepsis. Both sepsis and chronic alcohol use are associated with immune deficits such as decreased lymphocyte numbers, impaired innate immunity, delayed-type hypersensitivity reactions, and susceptibility to infections; however, understanding of specific pathways of interaction or synergy between these two states of immune dysregulation is lacking. This study therefore sought to elucidate mechanisms underlying the immune dysregulation observed during sepsis in the setting of chronic alcohol exposure. Using a murine model of chronic ethanol ingestion followed by sepsis induction via cecal ligation and puncture, we determined that while CD4+ and CD8+ T cells isolated from alcohol fed mice eventually expressed the same cellular activation markers (CD44, CD69, and CD43 and effector molecules (IFN-γ, TNF as their water fed counterparts, there was an overall delay in the acquisition of these phenotypes. This early lag in T cell activation was associated with significantly reduced IL-2 production at a later timepoint in both the CD4+ and CD8+ T cell compartments in alcohol sepsis, as well as with a reduced accumulation of CD8dim activated effectors. Taken together, these data suggest that delayed T cell activation may result in qualitative differences in the immune response to sepsis in the setting of chronic alcohol ingestion.

  19. Chronic Alcohol Ingestion Delays T Cell Activation and Effector Function in Sepsis.

    Science.gov (United States)

    Margoles, Lindsay M; Mittal, Rohit; Klingensmith, Nathan J; Lyons, John D; Liang, Zhe; Serbanescu, Mara A; Wagener, Maylene E; Coopersmith, Craig M; Ford, Mandy L

    2016-01-01

    Sepsis is the leading cause of death in intensive care units in the US, and it is known that chronic alcohol use is associated with higher incidence of sepsis, longer ICU stays, and higher mortality from sepsis. Both sepsis and chronic alcohol use are associated with immune deficits such as decreased lymphocyte numbers, impaired innate immunity, delayed-type hypersensitivity reactions, and susceptibility to infections; however, understanding of specific pathways of interaction or synergy between these two states of immune dysregulation is lacking. This study therefore sought to elucidate mechanisms underlying the immune dysregulation observed during sepsis in the setting of chronic alcohol exposure. Using a murine model of chronic ethanol ingestion followed by sepsis induction via cecal ligation and puncture, we determined that while CD4+ and CD8+ T cells isolated from alcohol fed mice eventually expressed the same cellular activation markers (CD44, CD69, and CD43) and effector molecules (IFN-γ, TNF) as their water fed counterparts, there was an overall delay in the acquisition of these phenotypes. This early lag in T cell activation was associated with significantly reduced IL-2 production at a later timepoint in both the CD4+ and CD8+ T cell compartments in alcohol sepsis, as well as with a reduced accumulation of CD8dim activated effectors. Taken together, these data suggest that delayed T cell activation may result in qualitative differences in the immune response to sepsis in the setting of chronic alcohol ingestion.

  20. Experimental comparison of models for ultrafast impact ionization is silicon

    DEFF Research Database (Denmark)

    Tarekegne, Abebe Tilahun; Iwaszczuk, Krzysztof; Jepsen, Peter Uhd

    2016-01-01

    We compare experimentally the exponential and quadratic (Keldysh formula) impact ionization models using THz induced impact ionization in silicon. We demonstrate that the exponential model offers the best description of impact ionization process for ultrashort electric filed pulses.......We compare experimentally the exponential and quadratic (Keldysh formula) impact ionization models using THz induced impact ionization in silicon. We demonstrate that the exponential model offers the best description of impact ionization process for ultrashort electric filed pulses....

  1. Experimental modeling of swirl flows in power plants

    Science.gov (United States)

    Shtork, S. I.; Litvinov, I. V.; Gesheva, E. S.; Tsoy, M. A.; Skripkin, S. G.

    2018-03-01

    The article presents an overview of the methods and approaches to experimental modeling of various thermal and hydropower units - furnaces of pulverized coal boilers and flow-through elements of hydro turbines. The presented modeling approaches based on a combination of experimentation and rapid prototyping of working parts may be useful in optimizing energy equipment to improve safety and efficiency of industrial energy systems.

  2. Association between interleukin 1 receptor antagonist gene 86-bp VNTR polymorphism and sepsis: a meta-analysis.

    Science.gov (United States)

    Fang, Fang; Pan, Jian; Li, Yiping; Xu, Lixiao; Su, Guanghao; Li, Gang; Wang, Jian

    2015-01-01

    Many studies have focused on the relationship between interleukin 1 receptor antagonist (IL1RN) gene 86-bp VNTR polymorphism and sepsis, but the results remain inconsistent. Thus, a meta-analysis was carried out to derive a more precise estimation of the association between IL1RN 86-bp VNTR polymorphism and risk of sepsis and sepsis-related mortality. Relevant publications were searched in several widely used databases and six eligible studies were included in the meta-analysis. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the association between IL1RN 86-bp VNTR polymorphism and risk of sepsis and sepsis-related mortality. Significant associations between IL1RN 86-bp VNTR polymorphism and sepsis risk were observed in both overall meta-analysis for L2 versus 22 (OR=0.75, 95% CI=0.59-0.94) and severe sepsis subgroup for LL+L2 versus 22 (OR=0.67, 95% CI=0.47-0.93). L stands for long alleles containing three to six repeats; 2 stands for short allele containing two repeats. However, no significant sepsis mortality variation was detected for all genetic models. According to the results of our meta-analysis, the IL1RN 86-bp VNTR polymorphism probably associates with sepsis risk but not with sepsis-related mortality. Copyright © 2014. Published by Elsevier Inc.

  3. Improving the physiological realism of experimental models

    NARCIS (Netherlands)

    Vinnakota, Kalyan C.; Cha, Chae Y.; Rorsman, Patrik; Balaban, Robert S.; La Gerche, Andre; Wade-Martins, Richard; Beard, Daniel A.; Jeneson, Jeroen A. L.

    The Virtual Physiological Human (VPH) project aims to develop integrative, explanatory and predictive computational models (C-Models) as numerical investigational tools to study disease, identify and design effective therapies and provide an in silico platform for drug screening. Ultimately, these

  4. Experimental models of the gut microbiome

    NARCIS (Netherlands)

    Venema, K.; Abbeele, P. van den

    2013-01-01

    The human gut contains a diverse microbiota with large potential to influence health. Given the difficulty to access the main sites of the gut, in vitro models have been developed to dynamically monitor microbial processes at the site of metabolic activity. These models range from simple batch

  5. [An experimental model of transgastric ooforectomy using a porcine model].

    Science.gov (United States)

    Tomulescu, V; Gheorghe, C; Piţigoi, D; Kosa, A; Ciocarlan, M; Pietrăreanu, D; Turcu, F; Copăescu, C; Droc, G; Popescu, H; Grigorescu, B; Stănciulea, O; Herlea, V; Popescu, I

    2010-01-01

    Transabdominal routes for surgery entail general anaesthesia with its inherent risks and complications (prolonged hospital stay, abdominal incisions that may be difficult in obese patients). Minimally invasive procedures require shorter hospitalization, have shorter recovery periods, less postoperative discomfort, and lower morbidity and complications. The purpose of this study was to use a porcine model to determine the feasibility and the safety of organ resection (oophorectomy and tubectomy). 10 Big White pigs between 25-30 kg underwent transgastric ooforectomy. The first 5 cases were performed in a hybrid procedure (laparoscopic-NOTES) in order to have a better control and supervise the maneuvers done by the mobile endoscope and to guide in the abdominal cavity. Adnexectomy was possible in all ten experiments. Full operative time (from starting endoscopy to complete gastrectomy closing) was 180 min to 270 min. The gastric defect closing was the most difficult manoever lasting from 10 min with OTSC clips to 100 using endoloops and clips. The animals have tolerated well the experiments and there have been no remarkable incidents during our 10 experments. In only one case a bleeding from gastotomy required electric coagulation. Transgastric ooforectomy in an experimental model is a procedure that requires advanced laparoscopical and endoscopical skills. Our early results are promissing. Its application in humans needs further confirmation of the method.

  6. Distribution characteristics of liquid sequestration in rats with sepsis

    Directory of Open Access Journals (Sweden)

    Bin LI

    2012-03-01

    Full Text Available Objective To investigate the distribution characteristics of organs with liquid sequestration during fluid resuscitation in rats with sepsis. Methods Fifty male Wistar rats were randomly divided into five groups: control group (n=10, sepsis group (n=10, crystalloid group (n=10, albumin group (n=10, and artificial colloid (HAES group (n=10. The sepsis model was reproduced by cecal ligation and puncture. The mean arterial pressure was monitored with carotid artery intubation. Twelve hours after fluid infusion by micro-infusion pump via the femoral vein, tissues from the heart, liver, lungs, kidney (right, and small intestine were harvested to observe the pathological changes and calculate the tissue water content. Results The water content of every visceral tissue was higher in the sepsis group than in the control group (P < 0.05; the water content in the heart, liver, and lung tissues was higher in the albumin group than in the crystalloid group (P < 0.05. The water content in both albumin and crystalloid groups was higher than that in the sepsis group (P < 0.05. Moreover, the water content in the heart, liver, and lungs in the HAES group was lower than that in the crystalloid and albumin groups (P < 0.05. Cellular injuries were more severe in the heart, liver, and lungs than in the intestine and kidney in the crystalloid group and albumin group under electron-microscope. Conclusion Liquid sequestration exists mainly in the lungs, heart, and liver of rats with sepsis during fluid resuscitation. The phenomenon is less evident in the kidney and small intestine. Artificial colloid can reduce capillary leak with a good volume expansion effect.

  7. Immunomodulatory intervention with Gamma interferon in mice with sepsis.

    Science.gov (United States)

    Wang, Yu; Kong, Bing-Bing; Yang, Wen-Ping; Zhao, Xin; Zhang, Rong

    2017-09-15

    Sepsis-triggered immune paralysis including T-cell dysfunction increase susceptibility to infection. Gamma interferon (IFNg) exert beneficial effects in patients with sepsis. Herein, we speculated that IFNg may attenuate T-cell dysfunction induced by sepsis, although the mechanisms remain elusive. To test this hypothesis, we used a model based on cecal ligation and puncture (CLP) to induce sepsis in mice. Male C57BL/6 mice were pretreated with recombinant human IFNg (0.01μg/g of body weight) before CLP. The immunophenotyping of cell surface receptor expression, and regulatory T cells (CD4+CD25+Foxp3+) were quantified by flow cytometry. Immunohistochemical staining was performed to evaluate the loss of immune effector cells. Formation of IFNg and interleukin 4 (IL-4) in the spleen and plasma levels of TNF-α, IL-6, high-mobility group box 1 (HMGB1) were determined using enzyme-linked immunosorbent assay. IFNg markedly inhibited the reduction in cytokine secretion from lipopolysaccharide (LPS)-stimulated splenocytes. IFNg-treated mices had significantly decreased percentages of programmed cell death 1 (PD-1) receptors, increased the percentages of positive costimulatory receptor CD28 on CD4 T cells expressing. IFNg markedly reduced T-cell apoptosis through upregulating the expression of Bcl-2. CLP-induced formation of regulatory T cells in the spleen was abolished in IFNg -treated mices. Moreover, IFNg treatment reduced plasma levels of TNF-α, IL-6, HMGB1. IFNg can be a powerful regulator of immune function under sepsis conditions. Therefore, targeted immune-enhancement with IFNg may be a valid therapeutic approach in sepsis. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Cooking Potatoes: Experimentation and Mathematical Modeling.

    Science.gov (United States)

    Chen, Xiao Dong

    2002-01-01

    Describes a laboratory activity involving a mathematical model of cooking potatoes that can be solved analytically. Highlights the microstructure aspects of the experiment. Provides the key aspects of the results, detailed background readings, laboratory procedures and data analyses. (MM)

  9. Optimization of experimental human leukemia models (review

    Directory of Open Access Journals (Sweden)

    D. D. Pankov

    2012-01-01

    Full Text Available Actual problem of assessing immunotherapy prospects including antigenpecific cell therapy using animal models was covered in this review.Describe the various groups of currently existing animal models and methods of their creating – from different immunodeficient mice to severalvariants of tumor cells engraftment in them. The review addresses the possibility of tumor stem cells studying using mouse models for the leukemia treatment with adoptive cell therapy including WT1. Also issues of human leukemia cells migration and proliferation in a mice withdifferent immunodeficiency degree are discussed. To assess the potential immunotherapy efficacy comparison of immunodeficient mouse model with clinical situation in oncology patients after chemotherapy is proposed.

  10. Ideal Experimental Rat Models for Liver Diseases

    OpenAIRE

    Lee, Sang Woo; Kim, Sung Hoon; Min, Seon Ok; Kim, Kyung Sik

    2011-01-01

    There are many limitations for conducting liver disease research in human beings due to the high cost and potential ethical issues. For this reason, conducting a study that is difficult to perform in humans using appropriate animal models, can be beneficial in ascertaining the pathological physiology, and in developing new treatment modalities. However, it is difficult to determine the appropriate animal model which is suitable for research purposes, since every patient has different and dive...

  11. Bioinformatical Analysis of Organ-Related (Heart, Brain, Liver, and Kidney and Serum Proteomic Data to Identify Protein Regulation Patterns and Potential Sepsis Biomarkers

    Directory of Open Access Journals (Sweden)

    Andreas Hohn

    2018-01-01

    Full Text Available During the last years, proteomic studies have revealed several interesting findings in experimental sepsis models and septic patients. However, most studies investigated protein alterations only in single organs or in whole blood. To identify possible sepsis biomarkers and to evaluate the relationship between protein alteration in sepsis affected organs and blood, proteomics data from the heart, brain, liver, kidney, and serum were analysed. Using functional network analyses in combination with hierarchical cluster analysis, we found that protein regulation patterns in organ tissues as well as in serum are highly dynamic. In the tissue proteome, the main functions and pathways affected were the oxidoreductive activity, cell energy generation, or metabolism, whereas in the serum proteome, functions were associated with lipoproteins metabolism and, to a minor extent, with coagulation, inflammatory response, and organ regeneration. Proteins from network analyses of organ tissue did not correlate with statistically significantly regulated serum proteins or with predicted proteins of serum functions. In this study, the combination of proteomic network analyses with cluster analyses is introduced as an approach to deal with high-throughput proteomics data to evaluate the dynamics of protein regulation during sepsis.

  12. Ideal Experimental Rat Models for Liver Diseases.

    Science.gov (United States)

    Lee, Sang Woo; Kim, Sung Hoon; Min, Seon Ok; Kim, Kyung Sik

    2011-05-01

    There are many limitations for conducting liver disease research in human beings due to the high cost and potential ethical issues. For this reason, conducting a study that is difficult to perform in humans using appropriate animal models, can be beneficial in ascertaining the pathological physiology, and in developing new treatment modalities. However, it is difficult to determine the appropriate animal model which is suitable for research purposes, since every patient has different and diverse clinical symptoms, adverse reactions, and complications due to the pathological physiology. Also, it is not easy to reproduce identically various clinical situations in animal models. Recently, the Guide for the Care and Use of Laboratory Animals has tightened up the regulations, and therefore it is advisable to select the appropriate animals and decide upon the appropriate quantities through scientific and systemic considerations before conducting animal testing. Therefore, in this review article the authors examined various white rat animal testing models and determined the appropriate usable rat model, and the pros and cons of its application in liver disease research. The authors believe that this review will be beneficial in selecting proper laboratory animals for research purposes.

  13. Experimental Verification of the Transient Model in an Enrichment Circuit

    International Nuclear Information System (INIS)

    Fernandino, Maria; Brasnarof, Daniel; Delmastro, Dario

    2003-01-01

    In the present work an experimental closed loop representing a single stage of an uranium gaseous diffusion enrichment cascade is described, loop that is used to experimentally validate an analytical model that describes the dynamics inside such a loop.The conditions established inside the experimental loop after a few working hours were reproduced by the analytical model, leaving the slower thermal phenomena taking place for future studies.Two kinds of perturbations were experimentally introduced: a change in the range of operation of one of the compressors and the addition of mass into the loop.Numerical and experimental results are compared and presented in this work. The analytical model proposed was verified against these two changes, with very good agreement in the time response and measured values.This analytical model allows us to determine the characteristic time response of the system

  14. Scaled Experimental Modeling of VHTR Plenum Flows

    Energy Technology Data Exchange (ETDEWEB)

    ICONE 15

    2007-04-01

    Abstract The Very High Temperature Reactor (VHTR) is the leading candidate for the Next Generation Nuclear Power (NGNP) Project in the U.S. which has the goal of demonstrating the production of emissions free electricity and hydrogen by 2015. Various scaled heated gas and water flow facilities were investigated for modeling VHTR upper and lower plenum flows during the decay heat portion of a pressurized conduction-cooldown scenario and for modeling thermal mixing and stratification (“thermal striping”) in the lower plenum during normal operation. It was concluded, based on phenomena scaling and instrumentation and other practical considerations, that a heated water flow scale model facility is preferable to a heated gas flow facility and to unheated facilities which use fluids with ranges of density to simulate the density effect of heating. For a heated water flow lower plenum model, both the Richardson numbers and Reynolds numbers may be approximately matched for conduction-cooldown natural circulation conditions. Thermal mixing during normal operation may be simulated but at lower, but still fully turbulent, Reynolds numbers than in the prototype. Natural circulation flows in the upper plenum may also be simulated in a separate heated water flow facility that uses the same plumbing as the lower plenum model. However, Reynolds number scaling distortions will occur at matching Richardson numbers due primarily to the necessity of using a reduced number of channels connected to the plenum than in the prototype (which has approximately 11,000 core channels connected to the upper plenum) in an otherwise geometrically scaled model. Experiments conducted in either or both facilities will meet the objectives of providing benchmark data for the validation of codes proposed for NGNP designs and safety studies, as well as providing a better understanding of the complex flow phenomena in the plenums.

  15. Experimental modeling of a deoiling hydrocyclone system

    DEFF Research Database (Denmark)

    Bram, Mads Valentin; Hassan, Abdiladif Ahmed; Hansen, Dennis Severin

    2015-01-01

    responses of PDR via dedicated experiments a set of first-order-plus-dead-time (FOPDT) models that represent the main characteristics of the concerned hydrocyclone system is developed and analyzed for the entire operating range. The obtained multiple FOPDT models can illustrate the system performance...... acrylic hydrocyclone was tested as proof of concept for obtaining its steady-state and dynamic performances. The steady-state performance is able to provide the proportional correlation between PDR and flow split which is essential for optimizing steady-state separation efficiency. By analyzing step...

  16. Experimental and modelling studies of infiltration

    International Nuclear Information System (INIS)

    Giudici, M.

    2004-01-01

    This presentation describes a study of infiltration in the unsaturated soil with the objective of estimating the recharge to a phreatic aquifer. The study area is at the border of the city of Milan (Northern Italy), which draws water for both domestic and industrial purposes from ground water resources located beneath the urban area. The rate of water pumping from the aquifer system has been varying during the XX century, depending upon the number of inhabitants and the development of industrial activities. This caused variations with time of the depth of the water table below the ground surface and in turn some emergencies: the two most prominent episodes correspond to the middle '70s, when the water table in the city centre was about 30 m below the undisturbed natural conditions, and to the last decade, when the water table has raised at a rate of approximately 1 m/year and caused infiltrations in deep constructions (garages and building foundations, the underground railways, etc.). We have developed four ground water flow models at different scales, which share some characteristics: they are based on quasi-3D approximation (horizontal flow in the aquifers and vertical flow in the aquitards), conservative finite-differences schemes for regular grid with square cells in the horizontal plane and are implemented with proprietary computer codes. Among the problems that were studied for the development of these models, I recall some numerical problems, related to the behaviour of the phreatic aquifer under conditions of strong exploitation. Model calibration and validation for ModMil has been performed with a two-stage process, i.e., using some of the available data for model calibration and the remaining data for model validation. The application of geophysical exploration techniques, in particular seismic and geo-electrical prospecting, has been very useful to complete the data and information on the hydro-geological structure obtained from stratigraphic logs

  17. Lung cancer risk models from experimental animals

    International Nuclear Information System (INIS)

    Gilbert, E.S.

    1988-03-01

    The objective of this paper is to present analyses of data based on methods that adequately account for time-related factors and competiting risks, and that yield results that are expressed in a form comparable to results obtained from recent analyses of epidemiological studies of humans exposed to radon and radon daughters. These epidemiological analyses have modeled the hazard, or age-specific death rates, as a function of factors such as dose and dose rate, time from exposure, and time from cessation of exposure. The starting point for many of the analyses of human data has been the constant relative risk modeling which the age-specific death rates are assumed to be a function of cumulative dose, and the risks due to exposure are assumed to be proportional to the age-specific baseline death rates. However, departures from this initial model, such as dependence of risks on age at risk and/or time from exposure, have been investigated. These analyses have frequently been based on a non-parametric model that requires minimal assumptions regarding the baseline risks and their dependence on age

  18. Isothermal coarse mixing: experimental and CFD modelling

    International Nuclear Information System (INIS)

    Gilbertson, M.A.; Kenning, D.B.R.; Hall, R.W.

    1992-01-01

    A plane, two-dimensional flow apparatus has been built which uses a jet of solid 6mm diameter balls to model a jet of molten drops falling into a tank of water to study premixing prior to a vapour explosion. Preliminary experiments with unheated stainless steel balls are here compared with computational fluid dynamics (CFD) calculations by the code CHYMES. (6 figures) (Author)

  19. New experimental model of multiple myeloma.

    Science.gov (United States)

    Telegin, G B; Kalinina, A R; Ponomarenko, N A; Ovsepyan, A A; Smirnov, S V; Tsybenko, V V; Homeriki, S G

    2001-06-01

    NSO/1 (P3x63Ay 8Ut) and SP20 myeloma cells were inoculated to BALB/c OlaHsd mice. NSO/1 cells allowed adequate stage-by-stage monitoring of tumor development. The adequacy of this model was confirmed in experiments with conventional cytostatics: prospidium and cytarabine caused necrosis of tumor cells and reduced animal mortality.

  20. Sepsis and cytomegalovirus: foes or conspirators?

    Science.gov (United States)

    Mansfield, Sara; Grießl, Marion; Gutknecht, Michael; Cook, Charles H

    2015-06-01

    Cytomegalovirus (CMV) reactivation in non-immune-suppressed critically ill patients is an area of increasing interest. CMV has long been appreciated as a pathogen in immunocompromised hosts. CMV reactivates in approximately one-third of latently infected non-immune-suppressed hosts during critical illness; however, its role as a pathogen in these patients remains unclear. CMV reactivation has been linked to bacterial sepsis and likely results from inflammation, transient immune compromise, and viral epigenetic changes. While CMV may improve immune response to some bacterial infections, other data suggest that CMV induces exaggerated responses to severe infections that may be harmful to latently infected hosts. These results also suggest that previous infection history may explain significant differences seen between human septic responses and murine models of sepsis. While critically ill human hosts clearly have worse outcomes associated with CMV reactivation, determining causality remains an area of investigation, with randomized control trials currently being performed. Here we review the current literature and highlight areas for future investigation.

  1. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)

    NARCIS (Netherlands)

    Singer, Mervyn; Deutschman, Clifford S.; Seymour, Christopher Warren; Shankar-Hari, Manu; Annane, Djillali; Bauer, Michael; Bellomo, Rinaldo; Bernard, Gordon R.; Chiche, Jean-Daniel; Coopersmith, Craig M.; Hotchkiss, Richard S.; Levy, Mitchell M.; Marshall, John C.; Martin, Greg S.; Opal, Steven M.; Rubenfeld, Gordon D.; van der Poll, Tom; Vincent, Jean-Louis; Angus, Derek C.

    2016-01-01

    IMPORTANCE Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need

  2. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016

    NARCIS (Netherlands)

    Rhodes, Andrew; Evans, Laura E.; Alhazzani, Waleed; Levy, Mitchell M.; Antonelli, Massimo; Ferrer, Ricard; Kumar, Anand; Sevransky, Jonathan E.; Sprung, Charles L.; Nunnally, Mark E.; Rochwerg, Bram; Rubenfeld, Gordon D.; Angus, Derek C.; Annane, Djillali; Beale, Richard J.; Bellinghan, Geoffrey J.; Bernard, Gordon R.; Chiche, Jean-Daniel; Coopersmith, Craig; de Backer, Daniel P.; French, Craig J.; Fujishima, Seitaro; Gerlach, Herwig; Hidalgo, Jorge Luis; Hollenberg, Steven M.; Jones, Alan E.; Karnad, Dilip R.; Kleinpell, Ruth M.; Koh, Younsuck; Lisboa, Thiago Costa; Machado, Flavia R.; Marini, John J.; Marshall, John C.; Mazuski, John E.; McIntyre, Lauralyn A.; McLean, Anthony S.; Mehta, Sangeeta; Moreno, Rui P.; Myburgh, John; Navalesi, Paolo; Nishida, Osamu; Osborn, Tiffany M.; Perner, Anders; Plunkett, Colleen M.; Ranieri, Marco; Schorr, Christa A.; Seckel, Maureen A.; Seymour, Christopher W.; Shieh, Lisa; Shukri, Khalid A.; Simpson, Steven Q.; Singer, Mervyn; Thompson, B. Taylor; Townsend, Sean R.; van der Poll, Thomas; Vincent, Jean-Louis; Wiersinga, W. Joost; Zimmerman, Janice L.; Dellinger, R. Phillip

    2017-01-01

    Objective: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012!' Design: A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings

  3. Sepsis-Induced Cardiomyopathy: Mechanisms and Treatments

    Directory of Open Access Journals (Sweden)

    Yan-Cun Liu

    2017-08-01

    Full Text Available Sepsis is a lethal syndrome with a high incidence and a weighty economy burden. The pathophysiology of sepsis includes inflammation, immune dysfunction, and dysfunction of coagulation, while sepsis-induced cardiomyopathy (SIC, defined as a global but reversible dysfunction of both sides of the heart induced by sepsis, plays a significant role in all of the aspects above in the pathogenesis of sepsis. The complex pathogenesis of SIC involves a combination of dysregulation of inflammatory mediators, mitochondrial dysfunction, oxidative stress, disorder of calcium regulation, autonomic nervous system dysregulation, and endothelial dysfunction. The treatments for SIC include the signal pathway intervention, Chinese traditional medicine, and other specific therapy. Here, we reviewed the latest literatures on the mechanisms and treatments of SIC and hope to provide further insights to researchers and create a new road for the therapy of sepsis.

  4. Experimental Validation of a Permeability Model for Enrichment Membranes

    International Nuclear Information System (INIS)

    Orellano, Pablo; Brasnarof, Daniel; Florido Pablo

    2003-01-01

    An experimental loop with a real scale diffuser, in a single enrichment-stage configuration, was operated with air at different process conditions, in order to characterize the membrane permeability.Using these experimental data, an analytical geometric-and-morphologic-based model was validated.It is conclude that a new set of independent measurements, i.e. enrichment, is necessary in order to fully characterize diffusers, because of its internal parameters are not univocally determinated with permeability experimental data only

  5. New experimental model for training in videosurgery Novo modelo experimental para treinamento em videocirurgia

    Directory of Open Access Journals (Sweden)

    Danilo Malta Batista

    2012-10-01

    Full Text Available PURPOSE: To develop a new experimental model of lower cost for training in videosurgery. METHODS: This project was performed at the Nucleus of Experimental Surgery of the Bahiana School of Medicine and Public Health, based on previous models described in the literature and under the supervision of the full professor of Operative Technique and Experimental Surgery II. It was made a model cube-shaped, made of wood, with holes distributed in various locations, rubber stoppers for the holes and lined externally with carpet, and internally with laminate. RESULTS: The new experimental model is of low cost and reproduces quite faithfully several videosurgical procedures. CONCLUSION: Medical schools interested in the subject may adopt the new model for training in videosurgery without the need of high costs for making and using these models.OBJETIVO: Desenvolver um novo modelo experimental de baixo custo para treinamento em videocirurgia MÉTODOS: Este projeto foi conduzido no Núcleo de Cirurgia Experimental da Escola Bahiana de Medicina e Saúde Pública, baseado em modelos prévios descritos na literatura e sob a supervisão do professor titular de Técnica Operatória e Cirurgia Experimental II. Foi feito um modelo em formato de cubo, de madeira, com furos distribuídos em vários locais, tampas de borracha para os orifícios e forrado externamente com carpete e internamente com laminado. RESULTADOS: O novo modelo experimental desenvolvido é de baixo custo e reproduz de forma bastante fiel diversos procedimentos videocirúrgicos. CONCLUSÃO: Faculdades médicas interessadas no tema poderão adotar o novo modelo para o treinamento em videocirurgia sem que sejam necessários gastos elevados para a confecção e o uso desses modelos.

  6. Experimentally testing the standard cosmological model

    Energy Technology Data Exchange (ETDEWEB)

    Schramm, D.N. (Chicago Univ., IL (USA) Fermi National Accelerator Lab., Batavia, IL (USA))

    1990-11-01

    The standard model of cosmology, the big bang, is now being tested and confirmed to remarkable accuracy. Recent high precision measurements relate to the microwave background; and big bang nucleosynthesis. This paper focuses on the latter since that relates more directly to high energy experiments. In particular, the recent LEP (and SLC) results on the number of neutrinos are discussed as a positive laboratory test of the standard cosmology scenario. Discussion is presented on the improved light element observational data as well as the improved neutron lifetime data. alternate nucleosynthesis scenarios of decaying matter or of quark-hadron induced inhomogeneities are discussed. It is shown that when these scenarios are made to fit the observed abundances accurately, the resulting conclusions on the baryonic density relative to the critical density, {Omega}{sub b}, remain approximately the same as in the standard homogeneous case, thus, adding to the robustness of the standard model conclusion that {Omega}{sub b} {approximately} 0.06. This latter point is the deriving force behind the need for non-baryonic dark matter (assuming {Omega}{sub total} = 1) and the need for dark baryonic matter, since {Omega}{sub visible} < {Omega}{sub b}. Recent accelerator constraints on non-baryonic matter are discussed, showing that any massive cold dark matter candidate must now have a mass M{sub x} {approx gt} 20 GeV and an interaction weaker than the Z{sup 0} coupling to a neutrino. It is also noted that recent hints regarding the solar neutrino experiments coupled with the see-saw model for {nu}-masses may imply that the {nu}{sub {tau}} is a good hot dark matter candidate. 73 refs., 5 figs.

  7. Experimentally testing the standard cosmological model

    International Nuclear Information System (INIS)

    Schramm, D.N.

    1990-11-01

    The standard model of cosmology, the big bang, is now being tested and confirmed to remarkable accuracy. Recent high precision measurements relate to the microwave background; and big bang nucleosynthesis. This paper focuses on the latter since that relates more directly to high energy experiments. In particular, the recent LEP (and SLC) results on the number of neutrinos are discussed as a positive laboratory test of the standard cosmology scenario. Discussion is presented on the improved light element observational data as well as the improved neutron lifetime data. alternate nucleosynthesis scenarios of decaying matter or of quark-hadron induced inhomogeneities are discussed. It is shown that when these scenarios are made to fit the observed abundances accurately, the resulting conclusions on the baryonic density relative to the critical density, Ω b , remain approximately the same as in the standard homogeneous case, thus, adding to the robustness of the standard model conclusion that Ω b ∼ 0.06. This latter point is the deriving force behind the need for non-baryonic dark matter (assuming Ω total = 1) and the need for dark baryonic matter, since Ω visible b . Recent accelerator constraints on non-baryonic matter are discussed, showing that any massive cold dark matter candidate must now have a mass M x approx-gt 20 GeV and an interaction weaker than the Z 0 coupling to a neutrino. It is also noted that recent hints regarding the solar neutrino experiments coupled with the see-saw model for ν-masses may imply that the ν τ is a good hot dark matter candidate. 73 refs., 5 figs

  8. Experimental modeling methods in Industrial Engineering

    Directory of Open Access Journals (Sweden)

    Peter Trebuňa

    2009-03-01

    Full Text Available Dynamic approaches to a management system of the present industrial practice, forcing businesses to address management issues in-house continuous improvement of production and non-production processes. Experience has repeatedly demonstrated the need for a system approach not only in analysis but also in the planning and actual implementation of these processes. Therefore, the contribution is focused on the description of the modeling in industrial practice by a system approach, in order to avoid erroneous application of the decision to the implementation phase, and thus prevent any longer applying methods "attempt - fallacy".

  9. CS model coil experimental log book

    International Nuclear Information System (INIS)

    Nishijima, Gen; Sugimoto, Makoto; Nunoya, Yoshihiko; Wakabayashi, Hiroshi; Tsuji, Hiroshi

    2001-02-01

    Charging test of the ITER CS Model Coil which is the world's largest superconducting pulse coil and the CS Insert Coil had started at April 11, 2000 and had completed at August 18, 2000. In the campaign, total shot numbers were 356 and the size of the data file in the DAS (Data Acquisition System) was over 20 GB. This report is a database that consists of the log list and the log sheets of every shot. One can access the database, make a search, and browse results via Internet (http://1ogwww.naka.jaeri.go.jp). The database will be useful to quick search to choose necessary shots. (author)

  10. Tesla coil theoretical model and experimental verification

    OpenAIRE

    Voitkans, Janis; Voitkans, Arnis

    2014-01-01

    Abstract – In this paper a theoretical model of a Tesla coil operation is proposed. Tesla coil is described as a long line with distributed parameters in a single-wired format, where the line voltage is measured against electrically neutral space. It is shown that equivalent two-wired scheme can be found for a single-wired scheme and already known long line theory can be applied to a Tesla coil. Formulas for calculation of voltage in a Tesla coil by coordinate and calculation of resonance fre...

  11. Advances in sepsis-associated liver dysfunction

    OpenAIRE

    Wang, Dawei; Yin, Yimei; Yao, Yongming

    2014-01-01

    Recent studies have revealed liver dysfunction as an early event in sepsis. Sepsis-associated liver dysfunction is mainly resulted from systemic or microcirculatory disturbances, spillovers of bacteria and endotoxin (lipopolysaccharide, LPS), and subsequent activation of inflammatory cytokines as well as mediators. Three main cell types of the liver which contribute to the hepatic response in sepsis are Kupffer cells (KCs), hepatocytes and liver sinusoidal endothelial cells (LSECs). In additi...

  12. Experimental photoallergic contact dermatitis: a mouse model

    International Nuclear Information System (INIS)

    Maguire, H.C. Jr.; Kaidbey, K.

    1982-01-01

    We have induced photoallergic contact dermatitis in mice to 3,3',4',5 tetrachlorosalicylanilide (TCSA), chlorpromazine and 6-methylcoumarin. These compounds are known to produce photoallergic contact dermatitis in humans. The photoallergic contact dermatitis reaction in the mouse is immunologically specific viz. mice photosensitized to TCSA react, by photochallenge, to that compound and not to chlorpromazine, and conversely. The reaction requires UVA at both sensitization and challenge. It appears to be T-cell mediated in that it can be passively transferred to syngeneic mice by lymph node cells from actively sensitized mice, the histology of the reactions resembles that of classic allergic contact dermatitis in mice, challenge reactions are seen at 24 but not at 4 hr, and photoallergic contact dermatitis can be induced in B-cell deficient mice. The availability of a mouse model for the study of photo-ACD will facilitate the identification of pertinent control mechanisms and may aid in the management of the disease. It is likely that a bioassay for photoallergens of humans can be based on this mouse model

  13. CS model coil experimental log book

    Energy Technology Data Exchange (ETDEWEB)

    Nishijima, Gen; Sugimoto, Makoto; Nunoya, Yoshihiko; Wakabayashi, Hiroshi; Tsuji, Hiroshi [Japan Atomic Energy Research Inst., Naka, Ibaraki (Japan). Naka Fusion Research Establishment

    2001-02-01

    Charging test of the ITER CS Model Coil which is the world's largest superconducting pulse coil and the CS Insert Coil had started at April 11, 2000 and had completed at August 18, 2000. In the campaign, total shot numbers were 356 and the size of the data file in the DAS (Data Acquisition System) was over 20 GB. This report is a database that consists of the log list and the log sheets of every shot. One can access the database, make a search, and browse results via Internet (http://1ogwww.naka.jaeri.go.jp). The database will be useful to quick search to choose necessary shots. (author)

  14. Microplasticity of MMC. Experimental results and modelling

    International Nuclear Information System (INIS)

    Maire, E.; Lormand, G.; Gobin, P.F.; Fougeres, R.

    1993-01-01

    The microplastic behavior of several MMC is investigated by means of tension and compression tests. This behavior is assymetric : the proportional limit is higher in tension than in compression but the work hardening rate is higher in compression. These differences are analysed in terms of maxium of the Tresca's shear stress at the interface (proportional limit) and of the emission of dislocation loops during the cooling (work hardening rate). On another hand, a model is proposed to calculate the value of the yield stress, describing the composite as a material composed of three phases : inclusion, unaffected matrix and matrix surrounding the inclusion having a gradient in the density of the thermally induced dilocations. (orig.)

  15. Experimental Tests of the Algebraic Cluster Model

    Science.gov (United States)

    Gai, Moshe

    2018-02-01

    The Algebraic Cluster Model (ACM) of Bijker and Iachello that was proposed already in 2000 has been recently applied to 12C and 16O with much success. We review the current status in 12C with the outstanding observation of the ground state rotational band composed of the spin-parity states of: 0+, 2+, 3-, 4± and 5-. The observation of the 4± parity doublet is a characteristic of (tri-atomic) molecular configuration where the three alpha- particles are arranged in an equilateral triangular configuration of a symmetric spinning top. We discuss future measurement with electron scattering, 12C(e,e’) to test the predicted B(Eλ) of the ACM.

  16. Microplasticity of MMC. Experimental results and modelling

    Energy Technology Data Exchange (ETDEWEB)

    Maire, E. (Groupe d' Etude de Metallurgie Physique et de Physique des Materiaux, INSA, 69 Villeurbanne (France)); Lormand, G. (Groupe d' Etude de Metallurgie Physique et de Physique des Materiaux, INSA, 69 Villeurbanne (France)); Gobin, P.F. (Groupe d' Etude de Metallurgie Physique et de Physique des Materiaux, INSA, 69 Villeurbanne (France)); Fougeres, R. (Groupe d' Etude de Metallurgie Physique et de Physique des Materiaux, INSA, 69 Villeurbanne (France))

    1993-11-01

    The microplastic behavior of several MMC is investigated by means of tension and compression tests. This behavior is assymetric : the proportional limit is higher in tension than in compression but the work hardening rate is higher in compression. These differences are analysed in terms of maxium of the Tresca's shear stress at the interface (proportional limit) and of the emission of dislocation loops during the cooling (work hardening rate). On another hand, a model is proposed to calculate the value of the yield stress, describing the composite as a material composed of three phases : inclusion, unaffected matrix and matrix surrounding the inclusion having a gradient in the density of the thermally induced dilocations. (orig.).

  17. Advances in sepsis-associated liver dysfunction

    Directory of Open Access Journals (Sweden)

    Dawei Wang

    2014-07-01

    Full Text Available Recent studies have revealed liver dysfunction as an early event in sepsis. Sepsis-associated liver dysfunction is mainly resulted from systemic or microcirculatory disturbances, spillovers of bacteria and endotoxin (lipopolysaccharide, LPS, and subsequent activation of inflammatory cytokines as well as mediators. Three main cell types of the liver which contribute to the hepatic response in sepsis are Kupffer cells (KCs, hepatocytes and liver sinusoidal endothelial cells (LSECs. In addition, activated neutrophils, which are also recruited to the liver and produce potentially destructive enzymes and oxygen-free radicals, may further enhance acute liver injury. The clinical manifestations of sepsis-associated liver dysfunction can roughly be divided into two categories: Hypoxic hepatitis and jaundice. The latter is much more frequent in the context of sepsis. Hepatic failure is traditionally considered as a late manifestation of sepsis-induced multiple organ dysfunction syndrome. To date, no specific therapeutics for sepsis-associated liver dysfunction are available. Treatment measure is mainly focused on eradication of the underlying infection and management for severe sepsis. A better understanding of the pathophysiology of liver response in sepsis may lead to further increase in survival rates.

  18. Beneficial Effects of Anti-Interleukin-6 Antibodies on Impaired Gastrointestinal Motility, Inflammation and Increased Colonic Permeability in a Murine Model of Sepsis Are Most Pronounced When Administered in a Preventive Setup.

    Directory of Open Access Journals (Sweden)

    Sara Nullens

    Full Text Available During sepsis, gastrointestinal ileus, mucosal barrier dysfunction and bacterial translocation are accepted to be important triggers that can maintain or exacerbate the septic state. In the caecal ligation and puncture animal model of sepsis, we demonstrated that systemic and colonic interleukin-6 levels are significantly increased coinciding with an impaired colonic barrier function. We therefore aimed to study the effect of therapeutic or curative administration of anti-IL6 antibodies on overall GI motility, colonic permeability and translocation of intestinal bacteria in blood and mesenteric lymph nodes in the mouse caecal ligation and puncture model.OF-1 mice were randomized to either the preventive or curative protocol, in which they received 1 mg/kg of antibodies to interleukin-6, or its IgG isotype control solution. They subsequently underwent either the caecal ligation and puncture procedure, or sham-surgery. GI motility was assessed 48 h following the procedure, as well as colonic permeability, serum and colon cytokines, colonic tight junction proteins at the mRNA level; cultures of blood and mesenteric lymph nodes were performed.Preventive administration of anti-interleukin-6 antibodies successfully counteracted the gastrointestinal motility disturbances and impaired colonic barrier function that could be observed in vehicle-treated septic animals. Serum and colonic levels of proinflammatory cytokines were significantly lower when animals were preventively treated with anti-interleukin-6 antibodies. A repetitive injection 24 h later resulted in the most pronounced effects. Curative treatment significantly lowered systemic and colonic inflammation markers while the effects on transit and permeability were unfortunately no longer significant.Caecal ligation and puncture resulted in septic ileus with an increased colonic permeability. Antibodies to interleukin-6 were able to ameliorate gastro-intestinal motility, suppress inflammation and

  19. Current insights in sepsis: from pathogenesis to new treatment targets

    NARCIS (Netherlands)

    Wiersinga, W. Joost

    2011-01-01

    Sepsis continues to be a leading cause of ICU death. This review summarizes current knowledge on sepsis pathogenesis and new therapeutical strategies. Although systemic inflammatory response syndrome predominates in early sepsis, the compensatory anti-inflammatory response syndrome causes

  20. Does Infection Site Matter? A Systematic Review of Infection Site Mortality in Sepsis.

    Science.gov (United States)

    Motzkus, Christine A; Luckmann, Roger

    2017-09-01

    Sepsis treatment protocols emphasize source control with empiric antibiotics and fluid resuscitation. Previous reviews have examined the impact of infection site and specific pathogens on mortality from sepsis; however, no recent review has addressed the infection site. This review focuses on the impact of infection site on hospital mortality among patients with sepsis. The PubMed database was searched for articles from 2001 to 2014. Studies were eligible if they included (1) one or more statistical models with hospital mortality as the outcome and considered infection site for inclusion in the model and (2) adult patients with sepsis, severe sepsis, or septic shock. Data abstracted included stage of sepsis, infection site, and raw and adjusted effect estimates. Nineteen studies were included. Infection sites most studied included respiratory (n = 19), abdominal (n = 19), genitourinary (n = 18), and skin and soft tissue infections (n = 11). Several studies found a statistically significant lower mortality risk for genitourinary infections on hospital mortality when compared to respiratory infections. Based on studies included in this review, the impact of infection site in patients with sepsis on hospital mortality could not be reliably estimated. Misclassification among infections and disease states remains a serious possibility in studies on this topic.

  1. Multiphysics modelling and experimental validation of high concentration photovoltaic modules

    International Nuclear Information System (INIS)

    Theristis, Marios; Fernández, Eduardo F.; Sumner, Mike; O'Donovan, Tadhg S.

    2017-01-01

    Highlights: • A multiphysics modelling approach for concentrating photovoltaics was developed. • An experimental campaign was conducted to validate the models. • The experimental results were in good agreement with the models. • The multiphysics modelling allows the concentrator’s optimisation. - Abstract: High concentration photovoltaics, equipped with high efficiency multijunction solar cells, have great potential in achieving cost-effective and clean electricity generation at utility scale. Such systems are more complex compared to conventional photovoltaics because of the multiphysics effect that is present. Modelling the power output of such systems is therefore crucial for their further market penetration. Following this line, a multiphysics modelling procedure for high concentration photovoltaics is presented in this work. It combines an open source spectral model, a single diode electrical model and a three-dimensional finite element thermal model. In order to validate the models and the multiphysics modelling procedure against actual data, an outdoor experimental campaign was conducted in Albuquerque, New Mexico using a high concentration photovoltaic monomodule that is thoroughly described in terms of its geometry and materials. The experimental results were in good agreement (within 2.7%) with the predicted maximum power point. This multiphysics approach is relatively more complex when compared to empirical models, but besides the overall performance prediction it can also provide better understanding of the physics involved in the conversion of solar irradiance into electricity. It can therefore be used for the design and optimisation of high concentration photovoltaic modules.

  2. Effects of intra-abdominal sepsis on atherosclerosis in mice.

    Science.gov (United States)

    Kaynar, Ata Murat; Yende, Sachin; Zhu, Lin; Frederick, Daniel R; Chambers, Robin; Burton, Christine L; Carter, Melinda; Stolz, Donna Beer; Agostini, Brittani; Gregory, Alyssa D; Nagarajan, Shanmugam; Shapiro, Steven D; Angus, Derek C

    2014-09-03

    and vascular cell adhesion molecule 1) and the adhesion assay, a functional measure of endothelial activation, were elevated at 72 hours and 120 hours in mice that underwent CLP versus sham-operations (all at P <0.05). Using a combination of existing murine models for atherosclerosis and sepsis, we found that CLP, a model of intra-abdominal sepsis, accelerates atheroma development. Accelerated atheroma burden was associated with prolonged systemic, endothelial and intimal inflammation and was not explained by ongoing infection. These findings support observations in humans and demonstrate the feasibility of a long-term follow-up murine model of sepsis.

  3. Experimental tests of the standard model

    International Nuclear Information System (INIS)

    Nodulman, L.

    1998-01-01

    The title implies an impossibly broad field, as the Standard Model includes the fermion matter states, as well as the forces and fields of SU(3) x SU(2) x U(1). For practical purposes, I will confine myself to electroweak unification, as discussed in the lectures of M. Herrero. Quarks and mixing were discussed in the lectures of R. Aleksan, and leptons and mixing were discussed in the lectures of K. Nakamura. I will essentially assume universality, that is flavor independence, rather than discussing tests of it. I will not pursue tests of QED beyond noting the consistency and precision of measurements of α EM in various processes including the Lamb shift, the anomalous magnetic moment (g-2) of the electron, and the quantum Hall effect. The fantastic precision and agreement of these predictions and measurements is something that convinces people that there may be something to this science enterprise. Also impressive is the success of the ''Universal Fermi Interaction'' description of beta decay processes, or in more modern parlance, weak charged current interactions. With one coupling constant G F , most precisely determined in muon decay, a huge number of nuclear instabilities are described. The slightly slow rate for neutron beta decay was one of the initial pieces of evidence for Cabbibo mixing, now generalized so that all charged current decays of any flavor are covered

  4. Mutant mice: experimental organisms as materialised models in biomedicine.

    Science.gov (United States)

    Huber, Lara; Keuck, Lara K

    2013-09-01

    Animal models have received particular attention as key examples of material models. In this paper, we argue that the specificities of establishing animal models-acknowledging their status as living beings and as epistemological tools-necessitate a more complex account of animal models as materialised models. This becomes particularly evident in animal-based models of diseases that only occur in humans: in these cases, the representational relation between animal model and human patient needs to be generated and validated. The first part of this paper presents an account of how disease-specific animal models are established by drawing on the example of transgenic mice models for Alzheimer's disease. We will introduce an account of validation that involves a three-fold process including (1) from human being to experimental organism; (2) from experimental organism to animal model; and (3) from animal model to human patient. This process draws upon clinical relevance as much as scientific practices and results in disease-specific, yet incomplete, animal models. The second part of this paper argues that the incompleteness of models can be described in terms of multi-level abstractions. We qualify this notion by pointing to different experimental techniques and targets of modelling, which give rise to a plurality of models for a specific disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. VIP as a potential therapeutic agent in gram negative sepsis.

    Science.gov (United States)

    Ibrahim, Hiba; Barrow, Paul; Foster, Neil

    2012-12-01

    Gram negative sepsis remains a high cause of mortality and places a great burden on public health finance in both the developed and developing world. Treatment of sepsis, using antibiotics, is often ineffective since pathology associated with the disease occurs due to dysregulation of the immune system (failure to return to steady state conditions) which continues after the bacteria, which induced the immune response, have been cleared. Immune modulation is therefore a rational approach to the treatment of sepsis but to date no drug has been developed which is highly effective, cheap and completely safe to use. One potential therapeutic agent is VIP, which is a natural peptide and is highly homologous in all vertebrates. In this review we will discuss the effect of VIP on components of the immune system, relevant to gram negative sepsis, and present data from animal models. Furthermore we will hypothesise on how these studies could be improved in future and speculate on the possible different ways in which VIP could be used in clinical medicine.

  6. Morphofunctional analysis of experimental model of esophageal achalasia in rats.

    Science.gov (United States)

    Sabirov, A G; Raginov, I S; Burmistrov, M V; Chelyshev, Y A; Khasanov, R Sh; Moroshek, A A; Grigoriev, P N; Zefirov, A L; Mukhamedyarov, M A

    2010-10-01

    We carried out a detailed analysis of rat model of esophageal achalasia previously developed by us. Manifest morphological and functional disorders were observed in experimental achalasia: hyperplasia of the squamous epithelium, reduced number of nerve fibers, excessive growth of fibrous connective tissue in the esophageal wall, high contractile activity of the lower esophageal sphincter, and reduced motility of the longitudinal muscle layer. Changes in rat esophagus observed in experimental achalasia largely correlate with those in esophageal achalasia in humans. Hence, our experimental model can be used for the development of new methods of disease treatment.

  7. The experimental and shell model approach to 100Sn

    International Nuclear Information System (INIS)

    Grawe, H.; Maier, K.H.; Fitzgerald, J.B.; Heese, J.; Spohr, K.; Schubart, R.; Gorska, M.; Rejmund, M.

    1995-01-01

    The present status of experimental approach to 100 Sn and its shell model structure is given. New developments in experimental techniques, such as low background isomer spectroscopy and charged particle detection in 4π are surveyed. Based on recent experimental data shell model calculations are used to predict the structure of the single- and two-nucleon neighbours of 100 Sn. The results are compared to the systematic of Coulomb energies and spin-orbit splitting and discussed with respect to future experiments. (author). 51 refs, 11 figs, 1 tab

  8. Paramedic-Initiated CMS Sepsis Core Measure Bundle Prior to Hospital Arrival: A Stepwise Approach.

    Science.gov (United States)

    Walchok, Jason G; Pirrallo, Ronald G; Furmanek, Douglas; Lutz, Martin; Shope, Colt; Giles, Brandi; Gue, Greta; Dix, Aaron

    2017-01-01

    To improve patient outcomes, the Center for Medicare and Medicaid Services (CMS) implemented core measures that outline the initial treatment of the septic patient. These measures include initial blood culture collection prior to antibiotics, adequate intravenous fluid resuscitation, and early administration of broad spectrum antibiotics. We sought to determine if Paramedics can initiate the CMS sepsis core measure bundle in the prehospital field reliably. This is a retrospective, case series from a 3rd service EMS system model in Greenville, South Carolina between November 17, 2014 and February 20, 2016. An adult Prehospital Sepsis Assessment Tool was created using the 2012 Surviving Sepsis guidelines: 2 of 3 signs of systemic inflammatory response (heart rate, respiratory rate, oral temperature) and a known or suspected source of infection. A "Sepsis Alert" was called by paramedics and upon IV access a set of blood cultures and blood for lactate analysis was collected prior to field antibiotic administration. The Sepsis Alert was compared to serum lactate levels and ICD 9 or 10 admitting diagnosis of Sepsis, Severe Sepsis, or Septic Shock. Blood culture contamination, serum lactate, and antibiotic match were determined by in-hospital laboratory analysis. A total of 120 trained paramedics called 1,185 "Sepsis Alerts" on 56,643 patients (50.3% Male, mean age 70). Patients with missing discharge diagnosis were eliminated (n = 31). The admitting diagnosis of sepsis overall was 73.5% (848/1154): Sepsis 50% (578/1154), Severe Sepsis 14.6% (169/1154), Septic Shock 8.9% (101/1154). A total of 946 blood cultures were collected in the prehospital setting, with a 95.04% (899/946) no contamination rate. Contamination was found in 4.96% (47/946). A total of 179 (18.9%) of the uncontaminated blood cultures were found to have positive growth with 720 (76.1%) having no growth. EMS administered antibiotics matched blood culture positive growth in 72% of patients. The lactate

  9. Therapeutic effects of compound hypertonic saline on rats with sepsis

    Directory of Open Access Journals (Sweden)

    Fang Dong

    2014-09-01

    Full Text Available Sepsis is one of the major causes of death and is the biggest obstacle preventing improvement of the success rate in curing critical illnesses. Currently, isotonic solutions are used in fluid resuscitation technique. Several studies have shown that hypertonic saline applied in hemorrhagic shock can rapidly increase the plasma osmotic pressure, facilitate the rapid return of interstitial fluid into the blood vessels, and restore the effective circulating blood volume. Here, we established a rat model of sepsis by using the cecal ligation and puncture approach. We found that intravenous injection of hypertonic saline dextran (7.5% NaCl/6% dextran after cecal ligation and puncture can improve circulatory failure at the onset of sepsis. We found that the levels of tumor necrosis factor-α, interleukin-1β, interleukin-6 and intracellular adhesion molecule 1 levels in the lung tissue of cecal ligation and puncture rats treated with hypertonic saline dextran were significantly lower than the corresponding levels in the control group. We inferred that hypertonic saline dextran has a positive immunoregulatory effect and inhibits the overexpression of the inflammatory response in the treatment of sepsis. The percentage of neutrophils, lung myeloperoxidase activity, wet to dry weight ratio of lung tissues, histopathological changes in lung tissues, and indicators of arterial blood gas analysis was significantly better in the hypertonic saline dextran-treated group than in the other groups in this study. Hypertonic saline dextran-treated rats had significantly improved survival rates at 9 and 18 h compared to the control group. Our results suggest that hypertonic saline dextran plays a protective role in acute lung injury caused after cecal ligation and puncture. In conclusion, hypertonic/hyperoncotic solutions have beneficial therapeutic effects in the treatment of an animal model of sepsis.

  10. Procalcitonin as an adjunctive biomarker in sepsis

    Directory of Open Access Journals (Sweden)

    Mahua Sinha

    2011-01-01

    Full Text Available Sepsis can sometimes be difficult to substantiate, and its distinction from non-infectious conditions in critically ill patients is often a challenge. Serum procalcitonin (PCT assay is one of the biomarkers of sepsis. The present study was aimed to assess the usefulness of PCT assay in critically ill patients with suspected sepsis. The study included 40 patients from the intensive care unit with suspected sepsis. Sepsis was confirmed clinically and/or by positive blood culture. Serum PCT was assayed semi-quantitatively by rapid immunochromatographic technique (within 2 hours of sample receipt. Among 40 critically ill patients, 21 had clinically confirmed sepsis. There were 12 patients with serum PCT ≥10 ng/ml (8, blood culture positive; 1, rickettsia; 2, post-antibiotic blood culture sterile; and 1, non-sepsis; 7 patients with PCT 2-10 ng/ml (4, blood culture positive; 1, falciparum malaria; 2, post-antibiotic blood culture sterile; 3 patients with PCT of 0.5 to 2 ng/ml (sepsis in 1 patient; and 18 patients with PCT < 0.5 ng/ml (sepsis in 2 patients. Patients with PCT ≥ 2 ng/ml had statistically significant correlation with the presence of sepsis (P<0.0001. The PCT assay revealed moderate sensitivity (86% and high specificity (95% at a cut-off ≥ 2 ng/ml. The PCT assay was found to be a useful biomarker of sepsis in this study. The assay could be performed and reported rapidly and provided valuable information before availability of culture results. This might assist in avoiding unwarranted antibiotic usage.

  11. I costi della sepsi in Italia

    Directory of Open Access Journals (Sweden)

    C. Lucioni

    2001-09-01

    Full Text Available The aim of this study is to evaluate additional hospitalisation costs and intangible costs (mortality in patients with sepsis (intended as severe sepsis or sepsis shock in Italy. The evaluation is based on clinical data from the Italian Sepsis Study, a prospective, multicentre study conducted in 99 Intensive Care Units (ICUslocated across Italy. Each ICU enrolled the first two (or three patients admitted each month, during the year April 1993 to March 1994. In particular, data collected included the Average Length Of Stay (ALOS in ICU and later in the regular ward, and the mortality within four weeks and in hospital. Out of the 2,946 patients enrolled, 2,641 never developed sepsis and were considered as the control group (comparability was confirmed based on gender, age, and comorbidity. The additional (respective to the control group ALOSs of the patients with sepsis were valued in monetary terms using per diem full costs, inflated to 2000: 1,033.43 Euro for l day in ICU (published data and 299.54 Euro for l day in the regular ward (estimated data based on published materials. Statistical significance was tested with Student t test. The hospitalisation cost of a patient with sepsis (21,571.88 Euro is significantly higher (+86% than that patient without sepsis (11,590.84 Euro, due to a longer (+ 163% stay in the expensive ICU, not balanced by shorter stay in the regular ward. Also intangible costs are significantly higher: the risk for an ICU patient with sepsis to die in hospital is 3 times higher than that of an ICU patient without sepsis. In particular, those patients developing sepsis after admission are more costly and with a higher mortality risk.

  12. Methionine Metabolites in Patients With Sepsis.

    Science.gov (United States)

    Wexler, Orren; Gough, Michael S; Morgan, Mary Anne M; Mack, Cynthia M; Apostolakos, Michael J; Doolin, Kathleen P; Mooney, Robert A; Arning, Erland; Bottiglieri, Teodoro; Pietropaoli, Anthony P

    2018-01-01

    Sepsis is characterized by microvascular dysfunction and thrombophilia. Several methionine metabolites may be relevant to this sepsis pathophysiology. S-adenosylmethionine (SAM) serves as the methyl donor for trans-methylation reactions. S-adenosylhomocysteine (SAH) is the by-product of these reactions and serves as the precursor to homocysteine. Relationships between plasma total homocysteine concentrations (tHcy) and vascular disease and thrombosis are firmly established. We hypothesized that SAM, SAH, and tHcy levels are elevated in patients with sepsis and associated with mortality. This was a combined case-control and prospective cohort study consisting of 109 patients with sepsis and 50 control participants without acute illness. The study was conducted in the medical and surgical intensive care units of the University of Rochester Medical Center. Methionine, SAM, SAH, and tHcy concentrations were compared in patients with sepsis versus control participants and in sepsis survivors versus nonsurvivors. Patients with sepsis had significantly higher plasma SAM and SAH concentrations than control participants (SAM: 164 [107-227] vs73 [59-87 nM], P sepsis patients compared to healthy control participants (4 [2-6]) vs 7 [5-9] μM; P = .04). In multivariable analysis, quartiles of SAM, SAH, and tHcy were independently associated with sepsis ( P = .006, P = .05, and P Sepsis nonsurvivors had significantly higher plasma SAM and SAH concentrations than survivors (SAM: 223 [125-260] vs 136 [96-187] nM; P = .01; SAH: 139 [81-197] vs 86 [55-130] nM, P = .006). Plasma tHcy levels were similar in survivors vs nonsurvivors. The associations between SAM or SAH and hospital mortality were no longer significant after adjusting for renal dysfunction. Methionine metabolite concentrations are abnormal in sepsis and linked with clinical outcomes. Further study is required to determine whether these abnormalities have pathophysiologic significance.

  13. Endogenous opioid antagonism in physiological experimental pain models

    DEFF Research Database (Denmark)

    Werner, Mads U; Pereira, Manuel P; Andersen, Lars Peter H

    2015-01-01

    hyperalgesia models (6 studies), 'pain' models (25 studies), summation models (2 studies), nociceptive reflex models (3 studies) and miscellaneous models (2 studies). A consistent reversal of analgesia by a MOR-antagonist was demonstrated in 10 of the 25 ITP-studies, including stress-induced analgesia and r...... ratings, threshold assessments and somatosensory evoked potentials (SSEP), did not appear consistent in 28 out of 32 'pain' model studies. In conclusion, only in 2 experimental human pain models, i.e., stress-induced analgesia and rTMS, administration of MOR-antagonist demonstrated a consistent effect......Opioid antagonists are pharmacological tools applied as an indirect measure to detect activation of the endogenous opioid system (EOS) in experimental pain models. The objective of this systematic review was to examine the effect of mu-opioid-receptor (MOR) antagonists in placebo-controlled, double...

  14. Determinants of Carboxyhemoglobin Levels and Relationship with Sepsis in a Retrospective Cohort of Preterm Neonates.

    Directory of Open Access Journals (Sweden)

    Andrew J McArdle

    Full Text Available Carboxyhemoglobin levels in blood reflect endogenous carbon monoxide production and are often measured during routine blood gas analysis. Endogenous carbon monoxide production has been reported to be increased during sepsis, but carboxyhemoglobin levels have not been thoroughly evaluated as a biomarker of sepsis. We sought to determine whether carboxyhemoglobin levels were elevated during sepsis in a high risk population of premature neonates. We conducted a retrospective cohort study of 30 infants in two neonatal intensive care units using electronic medical and laboratory records. The majority of infants were extremely premature and extremely low birth weight, and 25 had at least one episode of sepsis. We collected all carboxyhemoglobin measurements during their in-patient stay and examined the relationship between carboxyhemoglobin and a variety of clinical and laboratory parameters, in addition to the presence or absence of sepsis, using linear mixed-effect models. We found that postnatal age had the most significant effect on carboxyhemoglobin levels, and other significant associations were identified with gestational age, hemoglobin concentration, oxyhemoglobin saturation, and blood pH. Accounting for these covariates, there was no significant relationship between the onset of sepsis and carboxyhemoglobin levels. Our results show that carboxyhemoglobin is unlikely to be a clinically useful biomarker of sepsis in premature infants, and raise a note of caution about factors which may confound the use of carbon monoxide as a clinical biomarker for other disease processes such as hemolysis.

  15. Determinants of Carboxyhemoglobin Levels and Relationship with Sepsis in a Retrospective Cohort of Preterm Neonates.

    Science.gov (United States)

    McArdle, Andrew J; Webbe, James; Sim, Kathleen; Parrish, Graham; Hoggart, Clive; Wang, Yifei; Kroll, J Simon; Godambe, Sunit; Cunnington, Aubrey J

    2016-01-01

    Carboxyhemoglobin levels in blood reflect endogenous carbon monoxide production and are often measured during routine blood gas analysis. Endogenous carbon monoxide production has been reported to be increased during sepsis, but carboxyhemoglobin levels have not been thoroughly evaluated as a biomarker of sepsis. We sought to determine whether carboxyhemoglobin levels were elevated during sepsis in a high risk population of premature neonates. We conducted a retrospective cohort study of 30 infants in two neonatal intensive care units using electronic medical and laboratory records. The majority of infants were extremely premature and extremely low birth weight, and 25 had at least one episode of sepsis. We collected all carboxyhemoglobin measurements during their in-patient stay and examined the relationship between carboxyhemoglobin and a variety of clinical and laboratory parameters, in addition to the presence or absence of sepsis, using linear mixed-effect models. We found that postnatal age had the most significant effect on carboxyhemoglobin levels, and other significant associations were identified with gestational age, hemoglobin concentration, oxyhemoglobin saturation, and blood pH. Accounting for these covariates, there was no significant relationship between the onset of sepsis and carboxyhemoglobin levels. Our results show that carboxyhemoglobin is unlikely to be a clinically useful biomarker of sepsis in premature infants, and raise a note of caution about factors which may confound the use of carbon monoxide as a clinical biomarker for other disease processes such as hemolysis.

  16. Lactic acidosis, hyperlactatemia and sepsis

    Directory of Open Access Journals (Sweden)

    Andrea Montagnani

    2016-12-01

    Full Text Available Among hospitalized patients, lactic acidosis represents the most common cause of metabolic acidosis. Lactate is not just a metabolic product of anaerobic glycolysis but is triggered by a variety of metabolites even before the onset of anaerobic metabolism as part of an adaptive response to a hypermetabolic state. On the basis of such considerations, lactic acidosis is divided into two classes: inadequate tissue oxygenation (type A and absence of tissue hypoxia (type B. Lactic acidosis is characterized by non-specific symptoms but it should be suspected in all critical patients who show hypovolemic, hypoxic, in septic or cardiogenic shock or if in the presence of an unexplained high anion gap metabolic acidosis. Lactic acidosis in sepsis and septic shock has traditionally been explained as a result of tissue hypoxia when whole-body oxygen delivery fails to meet whole body oxygen requirements. In sepsis lactate levels correlate with increased mortality with a poor prognostic threshold of 4 mmol/L. In hemodynamically stable patients with sepsis, hyperlactatemia might be the result of impaired lactate clearance rather than overproduction. In critically ill patients the speed at which hyperlactatemia resolves with appropriate therapy may be considered a useful prognostic indicator. The measure of blood lactate should be performed within 3 h of presentation in acute care setting. The presence of lactic acidosis requires early identification of the primary cause of shock for the best appropriate treatment. Since most cases of lactic acidosis depend on whole-body oxygen delivery failure, the maximization of systemic oxygen delivery remains the primary therapeutic option. When initial resuscitation does not substantially or completely correct lactic acidosis, it is also essential to consider other causes. The treatment of acidosis with buffering agents (specifically bicarbonate is generally advocated only in the setting of severe acidosis. Ongoing

  17. Severe sepsis and septic shock [author's reply

    NARCIS (Netherlands)

    Angus, Derek C.; van der Poll, Tom

    2013-01-01

    To the Editor: We would like to address two potentially confusing issues concerning venous oxygen saturation (Svo(2)) as presented in Table 1 of the review by Angus and van der Poll (Aug. 29 issue).(1) First, Table 1 suggests that Svo(2) is raised in sepsis, severe sepsis, and septic shock.

  18. Neuro-oxidative-nitrosative stress in sepsis

    DEFF Research Database (Denmark)

    Berg, Ronan M G; Møller, Kirsten; Bailey, Damian M

    2011-01-01

    Neuro-oxidative-nitrosative stress may prove the molecular basis underlying brain dysfunction in sepsis. In the current review, we describe how sepsis-induced reactive oxygen and nitrogen species (ROS/RNS) trigger lipid peroxidation chain reactions throughout the cerebrovasculature and surrounding...

  19. Think Sepsis. Time Matters. PSA (:60)

    Centers for Disease Control (CDC) Podcasts

    2016-08-23

    This 60 second public service announcement is based on the August 2016 CDC Vital Signs report. Sepsis is a medical emergency and can happen quickly. Learn the signs of sepsis and how to prevent it.  Created: 8/23/2016 by National Center for Injury Prevention and Control (NCIPC).   Date Released: 8/23/2016.

  20. Age, exercise, and the outcome of sepsis.

    Science.gov (United States)

    Banerjee, Debasree; Opal, Steven M

    2017-11-23

    We report on the increasingly important need to diagnose and care for the elderly with sepsis as a distinct patient population. We share an overview of age-related changes in sepsis physiology and the potential role of exercise.See related research by Tyml et al., https://ccforum.biomedcentral.com/articles/10.1186/s13054-017-1783-1.

  1. Radiodiagnosis of lung syndrome in surgical sepsis

    International Nuclear Information System (INIS)

    Dvojnykh, V.P.; Palagin, E.K.

    1991-01-01

    The results of treatment of 23 patients with acute surgical sepsis were analysed. It was shown that the X-ray examination must be obligatory in surveillance of patients with purulent foci. Two roentgenological variants are possible in surgical sepsis: central and perepheric. X-ray examinations of chest organs should be conducted every 2-3 day

  2. Review for 'Nattoh' model and experimental findings during cold fusion

    International Nuclear Information System (INIS)

    Matsumoto, Takaaki

    1993-01-01

    A review is described for the Nattoh model that provides the framework of the mechanisms of cold fusion. The model classifies the reactions into two categories: fundamental and associated reactions. The former involves the new 'hydrogen-catalyzed' fusion reaction and the chain-reactions of hydrogens. And extremely exciting physics are involved in the latter. Furthermore experimental findings are described. (author)

  3. A Sepsis-related Diagnosis Impacts Interventions and Predicts Outcomes for Emergency Patients with Severe Sepsis.

    Science.gov (United States)

    Kim, Mitchell; Watase, Taketo; Jablonowski, Karl D; Gatewood, Medley O; Henning, Daniel J

    2017-10-01

    Many patients meeting criteria for severe sepsis are not given a sepsis-related diagnosis by emergency physicians (EP). This study 1) compares emergency department (ED) interventions and in-hospital outcomes among patients with severe sepsis, based on the presence or absence of sepsis-related diagnosis, and 2) assesses how adverse outcomes relate to three-hour sepsis bundle completion among patients fulfilling severe sepsis criteria but not given a sepsis-related diagnosis. We performed a retrospective cohort study using patients meeting criteria for severe sepsis at two urban, academic tertiary care centers from March 2015 through May 2015. We included all ED patients with the following: 1) the 1992 Consensus definition of severe sepsis, including two or more systemic inflammatory response syndrome criteria and evidence of organ dysfunction; or 2) physician diagnosis of severe sepsis or septic shock. We excluded patients transferred to or from another hospital and those <18 years old. Patients with an EP-assigned sepsis diagnosis created the "Physician Diagnosis" group; the remaining patients composed the "Consensus Criteria" group. The primary outcome was in-hospital mortality. Secondary outcomes included completed elements of the current three-hour sepsis bundle; non-elective intubation; vasopressor administration; intensive care unit (ICU) admission from the ED; and transfer to the ICU in < 24 hours. We compared proportions of each outcome between groups using the chi-square test, and we also performed a stratified analysis using chi square to assess the association between failure to complete the three-hour bundle and adverse outcomes in each group. Of 418 patients identified with severe sepsis we excluded 54, leaving 364 patients for analysis: 121 "Physician Diagnosis" and 243 "Consensus Criteria." The "Physician Diagnosis" group had a higher in-hospital mortality (12.4% vs 3.3%, P < 0.01) and compliance with the three-hour sepsis bundle (52.1% vs 20.2%, P

  4. Experimental study and modeling of a novel magnetorheological elastomer isolator

    International Nuclear Information System (INIS)

    Yang, Jian; Li, Weihua; Sun, Shuaishuai; Du, Haiping; Li, Yancheng; Li, Jianchun; Deng, H X

    2013-01-01

    This paper reports an experimental setup aiming at evaluating the performance of a newly designed magnetorheological elastomer (MRE) seismic isolator. As a further effort to explore the field-dependent stiffness/damping properties of the MRE isolator, a series of experimental testing were conducted. Based upon the analysis of the experimental responses and the characteristics of the MRE isolator, a new model that is capable of reproducing the unique MRE isolator dynamics behaviors is proposed. The validation results verify the model’s effectiveness to portray the MRE isolator. A study on the field-dependent parameters is then provided to make the model valid with fluctuating magnetic fields. To fully explore the mechanism of the proposed model, an investigation relating the dependence of the proposed model on every parameter is carried out. (technical note)

  5. Experimental models of hepatotoxicity related to acute liver failure

    Energy Technology Data Exchange (ETDEWEB)

    Maes, Michaël [Department of In Vitro Toxicology and Dermato-Cosmetology, Vrije Universiteit Brussel, Brussels (Belgium); Vinken, Mathieu, E-mail: mvinken@vub.ac.be [Department of In Vitro Toxicology and Dermato-Cosmetology, Vrije Universiteit Brussel, Brussels (Belgium); Jaeschke, Hartmut [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City (United States)

    2016-01-01

    Acute liver failure can be the consequence of various etiologies, with most cases arising from drug-induced hepatotoxicity in Western countries. Despite advances in this field, the management of acute liver failure continues to be one of the most challenging problems in clinical medicine. The availability of adequate experimental models is of crucial importance to provide a better understanding of this condition and to allow identification of novel drug targets, testing the efficacy of new therapeutic interventions and acting as models for assessing mechanisms of toxicity. Experimental models of hepatotoxicity related to acute liver failure rely on surgical procedures, chemical exposure or viral infection. Each of these models has a number of strengths and weaknesses. This paper specifically reviews commonly used chemical in vivo and in vitro models of hepatotoxicity associated with acute liver failure. - Highlights: • The murine APAP model is very close to what is observed in patients. • The Gal/ET model is useful to study TNFα-mediated apoptotic signaling mechanisms. • Fas receptor activation is an effective model of apoptosis and secondary necrosis. • The ConA model is a relevant model of auto-immune hepatitis and viral hepatitis. • Multiple time point evaluation needed in experimental models of acute liver injury.

  6. Hemostasis and endothelial damage during sepsis.

    Science.gov (United States)

    Johansen, Maria Egede

    2015-08-01

    The sepsis syndrome represents a disease continuum, including severe sepsis and septic shock associated with high mortality. One of the main problems in severe sepsis and septic shock, resulting in organ failure and death, are disturbances in the hemostasis due to sepsis-related coagulopathy. Sepsis-related coagulopathy affects not only traditional coagulation factors, but also the platelets and endothelium. Functional testing of the hemostatic system has found application in critical illness. Thrombelastography (TEG) provides an overview of the hemostatic system allowing for an evaluation of interactions between coagulation factors and platelets. Additionally, the role of the endothelium during sepsis can be explored through testing of biomarkers of endothelial damage. The three studies comprising this PhD thesis all investigate important aspects of the disturbed hemostasis during sepsis, including endothelial damage. Together, the specific findings from the three studies improve the existing understanding of sepsis-related coagulopathy, and the possible influences of some of the treatments offered these patients. The first study investigates the occurrence of antimicrobial-induced thrombocytopenia among critically ill patients. In sepsis, thrombocytopenia is a predictor of poor outcome, and reports, of mainly casuistic nature, have previously hypothesized that specific antimicrobial agents could induce in sepsis-related thrombocytopenia. This hypothesis was tested using a randomized designed set-up, encompassing 1147 critically ill patients, and no significant difference in risk of thrombocytopenia was observed among patients receiving large amounts of antimicrobials vs. patients receiving standard-of-care. As a consequence, the risk of antimicrobial-induced thrombocytopenia in the general population of critically ill patients seemingly does not represent a substantial problem and thrombocytopenia during critical illness is most likely due to other factors such

  7. Using an experimental model for the study of therapeutic touch.

    Science.gov (United States)

    dos Santos, Daniella Soares; Marta, Ilda Estéfani Ribeiro; Cárnio, Evelin Capellari; de Quadros, Andreza Urba; Cunha, Thiago Mattar; de Carvalho, Emilia Campos

    2013-02-01

    to verify whether the Paw Edema Model can be used in investigations about the effects of Therapeutic Touch on inflammation by measuring the variables pain, edema and neutrophil migration. this is a pilot and experimental study, involving ten male mice of the same genetic strain and divided into experimental and control group, submitted to the chemical induction of local inflammation in the right back paw. The experimental group received a daily administration of Therapeutic Touch for 15 minutes during three days. the data showed statistically significant differences in the nociceptive threshold and in the paw circumference of the animals from the experimental group on the second day of the experiment. the experiment model involving animals can contribute to study the effects of Therapeutic Touch on inflammation, and adjustments are suggested in the treatment duration, number of sessions and experiment duration.

  8. Development of a fault test experimental facility model using Matlab

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, Iraci Martinez; Moraes, Davi Almeida, E-mail: martinez@ipen.br, E-mail: dmoraes@dk8.com.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2015-07-01

    The Fault Test Experimental Facility was developed to simulate a PWR nuclear power plant and is instrumented with temperature, level and pressure sensors. The Fault Test Experimental Facility can be operated to generate normal and fault data, and these failures can be added initially small, and their magnitude being increasing gradually. This work presents the Fault Test Experimental Facility model developed using the Matlab GUIDE (Graphical User Interface Development Environment) toolbox that consists of a set of functions designed to create interfaces in an easy and fast way. The system model is based on the mass and energy inventory balance equations. Physical as well as operational aspects are taken into consideration. The interface layout looks like a process flowchart and the user can set the input variables. Besides the normal operation conditions, there is the possibility to choose a faulty variable from a list. The program also allows the user to set the noise level for the input variables. Using the model, data were generated for different operational conditions, both under normal and fault conditions with different noise levels added to the input variables. Data generated by the model will be compared with Fault Test Experimental Facility data. The Fault Test Experimental Facility theoretical model results will be used for the development of a Monitoring and Fault Detection System. (author)

  9. Development of a fault test experimental facility model using Matlab

    International Nuclear Information System (INIS)

    Pereira, Iraci Martinez; Moraes, Davi Almeida

    2015-01-01

    The Fault Test Experimental Facility was developed to simulate a PWR nuclear power plant and is instrumented with temperature, level and pressure sensors. The Fault Test Experimental Facility can be operated to generate normal and fault data, and these failures can be added initially small, and their magnitude being increasing gradually. This work presents the Fault Test Experimental Facility model developed using the Matlab GUIDE (Graphical User Interface Development Environment) toolbox that consists of a set of functions designed to create interfaces in an easy and fast way. The system model is based on the mass and energy inventory balance equations. Physical as well as operational aspects are taken into consideration. The interface layout looks like a process flowchart and the user can set the input variables. Besides the normal operation conditions, there is the possibility to choose a faulty variable from a list. The program also allows the user to set the noise level for the input variables. Using the model, data were generated for different operational conditions, both under normal and fault conditions with different noise levels added to the input variables. Data generated by the model will be compared with Fault Test Experimental Facility data. The Fault Test Experimental Facility theoretical model results will be used for the development of a Monitoring and Fault Detection System. (author)

  10. Investigation of wax precipitation in crude oil: Experimental and modeling

    Directory of Open Access Journals (Sweden)

    Taraneh Jafari Behbahani

    2015-09-01

    Full Text Available In this work, a series of experiments were carried to investigation of rheological behavior of crude oil using waxy crude oil sample in the absence/presence of flow improver such as ethylene-vinyl acetate copolymer. The rheological data covered the temperature range of 5–30 °C. The results indicated that the performance of flow improver was dependent on its molecular weight. Addition of small quantities of flow improver, can improve viscosity and pour point of crude oil. Also, an Artificial Neural Network (ANN model using Multi-Layer Perceptron (MLP topology has been developed to account wax appearance temperature and the amount of precipitated wax and the model was verified using experimental data given in this work and reported in the literature. In order to compare the performance of the proposed model based on Artificial Neural Network, the wax precipitation experimental data at different temperatures were predicted using solid solution model and multi-solid phase model. The results showed that the developed model based on Artificial Neural Network can predict more accurately the wax precipitation experimental data in comparison to the previous models such as solid solution and multi-solid phase model with AADs less than 0.5%. Furthermore, the number of parameters required for the Artificial Neural Network (ANN model is less than the studied thermodynamic models.

  11. Optimality models in the age of experimental evolution and genomics

    OpenAIRE

    Bull, J. J.; Wang, I.-N.

    2010-01-01

    Optimality models have been used to predict evolution of many properties of organisms. They typically neglect genetic details, whether by necessity or design. This omission is a common source of criticism, and although this limitation of optimality is widely acknowledged, it has mostly been defended rather than evaluated for its impact. Experimental adaptation of model organisms provides a new arena for testing optimality models and for simultaneously integrating genetics. First, an experimen...

  12. Confrontation of thermoluminescence models in lithium fluoride with experimental data

    International Nuclear Information System (INIS)

    Niewiadomski, T.

    1976-12-01

    The thermoluminescent properties of lithium fluoride depend on numerous factors and are much more complex than those of other phosphors. The so far developed fragmentary models are meant to explain the relationships between crystal defect structure and the processes involved in TL. An attempt has been made to compare these models with the veryfied experimental data and to point out the observations which are inconsistant with the models. (author)

  13. From traditional biochemical signals to molecular markers for detection of sepsis after burn injuries.

    Science.gov (United States)

    Muñoz, Balam; Suárez-Sánchez, Rocío; Hernández-Hernández, Oscar; Franco-Cendejas, Rafael; Cortés, Hernán; Magaña, Jonathan J

    2018-05-22

    Sepsis is a life-threatening organ-dysfunction condition caused by a dysregulated response to an infectious condition that can cause complications in patients with major trauma. Burns are one of the most destructive forms of trauma; despite the improvements in medical care, infections remain an important cause of burn injury-related mortality and morbidity, and complicated sepsis predisposes patients to diverse complications such as organ failure, lengthening of hospital stays, and increased costs. Accurate diagnosis and early treatment of sepsis may have a beneficial impact on clinical outcome of burn-injured patients. In this review, we offer a comprehensive description of the current and traditional markers used as indicative of sepsis in burned patients. However, although these are markers of the inflammatory post-burn response, they usually fail to predict sepsis in severely burned patients due to that they do not reflect the severity of the infection. Identification and measurement of biomarkers in early stages of infection is important in order to provide timely response and effective treatment of burned patients. Therefore, we compiled important experimental evidence, demonstrating novel biomarkers, including molecular markers such as genomic DNA variations, alterations of transcriptome profiling (mRNA, miRNAs, lncRNAs and circRNAs), epigenetic markers, and advances in proteomics and metabolomics. Finally, this review summarizes next-generation technologies for the identification of markers for detection of sepsis after burn injuries. Copyright © 2018 Elsevier Ltd and ISBI. All rights reserved.

  14. Physicians’ and nurses‘ knowledge and attitudes in management of sepsis: An Italian study

    Directory of Open Access Journals (Sweden)

    Gabriella Nucera

    2018-03-01

    Full Text Available Introduction: Sepsis is one of the most deadly and costly conditions at hospitals. Our study aimed to study levels of knowledge and attitudes in management of sepsis among nurses and physicians employed at Fatebenefratelli hospital, Milano, North-Italy, with particular regard to the analysis of the effects of educational training. Methods: A cross-sectional, quasi-experimental study was conducted between June 1 and October 30, 2017. Physicians and nurses from Intensive Care Unit (ICU and non-ICU hospital wards were recruited. The study participants were invited to attend some educational workshops and, after 6 months, to fill out a questionnaire based on the 2016 Surviving Sepsis Campaign guidelines. Descriptive statistics were expressed with frequency and percentage (%. Chi-square and Student’s t-test were performed to compare the differences in awareness and knowledge between groups. P-values 75% of knowledge of procedures that increase risk of sepsis, ‘fairly‘ (50-75% levels of knowledge, attitudes and behaviour towards blood culture techniques, and ‘poor’ ( 1 years or never trained (34.8 ± 7.4% nurses (n = 99 and physicians (n = 30 (t(10 = 11.72, P = < 0.001. Discussion and Conclusion: Our findings showed that levels of knowledge concerning methods and scores for early identification of sepsis can be significantly improved by educational training. A good knowledge of sepsis guidelines is essential to correct management of this condition.

  15. The role of heparin in sepsis: much more than just an anticoagulant.

    Science.gov (United States)

    Li, Xu; Ma, Xiaochun

    2017-11-01

    Despite progress in antibiotic treatment, mechanical ventilation, fluid resuscitation and blood glucose maintenance, sepsis remains a cause of high mortality in the intensive care unit to date, there are no proven treatment strategies for the routine management of septic patients. The extensive interaction between inflammation and coagulation contributes to the basic pathophysiology of sepsis. Thus, the agents that attenuate the activation of both inflammation and coagulation may improve the outcome in sepsis. Apart from the well-known anticoagulant effects of heparin, it also possesses various immunomodulatory properties and protects glycocalyx from shedding. Hence, heparin seems to be such an agent. Immunothrombosis plays an important role in early host defence against bacterial dissemination, thus the proper timing for anticoagulant therapy should be determined. We review the available experimental and clinical data supporting the use of heparin in sepsis. At this time the use of heparin in the treatment of sepsis is conflicting. Future trials of heparin therapy for sepsis should concentrate on the very severely ill patients, in whom benefit is most likely to be demonstrated. © 2017 John Wiley & Sons Ltd.

  16. Experimental Validation of a Dynamic Model for Lightweight Robots

    Directory of Open Access Journals (Sweden)

    Alessandro Gasparetto

    2013-03-01

    Full Text Available Nowadays, one of the main topics in robotics research is dynamic performance improvement by means of a lightening of the overall system structure. The effective motion and control of these lightweight robotic systems occurs with the use of suitable motion planning and control process. In order to do so, model-based approaches can be adopted by exploiting accurate dynamic models that take into account the inertial and elastic terms that are usually neglected in a heavy rigid link configuration. In this paper, an effective method for modelling spatial lightweight industrial robots based on an Equivalent Rigid Link System approach is considered from an experimental validation perspective. A dynamic simulator implementing the formulation is used and an experimental test-bench is set-up. Experimental tests are carried out with a benchmark L-shape mechanism.

  17. A sEMG model with experimentally based simulation parameters.

    Science.gov (United States)

    Wheeler, Katherine A; Shimada, Hiroshima; Kumar, Dinesh K; Arjunan, Sridhar P

    2010-01-01

    A differential, time-invariant, surface electromyogram (sEMG) model has been implemented. While it is based on existing EMG models, the novelty of this implementation is that it assigns more accurate distributions of variables to create realistic motor unit (MU) characteristics. Variables such as muscle fibre conduction velocity, jitter (the change in the interpulse interval between subsequent action potential firings) and motor unit size have been considered to follow normal distributions about an experimentally obtained mean. In addition, motor unit firing frequencies have been considered to have non-linear and type based distributions that are in accordance with experimental results. Motor unit recruitment thresholds have been considered to be related to the MU type. The model has been used to simulate single channel differential sEMG signals from voluntary, isometric contractions of the biceps brachii muscle. The model has been experimentally verified by conducting experiments on three subjects. Comparison between simulated signals and experimental recordings shows that the Root Mean Square (RMS) increases linearly with force in both cases. The simulated signals also show similar values and rates of change of RMS to the experimental signals.

  18. An international sepsis survey: a study of doctors' knowledge and perception about sepsis

    Science.gov (United States)

    Poeze, Martijn; Ramsay, Graham; Gerlach, Herwig; Rubulotta, Francesca; Levy, Mitchel

    2004-01-01

    Background To be able to diagnose and treat sepsis better it is important not only to improve the knowledge about definitions and pathophysiology, but also to gain more insight into specialists' perception of, and attitude towards, the current diagnosis and treatment of sepsis. Methods The study was conducted as a prospective, international survey by structured telephone interview. The subjects were intensive care physicians and other specialist physicians caring for intensive care unit (ICU) patients. Results The 1058 physicians who were interviewed (including 529 intensivists) agreed that sepsis is a leading cause of death on the ICU and that the incidence of sepsis is increasing, but that the symptoms of sepsis can easily be misattributed to other conditions. Physicians were concerned that this could lead to under-reporting of sepsis. Two-thirds (67%) were concerned that a common definition is lacking and 83% said it is likely that sepsis is frequently missed. Not more than 17% agreed on any one definition. Conclusion There is a general awareness about the inadequacy of the current definitions of sepsis. Physicians caring for patients with sepsis recognise the difficulty of defining and diagnosing sepsis and are aware that they miss the diagnosis frequently. PMID:15566585

  19. Sepsis

    Science.gov (United States)

    ... that may be done include: Blood differential Blood gases Kidney function tests Platelet count and fibrin degradation ... 2018, A.D.A.M., Inc. Duplication for commercial use must be authorized in writing by ADAM ...

  20. Loss of Sympathetic Nerves in Spleens from Patients with End Stage Sepsis

    Directory of Open Access Journals (Sweden)

    Donald B. Hoover

    2017-12-01

    Full Text Available The spleen is an important site for central regulation of immune function by noradrenergic sympathetic nerves, but little is known about this major region of neuroimmune communication in humans. Experimental studies using animal models have established that sympathetic innervation of the spleen is essential for cholinergic anti-inflammatory responses evoked by vagal nerve stimulation, and clinical studies are evaluating this approach for treating inflammatory diseases. Most data on sympathetic nerves in spleen derive from rodent studies, and this work has established that remodeling of sympathetic innervation can occur during inflammation. However, little is known about the effects of sepsis on spleen innervation. Our primary goals were to (i localize noradrenergic nerves in human spleen by immunohistochemistry for tyrosine hydroxylase (TH, a specific noradrenergic marker, (ii determine if nerves occur in close apposition to leukocytes, and (iii determine if splenic sympathetic innervation is altered in patients who died from end stage sepsis. Staining for vesicular acetylcholine transporter (VAChT was done to screen for cholinergic nerves. Archived paraffin tissue blocks were used. Control samples were obtained from trauma patients or patients who died after hemorrhagic stroke. TH + nerves were associated with arteries and arterioles in all control spleens, occurring in bundles or as nerve fibers. Individual TH + nerve fibers entered the perivascular region where some appeared in close apposition to leukocytes. In marked contrast, spleens from half of the septic patients lacked TH + nerves fibers and the average abundance of TH + nerves for the septic group was only 16% of that for the control group (control: 0.272 ± 0.060% area, n = 6; sepsis: 0.043 ± 0.026% area, n = 8; P < 0.005. All spleens lacked cholinergic innervation. Our results provide definitive evidence for the distribution of noradrenergic

  1. Experimental modeling of injectivity loss; Modelagem experimental da perda de injetividade

    Energy Technology Data Exchange (ETDEWEB)

    Bonato, Adriano Jose do Amaral Mello; Silva, Pedro Glauto de Farias e; Gomes, Vanessa Limeira Azevedo; Santos, Adriano dos [Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN (Brazil)

    2012-07-01

    Produced water reinjection, suspended particles are retained in the porous media causing formation damage and injectivity decline. In general the retention of the particles occurs near the side of injection, this fact occurs in most cases, due to the size exclusion. The modeling of filtration and the consequent formation damage is essential to the project management of water injection in oil reservoirs. Thus, mathematical models are studied to better predict the distribution of particles throughout the porous media and determine the parameters of adjustment to injectivity decline. Among these models, there is the classic model which consists in determining these parameters (coefficient of filtration and formation damage). The methodology used in modeling is given from the equations the mass conservation, kinetic particle retention, the modified Darcy equation and the function formation damage. This study aimed to improve experimental modeling, including development of software for acquisition and processing of experimental data, considering the variable number of pressure measurements along the sample. The software was developed using the Labview 2011 platform and allows the determination of relevant parameters to predict injectivity loss in water injection wells. Furthermore, based on the traditional model of filtration in porous media (including depth filtration and formation of the external plaster), the software was applied to predict injectivity loss in addition to the properties of the grout. Finally, the classical models for transporting suspensions and damage to the formation were observed. (author)

  2. Investigation of approximate models of experimental temperature characteristics of machines

    Science.gov (United States)

    Parfenov, I. V.; Polyakov, A. N.

    2018-05-01

    This work is devoted to the investigation of various approaches to the approximation of experimental data and the creation of simulation mathematical models of thermal processes in machines with the aim of finding ways to reduce the time of their field tests and reducing the temperature error of the treatments. The main methods of research which the authors used in this work are: the full-scale thermal testing of machines; realization of various approaches at approximation of experimental temperature characteristics of machine tools by polynomial models; analysis and evaluation of modelling results (model quality) of the temperature characteristics of machines and their derivatives up to the third order in time. As a result of the performed researches, rational methods, type, parameters and complexity of simulation mathematical models of thermal processes in machine tools are proposed.

  3. Contact Modelling in Resistance Welding, Part II: Experimental Validation

    DEFF Research Database (Denmark)

    Song, Quanfeng; Zhang, Wenqi; Bay, Niels

    2006-01-01

    Contact algorithms in resistance welding presented in the previous paper are experimentally validated in the present paper. In order to verify the mechanical contact algorithm, two types of experiments, i.e. sandwich upsetting of circular, cylindrical specimens and compression tests of discs...... with a solid ring projection towards a flat ring, are carried out at room temperature. The complete algorithm, involving not only the mechanical model but also the thermal and electrical models, is validated by projection welding experiments. The experimental results are in satisfactory agreement...

  4. Optimality models in the age of experimental evolution and genomics.

    Science.gov (United States)

    Bull, J J; Wang, I-N

    2010-09-01

    Optimality models have been used to predict evolution of many properties of organisms. They typically neglect genetic details, whether by necessity or design. This omission is a common source of criticism, and although this limitation of optimality is widely acknowledged, it has mostly been defended rather than evaluated for its impact. Experimental adaptation of model organisms provides a new arena for testing optimality models and for simultaneously integrating genetics. First, an experimental context with a well-researched organism allows dissection of the evolutionary process to identify causes of model failure--whether the model is wrong about genetics or selection. Second, optimality models provide a meaningful context for the process and mechanics of evolution, and thus may be used to elicit realistic genetic bases of adaptation--an especially useful augmentation to well-researched genetic systems. A few studies of microbes have begun to pioneer this new direction. Incompatibility between the assumed and actual genetics has been demonstrated to be the cause of model failure in some cases. More interestingly, evolution at the phenotypic level has sometimes matched prediction even though the adaptive mutations defy mechanisms established by decades of classic genetic studies. Integration of experimental evolutionary tests with genetics heralds a new wave for optimality models and their extensions that does not merely emphasize the forces driving evolution.

  5. Disruption of Brain-Heart Coupling in Sepsis

    NARCIS (Netherlands)

    Admiraal, Marjolein M.; Gilmore, Emily J.; Van Putten, Michel J.A.M.; Zaveri, Hitten P.; Hirsch, Lawrence J.; Gaspard, Nicolas

    2017-01-01

    Purpose: To investigate heart rate and EEG variability and their coupling in patients with sepsis and determine their relationship to sepsis severity and severity of sepsis-Associated brain dysfunction. Methods: Fifty-Two patients with sepsis were prospectively identified, categorized as comatose (N

  6. Team Modelling: Review of Experimental Scenarios and Computational Models

    Science.gov (United States)

    2006-09-01

    les auteurs ont réuni et examiné des scénarios ayant servi dans le cadre d’études antérieures sur les équipes, ils ont développé d’importants...cognition, perception, sensation, motor action and knowledge, that embody a principled underlying theory or framework for human information...Processing) integrates Qinetiq’s (POP) model with DRDC’s IP/PCT (Perceptual Control Theory ) models. In particular, the POP/IP model includes the

  7. Instrumental and ethical aspects of experimental research with animal models

    Directory of Open Access Journals (Sweden)

    Mirian Watanabe

    2014-02-01

    Full Text Available Experimental animal models offer possibilities of physiology knowledge, pathogenesis of disease and action of drugs that are directly related to quality nursing care. This integrative review describes the current state of the instrumental and ethical aspects of experimental research with animal models, including the main recommendations of ethics committees that focus on animal welfare and raises questions about the impact of their findings in nursing care. Data show that, in Brazil, the progress in ethics for the use of animals for scientific purposes was consolidated with Law No. 11.794/2008 establishing ethical procedures, attending health, genetic and experimental parameters. The application of ethics in handling of animals for scientific and educational purposes and obtaining consistent and quality data brings unquestionable contributions to the nurse, as they offer subsidies to relate pathophysiological mechanisms and the clinical aspect on the patient.

  8. Is hypertriglyceridemia a prognostic factor in sepsis?

    Directory of Open Access Journals (Sweden)

    Cetinkaya A

    2014-02-01

    Full Text Available Ali Cetinkaya,1 Abdulsamet Erden,1 Deniz Avci,1 Hatice Karagoz,1 Samet Karahan,1 Mustafa Basak,1 Kadir Bulut,1 Vedat Gencer,1 Hasan Mutlu2 1Internal Medicine Department, Kayseri Training and Research Hospital, Kayseri, Turkey; 2Medical Oncology Department, Acibadem Kayseri Hospital, Kayseri, Turkey Introduction: Sepsis and septic shock are important causes of mortality in intensive care unit patients, hence early diagnosis and therapy are important in management of their treatment. The available information on sepsis patients is not enough to recommend or to discard the routine evaluation of triglyceride (TG levels at the onset of sepsis. The aim of this study was to investigate the association of hypertriglyceridemia and clinical outcome (or mortality in patients with severe sepsis. Materials and methods: Between January 1 and December 31, 2011, a total of 84 patients with sepsis from the intensive internal care unit at the Kayseri Training and Research Hospital, Kayseri, Turkey, were investigated retrospectively. Sepsis was defined according to the American College of Chest Physicians/Society of Critical Care Medicine/European Society of Intensive Care Medicine consensus conference definitions. For each patient, survival was recorded at the end of the last day of hospitalization as dead or alive. The TG values were taken retrospectively from the records, which were performed routinely for each patient with sepsis at the time of diagnosis. TG >150 mg/dL was considered as hypertriglyceridemia. Results: The percentages of male and female patients were 44% and 56%, respectively. The mean age of patients was 71.49±11.071 years. The percentage of patients with TG values more than 150 mg/dL was 81% (25/31 in the non-survivor group and 19% (6/31 in the survivor group. There was a significant difference regarding TG values between groups (P=0.039. Discussion: It was observed in this study that patients in the intensive care unit with sepsis had high

  9. The intestinal microenvironment in sepsis.

    Science.gov (United States)

    Fay, Katherine T; Ford, Mandy L; Coopersmith, Craig M

    2017-10-01

    The gastrointestinal tract has long been hypothesized to function as "the motor" of multiple organ dysfunction syndrome. The gastrointestinal microenvironment is comprised of a single cell layer epithelia, a local immune system, and the microbiome. These three components of the intestine together play a crucial role in maintaining homeostasis during times of health. However, the gastrointestinal microenvironment is perturbed during sepsis, resulting in pathologic changes that drive both local and distant injury. In this review, we seek to characterize the relationship between the epithelium, gastrointestinal lymphocytes, and commensal bacteria during basal and pathologic conditions and how the intestinal microenvironment may be targeted for therapeutic gain in septic patients. Published by Elsevier B.V.

  10. Constitutive Model Calibration via Autonomous Multiaxial Experimentation (Postprint)

    Science.gov (United States)

    2016-09-17

    ABSTRACT (Maximum 200 words) Modern plasticity models contain numerous parameters that can be difficult and time consuming to fit using current...Abstract Modern plasticity models contain numerous parameters that can be difficult and time consuming to fit using current methods. Additional...complexity, is a difficult and time consuming process that has historically be a separate process from the experimental testing. As such, additional

  11. Experimental Analysis and Model Validation of an Opaque Ventilated Facade

    DEFF Research Database (Denmark)

    López, F. Peci; Jensen, Rasmus Lund; Heiselberg, Per

    2012-01-01

    Natural ventilation is a convenient way of reducing energy consumption in buildings. In this study an experimental module of an opaque ventilated façade (OVF) was built and tested for assessing its potential of supplying free ventilation and air preheating for the building. A numerical model was ...

  12. Capillary microreactors for lactic acid extraction: experimental and modelling study

    NARCIS (Netherlands)

    Susanti, Susanti; Winkelman, Jozef; Schuur, Boelo; Heeres, Hero; Yue, Jun

    2015-01-01

    Lactic acid is an important biobased chemical and, among others, is used for the production of poly-lactic acid. Down-stream processing using state of the art technology is energy intensive and leads to the formation of large amounts of salts. In this presentation, experimental and modeling studies

  13. Experimental data available for radiation damage modelling in reactor materials

    International Nuclear Information System (INIS)

    Wollenberger, H.

    Radiation damage modelling requires rate constants for production, annihilation and trapping of defects. The literature is reviewed with respect to experimental determination of such constants. Useful quantitative information exists only for Cu and Al. Special emphasis is given to the temperature dependence of the rate constants

  14. Low dose CT simulation using experimental noise model

    Energy Technology Data Exchange (ETDEWEB)

    Nakanishi, Satori; Zamyatin, Alexander A. [Toshiba Medical Systems Corporation, Tochigi, Otawarashi (Japan); Silver, Michael D. [Toshiba Medical Research Institute, Vernon Hills, IL (United States)

    2011-07-01

    We suggest a method to obtain system noise model experimentally without relying on assumptions on statistical distribution of the noise; also, knowledge of DAS gain and electronic noise level are not required. Evaluation with ultra-low dose CT data (5 mAs) shows good match between simulated and real data noise. (orig.)

  15. Novel sensors for food inspection modelling, fabrication and experimentation

    CERN Document Server

    Abdul Rahman, Mohd Syaifudin; Yu, Pak-Lam

    2014-01-01

    This book addresses presents recent developments of novel planar interdigital sensors for food inspection. It covers the fundamentals of sensors, their design, modelling and simulations, fabrications, characterizations, experimental investigations and analyses. This book will be useful for the engineers and researchers especially higher undergraduate, postgraduate students as well as practitioners working on the development of Electromagnetic Sensors.

  16. Robust Bayesian Experimental Design for Conceptual Model Discrimination

    Science.gov (United States)

    Pham, H. V.; Tsai, F. T. C.

    2015-12-01

    A robust Bayesian optimal experimental design under uncertainty is presented to provide firm information for model discrimination, given the least number of pumping wells and observation wells. Firm information is the maximum information of a system can be guaranteed from an experimental design. The design is based on the Box-Hill expected entropy decrease (EED) before and after the experiment design and the Bayesian model averaging (BMA) framework. A max-min programming is introduced to choose the robust design that maximizes the minimal Box-Hill EED subject to that the highest expected posterior model probability satisfies a desired probability threshold. The EED is calculated by the Gauss-Hermite quadrature. The BMA method is used to predict future observations and to quantify future observation uncertainty arising from conceptual and parametric uncertainties in calculating EED. Monte Carlo approach is adopted to quantify the uncertainty in the posterior model probabilities. The optimal experimental design is tested by a synthetic 5-layer anisotropic confined aquifer. Nine conceptual groundwater models are constructed due to uncertain geological architecture and boundary condition. High-performance computing is used to enumerate all possible design solutions in order to identify the most plausible groundwater model. Results highlight the impacts of scedasticity in future observation data as well as uncertainty sources on potential pumping and observation locations.

  17. Systematic integration of experimental data and models in systems biology.

    Science.gov (United States)

    Li, Peter; Dada, Joseph O; Jameson, Daniel; Spasic, Irena; Swainston, Neil; Carroll, Kathleen; Dunn, Warwick; Khan, Farid; Malys, Naglis; Messiha, Hanan L; Simeonidis, Evangelos; Weichart, Dieter; Winder, Catherine; Wishart, Jill; Broomhead, David S; Goble, Carole A; Gaskell, Simon J; Kell, Douglas B; Westerhoff, Hans V; Mendes, Pedro; Paton, Norman W

    2010-11-29

    The behaviour of biological systems can be deduced from their mathematical models. However, multiple sources of data in diverse forms are required in the construction of a model in order to define its components and their biochemical reactions, and corresponding parameters. Automating the assembly and use of systems biology models is dependent upon data integration processes involving the interoperation of data and analytical resources. Taverna workflows have been developed for the automated assembly of quantitative parameterised metabolic networks in the Systems Biology Markup Language (SBML). A SBML model is built in a systematic fashion by the workflows which starts with the construction of a qualitative network using data from a MIRIAM-compliant genome-scale model of yeast metabolism. This is followed by parameterisation of the SBML model with experimental data from two repositories, the SABIO-RK enzyme kinetics database and a database of quantitative experimental results. The models are then calibrated and simulated in workflows that call out to COPASIWS, the web service interface to the COPASI software application for analysing biochemical networks. These systems biology workflows were evaluated for their ability to construct a parameterised model of yeast glycolysis. Distributed information about metabolic reactions that have been described to MIRIAM standards enables the automated assembly of quantitative systems biology models of metabolic networks based on user-defined criteria. Such data integration processes can be implemented as Taverna workflows to provide a rapid overview of the components and their relationships within a biochemical system.

  18. Waste glass corrosion modeling: Comparison with experimental results

    International Nuclear Information System (INIS)

    Bourcier, W.L.

    1994-01-01

    Models for borosilicate glass dissolution must account for the processes of (1) kinetically-controlled network dissolution, (2) precipitation of secondary phases, (3) ion exchange, (4) rate-limiting diffusive transport of silica through a hydrous surface reaction layer, and (5) specific glass surface interactions with dissolved cations and anions. Current long-term corrosion models for borosilicate glass employ a rate equation consistent with transition state theory embodied in a geochemical reaction-path modeling program that calculates aqueous phase speciation and mineral precipitation/dissolution. These models are currently under development. Future experimental and modeling work to better quantify the rate-controlling processes and validate these models are necessary before the models can be used in repository performance assessment calculations

  19. An Agent-Based Model of a Hepatic Inflammatory Response to Salmonella: A Computational Study under a Large Set of Experimental Data.

    Science.gov (United States)

    Shi, Zhenzhen; Chapes, Stephen K; Ben-Arieh, David; Wu, Chih-Hang

    2016-01-01

    We present an agent-based model (ABM) to simulate a hepatic inflammatory response (HIR) in a mouse infected by Salmonella that sometimes progressed to problematic proportions, known as "sepsis". Based on over 200 published studies, this ABM describes interactions among 21 cells or cytokines and incorporates 226 experimental data sets and/or data estimates from those reports to simulate a mouse HIR in silico. Our simulated results reproduced dynamic patterns of HIR reported in the literature. As shown in vivo, our model also demonstrated that sepsis was highly related to the initial Salmonella dose and the presence of components of the adaptive immune system. We determined that high mobility group box-1, C-reactive protein, and the interleukin-10: tumor necrosis factor-α ratio, and CD4+ T cell: CD8+ T cell ratio, all recognized as biomarkers during HIR, significantly correlated with outcomes of HIR. During therapy-directed silico simulations, our results demonstrated that anti-agent intervention impacted the survival rates of septic individuals in a time-dependent manner. By specifying the infected species, source of infection, and site of infection, this ABM enabled us to reproduce the kinetics of several essential indicators during a HIR, observe distinct dynamic patterns that are manifested during HIR, and allowed us to test proposed therapy-directed treatments. Although limitation still exists, this ABM is a step forward because it links underlying biological processes to computational simulation and was validated through a series of comparisons between the simulated results and experimental studies.

  20. Seeking Sepsis in the Emergency Department- Identifying Barriers to Delivery of the Sepsis 6.

    Science.gov (United States)

    Bentley, James; Henderson, Susan; Thakore, Shobhan; Donald, Michael; Wang, Weijie

    2016-01-01

    The Sepsis 6 is an internationally accepted management bundle that, when initiated within one hour of identifying sepsis, can reduce morbidity and mortality. This management bundle was advocated by the Scottish Patient Safety Programme as part of its Acute Adult campaign launched in 2008 and adopted by NHS Tayside in 2012. Despite this, the Emergency Department (ED) of Ninewells Hospital, a tertiary referral centre and major teaching hospital in Scotland, was displaying poor success in the Sepsis 6. We therefore set out to improve compliance by evaluating the application of all aspects of the NHS Tayside Sepsis 6 bundle within one hour of ED triage time, to identify what human factors may influence achieving the one hour The Sepsis 6 bundle. This allowed us to tailor a number of specific interventions including educational sessions, regular audit and personal feedback and check list Sepsis 6 sticker. These interventions promoted a steady increase in compliance from an initial rate of 51.0% to 74.3%. The project highlighted that undifferentiated patients create a challenge in initiating the Sepsis 6. Pyrexia is a key human factor-trigger for recognising sepsis with initial nursing assessment being vital in recognition and identifying the best area (resus) of the department to manage severely septic patients. EDs need to recognise these challenges and develop educational and feedback plans for staff and utilise available resources to maximise the Sepsis 6 compliance.

  1. Platelets and Multi-Organ Failure in Sepsis

    Directory of Open Access Journals (Sweden)

    Elisabetta Greco

    2017-10-01

    Full Text Available Platelets have received increasing attention for their role in the pathophysiology of infectious disease, inflammation, and immunity. In sepsis, a low platelet count is a well-known biomarker for disease severity and more recently authors have focused their attention on the active role of platelets in the pathogenesis of multi-organ failure. Septic shock is characterised by a dysregulated inflammatory response, which can impair the microcirculation and lead to organ injury. Being at the crossroads between the immune system, clotting cascade, and endothelial cells, platelets seem to be an appealing central mediator and possible therapeutic target in sepsis. This review focuses on the pathogenic role of platelets in septic organ dysfunction in humans and animal models.

  2. Platelets and Multi-Organ Failure in Sepsis.

    Science.gov (United States)

    Greco, Elisabetta; Lupia, Enrico; Bosco, Ornella; Vizio, Barbara; Montrucchio, Giuseppe

    2017-10-20

    Platelets have received increasing attention for their role in the pathophysiology of infectious disease, inflammation, and immunity. In sepsis, a low platelet count is a well-known biomarker for disease severity and more recently authors have focused their attention on the active role of platelets in the pathogenesis of multi-organ failure. Septic shock is characterised by a dysregulated inflammatory response, which can impair the microcirculation and lead to organ injury. Being at the crossroads between the immune system, clotting cascade, and endothelial cells, platelets seem to be an appealing central mediator and possible therapeutic target in sepsis. This review focuses on the pathogenic role of platelets in septic organ dysfunction in humans and animal models.

  3. Modeling RERTR experimental fuel plates using the PLATE code

    International Nuclear Information System (INIS)

    Hayes, S.L.; Meyer, M.K.; Hofman, G.L.; Snelgrove, J.L.; Brazener, R.A.

    2003-01-01

    Modeling results using the PLATE dispersion fuel performance code are presented for the U-Mo/Al experimental fuel plates from the RERTR-1, -2, -3 and -5 irradiation tests. Agreement of the calculations with experimental data obtained in post-irradiation examinations of these fuels, where available, is shown to be good. Use of the code to perform a series of parametric evaluations highlights the sensitivity of U-Mo dispersion fuel performance to fabrication variables, especially fuel particle shape and size distributions. (author)

  4. Physics of human cooperation: experimental evidence and theoretical models

    Science.gov (United States)

    Sánchez, Angel

    2018-02-01

    In recent years, many physicists have used evolutionary game theory combined with a complex systems perspective in an attempt to understand social phenomena and challenges. Prominent among such phenomena is the issue of the emergence and sustainability of cooperation in a networked world of selfish or self-focused individuals. The vast majority of research done by physicists on these questions is theoretical, and is almost always posed in terms of agent-based models. Unfortunately, more often than not such models ignore a number of facts that are well established experimentally, and are thus rendered irrelevant to actual social applications. I here summarize some of the facts that any realistic model should incorporate and take into account, discuss important aspects underlying the relation between theory and experiments, and discuss future directions for research based on the available experimental knowledge.

  5. Experimental, statistical, and biological models of radon carcinogenesis

    International Nuclear Information System (INIS)

    Cross, F.T.

    1991-09-01

    Risk models developed for underground miners have not been consistently validated in studies of populations exposed to indoor radon. Imprecision in risk estimates results principally from differences between exposures in mines as compared to domestic environments and from uncertainties about the interaction between cigarette-smoking and exposure to radon decay products. Uncertainties in extrapolating miner data to domestic exposures can be reduced by means of a broad-based health effects research program that addresses the interrelated issues of exposure, respiratory tract dose, carcinogenesis (molecular/cellular and animal studies, plus developing biological and statistical models), and the relationship of radon to smoking and other copollutant exposures. This article reviews experimental animal data on radon carcinogenesis observed primarily in rats at Pacific Northwest Laboratory. Recent experimental and mechanistic carcinogenesis models of exposures to radon, uranium ore dust, and cigarette smoke are presented with statistical analyses of animal data. 20 refs., 1 fig

  6. The microcirculation is the motor of sepsis

    NARCIS (Netherlands)

    Ince, Can

    2005-01-01

    Regional tissue distress caused by microcirculatory dysfunction and mitochondrial depression underlies the condition in sepsis and shock where, despite correction of systemic oxygen delivery variables, regional hypoxia and oxygen extraction deficit persist. We have termed this condition

  7. Apolipoprotein M - a new biomarker in sepsis

    DEFF Research Database (Denmark)

    Christoffersen, Christina; Nielsen, Lars Bo

    2012-01-01

    Care Kumaraswamy and colleagues have investigated whether plasma apolipoprotein M (apoM) is affected during different grades of sepsis, septic shock and systemic inflammatory response syndrome. Interestingly, plasma apoM was significantly decreased in all groups of patients with a relationship...... to severity of disease. This identifies apoM as a potential new biomarker in sepsis. It also underscores the possibility that altered high-density lipoprotein in sepsis patients can affect the course of disease. Thus, since apoM is the carrier of Sphingosine-1-P (S1P), a molecule with great influence...... on vascular barrier function, the study presented raises the interest and relevance for further studies of apoM and S1P in relation to sepsis and inflammation....

  8. Thromboelastography in patients with severe sepsis

    DEFF Research Database (Denmark)

    Haase, Nicolai; Ostrowski, Sisse Rye; Wetterslev, Jørn

    2015-01-01

    PURPOSE: To investigate the association between consecutively measured thromboelastographic (TEG) tracings and outcome in patients with severe sepsis. METHODS: Multicentre prospective observational study in a subgroup of the Scandinavian Starch for Severe Sepsis/Septic Shock (6S) Trial (NCT00962156......) comparing hydroxyethyl starch (HES) 130/0.42 vs. Ringer's acetate for fluid resuscitation in severe sepsis. TEG (standard and functional fibrinogen) was measured consecutively for 5 days, and clinical data including bleeding and death was retrieved from the trial database. Statistical analyses included Cox...... bleeding [HR 2.43 (1.16-5.07)] and possibly explained the excess bleeding with HES in the 6S trial. CONCLUSIONS: In our cohort of patients with severe sepsis, progressive hypocoagulability defined by TEG variables was associated with increased risk of death and increased risk of bleeding....

  9. Development of experimental alloxan model of diabetes mellitus

    Directory of Open Access Journals (Sweden)

    V.V. Semenko

    2017-05-01

    Full Text Available Background. One of the main causes that lead to the disability of diabetic patients is diabetic retinopathy (DR. The relevance of the problem of DR necessitates the development of optimal experimental models on experimental animals to find effective ways of correcting this pathology. The purpose of our work was to develop an experimental alloxan model of type 1 diabetes mellitus (DM for the study of DR, which would not result in the lethal outcome of experimental animals under the action of alloxan; histological examination of changes in the tissues of the eyeball in the reproduction of the DM model for the selection of new effective methods for the metabolic treatment of DR in the early stages. Materials and methods. The experiment was carried out on white outbred Wistar rats weighing 180–200 g. The first group consisted of 20 animals that were not subjected to any influence, served as a control; second group — 30 animals, in which DM was modeled by administration of alloxan and fructose. Results. When modeling DR, vessel changes in the form of wall fibrosis, edema of the endothelium and vasospasm were found. There was also a decrease in the amount of pigment granules, dystrophic changes in the cells of the ganglionic layer and a layer of retinal rods and cones, which coincides with the descriptions of damage to the coats of the eyeball in patients with DM. Conclusions. In our studies, we have calculated the optimal dose of alloxan administration, which does not lead to the death of rats (the lethality of rats was absent and is an effective model not only of DM in general, but also of DR.

  10. Experimental Evaluation of Equivalent-Fluid Models for Melamine Foam

    Science.gov (United States)

    Allen, Albert R.; Schiller, Noah H.

    2016-01-01

    Melamine foam is a soft porous material commonly used in noise control applications. Many models exist to represent porous materials at various levels of fidelity. This work focuses on rigid frame equivalent fluid models, which represent the foam as a fluid with a complex speed of sound and density. There are several empirical models available to determine these frequency dependent parameters based on an estimate of the material flow resistivity. Alternatively, these properties can be experimentally educed using an impedance tube setup. Since vibroacoustic models are generally sensitive to these properties, this paper assesses the accuracy of several empirical models relative to impedance tube measurements collected with melamine foam samples. Diffuse field sound absorption measurements collected using large test articles in a laboratory are also compared with absorption predictions determined using model-based and measured foam properties. Melamine foam slabs of various thicknesses are considered.

  11. Experimental validation of a Bayesian model of visual acuity.

    LENUS (Irish Health Repository)

    Dalimier, Eugénie

    2009-01-01

    Based on standard procedures used in optometry clinics, we compare measurements of visual acuity for 10 subjects (11 eyes tested) in the presence of natural ocular aberrations and different degrees of induced defocus, with the predictions given by a Bayesian model customized with aberrometric data of the eye. The absolute predictions of the model, without any adjustment, show good agreement with the experimental data, in terms of correlation and absolute error. The efficiency of the model is discussed in comparison with image quality metrics and other customized visual process models. An analysis of the importance and customization of each stage of the model is also given; it stresses the potential high predictive power from precise modeling of ocular and neural transfer functions.

  12. Fine Particulate Matter Pollution and Risk of Community-Acquired Sepsis.

    Science.gov (United States)

    Sarmiento, Elisa J; Moore, Justin Xavier; McClure, Leslie A; Griffin, Russell; Al-Hamdan, Mohammad Z; Wang, Henry E

    2018-04-21

    While air pollution has been associated with health complications, its effect on sepsis risk is unknown. We examined the association between fine particulate matter (PM 2.5 ) air pollution and risk of sepsis hospitalization. We analyzed data from the 30,239 community-dwelling adults in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort linked with satellite-derived measures of PM 2.5 data. We defined sepsis as a hospital admission for a serious infection with ≥2 systemic inflammatory response (SIRS) criteria. We performed incidence density sampling to match sepsis cases with 4 controls by age (±5 years), sex, and race. For each matched group we calculated mean daily PM 2.5 exposures for short-term (30-day) and long-term (one-year) periods preceding the sepsis event. We used conditional logistic regression to evaluate the association between PM 2.5 exposure and sepsis, adjusting for education, income, region, temperature, urbanicity, tobacco and alcohol use, and medical conditions. We matched 1386 sepsis cases with 5544 non-sepsis controls. Mean 30-day PM 2.5 exposure levels (Cases 12.44 vs. Controls 12.34 µg/m³; p = 0.28) and mean one-year PM 2.5 exposure levels (Cases 12.53 vs. Controls 12.50 µg/m³; p = 0.66) were similar between cases and controls. In adjusted models, there were no associations between 30-day PM 2.5 exposure levels and sepsis (4th vs. 1st quartiles OR: 1.06, 95% CI: 0.85⁻1.32). Similarly, there were no associations between one-year PM 2.5 exposure levels and sepsis risk (4th vs. 1st quartiles OR: 0.96, 95% CI: 0.78⁻1.18). In the REGARDS cohort, PM 2.5 air pollution exposure was not associated with risk of sepsis.

  13. Procalcitonin ? Assisted Antibiotic Strategy in Sepsis

    OpenAIRE

    Tr?sy, Domonkos; Moln?r, Zsolt

    2017-01-01

    Sepsis is one of the biggest challenges in critical care nowadays. Defining sepsis is a difficult task on its own and its diagnosis and treatment requires well trained, devoted personnel with interdisciplinary collaboration in order to provide the patients the best chance for survival. Immediate resuscitation, early adequate antimicrobial therapy, source control and highly sophisticated organ support on the intensive care units are all inevitable necessities for successful recovery. To help f...

  14. Toll-like receptors in neonatal sepsis.

    LENUS (Irish Health Repository)

    O'Hare, Fiona M

    2013-06-01

    Toll-like receptors are vital transmembrane receptors that initiate the innate immune response to many micro-organisms. The discovery of these receptors has improved our understanding of host-pathogen interactions, and these receptors play an important role in the pathogenesis of multiple neonatal conditions such as sepsis and brain injury. Toll-like receptors, especially TLRs 2 and 4, are associated with necrotizing enterocolitis, periventricular leukomalacia and sepsis.

  15. Regulators of Intestinal Epithelial Migration in Sepsis.

    Science.gov (United States)

    Meng, Mei; Klingensmith, Nathan J; Liang, Zhe; Lyons, John D; Fay, Katherine T; Chen, Ching-Wen; Ford, Mandy L; Coopersmith, Craig M

    2018-02-08

    The gut is a continuously renewing organ, with cell proliferation, migration and death occurring rapidly under basal conditions. Since the impact of critical illness on cell movement from crypt base to villus tip is poorly understood, the purpose of this study was to determine how sepsis alters enterocyte migration. Wild type, transgenic and knockout mice were injected with 5-bromo-2'deoxyuridine (BrdU) to label cells in S phase before and after the onset of cecal ligation and puncture and were sacrificed at pre-determined endpoints to determine distance proliferating cells migrated up the crypt-villus unit. Enterocyte migration rate was decreased from 24-96 hours following sepsis. BrdU was not detectable on villi 6 days after sham laparotomy, meaning all cells had migrated the length of the gut and been exfoliated into its lumen. However, BrdU positive cells were detectable on villi 10 days after sepsis. Multiple components of gut integrity altered enterocyte migration. Sepsis decreased crypt proliferation, which further slowed enterocyte transit as mice injected with BrdU after the onset of sepsis (decreased proliferation) had slower migration than mice injected with BrdU prior to the onset of sepsis (normal proliferation). Decreasing intestinal apoptosis via gut-specific overexpression of Bcl-2 prevented sepsis-induced slowing of enterocyte migration. In contrast, worsened intestinal hyperpermeability by genetic deletion of JAM-A increased enterocyte migration. Sepsis therefore significantly slows enterocyte migration, and intestinal proliferation, apoptosis and permeability all affect migration time, which can potentially be targeted both genetically and pharmacologically.

  16. Uterus transplantation: Experimental animal models and recent experience in humans

    Directory of Open Access Journals (Sweden)

    Sadık Şahin

    2015-03-01

    Full Text Available Uterus transplantation has been considered as an alternative management modality in the last few years for adoption or gestational surrogacy for women with absence of uterus due to congenital or acquired reasons. Surrogacy is legal in only a few countries because of ethical, social and legal issues. Up to date, a total of 11 uterus transplantation cases have been reported in which uteri were harvested from ten live donors and one donor with brain death. After unsuccessful attempt of first uterus transplantation, many studies have been conducted in animals and these experimental models enabled our knowledge to increase on this topic. First experimental studies were performed in rodents; later uterus transplantation was accomplished in sheep, pigs and rabbits. Recently, researches in non-human primates have led the experience regarding transplantation technique and success to improve. In this review, we reviewed the experimental animal researches in the area of uterus transplantation and recent experience in humans.

  17. The rabbit as an experimental model in laryngology

    Directory of Open Access Journals (Sweden)

    Carneiro, Christiano de Giacomo

    2009-06-01

    Full Text Available Introduction: In the research in laryngology we normally use animal models. The animal experimentation may also contribute largely for this evolution, mainly for the easy access compared to human larynxes and for they are more easily controlled. Objective: The objective of this work is to analyze the laryngofissure with vocal cords graft as an experimental surgical technique in male adult rabbits. Method: We studied 46 New Zealand albino rabbits submitted to microsurgery in both vocal cords with autologous unilateral or bilateral graft of fat or fascia. Results: There were 4 losses of 3 animals until the first week of the postoperative period and another after 19 days after surgery. In the subsequent animals there were no infection, hematoma or sutures dehiscence. Conclusion: The study enables the conclusion that the experimental laryngofissure in rabbits is a safe method that may be used for laryngological studies.

  18. Genetic algorithms and experimental discrimination of SUSY models

    International Nuclear Information System (INIS)

    Allanach, B.C.; Quevedo, F.; Grellscheid, D.

    2004-01-01

    We introduce genetic algorithms as a means to estimate the accuracy required to discriminate among different models using experimental observables. We exemplify the technique in the context of the minimal supersymmetric standard model. If supersymmetric particles are discovered, models of supersymmetry breaking will be fit to the observed spectrum and it is beneficial to ask beforehand: what accuracy is required to always allow the discrimination of two particular models and which are the most important masses to observe? Each model predicts a bounded patch in the space of observables once unknown parameters are scanned over. The questions can be answered by minimising a 'distance' measure between the two hypersurfaces. We construct a distance measure that scales like a constant fraction of an observable, since that is how the experimental errors are expected to scale. Genetic algorithms, including concepts such as natural selection, fitness and mutations, provide a solution to the minimisation problem. We illustrate the efficiency of the method by comparing three different classes of string models for which the above questions could not be answered with previous techniques. The required accuracy is in the range accessible to the Large Hadron Collider (LHC) when combined with a future linear collider (LC) facility. The technique presented here can be applied to more general classes of models or observables. (author)

  19. Anaesthetic management of patients with severe sepsis.

    Science.gov (United States)

    Eissa, D; Carton, E G; Buggy, D J

    2010-12-01

    Severe sepsis, a syndrome characterized by systemic inflammation and acute organ dysfunction in response to infection, is a major healthcare problem affecting all age groups throughout the world. Anaesthetists play a central role in the multidisciplinary management of patients with severe sepsis from their initial deterioration at ward level, transfer to the diagnostic imaging suite, and intraoperative management for emergency surgery. The timely administration of appropriate i.v. antimicrobial therapy is a crucial step in the care of patients with severe sepsis who may require surgery to control the source of sepsis. Preoperative resuscitation, aimed at optimizing major organ perfusion, is based on judicious use of fluids, vasopressors, and inotropes. Intraoperative anaesthesia management requires careful induction and maintenance of anaesthesia, optimizing intravascular volume status, avoidance of lung injury during mechanical ventilation, and ongoing monitoring of arterial blood gases, lactate concentration, haematological and renal indices, and electrolyte levels. Postoperative care overlaps with ongoing management of the severe sepsis syndrome patient in the intensive care unit. These patients are by definition, high risk, already requiring multiple supports, and require experienced and skilful decision-making to optimize their chances of a favourable outcome. Similar to acute myocardial infarction, stroke, or acute trauma, the initial hours (golden hours) of clinical management of severe sepsis represent an important opportunity to reduce morbidity and mortality. Rapid clinical assessment, resuscitation and surgical management by a focused multidisciplinary team, and early effective antimicrobial therapy are the key components to improved patient outcome.

  20. Transvaginal ultrasound ovarian diathermy: sheep as an experimental model

    Directory of Open Access Journals (Sweden)

    Pimentel Anita M

    2012-01-01

    Full Text Available Abstract Background Some techniques of transvaginal ovarian drilling have been previously described. Nevertheless a monopolar transvaginal ovarian cauterization, that use the expertise and safety of transvaginal puncture for oocyte captation seems to be an easier and feasible approach. The aim of this study was to develop a minimally invasive ovarian cauterization technique under transvaginal ultrasound control, and to evaluate the safety of the transvaginal ovarian monopolar cauterization, female sheep at reproductive age were used as an experimental model. Findings An experimental study was performed in a university research center. Seventeen female sheep (15 Corriedale e 2 Suffolk in reproductive age were submitted to transvaginal ovarian cauterization with a monopolar Valleylab Force 2 electrocautery. Macroscopic and microscopic lesions were assessed. Ovarian size were 1.31 cm2 ± 0,43 (Corriedale and 3.41 cm2 ± 0,64 (Suffolk. From 30 ovaries from Corriedale sheep punctured, only 3 were cauterized, presenting macroscopic and typical microscopic lesion. In the Suffolk sheep group, only one ovary was cauterized. No lesion could be found in the needle path. Conclusions This is the first experimental animal model described for ovarian cauterization needle guided by transvaginal ultrasound. The sheep does not seem to be the ideal animal model to study this technique. Another animal model, whose ovaries are better identified by transvaginal ultrasound should be sought for this technique, theoretically less invasive, before it could be offered safely to women with polycystic ovary syndrome.

  1. Experimental designs for autoregressive models applied to industrial maintenance

    International Nuclear Information System (INIS)

    Amo-Salas, M.; López-Fidalgo, J.; Pedregal, D.J.

    2015-01-01

    Some time series applications require data which are either expensive or technically difficult to obtain. In such cases scheduling the points in time at which the information should be collected is of paramount importance in order to optimize the resources available. In this paper time series models are studied from a new perspective, consisting in the use of Optimal Experimental Design setup to obtain the best times to take measurements, with the principal aim of saving costs or discarding useless information. The model and the covariance function are expressed in an explicit form to apply the usual techniques of Optimal Experimental Design. Optimal designs for various approaches are computed and their efficiencies are compared. The methods working in an application of industrial maintenance of a critical piece of equipment at a petrochemical plant are shown. This simple model allows explicit calculations in order to show openly the procedure to find the correlation structure, needed for computing the optimal experimental design. In this sense the techniques used in this paper to compute optimal designs may be transferred to other situations following the ideas of the paper, but taking into account the increasing difficulty of the procedure for more complex models. - Highlights: • Optimal experimental design theory is applied to AR models to reduce costs. • The first observation has an important impact on any optimal design. • Either the lack of precision or small starting observations claim for large times. • Reasonable optimal times were obtained relaxing slightly the efficiency. • Optimal designs were computed in a predictive maintenance context

  2. Effects of Erdosteine on Experimental Acute Pancreatitis Model.

    Science.gov (United States)

    Karapolat, Banu; Karapolat, Sami; Gurleyik, Emin; Yasar, Mehmet

    2017-10-01

    To create acute pancreatitis condition experimentally in rats using cerulein, and to reveal histopathological effects in pancreatic tissue with erdosteine. An experimental study. Department of General Surgery, Duzce University, Turkey, from June to October 2014. Thirty male Wistar albino rats were divided into three groups. No procedures were applied to Group 1. The rats in Group 2 and Group 3 were injected cerulein, to establish an experimental pancreatitis model and the blood amylase and lipase values were examined. The rats in Group 3 were given 10 mg/kg erdosteine. This treatment was continued for another 2 days and the rats were sacrificed. The pancreatic tissues were examined histopathologically for edema, inflammation, acinar necrosis, fat necrosis, and vacuolization. The lipase and amylase values and the histopathological examination of pancreatic tissues evidenced that the experimental acute pancreatitis model was established and edema, inflammation, acinar necrosis, fat necrosis, and vacuolization were observed in the pancreatic tissues. The statistical results suggest that erdosteine can decrease the edema, inflammation, acinar necrosis, fat necrosis and vacuolization scores in the tissues. The severity of acute pancreatitis, induced by cerulein in rats, is reduced with the use of erdosteine.

  3. Experimental animal data and modeling of late somatic effects

    International Nuclear Information System (INIS)

    Fry, R.J.M.

    1988-01-01

    This section is restricted to radiation-induced life shortening and cancer and mainly to studies with external radiation. The emphasis will be on the experimental data that are available and the experimental systems that could provide the type of data with which to either formulate or test models. Genetic effects which are of concern are not discussed in this section. Experimental animal radiation studies fall into those that establish general principles and those that demonstrate mechanisms. General principles include the influence of dose, radiation quality, dose rate, fractionation, protraction and such biological factors as age and gender. The influence of these factors are considered as general principles because they are independent, at least qualitatively, of the species studied. For example, if an increase in the LET of the radiation causes an increased effectiveness in cancer induction in a mouse a comparable increase in effectiveness can be expected in humans. Thus, models, whether empirical or mechanistic, formulated from experimental animal data should be generally applicable

  4. Validation of the newborn larynx modeling with aerodynamical experimental data.

    Science.gov (United States)

    Nicollas, R; Giordano, J; Garrel, R; Medale, M; Caminat, P; Giovanni, A; Ouaknine, M; Triglia, J M

    2009-06-01

    Many authors have studied adult's larynx modelization, but the mechanisms of newborn's voice production have very rarely been investigated. After validating a numerical model with acoustic data, studies were performed on larynges of human fetuses in order to validate this model with aerodynamical experiments. Anatomical measurements were performed and a simplified numerical model was built using Fluent((R)) with the vocal folds in phonatory position. The results obtained are in good agreement with those obtained by laser Doppler velocimetry (LDV) and high-frame rate particle image velocimetry (HFR-PIV), on an experimental bench with excised human fetus larynges. It appears that computing with first cry physiological parameters leads to a model which is close to those obtained in experiments with real organs.

  5. Global trends in the awareness of sepsis: insights from search engine data between 2012 and 2017.

    Science.gov (United States)

    Jabaley, Craig S; Blum, James M; Groff, Robert F; O'Reilly-Shah, Vikas N

    2018-01-17

    Sepsis is an established global health priority with high mortality that can be curtailed through early recognition and intervention; as such, efforts to raise awareness are potentially impactful and increasingly common. We sought to characterize trends in the awareness of sepsis by examining temporal, geographic, and other changes in search engine utilization for sepsis information-seeking online. Using time series analyses and mixed descriptive methods, we retrospectively analyzed publicly available global usage data reported by Google Trends (Google, Palo Alto, CA, USA) concerning web searches for the topic of sepsis between 24 June 2012 and 24 June 2017. Google Trends reports aggregated and de-identified usage data for its search products, including interest over time, interest by region, and details concerning the popularity of related queries where applicable. Outlying epochs of search activity were identified using autoregressive integrated moving average modeling with transfer functions. We then identified awareness campaigns and news media coverage that correlated with epochs of significantly heightened search activity. A second-order autoregressive model with transfer functions was specified following preliminary outlier analysis. Nineteen significant outlying epochs above the modeled baseline were identified in the final analysis that correlated with 14 awareness and news media events. Our model demonstrated that the baseline level of search activity increased in a nonlinear fashion. A recurrent cyclic increase in search volume beginning in 2012 was observed that correlates with World Sepsis Day. Numerous other awareness and media events were correlated with outlying epochs. The average worldwide search volume for sepsis was less than that of influenza, myocardial infarction, and stroke. Analyzing aggregate search engine utilization data has promise as a mechanism to measure the impact of awareness efforts. Heightened information-seeking about sepsis

  6. Experimental Damage Identification of a Model Reticulated Shell

    Directory of Open Access Journals (Sweden)

    Jing Xu

    2017-04-01

    Full Text Available The damage identification of a reticulated shell is a challenging task, facing various difficulties, such as the large number of degrees of freedom (DOFs, the phenomenon of modal localization and transition, and low modeling accuracy. Based on structural vibration responses, the damage identification of a reticulated shell was studied. At first, the auto-regressive (AR time series model was established based on the acceleration responses of the reticulated shell. According to the changes in the coefficients of the AR model between the damaged conditions and the undamaged condition, the damage of the reticulated shell can be detected. In addition, the damage sensitive factors were determined based on the coefficients of the AR model. With the damage sensitive factors as the inputs and the damage positions as the outputs, back-propagation neural networks (BPNNs were then established and were trained using the Levenberg–Marquardt algorithm (L–M algorithm. The locations of the damages can be predicted by the back-propagation neural networks. At last, according to the experimental scheme of single-point excitation and multi-point responses, the impact experiments on a K6 shell model with a scale of 1/10 were conducted. The experimental results verified the efficiency of the proposed damage identification method based on the AR time series model and back-propagation neural networks. The proposed damage identification method can ensure the safety of the practical engineering to some extent.

  7. Peltier cells as temperature control elements: Experimental characterization and modeling

    International Nuclear Information System (INIS)

    Mannella, Gianluca A.; La Carrubba, Vincenzo; Brucato, Valerio

    2014-01-01

    The use of Peltier cells to realize compact and precise temperature controlled devices is under continuous extension in recent years. In order to support the design of temperature control systems, a simplified modeling of heat transfer dynamics for thermoelectric devices is presented. By following a macroscopic approach, the heat flux removed at the cold side of Peltier cell can be expressed as Q . c =γ(T c −T c eq ), where γ is a coefficient dependent on the electric current, T c and T c eq are the actual and steady state cold side temperature, respectively. On the other hand, a microscopic modeling approach was pursued via finite element analysis software packages. To validate the models, an experimental apparatus was designed and build-up, consisting in a sample vial with the surfaces in direct contact with Peltier cells. Both modeling approaches led to reliable prediction of transient and steady state sample temperature. -- Highlights: • Simplified modeling of heat transfer dynamics in Peltier cells. • Coupled macroscopic and microscopic approach. • Experimental apparatus: temperature control of a sample vial. • Both modeling approaches predict accurately the transient and steady state sample temperature

  8. Target Soil Impact Verification: Experimental Testing and Kayenta Constitutive Modeling.

    Energy Technology Data Exchange (ETDEWEB)

    Broome, Scott Thomas [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States); Flint, Gregory Mark [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States); Dewers, Thomas [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States); Newell, Pania [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States)

    2015-11-01

    This report details experimental testing and constitutive modeling of sandy soil deformation under quasi - static conditions. This is driven by the need to understand constitutive response of soil to target/component behavior upon impact . An experimental and constitutive modeling program was followed to determine elastic - plastic properties and a compressional failure envelope of dry soil . One hydrostatic, one unconfined compressive stress (UCS), nine axisymmetric compression (ACS) , and one uniaxial strain (US) test were conducted at room temperature . Elastic moduli, assuming isotropy, are determined from unload/reload loops and final unloading for all tests pre - failure and increase monotonically with mean stress. Very little modulus degradation was discernable from elastic results even when exposed to mean stresses above 200 MPa . The failure envelope and initial yield surface were determined from peak stresses and observed onset of plastic yielding from all test results. Soil elasto - plastic behavior is described using the Brannon et al. (2009) Kayenta constitutive model. As a validation exercise, the ACS - parameterized Kayenta model is used to predict response of the soil material under uniaxial strain loading. The resulting parameterized and validated Kayenta model is of high quality and suitable for modeling sandy soil deformation under a range of conditions, including that for impact prediction.

  9. A prospective treatment for sepsis

    Directory of Open Access Journals (Sweden)

    Shahidi Bonjar MR

    2015-05-01

    Full Text Available Mohammad Rashid Shahidi Bonjar,1 Leyla Shahidi Bonjar2 1School of Dentistry, 2College of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran Abstract: The present paper proposes a prospective auxiliary treatment for sepsis. There exists no record in the published media on the subject. As an auxiliary therapy, efficacious extracorporeal removal of sepsis-causing bacterial antigens and their toxins (BATs from the blood of septic patients is discussed. The principal component to this approach is a bacterial polyvalent antibody-column (BPVAC, which selectively traps wide spectrum of BATs from blood in an extracorporeal circuit, and detoxified blood returns back to the patient’s body. BPVAC treatment would be a device of targeted medicine. Detoxification is performed under supervision of trained personnel using simple blood-circulating machines in which blood circulates from the patient to BPVAC and back to the patient aseptically. BPVACs’ reactive sites consist of carbon nanotubes on which a vast spectra of polyvalent BATs-antibodies are bond to. The devise acts as a biological filter that selectively immobilizes harmful BATs from intoxicated blood; however, no dialysis is involved. For effective neutralization, BPVAC provides large contact surface area with blood. BPVAC approach would have advantages of: 1 urgent neutralization of notorious BATs from blood of septic patients; 2 applicability in parallel with conventional treatments; 3 potential to minimize side effects of the malady; 4 applicability for a vast range of BATs; 5 potential to eliminate contact of BATs with internal tissues and organs; 6 tolerability by patients sensitive to antiserum injections; 7 capability for universal application; 8 affectivity when antibiotic-resistant bacteria are involved and the physician has no or limited access to appropriate antibiotics; and 10 being a single-use, disposable, and stand-alone device. Before using it for clinical trials in

  10. WWER reactor fuel performance, modelling and experimental support. Proceedings

    International Nuclear Information System (INIS)

    Stefanova, S.; Chantoin, P.; Kolev, I.

    1994-01-01

    This publication is a compilation of 36 papers presented at the International Seminar on WWER Reactor Fuel Performance, Modelling and Experimental Support, organised by the Institute for Nuclear Research and Nuclear Energy (BG), in cooperation with the International Atomic Energy Agency. The Seminar was attended by 76 participants from 16 countries, including representatives of all major Russian plants and institutions responsible for WWER reactor fuel manufacturing, design and research. The reports are grouped in four chapters: 1) WWER Fuel Performance and Economics: Status and Improvement Prospects: 2) WWER Fuel Behaviour Modelling and Experimental Support; 3) Licensing of WWER Fuel and Fuel Analysis Codes; 4) Spent Fuel of WWER Plants. The reports from the corresponding four panel discussion sessions are also included. All individual papers are recorded in INIS as separate items

  11. WWER reactor fuel performance, modelling and experimental support. Proceedings

    Energy Technology Data Exchange (ETDEWEB)

    Stefanova, S; Chantoin, P; Kolev, I [eds.

    1994-12-31

    This publication is a compilation of 36 papers presented at the International Seminar on WWER Reactor Fuel Performance, Modelling and Experimental Support, organised by the Institute for Nuclear Research and Nuclear Energy (BG), in cooperation with the International Atomic Energy Agency. The Seminar was attended by 76 participants from 16 countries, including representatives of all major Russian plants and institutions responsible for WWER reactor fuel manufacturing, design and research. The reports are grouped in four chapters: (1) WWER Fuel Performance and Economics: Status and Improvement Prospects: (2) WWER Fuel Behaviour Modelling and Experimental Support; (3) Licensing of WWER Fuel and Fuel Analysis Codes; (4) Spent Fuel of WWER Plants. The reports from the corresponding four panel discussion sessions are also included. All individual papers are recorded in INIS as separate items.

  12. An Interactive Multimedia Based Instruction in Experimental Modelling

    DEFF Research Database (Denmark)

    Knudsen, Morten; Nielsen, J.N.; Østergaard, J.

    1997-01-01

    A CD-ROM based interactive multimedia instruction in experimental modelling for Danish Engineering School teachers is described. The content is based on a new sensitivity approach for direct estimation of physical parameters in linear and nonlinear dynamic systems. The presentation is inspired of...... of Solomans=s inventory of learning styles. To enhance active learning and motivation by real life problems, the simulation tool Matlab is integrated in the authoring program Medi8or....

  13. Numerical modeling of nitrogen oxide emission and experimental verification

    Directory of Open Access Journals (Sweden)

    Szecowka Lech

    2003-12-01

    Full Text Available The results of nitrogen reduction in combustion process with application of primary method are presented in paper. The reduction of NOx emission, by the recirculation of combustion gasses, staging of fuel and of air was investigated, and than the reduction of NOx emission by simultaneous usage of the mentioned above primary method with pulsatory disturbances.The investigations contain numerical modeling of NOx reduction and experimental verification of obtained numerical calculation results.

  14. Experimental model of cutaneous radiation injury in rabbits

    Energy Technology Data Exchange (ETDEWEB)

    Meirelles, Rafael Panisi de Campos [Universidade Federal de Sao Paulo (EPM/UNIFESP), SP (Brazil). Escola Paulista de Medicina; Hochman, Bernardo [Universidade Federal de Sao Paulo (EPM/UNIFESP), SP (Brazil). Escola Paulista de Medicina. Dept. de Cirurgia; Helene Junior, Americo; Fraga, Murillo Francisco Pires [Faculdade de Ciencias Medicas da Santa Casa de Sao Paulo (FCMSCSP), SP (Brazil). Dept. de Cirurgia. Divisao de Cirurgia Plastica; Lellis, Rute [Faculdade de Ciencias Medicas da Santa Casa de Sao Paulo (FCMSCSP), SP (Brazil). Divisao de Patologia; Ferreira, Lydia Masako, E-mail: rpcmeirelles@yahoo.com.br, E-mail: lydia.dcir@epm.br [Universidade Federal de Sao Paulo (EPM/UNIFESP), SP (Brazil). Escola Paulista de Mediciana. Divisao de Cirugia Plastica

    2013-07-01

    Purpose: to describe an experimental model of cutaneous radiation injury in rabbits. Methods: on this study eight six-month-old New Zealand male rabbits, with an average weight of 2.5kg were used. They were distributed in four groups (n=2 per group). The control group did not receive radiotherapy and the others received one radiotherapy session of 2000, 3000 and 4500 cGy, respectively. Photographic analysis and histopathological evaluation of the irradiated areas were carried out. Results: after 30 days, the animals from the control group had all their hair grown. In spite of that, the animals from group 2000 cGy had a 60-day alopecia and from group 3000 cGy, a 90-day alopecia. After the 30th day, the 3000cGy group demonstrated 90-day cutaneous radiation injuries, graded 3 and 4. One of the animals from group 4500 cGy died on the 7th day with visceral necrosis. The other from the same group had total skin necrosis. A progressive reduction of glands and blood vessels count and an increase on collagen deposition was observed. Conclusion: The proposed experimental model is reproducible. This study suggests that the dosage 4500cGy is excessive and the 3000 cGy is the most effective for this experimental model of cutaneous radiation injury in rabbits. (author)

  15. An experimental and kinetic modeling study of glycerol pyrolysis

    International Nuclear Information System (INIS)

    Fantozzi, F.; Frassoldati, A.; Bartocci, P.; Cinti, G.; Quagliarini, F.; Bidini, G.; Ranzi, E.M.

    2016-01-01

    Highlights: • Glycerol pyrolysis can produce about 44–48%v hydrogen at 750–800 °C. • A simplified 452 reactions kinetic model of glycerol pyrolysis has been developed. • The model has good agreement with experimental data. • Non condensable gas yields can reach 70%. - Abstract: Pyrolysis of glycerol, a by-product of the biodiesel industry, is an important potential source of hydrogen. The obtained high calorific value gas can be used either as a fuel for combined heat and power (CHP) generation or as a transportation fuel (for example hydrogen to be used in fuel cells). Optimal process conditions can improve glycerol pyrolysis by increasing gas yield and hydrogen concentration. A detailed kinetic mechanism of glycerol pyrolysis, which involves 137 species and more than 4500 reactions, was drastically simplified and reduced to a new skeletal kinetic scheme of 44 species, involved in 452 reactions. An experimental campaign with a batch pyrolysis reactor was properly designed to further validate the original and the skeletal mechanisms. The comparisons between model predictions and experimental data strongly suggest the presence of a catalytic process promoting steam reforming of methane. High pyrolysis temperatures (750–800 °C) improve process performances and non-condensable gas yields of 70%w can be achieved. Hydrogen mole fraction in pyrolysis gas is about 44–48%v. The skeletal mechanism developed can be easily used in Computational Fluid Dynamic software, reducing the simulation time.

  16. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016

    NARCIS (Netherlands)

    Rhodes, Andrew; Evans, Laura E.; Alhazzani, Waleed; Levy, Mitchell M.; Antonelli, Massimo; Ferrer, Ricard; Kumar, Anand; Sevransky, Jonathan E.; Sprung, Charles L.; Nunnally, Mark E.; Rochwerg, Bram; Rubenfeld, Gordon D.; Angus, Derek C.; Annane, Djillali; Beale, Richard J.; Bellinghan, Geoffrey J.; Bernard, Gordon R.; Chiche, Jean-Daniel; Coopersmith, Craig; de Backer, Daniel P.; French, Craig J.; Fujishima, Seitaro; Gerlach, Herwig; Hidalgo, Jorge Luis; Hollenberg, Steven M.; Jones, Alan E.; Karnad, Dilip R.; Kleinpell, Ruth M.; Koh, Younsuk; Lisboa, Thiago Costa; Machado, Flavia R.; Marini, John J.; Marshall, John C.; Mazuski, John E.; McIntyre, Lauralyn A.; McLean, Anthony S.; Mehta, Sangeeta; Moreno, Rui P.; Myburgh, John; Navalesi, Paolo; Nishida, Osamu; Osborn, Tiffany M.; Perner, Anders; Plunkett, Colleen M.; Ranieri, Marco; Schorr, Christa A.; Seckel, Maureen A.; Seymour, Christopher W.; Shieh, Lisa; Shukri, Khalid A.; Simpson, Steven Q.; Singer, Mervyn; Thompson, B. Taylor; Townsend, Sean R.; van der Poll, Thomas; Vincent, Jean-Louis; Wiersinga, W. Joost; Zimmerman, Janice L.; Dellinger, R. Phillip

    2017-01-01

    To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012". A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee

  17. Survey of experimental tests of the IBA model

    International Nuclear Information System (INIS)

    Casten, R.F.

    1980-01-01

    A survey of experimental tests of the Interacting Boson Approximation (IBA) Model is presented covering even and odd mass nuclei in the region from A approx. 80 to A approx. 230. Both positive and negative parity states with both high and low spin are discussed. Topics included concern energy levels, electromagnetic transition rates, two nucleon transfer and inelastic scattering. Special attention is given to nuclear symmetries and transitional regions. Comparison with other models is made where appropriate. The distinction between IBA-1 and IBA-2 is discussed including their respective areas of applicability

  18. Dynamic Modeling of Wind Turbine Gearboxes and Experimental Validation

    DEFF Research Database (Denmark)

    Pedersen, Rune

    Grinding corrections are often applied to gear teeth, which will alter the load distribution across the tooth. Grinding corrections will also change the load sharing between neighboring tooth pairs, and in turn the gear mesh stiffness. In this thesis, a model for calculating the gear mesh stiffness...... is presented. The model takes into account the effects of load and applied grinding corrections. The results are verified by comparing to simulated and experimental results reported in the existing literature. Using gear data loosely based on a 1 MW wind turbine gearbox, the gear mesh stiffness is expanded...

  19. Finite element modeling and experimentation of bone drilling forces

    International Nuclear Information System (INIS)

    Lughmani, W A; Bouazza-Marouf, K; Ashcroft, I

    2013-01-01

    Bone drilling is an essential part of many orthopaedic surgery procedures, including those for internal fixation and for attaching prosthetics. Estimation and control of bone drilling forces are critical to prevent drill breakthrough, excessive heat generation, and mechanical damage to the bone. This paper presents a 3D finite element (FE) model for prediction of thrust forces experienced during bone drilling. The model incorporates the dynamic characteristics involved in the process along with the accurate geometrical considerations. The average critical thrust forces and torques obtained using FE analysis, for set of machining parameters are found to be in good agreement with the experimental results

  20. Role of leucocytes cell population data in the early detection of sepsis.

    Science.gov (United States)

    Urrechaga, Eloísa; Bóveda, Oihane; Aguirre, Urko

    2018-03-01

    The cell population data (CPD) parameters reported by XN analyser (Sysmex, Kobe, Japan) reflect the size and internal structure of leucocytes. We aimed to assess the clinical utility of these parameters as biomarkers for the early diagnosis of sepsis. The study group (G1) included 586 controls (no quantitative or morphological alterations in the complete blood count) and 137 patients diagnosed with sepsis. The reliability of the model was evaluated using a validation group (G2) of 212 controls and 60 patients with sepsis. The optimal cut-off for the diagnosis of sepsis and the OR for CPD were established using a univariate logistic regression. A multivariate logistic regression model was then created. The OR and area under the curve were recorded. A risk stratification scale (neutrophils and monocytes (NEMO)) for diagnosing sepsis was established on the basis of the coefficients of the multivariate model. MO-X and neutrophils fluorescence intensity (NE-SFL) were found to be the most relevant of the CPD in predicting sepsis applying multivariate analysis to G1.NEMO score was composed using the above-mentioned CPD and subsequently stratified into three risk groups: mild (≤3), moderate (4≤NEMO≤5) and high (≥6). The OR for patients with a score of 4-5 was 10 and 249 for a score of ≥6. When applied to G2, the positive predictive value was 84.8 % and the negative predictive value was 96.0%. CPD are potentially useful for the early diagnosis of sepsis. Their values were used to compose in NEMO score can help in rapid and reliable decision making. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  1. Pneumatic Adaptive Absorber: Mathematical Modelling with Experimental Verification

    Directory of Open Access Journals (Sweden)

    Grzegorz Mikułowski

    2016-01-01

    Full Text Available Many of mechanical energy absorbers utilized in engineering structures are hydraulic dampers, since they are simple and highly efficient and have favourable volume to load capacity ratio. However, there exist fields of applications where a threat of toxic contamination with the hydraulic fluid contents must be avoided, for example, food or pharmacy industries. A solution here can be a Pneumatic Adaptive Absorber (PAA, which is characterized by a high dissipation efficiency and an inactive medium. In order to properly analyse the characteristics of a PAA, an adequate mathematical model is required. This paper proposes a concept for mathematical modelling of a PAA with experimental verification. The PAA is considered as a piston-cylinder device with a controllable valve incorporated inside the piston. The objective of this paper is to describe a thermodynamic model of a double chamber cylinder with gas migration between the inner volumes of the device. The specific situation considered here is that the process cannot be defined as polytropic, characterized by constant in time thermodynamic coefficients. Instead, the coefficients of the proposed model are updated during the analysis. The results of the experimental research reveal that the proposed mathematical model is able to accurately reflect the physical behaviour of the fabricated demonstrator of the shock absorber.

  2. Ultraviolet radiation-induced carcinogenesis: mechanisms and experimental models

    International Nuclear Information System (INIS)

    Ramasamy, Karthikeyan; Shanmugam, Mohana; Balupillai, Agilan; Govindhasamy, Kanimozhi; Gunaseelan, Srithar; Muthusamy, Ganesan; Robert, Beualah Mary; Nagarajan, Rajendra Prasad

    2017-01-01

    Ultraviolet radiation (UVR) is a very prominent environmental toxic agent. UVR has been implicated in the initiation and progression of photocarcinogenesis. UVR exposure elicits numerous cellular and molecular events which include the generation of inflammatory mediators, DNA damage, epigenetic modifications, and oxidative damages mediated activation of signaling pathways. UVR-initiated signal transduction pathways are believed to be responsible for tumor promotion effects. UVR-induced carcinogenic mechanism has been well studied using various animal and cellular models. Human skin-derived dermal fibroblasts, epidermal keratinocytes, and melanocytes served as excellent cellular model systems for the understanding of UVR-mediated carcinogenic events. Apart from this, scientists developed reconstituted three-dimensional normal human skin equivalent models for the study of UVR signaling pathways. Moreover, hairless mice such as SKH-1, devoid of Hr gene, served as a valuable model for experimental carcinogenesis. Scientists have also used transgenic mice and dorsal portion shaved Swiss albino mice for UVR carcinogenesis studies. In this review, we have discussed the current progress in the study on ultraviolet B (UVB)-mediated carcinogenesis and outlined appropriate experimental models for both ultraviolet A- and UVB-mediated carcinogenesis. (author)

  3. Pregnancy-associated severe sepsis.

    Science.gov (United States)

    Oud, Lavi

    2016-04-01

    This article examines the contemporary knowledge and uncertainties about the burden of pregnancy-associated severe sepsis (PASS), and its manifestations, management, and outcomes. There are relatively sparse data on PASS, related in part to infrequent reports and varying use of terminology and case definitions. PASS remains rare, although its incidence appears to be rapidly rising in some high-resource countries, affecting especially women with limited resources, minorities, and those with chronic illness. High level of clinician vigilance and rapid initiation of appropriate antimicrobial therapy, coupled with effective systemic support for organ dysfunction and correction of occult and overt hypoperfusion are the keys to limit adverse outcomes. However, timely diagnosis and provision of effective care remain a challenge, with reported prevalent delay in recognition and delivery of time-sensitive care interventions among maternal decedents. The mortality rate of PASS has been rising and its case fatality, although relatively low, has remained unchanged, in contrast to the outcome gains in the general population. The long-term sequelae of PASS remain unknown. The relatively limited contemporary data on PASS suggest a rising public health hazard in the obstetric population in high-resource countries, with ongoing challenges in assuring consistent provision of time-sensitive care.

  4. Waste glass corrosion modeling: Comparison with experimental results

    International Nuclear Information System (INIS)

    Bourcier, W.L.

    1993-11-01

    A chemical model of glass corrosion will be used to predict the rates of release of radionuclides from borosilicate glass waste forms in high-level waste repositories. The model will be used both to calculate the rate of degradation of the glass, and also to predict the effects of chemical interactions between the glass and repository materials such as spent fuel, canister and container materials, backfill, cements, grouts, and others. Coupling between the degradation processes affecting all these materials is expected. Models for borosilicate glass dissolution must account for the processes of (1) kinetically-controlled network dissolution, (2) precipitation of secondary phases, (3) ion exchange, (4) rate-limiting diffusive transport of silica through a hydrous surface reaction layer, and (5) specific glass surface interactions with dissolved cations and anions. Current long-term corrosion models for borosilicate glass employ a rate equation consistent with transition state theory embodied in a geochemical reaction-path modeling program that calculates aqueous phase speciation and mineral precipitation/dissolution. These models are currently under development. Future experimental and modeling work to better quantify the rate-controlling processes and validate these models are necessary before the models can be used in repository performance assessment calculations

  5. Experimental evaluation of analytical penumbra calculation model for wobbled beams

    International Nuclear Information System (INIS)

    Kohno, Ryosuke; Kanematsu, Nobuyuki; Yusa, Ken; Kanai, Tatsuaki

    2004-01-01

    The goal of radiotherapy is not only to apply a high radiation dose to a tumor, but also to avoid side effects in the surrounding healthy tissue. Therefore, it is important for carbon-ion treatment planning to calculate accurately the effects of the lateral penumbra. In this article, for wobbled beams under various irradiation conditions, we focus on the lateral penumbras at several aperture positions of one side leaf of the multileaf collimator. The penumbras predicted by an analytical penumbra calculation model were compared with the measured results. The results calculated by the model for various conditions agreed well with the experimental ones. In conclusion, we found that the analytical penumbra calculation model could predict accurately the measured results for wobbled beams and it was useful for carbon-ion treatment planning to apply the model

  6. A new dietary model to study colorectal carcinogenesis: experimental design, food preparation, and experimental findings.

    Science.gov (United States)

    Rozen, P; Liberman, V; Lubin, F; Angel, S; Owen, R; Trostler, N; Shkolnik, T; Kritchevsky, D

    1996-01-01

    Experimental dietary studies of human colorectal carcinogenesis are usually based on the AIN-76A diet, which is dissimilar to human food in source, preparation, and content. The aims of this study were to examine the feasibility of preparing and feeding rats the diet of a specific human population at risk for colorectal neoplasia and to determine whether changes in the colonic morphology and metabolic contents would differ from those resulting from a standard rat diet. The mean daily food intake composition of a previously evaluated adenoma patient case-control study was used for the "human adenoma" (HA) experimental diet. Foods were prepared as for usual human consumption and processed by dehydration to the physical characteristics of an animal diet. Sixty-four female Sprague-Dawley rats were randomized and fed ad libitum the HA or the AIN-76A diet. Every eight weeks, eight rats from each group were sacrificed, and the colons and contents were examined. Analysis of the prepared food showed no significant deleterious changes; food intake and weight gain were similar in both groups. Compared with the controls, the colonic contents of rats fed the HA diet contained significantly less calcium, concentrations of neutral sterols, total lipids, and cholic and deoxycholic acids were increased, and there were no colonic histological changes other than significant epithelial hyperproliferation. This initial study demonstrated that the HA diet can be successfully processed for feeding to experimental animals and is acceptable and adequate for growth but induces significant metabolic and hyperproliferative changes in the rat colon. This dietary model may be useful for studies of human food, narrowing the gap between animal experimentation and human nutritional research.

  7. Much Ado About the New Definitions of Sepsis

    Directory of Open Access Journals (Sweden)

    Copotoiu Sanda-Maria

    2016-04-01

    Full Text Available Following the publication of the new definition of sepsis (Sepsis-3, a plethora of articles have been published in medical journals. Recognizing the epidemiological importance of the previous definitions, first issued in 1992 (Sepsis-1, and subsequently revised in 2001 (Sepsis-2, the most recent opinion emphasizes the failure “to provide adequate groups of patients with homogenous aetiologies, presentations and outcomes”, and blamed one of the causes “for the failure of several randomized controlled trials (RCTs, that tested the efficacy of adjuvant sepsis therapies”. This review summarizes the recent advances in sepsis definition.

  8. Appropriate antibiotic therapy improves Ureaplasma sepsis outcome in the neonatal mouse.

    Science.gov (United States)

    Weisman, Leonard E; Leeming, Angela H; Kong, Lingkun

    2012-11-01

    Ureaplasma causes sepsis in human neonates. Although erythromycin has been the standard treatment, it is not always effective. No published reports have evaluated Ureaplasma sepsis in a neonatal model. We hypothesized that appropriate antibiotic treatment improves Ureaplasma sepsis in a neonatal mouse model. Two ATCC strains and two clinical strains of Ureaplasma were evaluated in vitro for antibiotic minimum inhibitory concentration (MIC). In addition, FVB albino mice pups infected with Ureaplasma were randomly assigned to saline, erythromycin, or azithromycin therapy and survival, quantitative blood culture, and growth were evaluated. MICs ranged from 0.125 to 62.5 µg/ml and 0.25 to 1.0 µg/ml for erythromycin and azithromycin, respectively. The infecting strain and antibiotic selected for treatment appeared to affect survival and bacteremia, but only the infecting strain affected growth. Azithromycin improved survival and bacteremia against each strain, whereas erythromycin was effective against only one of four strains. We have established a neonatal model of Ureaplasma sepsis and observed that treatment outcome is related to infecting strain and antibiotic treatment. We speculate that appropriate antibiotic selection and dosing are required for effective treatment of Ureaplasma sepsis in neonates, and this model could be used to further evaluate these relationships.

  9. Designing a Pediatric Severe Sepsis Screening Tool

    Directory of Open Access Journals (Sweden)

    Robert eSepanski

    2014-06-01

    Full Text Available We sought to create a screening tool with improved predictive value for pediatric severe sepsis 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 severe sepsis cases were identified using a combination of coded discharge diagnosis and physician chart review from 7,402 children who visited a pediatric ED over two months. The tool’s identification of severe sepsis 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 curve (ROC characteristics. 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 three years. Univariate analyses were performed for each measure in the tool to assess its association with severe sepsis and to characterize it as an early or late indicator of severe sepsis. 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 three-fold improvement over the original ICCPS tool. False positive Systemic Inflammatory Response Syndrome (SIRS identifications were nearly six-fold lower.

  10. Experimental model of cultured keratinocytes Modelo experimental de cultura de queratinócitos

    Directory of Open Access Journals (Sweden)

    Alfredo Gragnani

    2003-01-01

    Full Text Available The bioengineering research is essential in the development of ideal combination of biomaterials and cultured cells to produce the permanent wound coverage. The experimental model of cultured keratinocytes presents all steps of the culture, since the isolation of the keratinocytes, preparation of the human acellular dermis, preparation of the composite skin graft and their elevation to the air-liquid interface. The research in cultured keratinocytes model advances in two main ways: 1. optimization of the methods in vitro to the skin cells culture and proliferation and 2. developing biomaterials that present similar skin properties.A pesquisa em bioengenharia é primordial no desenvolvimento da combinação ideal de biomateriais e células cultivadas para produzir a cobertura definitiva das lesões. O modelo experimental da cultura de queratinócitos apresenta toda as etapas do cultivo, desde o isolamento dos queratinócitos, preparação da derme acelular humana, do enxerto composto e da sua elevação à interface ar-líquido. A pesquisa em modelo de cultura de queratinócitos desenvolve-se em duas vias principais: 1. otimização dos métodos in vitro para cultivo e proliferação de células da pele e 2. desenvolvimento de biomateriais que mimetizem as propriedades da pele.

  11. DMFC anode polarization: Experimental analysis and model validation

    Energy Technology Data Exchange (ETDEWEB)

    Casalegno, A.; Marchesi, R. [Dipartimento di Energetica, Politecnico di Milano, Piazza Leonardo da Vinci 32, 20133 Milano (Italy)

    2008-01-03

    Anode two-phase flow has an important influence on DMFC performance and methanol crossover. In order to elucidate two-phase flow influence on anode performance, in this work, anode polarization is investigated combining experimental and modelling approach. A systematic experimental analysis of operating conditions influence on anode polarization is presented. Hysteresis due to operating condition is observed; experimental results suggest that it arises from methanol accumulation and has to be considered in evaluating DMFC performances and measurements reproducibility. A model of DMFC anode polarization is presented and utilised as tool to investigate anode two-phase flow. The proposed analysis permits one to produce a confident interpretation of the main involved phenomena. In particular, it confirms that methanol electro-oxidation kinetics is weakly dependent on methanol concentration and that methanol transport in gas phase produces an important contribution in anode feeding. Moreover, it emphasises the possibility to optimise anode flow rate in order to improve DMFC performance and reduce methanol crossover. (author)

  12. Numerical modelling of negative discharges in air with experimental validation

    International Nuclear Information System (INIS)

    Tran, T N; Golosnoy, I O; Lewin, P L; Georghiou, G E

    2011-01-01

    Axisymmetric finite element models have been developed for the simulation of negative discharges in air without and with the presence of dielectrics. The models are based on the hydrodynamic drift-diffusion approximation. A set of continuity equations accounting for the movement, generation and loss of charge carriers (electrons, positive and negative ions) is coupled with Poisson's equation to take into account the effect of space and surface charges on the electric field. The model of a negative corona discharge (without dielectric barriers) in a needle-plane geometry is analysed first. The results obtained show good agreement with experimental observations for various Trichel pulse characteristics. With dielectric barriers introduced into the discharge system, the surface discharge exhibits some similarities and differences to the corona case. The model studies the dynamics of volume charge generation, electric field variations and charge accumulation over the dielectric surface. The predicted surface charge density is consistent with experimental results obtained from the Pockels experiment in terms of distribution form and magnitude.

  13. Modeling and experimental tests of a copper thermosyphon

    Directory of Open Access Journals (Sweden)

    Paulo Henrique Dias dos Santos

    2017-02-01

    Full Text Available Electrical energy, solar energy, and/or direct combustion of a fuel are the most common thermal sources for home water heating. In recent years, the use of solar energy has become popular because it is a renewable and economic energy source. Among the solar collectors, those assisted by thermosyphons are more efficient; therefore, they can enhance the heat transfer to water. A thermosyphon is basically a sealed tube filled with a working fluid and, normally, it has three regions: the evaporator, the adiabatic section and the condenser. The great advantage of this device is that the thermal resistance to heat transfer between its regions is very small, and as a result, there is a small temperature difference. This article aims to model a thermosyphon by using correlations based on its operation limits. This modeling will be used as a design tool for compact solar collectors assisted by thermosyphons. Based on the results obtained with the mathematical modeling, one copper thermosyphon, with deionized water as the working fluid, was developed and experimentally tested. The tests were carried out for a heat load varying from 30 to 60W in a vertical position. The theoretical and experimental results were compared to verify the mathematical model.

  14. An experimental and modeling study of diethyl carbonate oxidation

    KAUST Repository

    Nakamura, Hisashi; Curran, Henry J.; Polo-Có rdoba, Á ngel David; Pitz, William J.; Dagaut, P.; Togbé , Casimir; Sarathy, Mani; Mehl, Marco; Agudelo, John Ramiro; Bustamante, Felipe

    2015-01-01

    Diethyl carbonate (DEC) is an attractive biofuel that can be used to displace petroleum-derived diesel fuel, thereby reducing CO2 and particulate emissions from diesel engines. A better understanding of DEC combustion characteristics is needed to facilitate its use in internal combustion engines. Toward this goal, ignition delay times for DEC were measured at conditions relevant to internal combustion engines using a rapid compression machine (RCM) and a shock tube. The experimental conditions investigated covered a wide range of temperatures (660-1300K), a pressure of 30bar, and equivalence ratios of 0.5, 1.0 and 2.0 in air. To provide further understanding of the intermediates formed in DEC oxidation, species concentrations were measured in a jet-stirred reactor at 10atm over a temperature range of 500-1200K and at equivalence ratios of 0.5, 1.0 and 2.0. These experimental measurements were used to aid the development and validation of a chemical kinetic model for DEC.The experimental results for ignition in the RCM showed near negative temperature coefficient (NTC) behavior. Six-membered alkylperoxy radical (RO˙2) isomerizations are conventionally thought to initiate low-temperature branching reactions responsible for NTC behavior, but DEC has no such possible 6- and 7-membered ring isomerizations. However, its molecular structure allows for 5-, 8- and 9-membered ring RO˙2 isomerizations. To provide accurate rate constants for these ring structures, ab initio computations for RO˙2⇌Q˙OOH isomerization reactions were performed. These new RO˙2 isomerization rate constants have been implemented in a chemical kinetic model for DEC oxidation. The model simulations have been compared with ignition delay times measured in the RCM near the NTC region. Results of the simulation were also compared with experimental results for ignition in the high-temperature region and for species concentrations in the jet-stirred reactor. Chemical kinetic insights into the

  15. An experimental and modeling study of diethyl carbonate oxidation

    KAUST Repository

    Nakamura, Hisashi

    2015-04-01

    Diethyl carbonate (DEC) is an attractive biofuel that can be used to displace petroleum-derived diesel fuel, thereby reducing CO2 and particulate emissions from diesel engines. A better understanding of DEC combustion characteristics is needed to facilitate its use in internal combustion engines. Toward this goal, ignition delay times for DEC were measured at conditions relevant to internal combustion engines using a rapid compression machine (RCM) and a shock tube. The experimental conditions investigated covered a wide range of temperatures (660-1300K), a pressure of 30bar, and equivalence ratios of 0.5, 1.0 and 2.0 in air. To provide further understanding of the intermediates formed in DEC oxidation, species concentrations were measured in a jet-stirred reactor at 10atm over a temperature range of 500-1200K and at equivalence ratios of 0.5, 1.0 and 2.0. These experimental measurements were used to aid the development and validation of a chemical kinetic model for DEC.The experimental results for ignition in the RCM showed near negative temperature coefficient (NTC) behavior. Six-membered alkylperoxy radical (RO˙2) isomerizations are conventionally thought to initiate low-temperature branching reactions responsible for NTC behavior, but DEC has no such possible 6- and 7-membered ring isomerizations. However, its molecular structure allows for 5-, 8- and 9-membered ring RO˙2 isomerizations. To provide accurate rate constants for these ring structures, ab initio computations for RO˙2⇌Q˙OOH isomerization reactions were performed. These new RO˙2 isomerization rate constants have been implemented in a chemical kinetic model for DEC oxidation. The model simulations have been compared with ignition delay times measured in the RCM near the NTC region. Results of the simulation were also compared with experimental results for ignition in the high-temperature region and for species concentrations in the jet-stirred reactor. Chemical kinetic insights into the

  16. Experimental validation of solid rocket motor damping models

    Science.gov (United States)

    Riso, Cristina; Fransen, Sebastiaan; Mastroddi, Franco; Coppotelli, Giuliano; Trequattrini, Francesco; De Vivo, Alessio

    2017-12-01

    In design and certification of spacecraft, payload/launcher coupled load analyses are performed to simulate the satellite dynamic environment. To obtain accurate predictions, the system damping properties must be properly taken into account in the finite element model used for coupled load analysis. This is typically done using a structural damping characterization in the frequency domain, which is not applicable in the time domain. Therefore, the structural damping matrix of the system must be converted into an equivalent viscous damping matrix when a transient coupled load analysis is performed. This paper focuses on the validation of equivalent viscous damping methods for dynamically condensed finite element models via correlation with experimental data for a realistic structure representative of a slender launch vehicle with solid rocket motors. A second scope of the paper is to investigate how to conveniently choose a single combination of Young's modulus and structural damping coefficient—complex Young's modulus—to approximate the viscoelastic behavior of a solid propellant material in the frequency band of interest for coupled load analysis. A scaled-down test article inspired to the Z9-ignition Vega launcher configuration is designed, manufactured, and experimentally tested to obtain data for validation of the equivalent viscous damping methods. The Z9-like component of the test article is filled with a viscoelastic material representative of the Z9 solid propellant that is also preliminarily tested to investigate the dependency of the complex Young's modulus on the excitation frequency and provide data for the test article finite element model. Experimental results from seismic and shock tests performed on the test configuration are correlated with numerical results from frequency and time domain analyses carried out on its dynamically condensed finite element model to assess the applicability of different equivalent viscous damping methods to describe

  17. Experimental study of mass boiling in a porous medium model

    International Nuclear Information System (INIS)

    Sapin, Paul

    2014-01-01

    This manuscript presents a pore-scale experimental study of convective boiling heat transfer in a two-dimensional porous medium. The purpose is to deepen the understanding of thermohydraulics of porous media saturated with multiple fluid phases, in order to enhance management of severe accidents in nuclear reactors. Indeed, following a long-lasting failure in the cooling system of a pressurized water reactor (PWR) or a boiling water reactor (BWR) and despite the lowering of the control rods that stops the fission reaction, residual power due to radioactive decay keeps heating up the core. This induces water evaporation, which leads to the drying and degradation of the fuel rods. The resulting hot debris bed, comparable to a porous heat-generating medium, can be cooled down by reflooding, provided a water source is available. This process involves intense boiling mechanisms that must be modelled properly. The experimental study of boiling in porous media presented in this thesis focuses on the influence of different pore-scale boiling regimes on local heat transfer. The experimental setup is a model porous medium made of a bundle of heating cylinders randomly placed between two ceramic plates, one of which is transparent. Each cylinder is a resistance temperature detector (RTD) used to give temperature measurements as well as heat generation. Thermal measurements and high-speed image acquisition allow the effective heat exchanges to be characterized according to the observed local boiling regimes. This provides precious indications precious indications for the type of correlations used in the non-equilibrium macroscopic model used to model reflooding process. (author) [fr

  18. Experimental validation of solid rocket motor damping models

    Science.gov (United States)

    Riso, Cristina; Fransen, Sebastiaan; Mastroddi, Franco; Coppotelli, Giuliano; Trequattrini, Francesco; De Vivo, Alessio

    2018-06-01

    In design and certification of spacecraft, payload/launcher coupled load analyses are performed to simulate the satellite dynamic environment. To obtain accurate predictions, the system damping properties must be properly taken into account in the finite element model used for coupled load analysis. This is typically done using a structural damping characterization in the frequency domain, which is not applicable in the time domain. Therefore, the structural damping matrix of the system must be converted into an equivalent viscous damping matrix when a transient coupled load analysis is performed. This paper focuses on the validation of equivalent viscous damping methods for dynamically condensed finite element models via correlation with experimental data for a realistic structure representative of a slender launch vehicle with solid rocket motors. A second scope of the paper is to investigate how to conveniently choose a single combination of Young's modulus and structural damping coefficient—complex Young's modulus—to approximate the viscoelastic behavior of a solid propellant material in the frequency band of interest for coupled load analysis. A scaled-down test article inspired to the Z9-ignition Vega launcher configuration is designed, manufactured, and experimentally tested to obtain data for validation of the equivalent viscous damping methods. The Z9-like component of the test article is filled with a viscoelastic material representative of the Z9 solid propellant that is also preliminarily tested to investigate the dependency of the complex Young's modulus on the excitation frequency and provide data for the test article finite element model. Experimental results from seismic and shock tests performed on the test configuration are correlated with numerical results from frequency and time domain analyses carried out on its dynamically condensed finite element model to assess the applicability of different equivalent viscous damping methods to describe

  19. Experimental investigations and modelling of sodium-concrete interaction

    International Nuclear Information System (INIS)

    Schultheiss, G.F.; Deeg, H.J.

    1990-01-01

    The use of sodium as a coolant in liquid metal fast breeder reactors, fusion reactors, and solar plants requires special consideration of its chemical reactivity and related safety problems in the case of sodium leckage. On contact between hot sodium and concrete an interaction takes place resulting in energy release and hydrogen generation, which may contribute to containment loading by pressurization in a hypothetical accident situation. For this reason, sodium-concrete interactions were investigated experimentally and theoretically. The experiments revealed important effects of quartzitic material within the concrete and of the sodium temperature on the interaction mechanisms, the energy release and the consequent hydrogen production. The numerical model shows good agreement with the experimental results. (orig.) [de

  20. Numerical modeling and experimental validation of thermoplastic composites induction welding

    Science.gov (United States)

    Palmieri, Barbara; Nele, Luigi; Galise, Francesco

    2018-05-01

    In this work, a numerical simulation and experimental test of the induction welding of continuous fibre-reinforced thermoplastic composites (CFRTPCs) was provided. The thermoplastic Polyamide 66 (PA66) with carbon fiber fabric was used. Using a dedicated software (JMag Designer), the influence of the fundamental process parameters such as temperature, current and holding time was investigated. In order to validate the results of the simulations, and therefore the numerical model used, experimental tests were carried out, and the temperature values measured during the tests were compared with the aid of an optical pyrometer, with those provided by the numerical simulation. The mechanical properties of the welded joints were evaluated by single lap shear tests.

  1. Fatigue crack propagation: Probabilistic models and experimental evidence

    International Nuclear Information System (INIS)

    Lucia, A.C.; Jovanovic, A.

    1987-01-01

    The central aim of the LWR Primary Circuit Component Life Prediction Project, going on at JRC-Ispra, is to develop and check a 'procedure' (encompassing monitoring and inspection, data collection and analysis, prediction) allowing the quantitatives estimation of the accumulation of structural damage and of the residual lifetime. The ongoing activity matches theoretical development and experimentation, the latter being at present essentially based on a test-rig for room-temperature fatigue cycling of 1:5 scaled models of pressure vessels. During Phase I of fatigue testing of vessel R2, different pieces of information coming from material characterization, non-destructive inspection, continuous monitoring, stress analysis, have been merged and used to infere the future behaviour of the structure. The prediction of residual lifetime (cycles to failure), based on the outcomes of the ultrasonic continuous monitoring and made by means of the COVASTOL code, was in quite good agreement with experimental evidence. (orig./HP)

  2. Experimental limits from ATLAS on Standard Model Higgs production.

    CERN Multimedia

    ATLAS, collaboration

    2012-01-01

    Experimental limits from ATLAS on Standard Model Higgs production in the mass range 110-600 GeV. The solid curve reflects the observed experimental limits for the production of a Higgs of each possible mass value (horizontal axis). The region for which the solid curve dips below the horizontal line at the value of 1 is excluded with a 95% confidence level (CL). The dashed curve shows the expected limit in the absence of the Higgs boson, based on simulations. The green and yellow bands correspond (respectively) to 68%, and 95% confidence level regions from the expected limits. Higgs masses in the narrow range 123-130 GeV are the only masses not excluded at 95% CL

  3. Incidence, outcome and risk factors for sepsis - a two year retrospective study at surgical intensive care unit of a teaching hospital in Pakistan

    International Nuclear Information System (INIS)

    Asghar, A.; Hashmi, M.; Rashid, S.; Khan, F.H.

    2016-01-01

    Background: Sepsis is amongst the leading causes of admission to the intensive care units and is associated with a high mortality. However, data from developing countries is scarse. Aim of conducting this study was to determine the incidence, outcome and risk factors for sepsis on admission to surgical intensive care unit (SICU) of a teaching hospital in Pakistan. Methods: Two year retrospective observational study included all consecutive adult admissions to the surgical intensive care unit (SICU) of a University Hospital, from January 2012 to December 2013. Results: Two hundred and twenty-nine patients met the inclusion criteria. Average age of the patients was 46.35±18.23 years (16-85), mean Acute Physiology and Chronic Health Evaluation II (APACHE II) score was 15.92±8.13 and males were 67.6 percentage. Median length of ICU stay was 4 [IQR 5]. 43 percentage patients fulfilled the criteria of sepsis at the time of admission to the SICU and incidence of severe sepsis/septic shock was 35 percentage. Abdominal sepsis was the most frequent source of infection (57.5 percentage). The overall intensive care unit mortality was 32.31 percentage but the mortality of sepsis-group was 51.15 percentage as compared to 17.7 percentage of the non-sepsis group. Stepwise logistic regression model showed that increasing age, female gender, non-operative admission, admission under general surgery and co-morbidities like ischaemic heart disease and chronic kidney disease were significant predictors of sepsis. Conclusion: The incidence of sepsis and severe sepsis/septic shock, on admission to SICU is high and mortality of the sepsis group is nearly three times the mortality of the non-sepsis group. (author)

  4. Post–Acute Care Use and Hospital Readmission after Sepsis

    Science.gov (United States)

    Jones, Tiffanie K.; Fuchs, Barry D.; Small, Dylan S.; Halpern, Scott D.; Hanish, Asaf; Umscheid, Craig A.; Baillie, Charles A.; Kerlin, Meeta Prasad; Gaieski, David F.

    2015-01-01

    Rationale: The epidemiology of post–acute care use and hospital readmission after sepsis remains largely unknown. Objectives: To examine the rate of post–acute care use and hospital readmission after sepsis and to examine risk factors and outcomes for hospital readmissions after sepsis. Methods: In an observational cohort study conducted in an academic health care system (2010–2012), we compared post–acute care use at discharge and hospital readmission after 3,620 sepsis hospitalizations with 108,958 nonsepsis hospitalizations. We used three validated, claims-based approaches to identify sepsis and severe sepsis. Measurements and Main Results: Post–acute care use at discharge was more likely after sepsis, driven by skilled care facility placement (35.4% after sepsis vs. 15.8%; P Readmission rates at 7, 30, and 90 days were higher postsepsis (P readmission risk was present regardless of sepsis severity (27.3% after sepsis and 26.0–26.2% after severe sepsis). After controlling for presepsis characteristics, the readmission risk was found to be 1.51 times greater (95% CI, 1.38–1.66) than nonsepsis hospitalizations. Readmissions after sepsis were more likely to result in death or transition to hospice care (6.1% vs. 13.3% after sepsis; P readmissions after sepsis hospitalizations included age, malignancy diagnosis, hospitalizations in the year prior to the index hospitalization, nonelective index admission type, one or more procedures during the index hospitalization, and low hemoglobin and high red cell distribution width at discharge. Conclusions: Post–acute care use and hospital readmissions were common after sepsis. The increased readmission risk after sepsis was observed regardless of sepsis severity and was associated with adverse readmission outcomes. PMID:25751120

  5. Associations between interleukin-1 gene polymorphisms and sepsis risk: a meta-analysis

    Science.gov (United States)

    2014-01-01

    Background Previous epidemiological studies have presented conflicting evidence regarding associations between interleukin-1 (IL-1) polymorphisms and sepsis susceptibility. We have performed a meta-analysis to evaluate possible associations between IL-1 polymorphisms and sepsis risk. Methods Eligible literature was retrieved from PubMed, Embase and Web of Knowledge databases until Jun 15, 2013. The pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using random-effects model in the overall and subgroup analysis based on ethnicity, sepsis severity and quality score. Results Eighteen studies addressing five IL-1 polymorphisms were included in this meta-analysis. For IL-1A-889 (rs1800587) polymorphism, significant association was observed in overall comparison for allelic effect (OR = 1.47, 95% CI = 1.01-2.13, P = 0.04). There were no significant associations between either IL-1B-511 (rs16944) or IL-1B-31 (rs1143627) and sepsis susceptibility in overall or subgroup analyses. For IL-1B + 3594 (rs143634) polymorphism, genotype TT decreased sepsis risk in overall analysis (OR = 0.59, 95% CI = 0.36-0.97, P = 0.04), as well as in Caucasian (OR = 0.57, 95% CI = 0.34-0.95, P = 0.03) and sepsis (OR = 0.55, 95% CI = 0.31-0.97, P = 0.04) subgroup analysis. For IL-1RN VNTR polymorphism, significant association was observed in overall comparison for allelic effect (OR = 1.40, 95% CI = 1.01-1.95, P = 0.04). Furthermore, the effect sizes of IL-1RN VNTR on sepsis risk increased with disease severity (septic shock OR > severe sepsis OR > sepsis OR). Conclusions Our meta-analysis indicated that IL-1A-889, IL-1B + 3954 and IL-1RN VNTR might be associated with sepsis susceptibility. However, further studies with larger sample sizes and from homogenous populations would be necessary to validate these findings. PMID:24428862

  6. Experimental model of the burn wound topical treatment

    Directory of Open Access Journals (Sweden)

    Amra Čabaravdić

    2003-11-01

    Full Text Available AbstractBACKGROUND AND PURPOSE:Clinical research of drugs is a researching step subsequent to the preclinical studies in experimental animals. The aim of our research was to evaluate animal model of wound healing process after the burninducement and effects of the ointment containing natural plants on the process of burn healing.MATERIAL AND METHODS:Burn wounds were experimentally induced in two species of experimental animals which were treated with topically applied herbal preparation with concomitant monitoring of the healing process. Experimental groups (1 of 15 animals each (mice and rats, while control group (2 of 10 animals each (mice and rats that were not being treated with herbal ointment. After the hair removal, burn was induced on the back of animals by heated brass seal. Different clinical symptoms including oedema of surrounding tissue, redness, exudation, size of the burn surface, histological and microbiological findings were monitored on the days 1, 3, 7, 14 and 21. A statistically significant difference was observed throughout descriptive statistics and paired Student's t-test.CONCLUSION:Physiological healing processes of the acute burn wound following the topical application of herbal preparation can be monitored on the utilized animal model. A three-week treatment resulted in the 90% of completed epithelization in both animal species, indicating the effectiveness of topically applied herbal preparation.

  7. Short note: the experimental geopotential model XGM2016

    Science.gov (United States)

    Pail, R.; Fecher, T.; Barnes, D.; Factor, J. F.; Holmes, S. A.; Gruber, T.; Zingerle, P.

    2018-04-01

    As a precursor study for the upcoming combined Earth Gravitational Model 2020 (EGM2020), the Experimental Gravity Field Model XGM2016, parameterized as a spherical harmonic series up to degree and order 719, is computed. XGM2016 shares the same combination methodology as its predecessor model GOCO05c (Fecher et al. in Surv Geophys 38(3): 571-590, 2017. doi: 10.1007/s10712-016-9406-y). The main difference between these models is that XGM2016 is supported by an improved terrestrial data set of 15^' × 15^' gravity anomaly area-means provided by the United States National Geospatial-Intelligence Agency (NGA), resulting in significant upgrades compared to existing combined gravity field models, especially in continental areas such as South America, Africa, parts of Asia, and Antarctica. A combination strategy of relative regional weighting provides for improved performance in near-coastal ocean regions, including regions where the altimetric data are mostly unchanged from previous models. Comparing cumulative height anomalies, from both EGM2008 and XGM2016 at degree/order 719, yields differences of 26 cm in Africa and 40 cm in South America. These differences result from including additional information of satellite data, as well as from the improved ground data in these regions. XGM2016 also yields a smoother Mean Dynamic Topography with significantly reduced artifacts, which indicates an improved modeling of the ocean areas.

  8. Statistical approach for uncertainty quantification of experimental modal model parameters

    DEFF Research Database (Denmark)

    Luczak, M.; Peeters, B.; Kahsin, M.

    2014-01-01

    Composite materials are widely used in manufacture of aerospace and wind energy structural components. These load carrying structures are subjected to dynamic time-varying loading conditions. Robust structural dynamics identification procedure impose tight constraints on the quality of modal models...... represent different complexity levels ranging from coupon, through sub-component up to fully assembled aerospace and wind energy structural components made of composite materials. The proposed method is demonstrated on two application cases of a small and large wind turbine blade........ This paper aims at a systematic approach for uncertainty quantification of the parameters of the modal models estimated from experimentally obtained data. Statistical analysis of modal parameters is implemented to derive an assessment of the entire modal model uncertainty measure. Investigated structures...

  9. A two-Higgs-doublet model facing experimental hints

    Directory of Open Access Journals (Sweden)

    Crivellin Andreas

    2016-01-01

    Full Text Available Physics beyond the Standard Model has so far eluded our experimental probes. Nevertheless, a number of interesting anomalies have accumulated that can be taken as hints towards new physics: BaBar, Belle, and LHCb have found deviations of approximately 3:8σ in B → Dτν and B → D*τν; the anomalous magnetic moment of the muon differs by about 3σ from the theoretic prediction; the branching ratio for τ → μνν is about 2σ above the Standard Model expectation; and CMS and ATLAS found hints for a non-zero decay rate of h → μτ at 2.6σ. Here we consider these processes within a lepton-specific two-Higgs doublet model with additional non-standard Yukawa couplings and show how (and which of these excesses can be accommodated.

  10. Electrode-tissues interface: modeling and experimental validation

    International Nuclear Information System (INIS)

    Sawan, M; Laaziri, Y; Mounaim, F; Elzayat, E; Corcos, J; Elhilali, M M

    2007-01-01

    The electrode-tissues interface (ETI) is one of the key issues in implantable devices such as stimulators and sensors. Once the stimulator is implanted, safety and reliability become more and more critical. In this case, modeling and monitoring of the ETI are required. We propose an empirical model for the ETI and a dedicated integrated circuit to measure its corresponding complex impedance. These measurements in the frequency range of 1 Hz to 100 kHz were achieved in acute dog experiments. The model demonstrates a closer fitting with experimental measurements. In addition, a custom monitoring device based on a stimuli current generator has been completed to evaluate the phase shift and voltage across the electrodes and to transmit wirelessly the values to an external controller. This integrated circuit has been fabricated in a CMOS 0.18 μm process, which consumes 4 mW only during measurements and occupies an area of 1 mm 2 . (review article)

  11. Comparison of mixed layer models predictions with experimental data

    Energy Technology Data Exchange (ETDEWEB)

    Faggian, P.; Riva, G.M. [CISE Spa, Divisione Ambiente, Segrate (Italy); Brusasca, G. [ENEL Spa, CRAM, Milano (Italy)

    1997-10-01

    The temporal evolution of the PBL vertical structure for a North Italian rural site, situated within relatively large agricultural fields and almost flat terrain, has been investigated during the period 22-28 June 1993 by experimental and modellistic point of view. In particular, the results about a sunny day (June 22) and a cloudy day (June 25) are presented in this paper. Three schemes to estimate mixing layer depth have been compared, i.e. Holzworth (1967), Carson (1973) and Gryning-Batchvarova models (1990), which use standard meteorological observations. To estimate their degree of accuracy, model outputs were analyzed considering radio-sounding meteorological profiles and stability atmospheric classification criteria. Besides, the mixed layer depths prediction were compared with the estimated values obtained by a simple box model, whose input requires hourly measures of air concentrations and ground flux of {sup 222}Rn. (LN)

  12. Plasminogen activators in inflammation and sepsis.

    Science.gov (United States)

    Pechlaner, Ch

    2002-01-01

    Mortality of severe sepsis remains at 40% to 50%. Intensive efforts over the past two decades have only marginally improved outcome. Improving outcome in sepsis depends on understanding its pathophysiology, which involves triggers, responses of the organism, and dysfunction. Stress, injury, or infection trigger host responses, including local and systemic orchestrated mechanisms. Dysfunction and outcome depend on both trigger and response. Blood coagulation, inflammation, immunity, and fibrinolysis are critical components of the organism's responses. Understanding their role in sepsis pathophysiology is the key to effective treatment. Relevant studies were identified by a systematic literature search, complemented by manual search of individual citations. Using PubMed, 'sepsis' yields more than 62,000 references, 'plasminogen activators' more than 21,000. The selection of citations was guided by preference for reviews that expand important threads of argumentation. Single original studies were included when relevant to critical points. This analytical review describes the essential elements of pathophysiology and the current status of sepsis treatment. Based on this context, an emerging therapeutic option will be discussed: plasminogen activators.

  13. Improving Outcomes in Patients With Sepsis.

    Science.gov (United States)

    Armen, Scott B; Freer, Carol V; Showalter, John W; Crook, Tonya; Whitener, Cynthia J; West, Cheri; Terndrup, Thomas E; Grifasi, Marissa; DeFlitch, Christopher J; Hollenbeak, Christopher S

    2016-01-01

    Sepsis mortality may be improved by early recognition and appropriate treatment based on evidence-based guidelines. An intervention was developed that focused on earlier identification of sepsis, early antimicrobial administration, and an educational program that was disseminated throughout all hospital units and services. There were 1331 patients with sepsis during the intervention period and 1401 patients with sepsis during the control period. After controlling for expected mortality, patients in the intervention period had 30% lower odds of dying (odds ratio = 0.70, 95% confidence interval [CI] = 0.57 to 0.84). They also had 1.07 fewer days on average in the intensive care unit (95% CI = -1.98 to -0.16), 2.15 fewer hospital days (95% CI = -3.45 to -0.86), and incurred on average $1949 less in hospital costs, although the effect on costs was not statistically significant. Continued incremental improvement and sustainment is anticipated through organizational oversight, continued education, and initiation of an automated electronic sepsis alert function. © The Author(s) 2014.

  14. Experimentally driven atomistic model of 1,2 polybutadiene

    Energy Technology Data Exchange (ETDEWEB)

    Gkourmpis, Thomas, E-mail: thomas.gkourmpis@borealisgroup.com [Polymer Science Centre, J. J. Thomson Physical Laboratory, Department of Physics, University of Reading, Reading RG6 6AF (United Kingdom); Mitchell, Geoffrey R. [Polymer Science Centre, J. J. Thomson Physical Laboratory, Department of Physics, University of Reading, Reading RG6 6AF (United Kingdom); Centre for Rapid and Sustainable Product Development, Institute Polytechnic Leiria, Marinha Grande (Portugal)

    2014-02-07

    We present an efficient method of combining wide angle neutron scattering data with detailed atomistic models, allowing us to perform a quantitative and qualitative mapping of the organisation of the chain conformation in both glass and liquid phases. The structural refinement method presented in this work is based on the exploitation of the intrachain features of the diffraction pattern and its intimate linkage with atomistic models by the use of internal coordinates for bond lengths, valence angles, and torsion rotations. Atomic connectivity is defined through these coordinates that are in turn assigned by pre-defined probability distributions, thus allowing for the models in question to be built stochastically. Incremental variation of these coordinates allows for the construction of models that minimise the differences between the observed and calculated structure factors. We present a series of neutron scattering data of 1,2 polybutadiene at the region 120–400 K. Analysis of the experimental data yields bond lengths for Cî—¸C and C î—» C of 1.54 Å and 1.35 Å, respectively. Valence angles of the backbone were found to be at 112° and the torsion distributions are characterised by five rotational states, a three-fold trans-skew± for the backbone and gauche± for the vinyl group. Rotational states of the vinyl group were found to be equally populated, indicating a largely atactic chan. The two backbone torsion angles exhibit different behaviour with respect to temperature of their trans population, with one of them adopting an almost all trans sequence. Consequently, the resulting configuration leads to a rather persistent chain, something indicated by the value of the characteristic ratio extrapolated from the model. We compare our results with theoretical predictions, computer simulations, RIS models and previously reported experimental results.

  15. Experimental and numerical modeling of sulfur plugging in carbonate reservoirs

    Energy Technology Data Exchange (ETDEWEB)

    Abou-Kassem, J.H. [Chemical and Petroleum Engineering Department, UAE University, PO Box 17555, Al-Ain (United Arab Emirates)

    2000-05-01

    Sour gas, mainly in the form of hydrogen sulfide, is produced in large amounts from many oil and gas reservoirs in the United Arab Emirates. In addition to creating problems in production lines, the precipitation of elemental sulfur in vicinity of the wellbore is often reported to cause wellbore damage. While there have been several studies performed on the role of solid deposition in gas reservoirs, the role of sulfur deposition in oil reservoirs has not been investigated. This paper presents experimental results along with a comprehensive wellbore model that predicts sulfur precipitation as well as plugging. Two separate sets of experiments, one for a gas phase system and another for a crude oil system, were conducted to investigate the deposition of elemental sulfur in (linear) carbonate cores. The gas flow tests were conducted with elemental sulfur being carried with nitrogen through limestone cores. Changes in gas flow rate were monitored while the injection pressure was held constant. A series of experiments generated valuable data for plugging with elemental sulfur. X-ray diffraction tests provided evidence of sulfur deposition along the cores. The oil flow tests were carried out to observe sulfur precipitation and plugging in a carbonate core. The crude oil was de-asphalted before conducting these tests in order to isolate the effect of asphaltene plugging. Significant plugging was observed and was found to be dependent on flow rate and initial sulfur concentration. This information was used in a phenomenological model that was incorporated in the wellbore numerical model. The data for the numerical model were obtained from both test tube and oil flow experiments. By using a phenomenological model, the wellbore plugging was modeled with an excellent match (with experimental results)

  16. Neuroinflammatory targets and treatments for epilepsy validated in experimental models.

    Science.gov (United States)

    Aronica, Eleonora; Bauer, Sebastian; Bozzi, Yuri; Caleo, Matteo; Dingledine, Raymond; Gorter, Jan A; Henshall, David C; Kaufer, Daniela; Koh, Sookyong; Löscher, Wolfgang; Louboutin, Jean-Pierre; Mishto, Michele; Norwood, Braxton A; Palma, Eleonora; Poulter, Michael O; Terrone, Gaetano; Vezzani, Annamaria; Kaminski, Rafal M

    2017-07-01

    A large body of evidence that has accumulated over the past decade strongly supports the role of inflammation in the pathophysiology of human epilepsy. Specific inflammatory molecules and pathways have been identified that influence various pathologic outcomes in different experimental models of epilepsy. Most importantly, the same inflammatory pathways have also been found in surgically resected brain tissue from patients with treatment-resistant epilepsy. New antiseizure therapies may be derived from these novel potential targets. An essential and crucial question is whether targeting these molecules and pathways may result in anti-ictogenesis, antiepileptogenesis, and/or disease-modification effects. Therefore, preclinical testing in models mimicking relevant aspects of epileptogenesis is needed to guide integrated experimental and clinical trial designs. We discuss the most recent preclinical proof-of-concept studies validating a number of therapeutic approaches against inflammatory mechanisms in animal models that could represent novel avenues for drug development in epilepsy. Finally, we suggest future directions to accelerate preclinical to clinical translation of these recent discoveries. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  17. Tyre tread-block friction: modelling, simulation and experimental validation

    Science.gov (United States)

    Wallaschek, Jörg; Wies, Burkard

    2013-07-01

    Pneumatic tyres are used in vehicles since the beginning of the last century. They generate braking and steering forces for bicycles, motor cycles, cars, busses, trucks, agricultural vehicles and aircraft. These forces are generated in the usually very small contact area between tyre and road and their performance characteristics are of eminent importance for safety and comfort. Much research has been addressed to optimise tyre design with respect to footprint pressure and friction. In this context, the development of virtual tyre prototypes, that is, simulation models for the tyre, has grown to a science in its own. While the modelling of the structural dynamics of the tyre has reached a very advanced level, which allows to take into account effects like the rate-independent inelasticity of filled elastomers or the transient 3D deformations of the ply-reinforced tread, shoulder and sidewalls, little is known about the friction between tread-block elements and road. This is particularly obvious in the case when snow, ice, water or a third-body layer are present in the tyre-road contact. In the present paper, we give a survey on the present state of knowledge in the modelling, simulation and experimental validation of tyre tread-block friction processes. We concentrate on experimental techniques.

  18. Hepatoprotective activity of Musa paradisiaca on experimental animal models.

    Science.gov (United States)

    Nirmala, M; Girija, K; Lakshman, K; Divya, T

    2012-01-01

    To investigate the hepatoprotective activity of stem of Musa paradisiaca (M. paradisiaca) in CCl4 and paracetamol induced hepatotoxicity models in rats. Hepatoprotective activity of alcoholic and aqueous extracts of stem of M. paradisiaca was demonstrated by using two experimentally induced hepatotoxicity models. Administration of hepatotoxins (CCl4 and paracetamol) showed significant biochemical and histological deteriorations in the liver of experimental animals. Pretreatment with alcoholic extract (500 mg/kg), more significantly and to a lesser extent the alcoholic extract (250 mg/kg) and aqueous extract (500 mg/kg), reduced the elevated levels of the serum enzymes like serum glutamic-oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase (ALP) and bilirubin levels and alcoholic and aqueous extracts reversed the hepatic damage towards the normal, which further evidenced the hepatoprotective activity of stem of M. paradisiaca. The alcoholic extract at doses of 250 and 500 mg/kg, p.o. and aqueous extract at a dose of 500 mg/kg, p.o. of stem of M. paradisiaca have significant effect on the liver of CCl4 and paracetamol induced hepatotoxicity animal models.

  19. Experimental oligopolies modeling: A dynamic approach based on heterogeneous behaviors

    Science.gov (United States)

    Cerboni Baiardi, Lorenzo; Naimzada, Ahmad K.

    2018-05-01

    In the rank of behavioral rules, imitation-based heuristics has received special attention in economics (see [14] and [12]). In particular, imitative behavior is considered in order to understand the evidences arising in experimental oligopolies which reveal that the Cournot-Nash equilibrium does not emerge as unique outcome and show that an important component of the production at the competitive level is observed (see e.g.[1,3,9] or [7,10]). By considering the pioneering groundbreaking approach of [2], we build a dynamical model of linear oligopolies where heterogeneous decision mechanisms of players are made explicit. In particular, we consider two different types of quantity setting players characterized by different decision mechanisms that coexist and operate simultaneously: agents that adaptively adjust their choices towards the direction that increases their profit are embedded with imitator agents. The latter ones use a particular form of proportional imitation rule that considers the awareness about the presence of strategic interactions. It is noteworthy that the Cournot-Nash outcome is a stationary state of our models. Our thesis is that the chaotic dynamics arousing from a dynamical model, where heterogeneous players are considered, are capable to qualitatively reproduce the outcomes of experimental oligopolies.

  20. Experimental dynamic characterizations and modelling of disk vibrations for HDDs.

    Science.gov (United States)

    Pang, Chee Khiang; Ong, Eng Hong; Guo, Guoxiao; Qian, Hua

    2008-01-01

    Currently, the rotational speed of spindle motors in HDDs (Hard-Disk Drives) are increasing to improve high data throughput and decrease rotational latency for ultra-high data transfer rates. However, the disk platters are excited to vibrate at their natural frequencies due to higher air-flow excitation as well as eccentricities and imbalances in the disk-spindle assembly. These factors contribute directly to TMR (Track Mis-Registration) which limits achievable high recording density essential for future mobile HDDs. In this paper, the natural mode shapes of an annular disk mounted on a spindle motor used in current HDDs are characterized using FEM (Finite Element Methods) analysis and verified with SLDV (Scanning Laser Doppler Vibrometer) measurements. The identified vibration frequencies and amplitudes of the disk ODS (Operating Deflection Shapes) at corresponding disk mode shapes are modelled as repeatable disturbance components for servo compensation in HDDs. Our experimental results show that the SLDV measurements are accurate in capturing static disk mode shapes without the need for intricate air-flow aero-elastic models, and the proposed disk ODS vibration model correlates well with experimental measurements from a LDV.

  1. A comprehensive experimental and modeling study of 2-methylbutanol combustion

    KAUST Repository

    Park, Sungwoo

    2015-05-01

    2-Methylbutanol (2-methyl-1-butanol) is one of several next-generation biofuels that can be used as an alternative fuel or blending component for combustion engines. This paper presents new experimental data for 2-methylbutanol, including ignition delay times in a high-pressure shock tube and premixed laminar flame speeds in a constant volume combustion vessel. Shock tube ignition delay times were measured for 2-methylbutanol/air mixtures at three equivalence ratios, temperatures ranging from 750 to 1250. K, and at nominal pressures near 20 and 40. bar. Laminar flame speed data were obtained using the spherically propagating premixed flame configuration at pressures of 1, 2, and 5. bar. A detailed chemical kinetic model for 2-methylbutanol oxidation was developed including high- and low-temperature chemistry based on previous modeling studies on butanol and pentanol isomers. The proposed model was tested against new and existing experimental data at pressures of 1-40. atm, temperatures of 740-1636. K, equivalence ratios of 0.25-2.0. Reaction path and sensitivity analyses were conducted for identifying key reactions at various combustion conditions, and to obtain better understanding of the combustion characteristics of larger alcohols.

  2. Protection of estrogen in portal hypertension gastropathy: an experimental model

    Directory of Open Access Journals (Sweden)

    Maria Isabel Morgan-Martins

    2011-09-01

    Full Text Available CONTEXT: Portal hypertension is a complication secondary to cirrhosis that is characterized by increased blood flow and/or vascular resistance in the portal system, causing the appearance of a hyperdynamic collateral circulation. Partial portal vein ligation is an experimental model used in rats to study the pathophysiological mechanisms involved in pre-hepatic portal hypertension. Estrogen E2 is an antioxidant molecule with various physiological actions. OBJECTIVES: To evaluate the antioxidant activity of endogenous estrogen in an experimental model of partial portal vein ligation by comparing intact with castrated rats. METHODS: Twenty Wistar rats, weighing on average 250 g were used and divided into four groups: sham-operated (SO; intact (I with partial portal vein ligation (I + PPVL, castrated (C and castrated with partial ligation of the vein (C + PPVL. Day 1: castration or sham-operation; day 7, PPVL surgery; on day 15 post-PPVL, portal pressure in the mesenteric vein of rats was measured on polygraph Letica. Lipid peroxidation in the stomach was assessed using the technique of thiobarbituric acid reactive substances and activity of antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase. Statistical analysis was done with ANOVA - Student-Newman-Keuls (mean ± SE, and P<0.05 was considered as significant. RESULTS: Portal pressure was significantly increased in C + PPVL as compared to the other groups. There was no significant difference in the group of intact rats. TBARS showed significant damage in C and C + PPVL in relation to others. Antioxidant enzymes were significantly increased in the castrated rats with subsequent PPVL as compared to the other groups. CONCLUSION: We suggest that estrogen E2 plays a protective role in intact compared with castrated rats because it presents hydrophenolic radicals in its molecule, thus acting as an antioxidant in this experimental model.

  3. Protection of estrogen in portal hypertension gastropathy: an experimental model.

    Science.gov (United States)

    Morgan-Martins, Maria Isabel; Jacques, Simone Iahnig; Hartmann, Renata Minuzzo; Marques, Camila Moraes; Marroni, Cláudio Augusto; Marroni, Norma Possa

    2011-01-01

    Portal hypertension is a complication secondary to cirrhosis that is characterized by increased blood flow and/or vascular resistance in the portal system, causing the appearance of a hyperdynamic collateral circulation. Partial portal vein ligation is an experimental model used in rats to study the pathophysiological mechanisms involved in pre-hepatic portal hypertension. Estrogen E2 is an antioxidant molecule with various physiological actions. To evaluate the antioxidant activity of endogenous estrogen in an experimental model of partial portal vein ligation by comparing intact with castrated rats. Twenty Wistar rats, weighing on average 250 g were used and divided into four groups: sham-operated (SO); intact (I) with partial portal vein ligation (I + PPVL), castrated (C) and castrated with partial ligation of the vein (C + PPVL). Day 1: castration or sham-operation; day 7, PPVL surgery; on day 15 post-PPVL, portal pressure in the mesenteric vein of rats was measured on polygraph Letica. Lipid peroxidation in the stomach was assessed using the technique of thiobarbituric acid reactive substances and activity of antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase. Statistical analysis was done with ANOVA - Student-Newman-Keuls (mean ± SE), and P<0.05 was considered as significant. Portal pressure was significantly increased in C + PPVL as compared to the other groups. There was no significant difference in the group of intact rats. TBARS showed significant damage in C and C + PPVL in relation to others. Antioxidant enzymes were significantly increased in the castrated rats with subsequent PPVL as compared to the other groups. We suggest that estrogen E2 plays a protective role in intact compared with castrated rats because it presents hydrophenolic radicals in its molecule, thus acting as an antioxidant in this experimental model.

  4. Multiscale modelling and experimentation of hydrogen embrittlement in aerospace materials

    Science.gov (United States)

    Jothi, Sathiskumar

    Pulse plated nickel and nickel based superalloys have been used extensively in the Ariane 5 space launcher engines. Large structural Ariane 5 space launcher engine components such as combustion chambers with complex microstructures have usually been manufactured using electrodeposited nickel with advanced pulse plating techniques with smaller parts made of nickel based superalloys joined or welded to the structure to fabricate Ariane 5 space launcher engines. One of the major challenges in manufacturing these space launcher components using newly developed materials is a fundamental understanding of how different materials and microstructures react with hydrogen during welding which can lead to hydrogen induced cracking. The main objective of this research has been to examine and interpret the effects of microstructure on hydrogen diffusion and hydrogen embrittlement in (i) nickel based superalloy 718, (ii) established and (iii) newly developed grades of pulse plated nickel used in the Ariane 5 space launcher engine combustion chamber. Also, the effect of microstructures on hydrogen induced hot and cold cracking and weldability of three different grades of pulse plated nickel were investigated. Multiscale modelling and experimental methods have been used throughout. The effect of microstructure on hydrogen embrittlement was explored using an original multiscale numerical model (exploiting synthetic and real microstructures) and a wide range of material characterization techniques including scanning electron microscopy, 2D and 3D electron back scattering diffraction, in-situ and ex-situ hydrogen charged slow strain rate tests, thermal spectroscopy analysis and the Varestraint weldability test. This research shows that combined multiscale modelling and experimentation is required for a fundamental understanding of microstructural effects in hydrogen embrittlement in these materials. Methods to control the susceptibility to hydrogen induced hot and cold cracking and

  5. Experimental measurements and modelling of the WEGA boundary layer plasma

    International Nuclear Information System (INIS)

    El Shaer, M.; Ichtchenko, G.

    1983-02-01

    The boundary layer of the WEGA Tokamak has been investigated by using specific diagnostics: movable 4 mm microwave interferometer, several types of movable and fixed probes, Katsumata probe, and multigrid electrostatic analyzer. During the RF heating at the lower hybrid frequency, some modifications in the parameters of the boundary layer are observed which are interpreted by the ponderomotive force effects. A comparison between the measured reflection coefficients of the grill waveguides and their predicted values by a coupling theory (not taking into account the real conditions facing the Grill) is presented. A diffusion model was also made to describe this particular region and to fit the experimental results

  6. Sepsis: at-risk patients, clinical manifestations and management

    African Journals Online (AJOL)

    management of sepsis has resulted in a remarkable increase of new knowledge on the ... As sepsis progresses to septic shock, the risk of dying increases substantially. Where .... altered mental state, thrombocytopenia, raised serum lactate ...

  7. Prevalence and factors associated with neonatal sepsis among ...

    African Journals Online (AJOL)

    TOSHIBA

    Relationship between outcome variable and exposure variable was done using Chi ... A recent study in Ethiopia indicates that neonatal sepsis in the major newborn ... Neonatal sepsis was defined as infection that had occurred during the.

  8. Soluble L-selectin levels predict survival in sepsis

    DEFF Research Database (Denmark)

    Seidelin, Jakob B; Nielsen, Ole H; Strøm, Jens

    2002-01-01

    To evaluate serum soluble L-selectin as a prognostic factor for survival in patients with sepsis.......To evaluate serum soluble L-selectin as a prognostic factor for survival in patients with sepsis....

  9. The new sepsis definition: limitations and contribution to research and diagnosis of sepsis.

    Science.gov (United States)

    Verdonk, Franck; Blet, Alice; Mebazaa, Alexandre

    2017-04-01

    Based on recent clinical, epidemiological, and pathophysiological data, a third international consensus conference was carried out to define new criteria of sepsis in February 2016. This review presents the different items of this new definition, their limitations and their contribution to research and diagnosis of sepsis, in comparison with the previous definitions. Incidence, management, and pathophysiological knowledge of sepsis have improved over the past 20 years. However, sepsis still evolves to a mortal outcome, in one case out of five, with no new recent or specific therapy showing its efficacy on the patient's prognosis. These findings have led to the development of new definition. The new definition of sepsis incorporates relevant clinical and biological criteria such as SOFA score or serum lactate levels. It no longer takes into account the items of the systemic inflammatory response syndrome, which present a lack of specificity. It also simplifies the different stages of severity by deleting the term of 'severe sepsis' and by defining septic shock as a subset of sepsis. This definition, endorsed by only two international societies of intensive care, has some limitations and so merits prospective validation at different levels.

  10. Establishment of selected acute pulmonary thromboembolism model in experimental sheep

    International Nuclear Information System (INIS)

    Fan Jihai; Gu Xiulian; Chao Shengwu; Zhang Peng; Fan Ruilin; Wang Li'na; Wang Lulu; Wang Ling; Li Bo; Chen Taotao

    2010-01-01

    Objective: To establish a selected acute pulmonary thromboembolism model in experimental sheep suitable for animal experiment. Methods: By using Seldinger's technique the catheter sheath was placed in both the femoral vein and femoral artery in ten sheep. Under C-arm DSA guidance the catheter was inserted through the catheter sheath into the pulmonary artery. Via the catheter appropriate amount of sheep autologous blood clots was injected into the selected pulmonary arteries. The selected acute pulmonary thromboembolism model was thus established. Pulmonary angiography was performed to check the results. The pulmonary arterial pressure, femoral artery pressure,heart rates and partial pressure of oxygen in arterial blood (PaO 2 ) were determined both before and after the treatment. The above parameters obtained after the procedure were compared with the recorded parameters measured before the procedure, and the sheep model quality was evaluated. Results: The baseline of pulmonary arterial pressure was (27.30 ± 9.58) mmHg,femoral artery pressure was (126.4 ± 13.72) mmHg, heart rate was (103 ± 15) bpm and PaO 2 was (87.7 ± 12.04) mmHg. Sixty minutes after the injection of (30 ± 5) ml thrombotic agglomerates, the pulmonary arterial pressures rose to (52 ± 49) mmHg, femoral artery pressures dropped to (100 ± 21) mmHg. The heart rates went up to (150 ± 26) bpm. The PaO 2 fell to (25.3 ± 11.2) mmHg. After the procedure the above parameters were significantly different from that measured before the procedure in all ten animals (P < 0.01). The pulmonary arteriography clearly demonstrated that the selected pulmonary arteries were successfully embolized. Conclusion: The anatomy of sheep's femoral veins,vena cava system, pulmonary artery and right heart system are suitable for the establishment of the catheter passage, for this reason, selected acute pulmonary thromboembolism model can be easily created in experimental sheep. The technique is feasible and the model

  11. CFD Modeling and Experimental Validation of a Solar Still

    Directory of Open Access Journals (Sweden)

    Mahmood Tahir

    2017-01-01

    Full Text Available Earth is the densest planet of the solar system with total area of 510.072 million square Km. Over 71.68% of this area is covered with water leaving a scant area of 28.32% for human to inhabit. The fresh water accounts for only 2.5% of the total volume and the rest is the brackish water. Presently, the world is facing chief problem of lack of potable water. This issue can be addressed by converting brackish water into potable through a solar distillation process and solar still is specially assigned for this purpose. Efficiency of a solar still explicitly depends on its design parameters, such as wall material, chamber depth, width and slope of the zcondensing surface. This study was aimed at investigating the solar still parameters using CFD modeling and experimental validation. The simulation data of ANSYS-FLUENT was compared with actual experimental data. A close agreement among the simulated and experimental results was seen in the presented work. It reveals that ANSYS-FLUENT is a potent tool to analyse the efficiency of the new designs of the solar distillation systems.

  12. Computational and experimental model of transdermal iontophorethic drug delivery system.

    Science.gov (United States)

    Filipovic, Nenad; Saveljic, Igor; Rac, Vladislav; Graells, Beatriz Olalde; Bijelic, Goran

    2017-11-30

    The concept of iontophoresis is often applied to increase the transdermal transport of drugs and other bioactive agents into the skin or other tissues. It is a non-invasive drug delivery method which involves electromigration and electroosmosis in addition to diffusion and is shown to be a viable alternative to conventional administration routs such as oral, hypodermic and intravenous injection. In this study we investigated, experimentally and numerically, in vitro drug delivery of dexamethasone sodium phosphate to porcine skin. Different current densities, delivery durations and drug loads were investigated experimentally and introduced as boundary conditions for numerical simulations. Nernst-Planck equation was used for calculation of active substance flux through equivalent model of homogeneous hydrogel and skin layers. The obtained numerical results were in good agreement with experimental observations. A comprehensive in-silico platform, which includes appropriate numerical tools for fitting, could contribute to iontophoretic drug-delivery devices design and correct dosage and drug clearance profiles as well as to perform much faster in-silico experiments to better determine parameters and performance criteria of iontophoretic drug delivery. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. The inhibiting effect of intravenous anesthesia on adrenal gland functions under the sepsis condition.

    Science.gov (United States)

    Wang, Te; Liu, Changdong; Wei, Pihong; Lv, Lili; Yang, Zaiqi

    2017-06-01

    This study aims to explore the effect of intravenous anesthesia on the adrenal gland functions of rats with sepsis as well as on their lungs and adrenal gland tissues in order to provide a theoretical reference for the cure of sepsis. Female Sprague Dawley (SD) rats were taken as the research objects in this study. Venous channels of rats were constructed by catheterization through the external jugular vein, and the cecal ligation and puncture technique was adopted to duplicate the sepsis rat models. The level of tumor necrosis factor-α (TNF-α) in serum was detected using enzyme-linked immunosorbent assay (ELISA), and necrocytosis was observed by the fluorescent staining method. The results showed that the survival rates of groups A, B, C, and D were 100%, 60%, 60%, and 50%, respectively, while their concentrations of TNF-α in serum were101.26 ± 43.38, 1398.68 ± 178.56, 451.16 ± 78.68, and 649.83 ± 98.56 pg/mL, respectively. Results of fluorescent staining showed that the number of living cells per unit view in group A was 1428 ± 166 and those of groups B, C and D were 175 ± 56, 618 ± 76, and 468 ± 55, respectively. Besides, it was found that changes of inflammatory pathology of lung tissues of each group were significant. In conclusion, etomidate does not affect the survival of sepsis rats and does not exacerbate lung tissue inflammation in sepsis rats. Instead, it can inhibit TNF-α in serum of sepsis rats, as well as the apoptosis of adrenal cells in sepsis rats.

  14. Attrition of memory CD8 T cells during sepsis requires LFA-1.

    Science.gov (United States)

    Serbanescu, Mara A; Ramonell, Kimberly M; Hadley, Annette; Margoles, Lindsay M; Mittal, Rohit; Lyons, John D; Liang, Zhe; Coopersmith, Craig M; Ford, Mandy L; McConnell, Kevin W

    2016-11-01

    CD8 T cell loss and dysfunction have been implicated in the increased susceptibility to opportunistic infections during the later immunosuppressive phase of sepsis, but CD8 T cell activation and attrition in early sepsis remain incompletely understood. With the use of a CLP model, we assessed CD8 T cell activation at 5 consecutive time points and found that activation after sepsis results in a distinct phenotype (CD69 + CD25 int CD62L HI ) independent of cognate antigen recognition and TCR engagement and likely through bystander-mediated cytokine effects. Additionally, we observed that sepsis concurrently results in the preferential depletion of a subset of memory-phenotype CD8 T cells that remain "unactivated" (i.e., fail to up-regulate activation markers) by apoptosis. Unactivated CD44 HI OT-I cells were spared from sepsis-induced attrition, as were memory-phenotype CD8 T cells of mice treated with anti-LFA-1 mAb, 1 h after CLP. Perhaps most importantly, we demonstrate that attrition of memory phenotype cells may have a pathologic significance, as elevated IL-6 levels were associated with decreased numbers of memory-phenotype CD8 T cells in septic mice, and preservation of this subset after administration of anti-LFA-1 mAb conferred improved survival at 7 d. Taken together, these data identify potentially modifiable responses of memory-phenotype CD8 T cells in early sepsis and may be particularly important in the application of immunomodulatory therapies in sepsis. © Society for Leukocyte Biology.

  15. Immunotherapy in the management of sepsis.

    Science.gov (United States)

    Sikora, Janusz Piotr

    2002-01-01

    This work presents the role of Gram-negative bacteria endotoxins, pro- and anti-inflammatory cytokines and reactive oxygen species (ROS) in the complex and not fully explained pathogenesis of sepsis. The so-called "respiratory burst" of neutrophils and the antioxidant mechanisms of the host are also discussed. The work focuses on possible approaches to the management of sepsis connected with immunotherapy. Neutralization of endotoxin lipopolysaccharide (LPS), anti-tumor necrosis factor alpha (TNF-alpha) therapy with monoclonal antibodies or pentoxifylline (PTXF), as well as soluble recombinant cytokine agonists and antagonists used in clinical trials are taken into consideration. In addition, cytokine manipulation therapy, anti-adhesion techniques, glucocorticoides and antioxidant barrier interference are also described. So far there has been no immunotherapy of sepsis in children of proven clinical efficacy, which prompts an aggressive examination of the immune system aimed at affecting its function.

  16. Antipyretic Therapy in Critically Ill Patients with Sepsis: An Interaction with Body Temperature

    Science.gov (United States)

    Zhang, Zhongheng; Chen, Lin; Ni, Hongying

    2015-01-01

    Background and Objective The effect of antipyretic therapy on mortality in patients with sepsis remains undetermined. The present study aimed to investigate the role of antipyretic therapy in ICU patients with sepsis by using a large clinical database. Methods The multiparameter intelligent monitoring in intensive care II (MIMIC- II) database was employed for the study. Adult patients with sepsis were included for analysis. Antipyretic therapy included antipyretic medication and external cooling. Multivariable model with interaction terms were employed to explore the association of antipyretic therapy and mortality risk. Main Results A total of 15,268 patients fulfilled inclusion criteria and were included in the study. In multivariable model by treating temperature as a continuous variable, there was significant interaction between antipyretic therapy and the maximum temperature (Tmax). While antipyretic therapy had no significant effect on mortality in low temperature quintiles, antipyretic therapy was associated with increased risk of death in the quintile with body temperature >39°C (OR: 1.29, 95% CI: 1.04–1.61). Conclusion Our study shows that there is no beneficial effect on reducing mortality risk with the use of antipyretic therapy in ICU patients with sepsis. External cooling may even be harmful in patients with sepsis. PMID:25822614

  17. An efficient approach to bioconversion kinetic model generation based on automated microscale experimentation integrated with model driven experimental design

    DEFF Research Database (Denmark)

    Chen, B. H.; Micheletti, M.; Baganz, F.

    2009-01-01

    -erythrulose. Experiments were performed using automated microwell studies at the 150 or 800 mu L scale. The derived kinetic parameters were then verified in a second round of experiments where model predictions showed excellent agreement with experimental data obtained under conditions not included in the original......Reliable models of enzyme kinetics are required for the effective design of bioconversion processes. Kinetic expressions of the enzyme-catalysed reaction rate however, are frequently complex and establishing accurate values of kinetic parameters normally requires a large number of experiments....... These can be both time consuming and expensive when working with the types of non-natural chiral intermediates important in pharmaceutical syntheses. This paper presents ail automated microscale approach to the rapid and cost effective generation of reliable kinetic models useful for bioconversion process...

  18. Experimental Characterization and Modeling of PEM Fuel Cells

    DEFF Research Database (Denmark)

    Jespersen, Jesper Lebæk

    fundamental knowledge of the transport and electrochemical processes of PEM fuel cells and to provide methods for obtaining high quality data for PEM fuel cell simulation model validation. In this thesis three different areas of experimental characterization techniques was investigated, they include: Stack...... for obtaining very detailed data of the manifold flow. Moreover, the tools complement each other well, as high quality validation data can be obtained from PIV measurements to verify CFD models. AC Impedance Spectroscopy was used to thoroughly characterize a HTPEM single cell. The measurement method...... was furthermore transferred onto a Labview platform, which signiffcantly improves the exibility and lowers the cost of using this method. This technique is expected to bea very important future tool, used both for material characterization, celldiagnostic, system optimization and as a control input parameter...

  19. Experimental validation of models for Plasma Focus devices

    International Nuclear Information System (INIS)

    Rodriguez Palomino, Luis; Gonzalez, Jose; Clausse, Alejandro

    2003-01-01

    Plasma Focus(PF) Devices are thermonuclear pulsators that produce short pulsed radiation (X-ray, charged particles and neutrons). Since Filippov and Mather, investigations have been used to study plasma properties. Nowadays the interest about PF is focused in technology applications, related to the use of these devices as pulsed neutron sources. In the numerical calculus the Inter institutional PLADEMA (PLAsmas DEnsos MAgnetizados) network is developing three models. Each one is useful in different engineering stages of the Plasma Focus design. One of the main objectives in this work is a comparative study on the influence of the different parameters involved in each models. To validate these results, several experimental measurements under different geometry and initial conditions were performed. (author)

  20. Astrocyte regulation of sleep circuits: experimental and modeling perspectives

    Directory of Open Access Journals (Sweden)

    Tommaso eFellin

    2012-08-01

    Full Text Available Integrated within neural circuits, astrocytes have recently been shown to modulate brain rhythms thought to mediate sleep function. Experimental evidence suggests that local impact of astrocytes on single synapses translates into global modulation of neuronal networks and behavior. We discuss these findings in the context of current conceptual models of sleep generation and function, each of which have historically focused on neural mechanisms. We highlight the implications and the challenges introduced by these results from a conceptual and computational perspective. We further provide modeling directions on how these data might extend our knowledge of astrocytic properties and sleep function. Given our evolving understanding of how local cellular activities during sleep lead to functional outcomes for the brain, further mechanistic and theoretical understanding of astrocytic contribution to these dynamics will undoubtedly be of great basic and translational benefit.

  1. An experimental and modeling study of n-octanol combustion

    KAUST Repository

    Cai, Liming

    2015-01-01

    This study presents the first investigation on the combustion chemistry of n-octanol, a long chain alcohol. Ignition delay times were determined experimentally in a high-pressure shock tube, and stable species concentration profiles were obtained in a jet stirred reactor for a range of initial conditions. A detailed kinetic model was developed to describe the oxidation of n-octanol at both low and high temperatures, and the model shows good agreement with the present dataset. The fuel\\'s combustion characteristics are compared to those of n-alkanes and to short chain alcohols to illustrate the effects of the hydroxyl moiety and the carbon chain length on important combustion properties. Finally, the results are discussed in detail. © 2014 The Combustion Institute.

  2. Experimentally supported mathematical modeling of continuous baking processes

    DEFF Research Database (Denmark)

    Stenby Andresen, Mette

    and temperature) and control the process (air flow, temperature, and humidity) are therefore emphasized. The oven is furthermore designed to work outside the range of standard tunnel ovens, making it interesting for manufacturers of both baking products and baking equipment. A mathematical model describing......The scope of the PhD project was to increase knowledge on the process-to-product interactions in continuous tunnel ovens. The work has focused on five main objectives. These objectives cover development of new experimental equipment for pilot plant baking experiments, mathematical modeling of heat...... and mass transfer in a butter cookie product, and evaluation of quality assessment methods. The pilot plant oven is a special batch oven designed to emulate continuous convection tunnel oven baking. The design, construction, and validation of the oven has been part of the project and is described...

  3. Simulator for candu600 fuel handling system. the experimental model

    International Nuclear Information System (INIS)

    Marinescu, N.; Predescu, D.; Valeca, S.

    2013-01-01

    A main way to increase the nuclear plant safety is related to selection and continuous training of the operation staff. In this order, the computer programs for training, testing and evaluation of the knowledge get, or training simulators including the advanced analytical models of the technological systems are using. The Institute for Nuclear Research from Pitesti, Romania intend to design and build an Fuel Handling Simulator at his F/M Head Test Rig facility, that will be used for training of operating personnel. This paper presents simulated system, advantages to use the simulator, and the experimental model of simulator, that has been built to allows setting of the requirements and fabrication details, especially for the software kit that will be designed and implement on main simulator. (authors)

  4. Antioxidant Capacity: Experimental Determination by EPR Spectroscopy and Mathematical Modeling.

    Science.gov (United States)

    Polak, Justyna; Bartoszek, Mariola; Chorążewski, Mirosław

    2015-07-22

    A new method of determining antioxidant capacity based on a mathematical model is presented in this paper. The model was fitted to 1000 data points of electron paramagnetic resonance (EPR) spectroscopy measurements of various food product samples such as tea, wine, juice, and herbs with Trolox equivalent antioxidant capacity (TEAC) values from 20 to 2000 μmol TE/100 mL. The proposed mathematical equation allows for a determination of TEAC of food products based on a single EPR spectroscopy measurement. The model was tested on the basis of 80 EPR spectroscopy measurements of herbs, tea, coffee, and juice samples. The proposed model works for both strong and weak antioxidants (TEAC values from 21 to 2347 μmol TE/100 mL). The determination coefficient between TEAC values obtained experimentally and TEAC values calculated with proposed mathematical equation was found to be R(2) = 0.98. Therefore, the proposed new method of TEAC determination based on a mathematical model is a good alternative to the standard EPR method due to its being fast, accurate, inexpensive, and simple to perform.

  5. Experimental Human Cell and Tissue Models of Pemphigus

    Science.gov (United States)

    van der Wier, Gerda; Pas, Hendri H.; Jonkman, Marcel F.

    2010-01-01

    Pemphigus is a chronic mucocutaneous autoimmune bullous disease that is characterized by loss of cell-cell contact in skin and/or mucous membranes. Past research has successfully identified desmosomes as immunological targets and has demonstrated that acantholysis is initiated through direct binding of IgG. The exact mechanisms of acantholysis, however, are still missing. Experimental model systems have contributed considerably to today's knowledge and are still a favourite tool of research. In this paper we will describe to what extent human cell and tissue models represent the in vivo situation, for example, organ cultures of human skin, keratinocyte cultures, and human skin grafted on mice and, furthermore, how suitable they are to study the pathogenesis of pemphigus. Organ cultures closely mimic the architecture of the epidermis but are less suitable to answer posed biochemical questions. Cultured keratinocyte monolayers are convenient in this respect, but their desmosomal make-up in terms of adhesion molecules does not exactly reflect the in vivo situation. Reconstituted skin is a relatively new model that approaches organ culture. In models of human skin grafted on mice, acantholysis can be studied in actual human skin but now with all the advantages of an animal model. PMID:20585596

  6. Experimental and modeling investigation on structure H hydrate formation kinetics

    International Nuclear Information System (INIS)

    Mazraeno, M. Seyfi; Varaminian, F.; Vafaie sefti, M.

    2013-01-01

    Highlights: • Applying affinity model for the formation kinetics of sH hydrate and two stage kinetics. • Performing the experiments of hydrate formation of sH with MCP. • A unique path for the SH hydrate formation. - Abstract: In this work, the kinetics of crystal H hydrate and two stage kinetics formation is modeled by using the chemical affinity model for the first time. The basic idea is that there is a unique path for each experiment by which the crystallization process decays the affinity. The experiments were performed at constant temperatures of 274.15, 275.15, 275.65, 276.15 and 277.15 K. The initial pressure of each experiment is up to 25 bar above equilibrium pressure of sI. Methylcyclohexane (MCH), methylcyclopentane (MCP) and tert-butyl methyl ether (TBME) are used as sH former and methane is used as a help gas. The parameters of the affinity model (A r and t k ) are determined and the results show that the parameter of (A r )/(RT) has not a constant value when temperature changes in each group of experiments. The results indicate that this model can predict experimental data very well at several conditions

  7. Maternal hypothyroidism: An overview of current experimental models.

    Science.gov (United States)

    Ghanbari, Mahboubeh; Ghasemi, Asghar

    2017-10-15

    Maternal hypothyroidism (MH) is the most common cause of transient congenital hypothyroidism. Different animal models are used for assessing developmental effects of MH in offspring. The severity and status of hypothyroidism in animal models must be a reflection of the actual conditions in humans. To obtain comparable results with different clinical conditions, which lead to MH in humans, several factors have been suggested for researchers to consider before designing the experimental models. Regarding development of fetal body systems during pregnancy, interference at different times provides different results and the appropriate time for induction of hypothyroidism should be selected based on accurate time of development of the system under assessment. Other factors that should be taken into consideration include, physiological and biochemical differences between humans and other species, thyroid hormone-independent effects of anti-thyroid drugs, circadian rhythms in TSH secretion, sex differences, physical and psychological stress. This review addresses essential guidelines for selecting and managing the optimal animal model for MH as well as discussing the pros and cons of currently used models. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. An experimental methodology for a fuzzy set preference model

    Science.gov (United States)

    Turksen, I. B.; Willson, Ian A.

    1992-01-01

    models and vague linguistic preferences has greatly limited the usefulness and predictive validity of existing preference models. A fuzzy set preference model that uses linguistic variables and a fully interactive implementation should be able to simultaneously address these issues and substantially improve the accuracy of demand estimates. The parallel implementation of crisp and fuzzy conjoint models using identical data not only validates the fuzzy set model but also provides an opportunity to assess the impact of fuzzy set definitions and individual attribute choices implemented in the interactive methodology developed in this research. The generalized experimental tools needed for conjoint models can also be applied to many other types of intelligent systems.

  9. Experimental model for research on the blood-ocular barrier

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hak Jin; Jea, Seung Youn; Park, Jae Sung; Jung, Yeon Joo [Pusan National University, Pusan (Korea, Republic of); Kim, Yong Woo [Inje University, Kimhae (Korea, Republic of); Park, Byung Rae [Catholic University, Seoul (Korea, Republic of)

    2006-03-15

    The eyeball has 2 blood-ocular barriers, i.e, the blood-retinal and blood-aqueous barriers. The purpose of this study was to evaluate if triolein emulsion could disrupt the barriers, and we wanted to suggest as an experimental model for future blood-ocular barrier studies. The triolein emulsion was made of 0.1 ml triolein and 20 ml normal saline, and this was infused into the carotid artery of ten cats (the experimental group). As a control group, only normal saline was infused in another ten cats. Precontrast and postcontrast T1-weighted MR images were obtained at 30 minutes and 3 hours after embolization in both groups. The signal intensities were evaluate qualitatively and quantitatively in the anterior and posterior chambers and also in the vitreus fluid. Statistical analysis was performed by employing the Kruskal Wallist test, Dunn's Multiple Comparison test and the wilcoxon signed rank test. In the control group, no contrast enhancement was demonstrated in the anterior or posterior chamber or in the vitreus fluid of the ipsilateral or contralateral eyeball on the 30 minutes MR images. The anterior chambers of the ipsilateral and contralateral eyeballs revealed delayed contrast enhancement on the 3 hour MR images. In the experimental group, the 30 minute-postembolization MR images were not different from those of the control group. The 30 minute-postembolization MR images demonstrated delayed contrast enhancement in the anterior chamber of the ipsilateral and contralateral eyeballs and in the posterior chamber of the ipsilateral eyeball. The delayed contrast enhancement of the posterior chamber of the ipsilateral eyeball was statistically significant ({rho} < 0.05). The present study demonstrated significant contrast enhancement in the posterior chamber with infusion of the triolein emulsion, and this can serve as a model for blood-aqueous barrier studies.

  10. Experimental model for research on the blood-ocular barrier

    International Nuclear Information System (INIS)

    Kim, Hak Jin; Jea, Seung Youn; Park, Jae Sung; Jung, Yeon Joo; Kim, Yong Woo; Park, Byung Rae

    2006-01-01

    The eyeball has 2 blood-ocular barriers, i.e, the blood-retinal and blood-aqueous barriers. The purpose of this study was to evaluate if triolein emulsion could disrupt the barriers, and we wanted to suggest as an experimental model for future blood-ocular barrier studies. The triolein emulsion was made of 0.1 ml triolein and 20 ml normal saline, and this was infused into the carotid artery of ten cats (the experimental group). As a control group, only normal saline was infused in another ten cats. Precontrast and postcontrast T1-weighted MR images were obtained at 30 minutes and 3 hours after embolization in both groups. The signal intensities were evaluate qualitatively and quantitatively in the anterior and posterior chambers and also in the vitreus fluid. Statistical analysis was performed by employing the Kruskal Wallist test, Dunn's Multiple Comparison test and the wilcoxon signed rank test. In the control group, no contrast enhancement was demonstrated in the anterior or posterior chamber or in the vitreus fluid of the ipsilateral or contralateral eyeball on the 30 minutes MR images. The anterior chambers of the ipsilateral and contralateral eyeballs revealed delayed contrast enhancement on the 3 hour MR images. In the experimental group, the 30 minute-postembolization MR images were not different from those of the control group. The 30 minute-postembolization MR images demonstrated delayed contrast enhancement in the anterior chamber of the ipsilateral and contralateral eyeballs and in the posterior chamber of the ipsilateral eyeball. The delayed contrast enhancement of the posterior chamber of the ipsilateral eyeball was statistically significant (ρ < 0.05). The present study demonstrated significant contrast enhancement in the posterior chamber with infusion of the triolein emulsion, and this can serve as a model for blood-aqueous barrier studies

  11. Contaminant plume configuration and movement: an experimental model

    Science.gov (United States)

    Alencoao, A.; Reis, A.; Pereira, M. G.; Liberato, M. L. R.; Caramelo, L.; Amraoui, M.; Amorim, V.

    2009-04-01

    The relevance of Science and Technology in our daily routines makes it compulsory to educate citizens who have both scientific literacy and scientific knowledge. These will allow them to be intervening citizens in a constantly changing society. Thus, physical and natural sciences are included in school curricula, both in primary and secondary education, with the fundamental aim of developing in the students the skills, attitudes and knowledge needed for the understanding of the planet Earth and its real problems. On the other hand, teaching in Geosciences is more and more based on practical methodologies which use didactic material, sustaining teachers' pedagogical practices and facilitating students' learning tasks suggested on the syllabus defined for each school level. Themes related to exploring the different components of the Hydrological Cycle and themes related to natural environment protection and preservation, namely water resources and soil contamination by industrial and urban sewage are examples of subject matters included on the Portuguese syllabus. These topics motivated the conception and construction of experimental models for the study of the propagation of pollutants on a porous medium. The experimental models allow inducing a horizontal flux of water though different kinds of permeable substances (e.g. sand, silt), with contamination spots on its surface. These experimental activities facilitate the student to understand the flow path of contaminating substances on the saturated zone and to observe the contaminant plume configuration and movement. The activities are explored in a teaching and learning process perspective where the student builds its own knowledge through real question- problem based learning which relate Science, Technology and Society. These activities have been developed in the framework of project ‘Water in the Environment' (CV/PVI/0854) of the POCTI Program (Programa Operacional "Ciência, Tecnologia, Inovação") financed

  12. Sparse linear models: Variational approximate inference and Bayesian experimental design

    International Nuclear Information System (INIS)

    Seeger, Matthias W

    2009-01-01

    A wide range of problems such as signal reconstruction, denoising, source separation, feature selection, and graphical model search are addressed today by posterior maximization for linear models with sparsity-favouring prior distributions. The Bayesian posterior contains useful information far beyond its mode, which can be used to drive methods for sampling optimization (active learning), feature relevance ranking, or hyperparameter estimation, if only this representation of uncertainty can be approximated in a tractable manner. In this paper, we review recent results for variational sparse inference, and show that they share underlying computational primitives. We discuss how sampling optimization can be implemented as sequential Bayesian experimental design. While there has been tremendous recent activity to develop sparse estimation, little attendance has been given to sparse approximate inference. In this paper, we argue that many problems in practice, such as compressive sensing for real-world image reconstruction, are served much better by proper uncertainty approximations than by ever more aggressive sparse estimation algorithms. Moreover, since some variational inference methods have been given strong convex optimization characterizations recently, theoretical analysis may become possible, promising new insights into nonlinear experimental design.

  13. Sparse linear models: Variational approximate inference and Bayesian experimental design

    Energy Technology Data Exchange (ETDEWEB)

    Seeger, Matthias W [Saarland University and Max Planck Institute for Informatics, Campus E1.4, 66123 Saarbruecken (Germany)

    2009-12-01

    A wide range of problems such as signal reconstruction, denoising, source separation, feature selection, and graphical model search are addressed today by posterior maximization for linear models with sparsity-favouring prior distributions. The Bayesian posterior contains useful information far beyond its mode, which can be used to drive methods for sampling optimization (active learning), feature relevance ranking, or hyperparameter estimation, if only this representation of uncertainty can be approximated in a tractable manner. In this paper, we review recent results for variational sparse inference, and show that they share underlying computational primitives. We discuss how sampling optimization can be implemented as sequential Bayesian experimental design. While there has been tremendous recent activity to develop sparse estimation, little attendance has been given to sparse approximate inference. In this paper, we argue that many problems in practice, such as compressive sensing for real-world image reconstruction, are served much better by proper uncertainty approximations than by ever more aggressive sparse estimation algorithms. Moreover, since some variational inference methods have been given strong convex optimization characterizations recently, theoretical analysis may become possible, promising new insights into nonlinear experimental design.

  14. Experimental Investigation and Theoretical Modeling of Nanosilica Activity in Concrete

    Directory of Open Access Journals (Sweden)

    Han-Seung Lee

    2014-01-01

    Full Text Available This paper presents experimental investigations and theoretical modeling of the hydration reaction of nanosilica blended concrete with different water-to-binder ratios and different nanosilica replacement ratios. The developments of chemically bound water contents, calcium hydroxide contents, and compressive strength of Portland cement control specimens and nanosilica blended specimens were measured at different ages: 1 day, 3 days, 7 days, 14 days, and 28 days. Due to the pozzolanic reaction of nanosilica, the contents of calcium hydroxide in nanosilica blended pastes are considerably lower than those in the control specimens. Compared with the control specimens, the extent of compressive strength enhancement in the nanosilica blended specimens is much higher at early ages. Additionally, a blended cement hydration model that considers both the hydration reaction of cement and the pozzolanic reaction of nanosilica is proposed. The properties of nanosilica blended concrete during hardening were evaluated using the degree of hydration of cement and the reaction degree of nanosilica. The calculated chemically bound water contents, calcium hydroxide contents, and compressive strength were generally consistent with the experimental results.

  15. Tobacco experimental model to induce urinary bladder neoplasms

    Directory of Open Access Journals (Sweden)

    José Alexandre Colli Neto

    2014-01-01

    Full Text Available OBJECTIVE: to develop an experimental model of exposure to tobacco burning (cigarette products to assess the effects of its chronic use in relation to cancers of the bladder. METHODS: the animals were chronically exposed to the burning tobacco products in a semi-open chamber to simulate smoking. Thirty young Wistar rats were divided into two groups: one with 20 animals simulating smoking for six months, and ten not exposed control animals for the same period. After exposure by inhalation of cigarette smoke, animals were euthanized and subjected to histopathological study of the bladder wall. RESULTS: no tumor was found but mild and non significant alterations. The studies of hemo-oximetry (carboxyhemoglobin and methemoglobin and the concentration of carbon dioxide (CO2 confirm that the animals were exposed to high concentrations of tobacco smoke and its derivatives. CONCLUSION: no bladder mucosal neoplasia was found in the pathological study of animals. The developed experimental models were highly efficient, practical and easy to use and can be used in other similar studies to determine the harmful effects caused by smoking.

  16. Murine Lung Cancer Increases CD4+ T Cell Apoptosis and Decreases Gut Proliferative Capacity in Sepsis.

    Science.gov (United States)

    Lyons, John D; Mittal, Rohit; Fay, Katherine T; Chen, Ching-Wen; Liang, Zhe; Margoles, Lindsay M; Burd, Eileen M; Farris, Alton B; Ford, Mandy L; Coopersmith, Craig M

    2016-01-01

    Mortality is significantly higher in septic patients with cancer than in septic patients without a history of cancer. We have previously described a model of pancreatic cancer followed by sepsis from Pseudomonas aeruginosa pneumonia in which cancer septic mice have higher mortality than previously healthy septic mice, associated with increased gut epithelial apoptosis and decreased T cell apoptosis. The purpose of this study was to determine whether this represents a common host response by creating a new model in which both the type of cancer and the model of sepsis are altered. C57Bl/6 mice received an injection of 250,000 cells of the lung cancer line LLC-1 into their right thigh and were followed three weeks for development of palpable tumors. Mice with cancer and mice without cancer were then subjected to cecal ligation and puncture and sacrificed 24 hours after the onset of sepsis or followed 7 days for survival. Cancer septic mice had a higher mortality than previously healthy septic mice (60% vs. 18%, p = 0.003). Cancer septic mice had decreased number and frequency of splenic CD4+ lymphocytes secondary to increased apoptosis without changes in splenic CD8+ numbers. Intestinal proliferation was also decreased in cancer septic mice. Cancer septic mice had a higher bacterial burden in the peritoneal cavity, but this was not associated with alterations in local cytokine, neutrophil or dendritic cell responses. Cancer septic mice had biochemical evidence of worsened renal function, but there was no histologic evidence of renal injury. Animals with cancer have a significantly higher mortality than previously healthy animals following sepsis. The potential mechanisms associated with this elevated mortality differ significantly based upon the model of cancer and sepsis utilized. While lymphocyte apoptosis and intestinal integrity are both altered by the combination of cancer and sepsis, the patterns of these alterations vary greatly depending on the models used.

  17. Murine Lung Cancer Increases CD4+ T Cell Apoptosis and Decreases Gut Proliferative Capacity in Sepsis.

    Directory of Open Access Journals (Sweden)

    John D Lyons

    Full Text Available Mortality is significantly higher in septic patients with cancer than in septic patients without a history of cancer. We have previously described a model of pancreatic cancer followed by sepsis from Pseudomonas aeruginosa pneumonia in which cancer septic mice have higher mortality than previously healthy septic mice, associated with increased gut epithelial apoptosis and decreased T cell apoptosis. The purpose of this study was to determine whether this represents a common host response by creating a new model in which both the type of cancer and the model of sepsis are altered.C57Bl/6 mice received an injection of 250,000 cells of the lung cancer line LLC-1 into their right thigh and were followed three weeks for development of palpable tumors. Mice with cancer and mice without cancer were then subjected to cecal ligation and puncture and sacrificed 24 hours after the onset of sepsis or followed 7 days for survival.Cancer septic mice had a higher mortality than previously healthy septic mice (60% vs. 18%, p = 0.003. Cancer septic mice had decreased number and frequency of splenic CD4+ lymphocytes secondary to increased apoptosis without changes in splenic CD8+ numbers. Intestinal proliferation was also decreased in cancer septic mice. Cancer septic mice had a higher bacterial burden in the peritoneal cavity, but this was not associated with alterations in local cytokine, neutrophil or dendritic cell responses. Cancer septic mice had biochemical evidence of worsened renal function, but there was no histologic evidence of renal injury.Animals with cancer have a significantly higher mortality than previously healthy animals following sepsis. The potential mechanisms associated with this elevated mortality differ significantly based upon the model of cancer and sepsis utilized. While lymphocyte apoptosis and intestinal integrity are both altered by the combination of cancer and sepsis, the patterns of these alterations vary greatly depending on

  18. Sepsis: Current Definition, Pathophysiology, Diagnosis, and Management.

    Science.gov (United States)

    Taeb, Abdalsamih M; Hooper, Michael H; Marik, Paul E

    2017-06-01

    Sepsis is a clinical syndrome that results from the dysregulated inflammatory response to infection that leads to organ dysfunction. The resulting losses to society in terms of financial burden, morbidity, and mortality are enormous. We provide a review of sepsis, its underlying pathophysiology, and guidance for diagnosis and management of this common disease. Current established treatments include appropriate antimicrobial agents to target the underlying infection, optimization of intravascular volume to improve stroke volume, vasopressors to counteract vasoplegic shock, and high-quality supportive care. Appropriate implementation of established treatments combined with novel therapeutic approaches promises to continue to decrease the impact of this disease.

  19. Indium 111 leucocyte scintigraphy in abdominal sepsis

    International Nuclear Information System (INIS)

    Baba, A.A.; McKillop, J.H.; Gray, H.W.; Cuthbert, G.F.; Neilson, W.; Anderson, J.R.

    1990-01-01

    We have studied the clinical utility of indium 111 autologous leucocyte scintigraphy retrospectively in 45 patients presenting with suspected intra-abdominal sepsis. The sensitivity was 95% (21/22) and the specificity was 91% (21/23). Some 34 of the studies (17 positive and 17 negative) were considered helpful in furthering patient management (76%) and 8, unhelpful (18%). In 3, the study results were misleading and led to inappropriate treatment. Indium 111 scintigraphy, whether positive or negative, provides information in patients with suspected intra-abdominal sepsis upon which therapeutic decisions can be based. (orig.)

  20. Neonatal Sepsis: past, present and future; a review article | Tripathi ...

    African Journals Online (AJOL)

    Sepsis is the most common cause of neonatal mortality. As per National Neonatal Perinatal Database (NNPD) 2002-2003, the incidence of neonatal sepsis in India was 30 per 1000 live birth. It is 3% among intramural babies and 39.7% among extramural admissions. The early manifestations of neonatal sepsis are vague ...

  1. Severe hyperglycaemia due to neonatal sepsis - A case report ...

    African Journals Online (AJOL)

    Neonatal sepsis is a clinical syndrome characterized by signs and symptoms of infection with or without accompanying bacteremia in the first month of life. The clinical signs of neonatal sepsis are neither specific nor uniform. Neonatal sepsis may present with fever, hypotonia, respiratory distress, apnea and hyperglycaemia.

  2. Thrombocytopenia in neonatal sepsis: Incidence, severity and risk factors

    NARCIS (Netherlands)

    Ree, Isabelle M. C.; Fustolo-Gunnink, Suzanne F.; Bekker, Vincent; Fijnvandraat, Karin J.; Steggerda, Sylke J.; Lopriore, Enrico

    2017-01-01

    Thrombocytopenia is a frequent problem in neonatal sepsis and is among the most predictive, independent risk factors for sepsis-associated mortality. This study aims to clarify the occurrence, severity and duration of thrombocytopenia in neonatal sepsis. A cohort study was carried out among all

  3. Can Resistin be a New Indicator of Neonatal Sepsis?

    Directory of Open Access Journals (Sweden)

    Didem Aliefendioglu

    2014-02-01

    Conclusion: Resistin levels were higher in premature newborns with sepsis and correlated with IL-6 levels, which is an indicator of neonatal sepsis. This suggests that resistin may also be used in the diagnosis of neonatal sepsis. However, it has limited value when compared with the other inflammatory markers including C-reactive protein, procalcitonin, and IL-6.

  4. Sepsis in HIV-infected patients; epidemiology and host response

    NARCIS (Netherlands)

    Huson, M.A.M.

    2016-01-01

    In this thesis, we examined the impact of HIV infection on the epidemiology (Part I) of sepsis, and host response (Part II) to sepsis. We studied sepsis patients in Gabon, a setting with a high prevalence of HIV, and in Dutch intensive care units (ICUs). In Part I, we found that HIV positive

  5. Sepsis in intensive care patients: challenges in diagnosis and prognostication

    NARCIS (Netherlands)

    Klein Klouwenberg, P.M.C.

    2015-01-01

    Sepsis is a syndrome that arises when the body’s response to a severe infection injures its own tissues. It is a major and increasing cause of in-hospital morbidity and mortality. Despite recent advances in the management of sepsis, the morbidity and mortality caused by sepsis remain unacceptably

  6. Implementatie van de Surviving Sepsis Campaign bundels : Monitoring van ervaringen

    NARCIS (Netherlands)

    Lilian Vloet; J. Schouten; N. Stevens; A. Rensen; A. Willems; F. Zeegers

    2011-01-01

    Sepsis komt vaak voor in ziekenhuizen. Ernstige sepsis is verantwoordelijk voor 10 - 20% van alle Intensive Care (IC) opnames en is de belangrijkste doodsoorzaak op niet-cardiale IC?s. De gemiddelde mortaliteit van volwassenen met ernstige sepsis op de IC is 33% en van volwassenen met septische

  7. Application of Iterative Robust Model-based Optimal Experimental Design for the Calibration of Biocatalytic Models

    DEFF Research Database (Denmark)

    Van Daele, Timothy; Gernaey, Krist V.; Ringborg, Rolf Hoffmeyer

    2017-01-01

    The aim of model calibration is to estimate unique parameter values from available experimental data, here applied to a biocatalytic process. The traditional approach of first gathering data followed by performing a model calibration is inefficient, since the information gathered during...... experimentation is not actively used to optimise the experimental design. By applying an iterative robust model-based optimal experimental design, the limited amount of data collected is used to design additional informative experiments. The algorithm is used here to calibrate the initial reaction rate of an ω......-transaminase catalysed reaction in a more accurate way. The parameter confidence region estimated from the Fisher Information Matrix is compared with the likelihood confidence region, which is a more accurate, but also a computationally more expensive method. As a result, an important deviation between both approaches...

  8. Learning representations for the early detection of sepsis with deep neural networks.

    Science.gov (United States)

    Kam, Hye Jin; Kim, Ha Young

    2017-10-01

    Sepsis is one of the leading causes of death in intensive care unit patients. Early detection of sepsis is vital because mortality increases as the sepsis stage worsens. This study aimed to develop detection models for the early stage of sepsis using deep learning methodologies, and to compare the feasibility and performance of the new deep learning methodology with those of the regression method with conventional temporal feature extraction. Study group selection adhered to the InSight model. The results of the deep learning-based models and the InSight model were compared. With deep feedforward networks, the area under the ROC curve (AUC) of the models were 0.887 and 0.915 for the InSight and the new feature sets, respectively. For the model with the combined feature set, the AUC was the same as that of the basic feature set (0.915). For the long short-term memory model, only the basic feature set was applied and the AUC improved to 0.929 compared with the existing 0.887 of the InSight model. The contributions of this paper can be summarized in three ways: (i) improved performance without feature extraction using domain knowledge, (ii) verification of feature extraction capability of deep neural networks through comparison with reference features, and (iii) improved performance with feedforward neural networks using long short-term memory, a neural network architecture that can learn sequential patterns. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Integral Reactor Containment Condensation Model and Experimental Validation

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Qiao [Oregon State Univ., Corvallis, OR (United States); Corradini, Michael [Univ. of Wisconsin, Madison, WI (United States)

    2016-05-02

    This NEUP funded project, NEUP 12-3630, is for experimental, numerical and analytical studies on high-pressure steam condensation phenomena in a steel containment vessel connected to a water cooling tank, carried out at Oregon State University (OrSU) and the University of Wisconsin at Madison (UW-Madison). In the three years of investigation duration, following the original proposal, the planned tasks have been completed: (1) Performed a scaling study for the full pressure test facility applicable to the reference design for the condensation heat transfer process during design basis accidents (DBAs), modified the existing test facility to route the steady-state secondary steam flow into the high pressure containment for controllable condensation tests, and extended the operations at negative gage pressure conditions (OrSU). (2) Conducted a series of DBA and quasi-steady experiments using the full pressure test facility to provide a reliable high pressure condensation database (OrSU). (3) Analyzed experimental data and evaluated condensation model for the experimental conditions, and predicted the prototypic containment performance under accidental conditions (UW-Madison). A film flow model was developed for the scaling analysis, and the results suggest that the 1/3 scaled test facility covers large portion of laminar film flow, leading to a lower average heat transfer coefficient comparing to the prototypic value. Although it is conservative in reactor safety analysis, the significant reduction of heat transfer coefficient (50%) could under estimate the prototypic condensation heat transfer rate, resulting in inaccurate prediction of the decay heat removal capability. Further investigation is thus needed to quantify the scaling distortion for safety analysis code validation. Experimental investigations were performed in the existing MASLWR test facility at OrST with minor modifications. A total of 13 containment condensation tests were conducted for pressure

  10. Experimental investigation and mathematical modeling of triode PEM fuel cells

    International Nuclear Information System (INIS)

    Martino, E.; Koilias, G.; Athanasiou, M.; Katsaounis, A.; Dimakopoulos, Y.; Tsamopoulos, J.; Vayenas, C.G.

    2017-01-01

    Highlights: •The triode fuel cell operation was tested using novel comb-type electrode designs. •Triode operation enhances the PEMFC power output by up to 500%. •Power output enhancement exceeds auxiliary power by up to 20%. •Good agreement with mathematical model based on the laws of Kirchhoff. •Proton fluxes in the membrane found via solution of the Nernst Planck equation -- Abstract: The triode operation of humidified PEM fuel cells has been investigated both with pure H 2 and with CO poisoned H 2 feed over commercial Vulcan supported Pt(30%)-Ru(15%) anodes. It was found that triode operation, which involves the use of a third, auxiliary, electrode, leads to up to 400% power output increase with the same CO poisoned H 2 gas feed. At low current densities, the power increase is accompanied by an increase in overall thermodynamic efficiency. A mathematical model, based on Kirchhoff’s laws, has been developed which is in reasonably good agreement with the experimental results. In order to gain some additional insight into the mechanism of triode operation, the model has been also extended to describe the potential distribution inside the Nafion membrane via the numerical solution of the Nernst-Planck equation. Both model and experiment have shown the critical role of minimizing the auxiliary-anode or auxiliary-cathode resistance, and this has led to improved comb-shaped anode or cathode electrode geometries.

  11. Experimental study and modelling of iron ore reduction by hydrogen

    International Nuclear Information System (INIS)

    Wagner, D.

    2008-01-01

    In an effort to find new ways to drastically reduce the CO 2 emissions from the steel industry (ULCOS project), the reduction of iron ore by pure hydrogen in a shaft furnace was investigated. The work consisted of literature, experimental, and modelling studies. The chemical reaction and its kinetics were analysed on the basis of thermogravimetric experiments and physicochemical characterizations of partially reduced samples. A specific kinetic model was designed, which simulates the successive reactions, the different steps of mass transport, and possible iron sintering, at the particle scale. Finally, a 2-dimensional numerical model of a shaft furnace was developed. It depicts the variation of the solid and gas temperatures and compositions throughout the reactor. One original feature of the model is using the law of additive characteristic times for calculating the reaction rates. This allowed us to handle both the particle and the reactor scale, while keeping reasonable calculation time. From the simulation results, the influence of the process parameters was assessed. Optimal operating conditions were concluded, which reveal the efficiency of the hydrogen process. (author)

  12. Toxin-Induced Experimental Models of Learning and Memory Impairment.

    Science.gov (United States)

    More, Sandeep Vasant; Kumar, Hemant; Cho, Duk-Yeon; Yun, Yo-Sep; Choi, Dong-Kug

    2016-09-01

    Animal models for learning and memory have significantly contributed to novel strategies for drug development and hence are an imperative part in the assessment of therapeutics. Learning and memory involve different stages including acquisition, consolidation, and retrieval and each stage can be characterized using specific toxin. Recent studies have postulated the molecular basis of these processes and have also demonstrated many signaling molecules that are involved in several stages of memory. Most insights into learning and memory impairment and to develop a novel compound stems from the investigations performed in experimental models, especially those produced by neurotoxins models. Several toxins have been utilized based on their mechanism of action for learning and memory impairment such as scopolamine, streptozotocin, quinolinic acid, and domoic acid. Further, some toxins like 6-hydroxy dopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and amyloid-β are known to cause specific learning and memory impairment which imitate the disease pathology of Parkinson's disease dementia and Alzheimer's disease dementia. Apart from these toxins, several other toxins come under a miscellaneous category like an environmental pollutant, snake venoms, botulinum, and lipopolysaccharide. This review will focus on the various classes of neurotoxin models for learning and memory impairment with their specific mechanism of action that could assist the process of drug discovery and development for dementia and cognitive disorders.

  13. The Non-Human Primate Experimental Glaucoma Model

    Science.gov (United States)

    Burgoyne, Claude F.

    2015-01-01

    The purpose of this report is to summarize the current strengths and weaknesses of the non-human primate (NHP) experimental glaucoma (EG) model through sections devoted to its history, methods, important findings, alternative optic neuropathy models and future directions. NHP EG has become well established for studying human glaucoma in part because the NHP optic nerve head (ONH) shares a close anatomic association with the human ONH and because it provides the only means of systematically studying the very earliest visual system responses to chronic IOP elevation, i.e. the conversion from ocular hypertension to glaucomatous damage. However, NHPs are impractical for studies that require large animal numbers, demonstrate spontaneous glaucoma only rarely, do not currently provide a model of the neuropathy at normal levels of IOP, and cannot easily be genetically manipulated, except through tissue-specific, viral vectors. The goal of this summary is to direct NHP EG and non-NHP EG investigators to the previous, current and future accomplishment of clinically relevant knowledge in this model. PMID:26070984

  14. Autonomous learning derived from experimental modeling of physical laws.

    Science.gov (United States)

    Grabec, Igor

    2013-05-01

    This article deals with experimental description of physical laws by probability density function of measured data. The Gaussian mixture model specified by representative data and related probabilities is utilized for this purpose. The information cost function of the model is described in terms of information entropy by the sum of the estimation error and redundancy. A new method is proposed for searching the minimum of the cost function. The number of the resulting prototype data depends on the accuracy of measurement. Their adaptation resembles a self-organized, highly non-linear cooperation between neurons in an artificial NN. A prototype datum corresponds to the memorized content, while the related probability corresponds to the excitability of the neuron. The method does not include any free parameters except objectively determined accuracy of the measurement system and is therefore convenient for autonomous execution. Since representative data are generally less numerous than the measured ones, the method is applicable for a rather general and objective compression of overwhelming experimental data in automatic data-acquisition systems. Such compression is demonstrated on analytically determined random noise and measured traffic flow data. The flow over a day is described by a vector of 24 components. The set of 365 vectors measured over one year is compressed by autonomous learning to just 4 representative vectors and related probabilities. These vectors represent the flow in normal working days and weekends or holidays, while the related probabilities correspond to relative frequencies of these days. This example reveals that autonomous learning yields a new basis for interpretation of representative data and the optimal model structure. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Mass spectrometry analysis of hepcidin peptides in experimental mouse models.

    Directory of Open Access Journals (Sweden)

    Harold Tjalsma

    Full Text Available The mouse is a valuable model for unravelling the role of hepcidin in iron homeostasis, however, such studies still report hepcidin mRNA levels as a surrogate marker for bioactive hepcidin in its pivotal function to block ferroportin-mediated iron transport. Here, we aimed to assess bioactive mouse Hepcidin-1 (Hep-1 and its paralogue Hepcidin-2 (Hep-2 at the peptide level. To this purpose, Fourier transform ion cyclotron resonance (FTICR and tandem-MS was used for hepcidin identification, after which a time-of-flight (TOF MS-based methodology was exploited to routinely determine Hep-1 and -2 levels in mouse serum and urine. This method was biologically validated by hepcidin assessment in: i 3 mouse strains (C57Bl/6; DBA/2 and BABL/c upon stimulation with intravenous iron and LPS, ii homozygous Hfe knock out, homozygous transferrin receptor 2 (Y245X mutated mice and double affected mice, and iii mice treated with a sublethal hepatotoxic dose of paracetamol. The results showed that detection of Hep-1 was restricted to serum, whereas Hep-2 and its presumed isoforms were predominantly present in urine. Elevations in serum Hep-1 and urine Hep-2 upon intravenous iron or LPS were only moderate and varied considerably between mouse strains. Serum Hep-1 was decreased in all three hemochromatosis models, being lowest in the double affected mice. Serum Hep-1 levels correlated with liver hepcidin-1 gene expression, while acute liver damage by paracetamol depleted Hep-1 from serum. Furthermore, serum Hep-1 appeared to be an excellent indicator of splenic iron accumulation. In conclusion, Hep-1 and Hep-2 peptide responses in experimental mouse agree with the known biology of hepcidin mRNA regulators, and their measurement can now be implemented in experimental mouse models to provide novel insights in post-transcriptional regulation, hepcidin function, and kinetics.

  16. Concise Review: Mesenchymal Stem (Stromal) Cells: Biology and Preclinical Evidence for Therapeutic Potential for Organ Dysfunction Following Trauma or Sepsis.

    Science.gov (United States)

    Matthay, Michael A; Pati, Shibani; Lee, Jae-Woo

    2017-02-01

    Several experimental studies have provided evidence that bone-marrow derived mesenchymal stem (stromal) cells (MSC) may be effective in treating critically ill surgical patients who develop traumatic brain injury, acute renal failure, or the acute respiratory distress syndrome. There is also preclinical evidence that MSC may be effective in treating sepsis-induced organ failure, including evidence that MSC have antimicrobial properties. This review considers preclinical studies with direct relevance to organ failure following trauma, sepsis or major infections that apply to critically ill patients. Progress has been made in understanding the mechanisms of benefit, including MSC release of paracrine factors, transfer of mitochondria, and elaboration of exosomes and microvesicles. Regardless of how well they are designed, preclinical studies have limitations in modeling the complexity of clinical syndromes, especially in patients who are critically ill. In order to facilitate translation of the preclinical studies of MSC to critically ill patients, there will need to be more standardization regarding MSC production with a focus on culture methods and cell characterization. Finally, well designed clinical trials will be needed in critically ill patient to assess safety and efficacy. Stem Cells 2017;35:316-324. © 2016 AlphaMed Press.

  17. Hepatoprotective Effect of Essential Oils from Hyptis crenata in Sepsis-Induced Liver Dysfunction.

    Science.gov (United States)

    Lima, Glauber Cruz; Vasconcelos, Yuri de Abreu Gomes; de Santana Souza, Marilia Trindade; Oliveira, Alan Santos; Bomfim, Rangel Rodrigues; de Albuquerque Júnior, Ricardo Luiz Cavalcanti; Camargo, Enilton Aparecido; Portella, Viviane Gomes; Coelho-de-Souza, Andrelina Noronha; Diniz, Lúcio Ricardo Leite

    2018-02-28

    No specific therapeutics are available for the treatment of sepsis-induced liver dysfunction, a clinical complication strongly associated with the high mortality rate of septic patients. This study investigated the effect of the essential oil of Hyptis crenata (EOHc), a lamiaceae plant used to treat liver disturbances in Brazilian folk medicine, on liver function during early sepsis. Sepsis was induced by the cecal ligation and puncture (CLP) model. Rats were divided into four groups: Sham, Sham+EOHc, CLP, and CLP+EOHc. EOHc (300 mg/kg) was orally administered 12 and 24 h after surgery. The animals were sacrificed for blood collection and liver tissue samples 48 h after surgery. Hepatic function was evaluated by measuring serum bilirubin, alkaline phosphatase (ALP), aspartate aminotransferase, and alanine aminotransferase (ALT) levels. The levels of malondialdehyde and the activity of superoxide dismutase, catalase, and GSH peroxidase (GSH-Px) were measured for assessment of oxidative stress. Liver morphology was analyzed by hematoxylin and eosin staining. EOHc normalized serum ALP, ALT, and bilirubin levels and inhibited morphological changes. In addition, we observed that EOHc inhibited elevation in hepatic lipid peroxidation and reduction of the glutathione peroxidase activity induced by sepsis. Our data show that EOHc plays a protective effect against liver injury induced by sepsis.

  18. Isoliquiritigenin protects against sepsis-induced lung and liver injury by reducing inflammatory responses.

    Science.gov (United States)

    Chen, Xiong; Cai, Xueding; Le, Rongrong; Zhang, Man; Gu, Xuemei; Shen, Feixia; Hong, Guangliang; Chen, Zimiao

    2018-02-05

    Sepsis, one of the most fatal diseases worldwide, often leads to multiple organ failure, mainly due to uncontrolled inflammatory responses. Despite accumulating knowledge obtained in recent years, effective drugs to treat sepsis in the clinic are still urgently needed. Isoliquiritigenin (ISL), a chalcone compound, has been reported to exert anti-inflammatory properties. However, little is known about the effects of ISL on sepsis and its related complications. In this study, we investigated the potential protective effects of ISL on lipopolysaccharide (LPS)-induced injuries and identified the mechanisms underlying these effects. ISL inhibited inflammatory cytokine expression in mouse primary peritoneal macrophages (MPMs) exposed to LPS. In an acute lung injury (ALI) mouse model, ISL prevented LPS-induced structural damage and inflammatory cell infiltration. Additionally, pretreatment with ISL attenuated sepsis-induced lung and liver injury, accompanied by a reduction in inflammatory responses. Moreover, these protective effects were mediated by the nuclear factor kappa B (NF-κB) pathway-mediated inhibition of inflammatory responses in vitro and in vivo. Our study suggests that ISL may be a potential therapeutic agent for sepsis-induced injuries. Copyright © 2017. Published by Elsevier Inc.

  19. Modelling and Experimental Investigation of an Active Damper

    Directory of Open Access Journals (Sweden)

    Rafael Luís Teixeira

    2006-01-01

    Full Text Available This paper presents a validation methodology of the dynamic behavior of an active viscous damper. The damper has two flexible metallic bellows connected to a rigid reservoir filled with fluid. When one of the bellows is connected to a vibrating structure a periodic flow passes through a variable internal orifice and the damping effect is produced. The size of the orifice is adjusted by a controlled linear piezoelectric actuator that positions the conical core into a conical cavity. The device finite element structural model consists of the valve body and its conical core that are assumed rigid and the flexible bellows are represented by two pistons with elastic suspensions. The flow developed inside the damper is modeled considering the fluid-structure interation, using the Lagrangean-Eulerian formulation. To validate the proposed model a prototype was constructed and experimental tests and numerical simulations are accomplished in the time domain, applying harmonic excitations. The results are compared using curves that relate the damping coefficient with the orifice size and with the input velocity applied at the bellows face. However, for the proper control design and system operation, the direct use of the finite element model becomes unviable due to its high computational time. Then, a reduced second order discrete dynamic model for the damper was developed. The model parameters are identified by analysis in the frequency domain, using impulsive excitation force, for constant and variable orifice sizes. At low excitation frequencies, the damper prototype behaves like a single degree of freedom system which damping factor changes with the orifice size A fuzzy controller was designed and it generates the orifice reference size associated to the desired damping factor. The active system presented better performance when compared to the passive one.

  20. Pulmonary dynamics of radiolabelled erythrocytes and leucocytes in early gram-negative sepsis in pigs

    International Nuclear Information System (INIS)

    Walther, Sten; Wenyao, Shi; Lennquist, Sten

    1999-01-01

    objective: to study the pulmonary dynamic of erythrocytes and leucocytes in vivo in early experimental sepsis. design: open, experimental study. setting: academic research laboratory, Sweden. material: 10 adolescent, domestic pigs. interventions: technetium (Tc 99) labelling of erythrocytes (n=5) and indium (In 111) labelling of autologous leucocytes (n=10). sepsis was induced by endotoxin (n=4) or live Escherichia Coli (n=3), given intravenously. major outcome measures: regional pulmonary scintigraphy, central haemodynamics and gas exchange followed for 180 minutes. results: septic animals developed arterial hypoxia, pulmonary hypertension and systemic hypotension. They also had an early increase in mean (SD) regional pulmonary erythrocyte and leucocyte counts (+10.3(7.7%) and + 12.0 (3.5%) respectively) with simultaneous maximum 27-32 minutes after the start of the septic insult. Conclusions: The immediate sepsis-induced pulmonary accumulation of leucocytes as detected by external scintigraphy can be ascribed at least in part, to a simultaneous sepsis-induced increase in pulmonary blood volume. 3 figs., 1 tab., 19 refs

  1. Activation of the Akt/mTOR signaling pathway: A potential response to long-term neuronal loss in the hippocampus after sepsis

    Directory of Open Access Journals (Sweden)

    Jia-nan Guo

    2017-01-01

    Full Text Available Survivors of sepsis may suffer chronic cognitive impairment as a long-term sequela. However, the precise mechanisms of cognitive dysfunction after sepsis are not well understood. We employed the cecal ligation-and-puncture-induced septic mouse model. We observed elevated phosphorylation of Akt, mammalian target of rapamycin (mTOR and p70S6K on days 14 and 60, progressive neuronal loss in the cornu ammonis 1 region, and abnormal neuronal morphology in the hippocampus in the sepsis mouse model. These findings indicate that changes in neuronal morphology and number in the hippocampus after sepsis were associated with strong activation of the Akt/mTOR signaling pathway, and may reflect a “self-rescuing” feedback response to neuronal loss after sepsis.

  2. Experimental investigation and mechanistic modelling of dilute bubbly bulk boiling

    Energy Technology Data Exchange (ETDEWEB)

    Kutnjak, Josip

    2013-06-27

    During evaporation the geometric shape of the vapour is not described using thermodynamics. In bubbly flows the bubble shape is considered spheric with small diameters and changing into various shapes upon growth. The heat and mass transfer happens at the interfacial area. The forces acting on the bubbles depend on the bubble diameter and shape. In this work the prediction of the bubble diameter and/or bubble number density in bulk boiling was considered outside the vicinity of the heat input area. Thus the boiling effects that happened inside the nearly saturated bulk were under investigation. This situation is relevant for nuclear safety analysis concerning a stagnant coolant in the spent fuel pool. In this research project a new experimental set-up to investigate was built. The experimental set-up consists of an instrumented, partly transparent, high and slender boiling container for visual observation. The direct visual observation of the boiling phenomena is necessary for the identification of basic mechanisms, which should be incorporated in the simulation model. The boiling process has been recorded by means of video images and subsequently was evaluated by digital image processing methods, and by that data concerning the characteristics of the boiling process were generated for the model development and validation. Mechanistic modelling is based on the derivation of relevant mechanisms concluded from observation, which is in line with physical knowledge. In this context two mechanisms were identified; the growth/-shrink mechanism (GSM) of the vapour bubbles and sudden increases of the bubble number density. The GSM was implemented into the CFD-Code ANSYS-CFX using the CFX Expression Language (CEL) by calculation of the internal bubble pressure using the Young-Laplace-Equation. This way a hysteresis is realised as smaller bubbles have an increased internal pressure. The sudden increases of the bubble number density are explainable by liquid super

  3. Experimental investigation and mechanistic modelling of dilute bubbly bulk boiling

    International Nuclear Information System (INIS)

    Kutnjak, Josip

    2013-01-01

    During evaporation the geometric shape of the vapour is not described using thermodynamics. In bubbly flows the bubble shape is considered spheric with small diameters and changing into various shapes upon growth. The heat and mass transfer happens at the interfacial area. The forces acting on the bubbles depend on the bubble diameter and shape. In this work the prediction of the bubble diameter and/or bubble number density in bulk boiling was considered outside the vicinity of the heat input area. Thus the boiling effects that happened inside the nearly saturated bulk were under investigation. This situation is relevant for nuclear safety analysis concerning a stagnant coolant in the spent fuel pool. In this research project a new experimental set-up to investigate was built. The experimental set-up consists of an instrumented, partly transparent, high and slender boiling container for visual observation. The direct visual observation of the boiling phenomena is necessary for the identification of basic mechanisms, which should be incorporated in the simulation model. The boiling process has been recorded by means of video images and subsequently was evaluated by digital image processing methods, and by that data concerning the characteristics of the boiling process were generated for the model development and validation. Mechanistic modelling is based on the derivation of relevant mechanisms concluded from observation, which is in line with physical knowledge. In this context two mechanisms were identified; the growth/-shrink mechanism (GSM) of the vapour bubbles and sudden increases of the bubble number density. The GSM was implemented into the CFD-Code ANSYS-CFX using the CFX Expression Language (CEL) by calculation of the internal bubble pressure using the Young-Laplace-Equation. This way a hysteresis is realised as smaller bubbles have an increased internal pressure. The sudden increases of the bubble number density are explainable by liquid super

  4. Experimental Modeling of the Formation of Saucer-Shaped sills

    Science.gov (United States)

    Galland, O.; Planke, S.; Malthe-Sorenssen, A.

    2007-12-01

    Many magma intrusions in sedimentary basins are sills, and especially saucer-shaped sills. These features are observed in many places (i.e. South Africa; the Norwegian and North Sea; Siberia; Argentina). Sand injectites exhibit similar geometries. The occurrence of such features in so various settings suggests that their emplacement results from fundamental processes in sedimentary basins. To understand such processes, we performed experimental modeling of saucer-shaped sill emplacement. The experiments consist of injecting a molten low viscosity vegetable oil (model magma) at a constant flow rate into a fine-grained Coulomb silica flour (model rock). When the oil starts intruding, the initially flat surface of the model inflates and forms a smooth dome. At the end of the experiment, the oil erupts at the edge of the dome. After the experiment, the oil cools and solidifies, the resulting solid intrusion is unburied and exposed, and its upper surface digitalized. For our purpose, we did our experiments without external deformation. We performed two series of experiments with varying depth of injection. The first series consisted of injection into a homogeneous medium. The resulting intrusions were cone-sheets and dykes. The second series consisted of heterogeneous models where the heterogeneity was a weak layer made of a flexible net. The resulting intrusions were made of (1) a horizontal basal sill emplaced along the weakness, and (2) inclined sheets nucleating at the edges of the basal sill and propagating upward and outward. The inclined sheets exhibited a convex shape, i.e. a decreasing slope outward. In addition, the deeper the sills emplaced, the larger they were. Our experimental results are consistent with saucer-shaped features in nature. We infer from our results that the transition between the basal sills and the inclined sheets results from a transition of emplacement processes. We suggest that the basal sill emplace by open (mode I) fracturing, whereas

  5. Human embryonic stem cell lines model experimental human cytomegalovirus latency.

    Science.gov (United States)

    Penkert, Rhiannon R; Kalejta, Robert F

    2013-05-28

    Herpesviruses are highly successful pathogens that persist for the lifetime of their hosts primarily because of their ability to establish and maintain latent infections from which the virus is capable of productively reactivating. Human cytomegalovirus (HCMV), a betaherpesvirus, establishes latency in CD34(+) hematopoietic progenitor cells during natural infections in the body. Experimental infection of CD34(+) cells ex vivo has demonstrated that expression of the viral gene products that drive productive infection is silenced by an intrinsic immune defense mediated by Daxx and histone deacetylases through heterochromatinization of the viral genome during the establishment of latency. Additional mechanistic details about the establishment, let alone maintenance and reactivation, of HCMV latency remain scarce. This is partly due to the technical challenges of CD34(+) cell culture, most notably, the difficulty in preventing spontaneous differentiation that drives reactivation and renders them permissive for productive infection. Here we demonstrate that HCMV can establish, maintain, and reactivate in vitro from experimental latency in cultures of human embryonic stem cells (ESCs), for which spurious differentiation can be prevented or controlled. Furthermore, we show that known molecular aspects of HCMV latency are faithfully recapitulated in these cells. In total, we present ESCs as a novel, tractable model for studies of HCMV latency.

  6. [Intestinal lengthening techniques: an experimental model in dogs].

    Science.gov (United States)

    Garibay González, Francisco; Díaz Martínez, Daniel Alberto; Valencia Flores, Alejandro; González Hernández, Miguel Angel

    2005-01-01

    To compare two intestinal lengthening procedures in an experimental dog model. Intestinal lengthening is one of the methods for gastrointestinal reconstruction used for treatment of short bowel syndrome. The modification to the Bianchi's technique is an alternative. The modified technique decreases the number of anastomoses to a single one, thus reducing the risk of leaks and strictures. To our knowledge there is not any clinical or experimental report that studied both techniques, so we realized the present report. Twelve creole dogs were operated with the Bianchi technique for intestinal lengthening (group A) and other 12 creole dogs from the same race and weight were operated by the modified technique (Group B). Both groups were compared in relation to operating time, difficulties in technique, cost, intestinal lengthening and anastomoses diameter. There were no statistical difference in the anastomoses diameter (A = 9.0 mm vs. B = 8.5 mm, p = 0.3846). Operating time (142 min vs. 63 min) cost and technique difficulties were lower in group B (p anastomoses (of Group B) and intestinal segments had good blood supply and were patent along their full length. Bianchi technique and the modified technique offer two good reliable alternatives for the treatment of short bowel syndrome. The modified technique improved operating time, cost and technical issues.

  7. Tesla Coil Theoretical Model and its Experimental Verification

    Directory of Open Access Journals (Sweden)

    Voitkans Janis

    2014-12-01

    Full Text Available In this paper a theoretical model of Tesla coil operation is proposed. Tesla coil is described as a long line with distributed parameters in a single-wire form, where the line voltage is measured across electrically neutral space. By applying the principle of equivalence of single-wire and two-wire schemes an equivalent two-wire scheme can be found for a single-wire scheme and the already known long line theory can be applied to the Tesla coil. A new method of multiple reflections is developed to characterize a signal in a long line. Formulas for calculation of voltage in Tesla coil by coordinate and calculation of resonance frequencies are proposed. The theoretical calculations are verified experimentally. Resonance frequencies of Tesla coil are measured and voltage standing wave characteristics are obtained for different output capacities in the single-wire mode. Wave resistance and phase coefficient of Tesla coil is obtained. Experimental measurements show good compliance with the proposed theory. The formulas obtained in this paper are also usable for a regular two-wire long line with distributed parameters.

  8. An experimental model for the surgical correction of tracheomalacia.

    Science.gov (United States)

    Shaha, A R; Burnett, C; DiMaio, T; Jaffe, B M

    1991-10-01

    Tracheomalacia may result from large intrathoracic goiters. Due to the chronic compression, particularly within the confines of the thoracic inlet, the tracheal wall weakens, with disintegration of some of the cartilaginous rings. Tracheomalacia can cause acute airway distress, particularly during the post-operative period, and may occasionally result in death. The other major cause of tracheomalacia is related to either prolonged endotracheal intubation or over-inflation of the tracheostomy cuff. While various techniques such as internal stenting, external support devices, tracheostomy, and tracheal resection have been used based on individual circumstances, no one method appears to be perfect. To further study this difficult problem, an experimental model of tracheomalacia was created in eight dogs. Six to seven rings of the tracheal cartilages were dissected submucosally. More than half of the circumference of the tracheal rings was resected. The tracheal walls were reconstructed with polytetrafluoroethylene (PTFE) grafts. The grafts strengthened the tracheal wall without causing luminal constriction. Tracheostomy was not performed on any of the dogs. All dogs tolerated the procedure well and were extubated at the conclusion of the experiment. The dogs were followed for 4 to 6 months and then sacrificed so that the tracheal wall could be examined histologically. There was considerable fibrosis leading to stiff neotrachea. The results of this experimental technique for prosthetic reconstruction to counteract problems simulating tracheomalacia are very encouraging.

  9. Induction of Bim and Bid gene expression during accelerated apoptosis in severe sepsis.

    Science.gov (United States)

    Weber, Stefan U; Schewe, Jens-Christian; Lehmann, Lutz E; Müller, Stefan; Book, Malte; Klaschik, Sven; Hoeft, Andreas; Stüber, Frank

    2008-01-01

    In transgenic animal models of sepsis, members of the Bcl-2 family of proteins regulate lymphocyte apoptosis and survival of sepsis. This study investigates the gene regulation of pro-apoptotic and anti-apoptotic members of the Bcl-2 family of proteins in patients with early stage severe sepsis. In this prospective case-control study, patients were recruited from three intensive care units (ICUs) in a university hospital. Sixteen patients were enrolled when they fulfilled the criteria of severe sepsis. Ten critically ill but non-septic patients and 11 healthy volunteers served as controls. Blood samples were immediately obtained at inclusion. To confirm the presence of accelerated apoptosis in the patient groups, caspase-3 activation and phosphatidylserine externalisation in CD4+, CD8+ and CD19+ lymphocyte subsets were assessed using flow cytometry. Specific mRNAs of Bcl-2 family members were quantified from whole blood by real-time PCR. To test for statistical significance, Kruskal-Wallis testing with Dunn's multiple comparison test for post hoc analysis was performed. In all lymphocyte populations caspase-3 (p < 0.05) was activated, which was reflected in an increased phosphatidylserine externalisation (p < 0.05). Accordingly, lymphocyte counts were decreased in early severe sepsis. In CD4+ T-cells (p < 0.05) and B-cells (p < 0.001) the Bcl-2 protein was decreased in severe sepsis. Gene expression of the BH3-only Bim was massively upregulated as compared with critically ill patients (p < 0.001) and 51.6-fold as compared with healthy controls (p < 0.05). Bid was increased 12.9-fold compared with critically ill patients (p < 0.001). In the group of mitochondrial apoptosis inducers, Bak was upregulated 5.6-fold, while the expression of Bax showed no significant variations. By contrast, the pro-survival members Bcl-2 and Bcl-xl were both downregulated in severe sepsis (p < 0.001 and p < 0.05, respectively). In early severe sepsis a gene expression pattern with

  10. Polarization of microglia and its role in bacterial sepsis.

    Science.gov (United States)

    Michels, Monique; Sonai, Beatriz; Dal-Pizzol, Felipe

    2017-02-15

    Microglial polarization in response to brain inflammatory conditions is a crescent field in neuroscience. However, the effect of systemic inflammation, and specifically sepsis, is a relatively unexplored field that has great interest and relevance. Sepsis has been associated with both early and late harmful events of the central nervous system, suggesting that there is a close link between sepsis and neuroinflammation. During sepsis evolution it is supposed that microglial could exert both neurotoxic and repairing effects depending on the specific microglial phenotype assumed. In this context, here it was reviewed the role of microglial polarization during sepsis-associated brain dysfunction. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Modelling concentration-analgesia relationships for morphine to evaluate experimental pain models

    DEFF Research Database (Denmark)

    Sverrisdóttir, Eva; Foster, David John Richard; Upton, Richard Neil

    2015-01-01

    The aim of this study was to develop population pharmacokinetic-pharmacodynamic models for morphine in experimental pain induced by skin heat and muscle pressure, and to evaluate the experimental pain models with regard to assessment of morphine pharmacodynamics. In a randomized, double......-blind, placebo-controlled, crossover study, 39 healthy volunteers received an oral dose of 30 mg morphine hydrochloride or placebo. Non-linear mixed effects modelling was used to describe the plasma concentrations of morphine and metabolites, and the analgesic effect of morphine on experimental pain in skin...... and muscle. Baseline pain metrics varied between individuals and occasions, and were described with interindividual and interoccasion variability. Placebo-response did not change with time. For both pain metrics, morphine effect was proportional to baseline pain and was described with a linear model...

  12. Neutrophil migration under normal and sepsis conditions.

    Science.gov (United States)

    Lerman, Yelena V; Kim, Minsoo

    2015-01-01

    Neutrophil migration is critical for pathogen clearance and host survival during severe sepsis. Interaction of neutrophil adhesion receptors with ligands on endothelial cells results in firm adhesion of the circulating neutrophils, followed by neutrophil activation and directed migration to sites of infection through the basement membrane and interstitial extracellular matrix. Proteolytic enzymes and reactive oxygen species are produced and released by neutrophils in response to a variety of inflammatory stimuli. Although these mediators are important for host defense, they also promote tissue damage. Excessive neutrophil migration during the early stages of sepsis may lead to an exaggerated inflammatory response with associated tissue damage and subsequent organ dysfunction. On the other hand, dysregulation of migration and insufficient migratory response that occurs during the latter stages of severe sepsis contributes to neutrophils' inability to contain and control infection and impaired wound healing. This review discusses the major steps and associated molecules involved in the balance of neutrophil trafficking, the precise regulation of which during sepsis spells life or death for the host.

  13. Procalcitonin - Assisted Antibiotic Strategy in Sepsis.

    Science.gov (United States)

    Trásy, Domonkos; Molnár, Zsolt

    2017-05-01

    Sepsis is one of the biggest challenges in critical care nowadays. Defining sepsis is a difficult task on its own and its diagnosis and treatment requires well trained, devoted personnel with interdisciplinary collaboration in order to provide the patients the best chance for survival. Immediate resuscitation, early adequate antimicrobial therapy, source control and highly sophisticated organ support on the intensive care units are all inevitable necessities for successful recovery. To help fast and accurate diagnosis biomarkers have been measured for decades. Procalcitonin (PCT) is one of the most studied, but the results are conflicting. Sepsis means a very loose cohort of a large heterogeneous patient population, hence defining certain cut off values for PCT to differentiate between different severities of the disease is almost impossible. Clinicians first have to understand the pathophysiological background of sepsis to be able to interpret correctly the PCT results. Nevertheless, PCT has been shown to have the best sensitivity and specificity to indicate infection, antibiotic appropriateness and stopping therapy. In this article we will focus on some important aspects of pathophysiology and advice on how to implement that in the everyday clinical practice. We believe that this multimodal evaluation of the clinical picture together with PCT results can be a useful tool to make the most out of the PCT results, and do the best for patients on the ICU.

  14. Diagnostic value of procalcitonin in neonatal sepsis

    African Journals Online (AJOL)

    2015-04-27

    Apr 27, 2015 ... Abstract: Introduction: Neonatal sepsis is a major cause of mortal- ity in developing countries. Accu- rate and quick diagnosis are diffi- cult because clinical presentation are non-specific, bacterial cultures are time-consuming and other laboratory tests lack sensitivity and specificity. Serum procalci-.

  15. [Pharmaconutrition with parenteral selenium in sepsis].

    Science.gov (United States)

    Langlois, P L; de Oliveira Figliolino, L F; Hardy, G; Manzanares, W

    2014-04-01

    Critical illness is characterized by oxidative stress which leads to multiple organ failure, and sepsis-related organ dysfunction remains the most common cause of death in the intensive care unit. Over the last 2 decades, different antioxidant therapies have been developed to improve outcomes in septic patients. According to recent evidence, selenium therapy should be considered the cornerstone of the antioxidant strategies. Selenium given as selenious acid or sodium selenite should be considered as a drug or pharmaconutrient with prooxidant and cytotoxic effects when a loading dose in intravenous bolus form is administered, particularly in the early stage of severe sepsis/septic shock. To date, several phase ii trials have demonstrated that selenium therapy may be able to decrease mortality, improve organ dysfunction and reduce infections in critically ill septic patients. The effect of selenium therapy in sepsis syndrome must be confirmed by large, well designed phase iii clinical trials. The purpose of this review is to discuss current evidence on selenium pharmaconutrition in sepsis syndrome. Copyright © 2013 Elsevier España, S.L. and SEMICYUC. All rights reserved.

  16. Perioperative treatment of patients with sepsis

    DEFF Research Database (Denmark)

    Ibsen, Michael; Perner, Anders

    2013-01-01

    Key elements in the initial resuscitation and stabilization of the patient with sepsis are fluid therapy, vasopressor or inotropic support, administration of adequate antibiotics and source control. This review will primarily discuss fluid, vasopressor and antibiotic therapy because these have been...

  17. Immunotolerance during bacterial pneumonia and sepsis

    NARCIS (Netherlands)

    Hoogerwerf, J.J.

    2010-01-01

    Bacterial pneumonia and sepsis are a major cause of morbidity and mortality worldwide. Massive use of antibiotics promotes pathogen resistance, and, as a consequence, the incidence of drug-resistant bacteria is increasing. Therefore, it is of the utmost importance to expand our comprehension of host

  18. Experimental study and modelization of a propane storage tank depressurization

    International Nuclear Information System (INIS)

    Veneau, Tania

    1995-01-01

    The risks associated with the fast depressurization of propane storage tanks reveals the importance of the 'source term' determination. This term is directly linked, among others, to the characteristics of the jet developed downstream of the breach. The first aim of this work was to provide an original data bank concerning drop velocity and diameter distributions in a propane jet. For this purpose, a phase Doppler anemometer bas been implemented on an experimental set-up. Propane blowdowns have been performed with different breach sizes and several initial pressures in the storage tank. Drop diameter and velocity distributions have been investigated at different locations in the jet zone. These measurements exhibited the fragmentation and vaporisation trends in the jet. The second aim of this work concerned the 'source term'. lt required to study the coupling between the fluid behaviour inside the tank and the flow through the breach. This model took into account the phase exchange when flashing occurred in the tank. The flow at the breach was described with an homogeneous relaxation model. This coupled modelization has been successfully and exhaustively validated. lt originality lies on the application to propane flows. (author) [fr

  19. Computational reverse shoulder prosthesis model: Experimental data and verification.

    Science.gov (United States)

    Martins, A; Quental, C; Folgado, J; Ambrósio, J; Monteiro, J; Sarmento, M

    2015-09-18

    The reverse shoulder prosthesis aims to restore the stability and function of pathological shoulders, but the biomechanical aspects of the geometrical changes induced by the implant are yet to be fully understood. Considering a large-scale musculoskeletal model of the upper limb, the aim of this study is to evaluate how the Delta reverse shoulder prosthesis influences the biomechanical behavior of the shoulder joint. In this study, the kinematic data of an unloaded abduction in the frontal plane and an unloaded forward flexion in the sagittal plane were experimentally acquired through video-imaging for a control group, composed of 10 healthy shoulders, and a reverse shoulder group, composed of 3 reverse shoulders. Synchronously, the EMG data of 7 superficial muscles were also collected. The muscle force sharing problem was solved through the minimization of the metabolic energy consumption. The evaluation of the shoulder kinematics shows an increase in the lateral rotation of the scapula in the reverse shoulder group, and an increase in the contribution of the scapulothoracic joint to the shoulder joint. Regarding the muscle force sharing problem, the musculoskeletal model estimates an increased activity of the deltoid, teres minor, clavicular fibers of the pectoralis major, and coracobrachialis muscles in the reverse shoulder group. The comparison between the muscle forces predicted and the EMG data acquired revealed a good correlation, which provides further confidence in the model. Overall, the shoulder joint reaction force was lower in the reverse shoulder group than in the control group. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Models of Investor Forecasting Behavior — Experimental Evidence

    Directory of Open Access Journals (Sweden)

    Federico Bonetto

    2017-12-01

    Full Text Available Different forecasting behaviors affect investors’ trading decisions and lead to qualitatively different asset price trajectories. It has been shown in the literature that the weights that investors place on observed asset price changes when forecasting future price changes, and the nature of their confidence when price changes are forecast, determine whether price bubbles, price crashes, and unpredictable price cycles occur. In this paper, we report the results of behavioral experiments involving multiple investors who participated in a market for a virtual asset. Our goal is to study investors’ forecast formation. We conducted three experimental sessions with different participants in each session. We fit different models of forecast formation to the observed data. There is strong evidence that the investors forecast future prices by extrapolating past price changes, even when they know the fundamental value of the asset exactly and the extrapolated forecasts differ significantly from the fundamental value. The rational expectations hypothesis seems inconsistent with the observed forecasts. The forecasting models of all participants that best fit the observed forecasting data were of the type that cause price bubbles and cycles in dynamical systems models, and price bubbles and cycles ended up occurring in all three sessions.

  1. Optimization of Experimental Model Parameter Identification for Energy Storage Systems

    Directory of Open Access Journals (Sweden)

    Rosario Morello

    2013-09-01

    Full Text Available The smart grid approach is envisioned to take advantage of all available modern technologies in transforming the current power system to provide benefits to all stakeholders in the fields of efficient energy utilisation and of wide integration of renewable sources. Energy storage systems could help to solve some issues that stem from renewable energy usage in terms of stabilizing the intermittent energy production, power quality and power peak mitigation. With the integration of energy storage systems into the smart grids, their accurate modeling becomes a necessity, in order to gain robust real-time control on the network, in terms of stability and energy supply forecasting. In this framework, this paper proposes a procedure to identify the values of the battery model parameters in order to best fit experimental data and integrate it, along with models of energy sources and electrical loads, in a complete framework which represents a real time smart grid management system. The proposed method is based on a hybrid optimisation technique, which makes combined use of a stochastic and a deterministic algorithm, with low computational burden and can therefore be repeated over time in order to account for parameter variations due to the battery’s age and usage.

  2. Integration of THM-experimental work and modelling

    International Nuclear Information System (INIS)

    Pintado, Xavier; Autio, Jorma; Koskinen, Kari

    2010-01-01

    Document available in extended abstract form only. Long-term safety of the bentonite buffer relies heavily on appropriate saturation of bentonite buffer resulting evidently on adequate swelling pressure low hydraulic conductivity. After transient period after installation of buffer components the buffer swelling pressure is to remain sufficiently high regardless of e.g. the conditions during the early evolution promoting hydrothermal alteration. For these reasons it is of central importance to characterise different 'underlying saturation flow regimes', USFRs, and the related time dependent fluxes in various parts of buffer in then currently prevailing conditions. The THM processes govern the behaviour from transient to fully saturated state and occur during long periods of time from tens of years up to hundreds or even more. Therefore it is important to be able to understand the underlying processes sufficiently and to develop proper modelling techniques. This can be carried out only by integrating testing and modelling. THM-modelling has also important role in design development phase when different engineering techniques e.g. for wetting of buffer are evaluated. This paper presents the integration of THM-experimental work and modelling carried out in Finland and elsewhere for the development of the buffer designs. The primary objective of this work is to provide experimental and modelling data for assessing the behaviour of bentonite buffer during saturation with respect to fulfilling the performance targets. The development of numerical methods allows to simulate the different processes which take place in materials and to understand them better. In laboratory testing, the numerical methods allow us to simulate the tests and to choose the best geometry and boundary conditions and to verify the experimental designs. The clay barrier behaviour is complex because there are some phenomena coupled: heat flow, water flow in vapour and liquid phases and

  3. Cracking in autoclaved aerated concrete: Experimental investigation and XFEM modeling

    International Nuclear Information System (INIS)

    Ferretti, D.; Michelini, E.; Rosati, G.

    2015-01-01

    The paper aims to investigate and model cracking development in beams and deep-beams made of autoclaved aerated concrete (AAC). Fracture mechanics of AAC has been first studied by performing three-point bending tests on beams, similar to those commonly used for ordinary concrete elements. In some of these tests, crack growth has been also monitored by using ESPI laser technique. In this way, it has been possible to calibrate the main parameters of a proper cohesive law by means of extended finite element inverse analysis. Subsequently, cracking tests have been also performed on deep-beams, whose behavior is more representative of full scale walls. To validate the proposed cohesive law, deep-beam experimental behavior has been finally simulated through XFEM

  4. Cracking in autoclaved aerated concrete: Experimental investigation and XFEM modeling

    Energy Technology Data Exchange (ETDEWEB)

    Ferretti, D., E-mail: daniele.ferretti@unipr.it [Department of Civil, Environmental, Land Management Engineering and Architecture, University of Parma, P.co Area delle Scienze 181/A, 43124 Parma (Italy); Michelini, E. [Department of Civil, Environmental, Land Management Engineering and Architecture, University of Parma, P.co Area delle Scienze 181/A, 43124 Parma (Italy); Rosati, G. [Department of Civil and Environmental Engineering, Politecnico di Milano, Piazza L. Da Vinci 32, 20133 Milano (Italy)

    2015-01-15

    The paper aims to investigate and model cracking development in beams and deep-beams made of autoclaved aerated concrete (AAC). Fracture mechanics of AAC has been first studied by performing three-point bending tests on beams, similar to those commonly used for ordinary concrete elements. In some of these tests, crack growth has been also monitored by using ESPI laser technique. In this way, it has been possible to calibrate the main parameters of a proper cohesive law by means of extended finite element inverse analysis. Subsequently, cracking tests have been also performed on deep-beams, whose behavior is more representative of full scale walls. To validate the proposed cohesive law, deep-beam experimental behavior has been finally simulated through XFEM.

  5. Tupaia belangeri as an experimental animal model for viral infection.

    Science.gov (United States)

    Tsukiyama-Kohara, Kyoko; Kohara, Michinori

    2014-01-01

    Tupaias, or tree shrews, are small mammals that are similar in appearance to squirrels. The morphological and behavioral characteristics of the group have been extensively characterized, and despite previously being classified as primates, recent studies have placed the group in its own family, the Tupaiidae. Genomic analysis has revealed that the genus Tupaia is closer to humans than it is to rodents. In addition, tupaias are susceptible to hepatitis B virus and hepatitis C virus. The only other experimental animal that has been demonstrated to be sensitive to both of these viruses is the chimpanzee, but restrictions on animal testing have meant that experiments using chimpanzees have become almost impossible. Consequently, the development of the tupaia for use as an animal infection model could become a powerful tool for hepatitis virus research and in preclinical studies on drug development.

  6. Practical application of stereological methods in experimental kidney animal models.

    Science.gov (United States)

    Fernández García, María Teresa; Núñez Martínez, Paula; García de la Fuente, Vanessa; Sánchez Pitiot, Marta; Muñiz Salgueiro, María Del Carmen; Perillán Méndez, Carmen; Argüelles Luis, Juan; Astudillo González, Aurora

    The kidneys are vital organs responsible for excretion, fluid and electrolyte balance and hormone production. The nephrons are the kidney's functional and structural units. The number, size and distribution of the nephron components contain relevant information on renal function. Stereology is a branch of morphometry that applies mathematical principles to obtain three-dimensional information from serial, parallel and equidistant two-dimensional microscopic sections. Because of the complexity of stereological studies and the lack of scientific literature on the subject, the aim of this paper is to clearly explain, through animal models, the basic concepts of stereology and how to calculate the main kidney stereological parameters that can be applied in future experimental studies. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  7. Hadronic models and experimental data for the neutrino beam production

    CERN Document Server

    Collazuol, G; Guglielmi, A M; Sala, P R

    2000-01-01

    The predictions of meson production by 450 GeV