Damage mechanisms in PBT-GF30 under thermo-mechanical cyclic loading

NASA Astrophysics Data System (ADS)

Schaaf, A.; De Monte, M.; Hoffmann, C.; Vormwald, M.; Quaresimin, M.

2014-05-01

The scope of this paper is the investigation of damage mechanisms at microscopic scale on a short glass fiber reinforced polybutylene terephthalate (PBT-GF30) under thermo-mechanical cyclic loading. In addition the principal mechanisms are verified through micro mechanical FE models. In order to investigate the fatigue behavior of the material both isothermal strain controlled fatigue (ISCF) tests at three different temperatures and thermo-mechanical fatigue (TMF) tests were conducted on plain and notched specimens, manufactured by injection molding. The goal of the work is to determine the damage mechanisms occurring under TMF conditions and to compare them with the mechanisms occurring under ISCF. For this reason fracture surfaces of TMF and ISCF samples loaded at different temperature levels were analyzed using scanning electron microscopy. Furthermore, specimens that failed under TMF were examined on microsections revealing insight into both crack initiation and crack propagation. The findings of this investigation give valuable information about the main damage mechanisms of PBT-GF30 under TMF loading and serve as basis for the development of a TMF life estimation methodology.

Leukotriene-mediated neuroinflammation, toxic brain damage, and neurodegeneration in acute methanol poisoning.

PubMed

Zakharov, Sergey; Kotikova, Katerina; Nurieva, Olga; Hlusicka, Jiri; Kacer, Petr; Urban, Pavel; Vaneckova, Manuela; Seidl, Zdenek; Diblik, Pavel; Kuthan, Pavel; Navratil, Tomas; Pelclova, Daniela

2017-04-01

The role of neuroinflammation in methanol-induced toxic brain damage has not been studied. We studied acute concentrations and the dynamics of leukotrienes (LT) in serum in hospitalized patients with acute methanol poisoning and in survivors. Series of acute cysteinyl-LT and LTB4 concentration measurements were performed in 28/101 hospitalized patients (mean observation time: 88 ± 20 h). In 36 survivors, control LT measurements were performed 2 years after discharge. The acute maximum (C max ) LT concentrations were higher than concentrations in survivors: C max for LTC4 was 80.7 ± 5.6 versus 47.9 ± 4.5 pg/mL; for LTD4, 51.0 ± 6.6 versus 23.1 ± 2.1 pg/mL; for LTE4, 64.2 ± 6.0 versus 26.2 ± 3.9 pg/mL; for LTB4, 59.8 ± 6.2 versus 27.2 ± 1.4 pg/mL (all p < 0.001). The patients who survived had higher LT concentrations than those who died (all p < 0.01). Among survivors, patients with CNS sequelae had lower LTE4 and LTB4 than did those without sequelae (both p < 0.05). The LT concentrations increased at a rate of 0.4-0.5 pg/mL/h and peaked 4-5 days after admission. The patients with better outcomes had higher cys-LTs (all p < 0.01) and LTB4 (p < 0.05). More severely poisoned patients had lower acute LT concentrations than those with minor acidemia. The follow-up LT concentrations in survivors with and without CNS sequelae did not differ (all p > 0.05). The mean decrease in LT concentration was 30.9 ± 9.0 pg/mL for LTC4, 26.3 ± 8.6 pg/mL for LTD4, 37.3 ± 6.4 pg/mL for LTE4, and 32.0 ± 8.8 pg/mL for LTB4. Our findings suggest that leukotriene-mediated neuroinflammation may play an important role in the mechanisms of toxic brain damage in acute methanol poisoning in humans. Acute elevation of LT concentrations was moderate, transitory, and was not followed by chronic neuroinflammation in survivors.

Oxidative stress, inflammation, and DNA damage in multiple organs of mice acutely exposed to amorphous silica nanoparticles.

PubMed

Nemmar, Abderrahim; Yuvaraju, Priya; Beegam, Sumaya; Yasin, Javed; Kazzam, Elsadig E; Ali, Badreldin H

2016-01-01

The use of amorphous silica (SiO2) in biopharmaceutical and industrial fields can lead to human exposure by injection, skin penetration, ingestion, or inhalation. However, the in vivo acute toxicity of amorphous SiO2 nanoparticles (SiNPs) on multiple organs and the mechanisms underlying these effects are not well understood. Presently, we investigated the acute (24 hours) effects of intraperitoneally administered 50 nm SiNPs (0.25 mg/kg) on systemic toxicity, oxidative stress, inflammation, and DNA damage in the lung, heart, liver, kidney, and brain of mice. Lipid peroxidation was significantly increased by SiNPs in the lung, liver, kidney, and brain, but was not changed in the heart. Similarly, superoxide dismutase and catalase activities were significantly affected by SiNPs in all organs studied. While the concentration of tumor necrosis factor α was insignificantly increased in the liver and brain, its increase was statistically significant in the lung, heart, and kidney. SiNPs induced a significant elevation in pulmonary and renal interleukin 6 and interleukin-1 beta in the lung, liver, and brain. Moreover, SiNPs caused a significant increase in DNA damage, assessed by comet assay, in all the organs studied. SiNPs caused leukocytosis and increased the plasma activities of lactate dehydrogenase, creatine kinase, alanine aminotranferase, and aspartate aminotransferase. These results indicate that acute systemic exposure to SiNPs causes oxidative stress, inflammation, and DNA damage in several major organs, and highlight the need for thorough evaluation of SiNPs before they can be safely used in human beings.

Mechanisms of haptoglobin protection against hemoglobin peroxidation triggered endothelial damage.

PubMed

Schaer, C A; Deuel, J W; Bittermann, A G; Rubio, I G; Schoedon, G; Spahn, D R; Wepf, R A; Vallelian, F; Schaer, D J

2013-11-01

Extracellular hemoglobin (Hb) has been recognized as a disease trigger in hemolytic conditions such as sickle cell disease, malaria, and blood transfusion. In vivo, many of the adverse effects of free Hb can be attenuated by the Hb scavenger acute-phase protein haptoglobin (Hp). The primary physiologic disturbances that can be caused by free Hb are found within the cardiovascular system and Hb-triggered oxidative toxicity toward the endothelium has been promoted as a potential mechanism. The molecular mechanisms of this toxicity as well as of the protective activities of Hp are not yet clear. Within this study, we systematically investigated the structural, biochemical, and cell biologic nature of Hb toxicity in an endothelial cell system under peroxidative stress. We identified two principal mechanisms of oxidative Hb toxicity that are mediated by globin degradation products and by modified lipoprotein species, respectively. The two damage pathways trigger diverse and discriminative inflammatory and cytotoxic responses. Hp provides structural stabilization of Hb and shields Hb's oxidative reactions with lipoproteins, providing dramatic protection against both pathways of toxicity. By these mechanisms, Hp shifts Hb's destructive pseudo-peroxidative reaction to a potential anti-oxidative function during peroxidative stress.

The Potential Neural Mechanisms of Acute Indirect Vibration

PubMed Central

2011-01-01

There is strong evidence to suggest that acute indirect vibration acts on muscle to enhance force, power, flexibility, balance and proprioception suggesting neural enhancement. Nevertheless, the neural mechanism(s) of vibration and its potentiating effect have received little attention. One proposal suggests that spinal reflexes enhance muscle contraction through a reflex activity known as tonic vibration stretch reflex (TVR), which increases muscle activation. However, TVR is based on direct, brief, and high frequency vibration (>100 Hz) which differs to indirect vibration, which is applied to the whole body or body parts at lower vibration frequency (5-45 Hz). Likewise, muscle tuning and neuromuscular aspects are other candidate mechanisms used to explain the vibration phenomenon. But there is much debate in terms of identifying which neural mechanism(s) are responsible for acute vibration; due to a number of studies using various vibration testing protocols. These protocols include: different methods of application, vibration variables, training duration, exercise types and a range of population groups. Therefore, the neural mechanism of acute vibration remain equivocal, but spinal reflexes, muscle tuning and neuromuscular aspects are all viable factors that may contribute in different ways to increasing muscular performance. Additional research is encouraged to determine which neural mechanism(s) and their contributions are responsible for acute vibration. Testing variables and vibration applications need to be standardised before reaching a consensus on which neural mechanism(s) occur during and post-vibration. Key points There is strong evidence to suggest that acute indirect vibration acts on muscle to enhance force, power, flexibility, balance and proprioception, but little attention has been given to the neural mechanism(s) of acute indirect vibration. Current findings suggest that acute vibration exposure may cause a neural response, but there is little

Mechanisms of DNA damage, repair and mutagenesis

PubMed Central

Chatterjee, Nimrat; Walker, Graham C.

2017-01-01

Living organisms are continuously exposed to a myriad of DNA damaging agents that can impact health and modulate disease-states. However, robust DNA repair and damage-bypass mechanisms faithfully protect the DNA by either removing or tolerating the damage to ensure an overall survival. Deviations in this fine-tuning are known to destabilize cellular metabolic homeostasis, as exemplified in diverse cancers where disruption or deregulation of DNA repair pathways results in genome instability. Because routinely used biological, physical and chemical agents impact human health, testing their genotoxicity and regulating their use have become important. In this introductory review, we will delineate mechanisms of DNA damage and the counteracting repair/tolerance pathways to provide insights into the molecular basis of genotoxicity in cells that lays the foundation for subsequent articles in this issue. PMID:28485537

Blood Aggravates Histological and Functional Damage after Acute Subdural Hematoma in Rats.

PubMed

Jussen, Daniel; Krenzlin, Harald; Papaioannou, Chrysostomos; Ens, Swetlana; Kempski, Oliver; Alessandri, Beat

2017-02-15

Acute subdural hematoma (ASDH) is associated with high morbidity and mortality. Whether the volume effect of the hematoma and increase of intracranial pressure (ICP) or the local effect of blood are responsible for this severe pathophysiology is unclear. Therefore, we compared subdural infusion of autologous blood and paraffin oil in a rat model of ASDH. In a histological study, we investigated the effects on acute ICP, cerebral perfusion pressure (CPP), cerebral blood flow (CBF), tissue oxygen changes, and brain damage at 2, 24, and 96 h post-infusion. Inflammatory reaction was analyzed by immuno-staining for microglia (ionized calcium binding adaptor molecule 1 [Iba1]) and activated astrocytes (glial fibrillary acidic protein [GFAP]). Besides acute ICP and CBF changes, we investigated the development of behavior (neuroscore and beamwalk test) for up to 4 days after injury in a behavioral study. Despite comparably increased ICP, there was a more pronounced lesion growth in the blood infusion group during the first 96 h. Further, there was an increased peri-lesional immunoreactive area of Iba1 and GFAP 96 h post-infusion, primarily in the blood infusion group, whereas hippocampal damage was comparable in both infusion groups. In the behavioral evaluation, paraffin-infused animals showed a better recovery, compared with the blood infusion group. In conclusion, comparable acute time-course of ICP, CPP, and CBF clearly indicates that the differences in lesion size, inflammatory reaction, and behavioral deficits after blood- and paraffin oil-induced ASDH are partially due to blood constituents. Therefore, current data suggest that subdural hematomas should be completely removed as quickly as possible; decompression alone may not be sufficient to prevent secondary brain damage.

Mechanism of mitochondrial permeability transition pore induction and damage in the pancreas: inhibition prevents acute pancreatitis by protecting production of ATP

PubMed Central

Mukherjee, Rajarshi; Mareninova, Olga A; Odinokova, Irina V; Huang, Wei; Murphy, John; Chvanov, Michael; Javed, Muhammad A; Wen, Li; Booth, David M; Cane, Matthew C; Awais, Muhammad; Gavillet, Bruno; Pruss, Rebecca M; Schaller, Sophie; Molkentin, Jeffery D; Tepikin, Alexei V; Petersen, Ole H; Pandol, Stephen J; Gukovsky, Ilya; Criddle, David N; Gukovskaya, Anna S

2016-01-01

Objective Acute pancreatitis is caused by toxins that induce acinar cell calcium overload, zymogen activation, cytokine release and cell death, yet is without specific drug therapy. Mitochondrial dysfunction has been implicated but the mechanism not established. Design We investigated the mechanism of induction and consequences of the mitochondrial permeability transition pore (MPTP) in the pancreas using cell biological methods including confocal microscopy, patch clamp technology and multiple clinically representative disease models. Effects of genetic and pharmacological inhibition of the MPTP were examined in isolated murine and human pancreatic acinar cells, and in hyperstimulation, bile acid, alcoholic and choline-deficient, ethionine-supplemented acute pancreatitis. Results MPTP opening was mediated by toxin-induced inositol trisphosphate and ryanodine receptor calcium channel release, and resulted in diminished ATP production, leading to impaired calcium clearance, defective autophagy, zymogen activation, cytokine production, phosphoglycerate mutase 5 activation and necrosis, which was prevented by intracellular ATP supplementation. When MPTP opening was inhibited genetically or pharmacologically, all biochemical, immunological and histopathological responses of acute pancreatitis in all four models were reduced or abolished. Conclusions This work demonstrates the mechanism and consequences of MPTP opening to be fundamental to multiple forms of acute pancreatitis and validates the MPTP as a drug target for this disease. PMID:26071131

A Hybrid Approach to Composite Damage and Failure Analysis Combining Synergistic Damage Mechanics and Peridynamics

DTIC Science & Technology

2017-03-30

Composite Damage and Failure Analysis Combining Synergistic Damage Mechanics and Peridynamics 5b. GRANT NUMBER NOOO 14-16-1-21 73 5c. PROGRAM...ES) 8. PERFORMING ORGANIZATION REPORT NUMBER Texas A&M Engineering Experiment Station (TEES) 400 Harvey Mitchell Parkway, Suite 300 M160 1473 I...Failure Analysis Combining Synergistic Damage Mechanics and Peridynamics Award Number N00014-16-1-2173 DOD-NAVY- Office of Naval Research PI: Ramesh

Digital Imaging of Pipeline Mechanical Damage and Residual Stress

DOT National Transportation Integrated Search

2010-02-19

The purpose of this program was to enhance characterization of mechanical damage in pipelines through application of digital eddy current imaging. Lift-off maps can be used to develop quantitative representations of mechanical damage and magnetic per...

Structural significance of mechanical damage.

DOT National Transportation Integrated Search

2012-05-01

The letter transmits the Final Report for work completed under US DOT PHMSA Other Transaction Agreement (OTA) DTPH56-08-T-000011, Structural Significance of Mechanical Damage. The project was implemented to develop a detailed experimental database on...

Study on Excitation-triggered Damage Mechanism in Perilous Rock

NASA Astrophysics Data System (ADS)

Chen, Hongkai; Wang, Shengjuan

2017-12-01

Chain collapse is easy to happen for perilous rock aggregate locating on steep high slope, and one of the key scientific problems is the damage mechanism of perilous rock under excitation action at perilous rock rupture. This paper studies excitation-triggered damage mechanism in perilous rock by wave mechanics, which gives three conclusions. Firstly, when only the normal incidence attenuation spread of excitation wave is considered, while the energy loss is ignored for excitation wave to spread in perilous rock aggregate, the paper establishes one method to calculate peak velocity when excitation wave passes through boundary between any two perilous rock blocks in perilous rock aggregate. Secondly, following by Sweden and Canmet criteria, the paper provides one wave velocity criterion for excitation-triggered damage in the aggregate. Thirdly, assuming double parameters of volume strain of cracks or fissures in rock meet the Weibull distribution, one method to estimate micro-fissure in excitation-triggered damage zone in perilous rock aggregate is established. The studies solve the mechanical description problem for excitation-triggered damage in perilous rock, which is valuable in studies on profoundly rupture mechanism.

Cerebrovascular Acute Radiation Syndrome : Radiation Neurotoxins, Mechanisms of Toxicity, Neuroimmune Interactions.

NASA Astrophysics Data System (ADS)

Popov, Dmitri; Maliev, Slava

Introduction: Cerebrovascular Acute Radiation Syndrome (CvARS) is an extremely severe in-jury of Central Nervous System (CNS) and Peripheral Nervous System (PNS). CvARS can be induced by the high doses of neutron, heavy ions, or gamma radiation. The Syndrome clinical picture depends on a type, timing, and the doses of radiation. Four grades of the CvARS were defined: mild, moderate, severe, and extremely severe. Also, four stages of CvARS were developed: prodromal, latent, manifest, outcome -death. Duration of stages depends on the types, doses, and time of radiation. The CvARS clinical symptoms are: respiratory distress, hypotension, cerebral edema, severe disorder of cerebral blood microcirculation, and acute motor weakness. The radiation toxins, Cerebro-Vascular Radiation Neurotoxins (SvARSn), determine development of the acute radiation syndrome. Mechanism of action of the toxins: Though pathogenesis of radiation injury of CNS remains unknown, our concept describes the Cv ARS as a result of Neurotoxicity and Excitotoxicity, cell death through apoptotic necrosis. Neurotoxicity occurs after the high doses radiation exposure, formation of radiation neuro-toxins, possible bioradicals, or group of specific enzymes. Intracerebral hemorrhage can be a consequence of the damage of endothelial cells caused by radiation and the radiation tox-ins. Disruption of blood-brain barrier (BBB)and blood-cerebrospinal fluid barrier (BCFB)is possibly the most significant effect of microcirculation disorder and metabolic insufficiency. NMDA-receptors excitotoxic injury mediated by cerebral ischemia and cerebral hypoxia. Dam-age of the pyramidal cells in layers 3 and 5 and Purkinje cell layer the cerebral cortex , damage of pyramidal cells in the hippocampus occur as a result of cerebral ischemia and intracerebral bleeding. Methods: Radiation Toxins of CV ARS are defined as glycoproteins with the molec-ular weight of RT toxins ranges from 200-250 kDa and with high enzymatic activity

Acute interstitial pneumonia (AIP): relationship to Hamman-Rich syndrome, diffuse alveolar damage (DAD), and acute respiratory distress syndrome (ARDS).

PubMed

Mukhopadhyay, Sanjay; Parambil, Joseph G

2012-10-01

Acute interstitial pneumonia (AIP) is a term used for an idiopathic form of acute lung injury characterized clinically by acute respiratory failure with bilateral lung infiltrates and histologically by diffuse alveolar damage (DAD), a combination of findings previously known as the Hamman-Rich syndrome. This review aims to clarify the diagnostic criteria of AIP, its relationship with DAD and acute respiratory distress syndrome (ARDS), key etiologies that need to be excluded before making the diagnosis, and the salient clinical features. Cases that meet clinical and pathologic criteria for AIP overlap substantially with those that fulfill clinical criteria for ARDS. The main differences between AIP and ARDS are that AIP requires a histologic diagnosis of DAD and exclusion of known etiologies. AIP should also be distinguished from "acute exacerbation of IPF," a condition in which acute lung injury (usually DAD) supervenes on underlying usual interstitial pneumonia (UIP)/idiopathic pulmonary fibrosis (IPF). Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Quantification of vascular damage in acute kidney injury with fluorine magnetic resonance imaging and spectroscopy.

PubMed

Moore, Jeremy K; Chen, Junjie; Pan, Hua; Gaut, Joseph P; Jain, Sanjay; Wickline, Samuel A

2018-06-01

To design a fluorine MRI/MR spectroscopy approach to quantify renal vascular damage after ischemia-reperfusion injury, and the therapeutic response to antithrombin nanoparticles (NPs) to protect kidney function. A total of 53 rats underwent 45 min of bilateral renal artery occlusion and were treated at reperfusion with either plain perfluorocarbon NPs or NPs functionalized with a direct thrombin inhibitor (PPACK:phenyalanine-proline-arginine-chloromethylketone). Three hours after reperfusion, kidneys underwent ex vivo fluorine MRI/MR spectroscopy at 4.7 T to quantify the extent and volume of trapped NPs, as an index of vascular damage and ischemia-reperfusion injury. Microscopic evaluation of structural damage and NP trapping in non-reperfused renal segments was performed. Serum creatinine was quantified serially over 7 days. The damaged renal cortico-medullary junction trapped a significant volume of NPs (P = 0.04), which correlated linearly (r = 0.64) with the severity of kidney injury 3 h after reperfusion. Despite global large vessel reperfusion, non-reperfusion in medullary peritubular capillaries was confirmed by MRI and microscopy, indicative of continuing hypoxia due to vascular compromise. Treatment of animals with PPACK NPs after acute kidney injury did not accelerate kidney functional recovery. Quantification of ischemia-reperfusion injury after acute kidney injury with fluorine MRI/MR spectroscopy of perfluorocarbon NPs objectively depicts the extent and severity of vascular injury and its linear relationship to renal dysfunction. The lack of kidney function improvement after early posttreatment thrombin inhibition confirms the rapid onset of ischemia-reperfusion injury as a consequence of vascular damage and non-reperfusion. The prolongation of medullary ischemia renders cortico-medullary tubular structures susceptible to continued necrosis despite restoration of large vessel flow, which suggests limitations to acute interventions after

Diagnostic usefulness of the oedema-infarct ratio to differentiate acute from chronic myocardial damage using magnetic resonance imaging.

PubMed

Yamada, Kiyoyasu; Isobe, Satoshi; Suzuki, Susumu; Kinoshita, Kousuke; Yokouchi, Kazuhiko; Iwata, Hirokazu; Ohshima, Satoru; Hirai, Makoto; Sawada, Ken; Murohara, Toyoaki

2012-04-01

To differentiate acute from chronic damage to the myocardium in patients with myocardial infarction (MI) using DE and T2w MR. Short-axis T2w and DE MR images were acquired twice after the onset of MI in 36 patients who successfully underwent emergency coronary revascularisation. The areas of infarct and oedema were measured. The oedema-infarct ratio (O/I) of the left ventricular area was calculated by dividing the oedema by the infarct area. The oedema size on T2w MR was significantly larger than the infarct size on DE MR in the acute phase. Both the oedema size on T2w MR and the infarct size on DE MR in the acute phase were significantly larger than those in the chronic phase. The O/I was significantly greater in the acute phase compared with that in the chronic phase (P < 0.05). An analysis of relative cumulative frequency distributions revealed an O/I of 1.4 as a cut-off value for differentiating acute from chronic myocardial damage with the sensitivity, specificity, and accuracy of 85.1%, 82.7% and 83.9%, respectively. The oedema-infarct ratio may be a useful index in differentiating acute from chronic myocardial damage in patients with MI. MR can differentiate reversible from irreversible myocardial damage after myocardial infarction. MR is a useful modality to noninvasively differentiate the infarct stages. The O/I is an important index to decide therapeutic strategies.

Advancements in mechanical circulatory support for patients in acute and chronic heart failure

PubMed Central

Csepe, Thomas A.

2017-01-01

Cardiogenic shock (CS) continues to have high mortality and morbidity despite advances in pharmacological, mechanical, and reperfusion approaches to treatment. When CS is refractory to medical therapy, percutaneous mechanical circulatory support (MCS) should be considered. Acute MCS devices, ranging from intra-aortic balloon pumps (IABPs) to percutaneous temporary ventricular assist devices (VAD) to extracorporeal membrane oxygenation (ECMO), can aid, restore, or maintain appropriate tissue perfusion before the development of irreversible end-organ damage. Technology has improved patient survival to recovery from CS, but in patients whom cardiac recovery does not occur, acute MCS can be effectively utilized as a bridge to long-term MCS devices and/or heart transplantation. Heart transplantation has been limited by donor heart availability, leading to a greater role of left ventricular assist device (LVAD) support. In patients with biventricular failure that are ineligible for LVAD implantation, further advancements in the total artificial heart (TAH) may allow for improved survival compared to medical therapy alone. In this review, we discuss the current state of acute and durable MCS, ongoing advances in LVADs and TAH devices, improved methods of durable MCS implantation and patient selection, and future MCS developments in this dynamic field that may allow for optimization of HF treatment. PMID:29268418

Recent advances in the pathogenetic mechanisms of sepsis-associated acute kidney injury.

PubMed

Fani, Filippo; Regolisti, Giuseppe; Delsante, Marco; Cantaluppi, Vincenzo; Castellano, Giuseppe; Gesualdo, Loreto; Villa, Gianluca; Fiaccadori, Enrico

2018-06-01

Sepsis is a serious medical condition that can lead to multi-organ failure and shock, and it is associated with increased mortality. Acute kidney injury (AKI) is a frequent complication of sepsis in critically ill patients, and often requires renal replacement therapy. The pathophysiology of AKI in sepsis has not yet been fully defined. In the past, classic theories were mainly focused on systemic hemodynamic derangements, underscoring the key role of whole kidney hypoperfusion due to reduced renal blood flow. However, a growing body of experimental and clinical evidence now shows that, at least in the early phase of sepsis-associated AKI, renal blood flow is normal, or even increased. This could suggest a dissociation between renal blood flow and kidney function. In addition, the scant data available from kidney biopsies in human studies do not support diffuse acute tubular necrosis as the predominant lesion. Instead, increasing importance is now attributed to kidney damage resulting from a complex interaction between immunologic mechanisms, inflammatory cascade activation, and deranged coagulation pathways, leading to microvascular dysfunction, endothelial damage, leukocyte/platelet activation with the formation of micro-thrombi, epithelial tubular cell injury and dysfunction. Moreover, the same processes, through maladaptive responses leading to fibrosis acting from the very beginning, may set the stage for progression to chronic kidney disease in survivors from sepsis-associated AKI episodes. The aim of this narrative review is to summarize and discuss the latest evidence on the pathophysiological mechanisms involved in septic AKI, based on the most recent data from the literature.

DNA Damage and Repair: Relevance to Mechanisms of Neurodegeneration

PubMed Central

Martin, Lee J.

2008-01-01

DNA damage is a form of cell stress and injury that has been implicated in the pathogenesis of many neurologic disorders, including amyotrophic lateral sclerosis, Alzheimer disease, Down syndrome, Parkinson disease, cerebral ischemia, and head trauma. However, most data reveal only associations, and the role for DNA damage in direct mechanisms of neurodegeneration is vague with respect to being a definitive upstream cause of neuron cell death, rather than a consequence of the degeneration. Although neurons seem inclined to develop DNA damage during oxidative stress, most of the existing work on DNA damage and repair mechanisms has been done in the context of cancer biology using cycling non-neuronal cells but not nondividing (i.e. postmitotic) neurons. Nevertheless, the identification of mutations in genes that encode proteins that function in DNA repair and DNA damage response in human hereditary DNA repair deficiency syndromes and ataxic disorders is establishing a mechanistic precedent that clearly links DNA damage and DNA repair abnormalities with progressive neurodegeneration. This review summarizes DNA damage and repair mechanisms and their potential relevance to the evolution of degeneration in postmitotic neurons. PMID:18431258

Discovering mechanisms relevant for radiation damage evolution

DOE PAGES

Uberuaga, Blas Pedro; Martinez, Enrique Saez; Perez, Danny; ...

2018-02-22

he response of a material to irradiation is a consequence of the kinetic evolution of defects produced during energetic damage events. Thus, accurate predictions of radiation damage evolution require knowing the atomic scale mechanisms associated with those defects. Atomistic simulations are a key tool in providing insight into the types of mechanisms possible. Further, by extending the time scale beyond what is achievable with conventional molecular dynamics, even greater insight can be obtained. Here, we provide examples in which such simulations have revealed new kinetic mechanisms that were not obvious before performing the simulations. We also demonstrate, through the couplingmore » with higher level models, how those mechanisms impact experimental observables in irradiated materials. Lastly, we discuss the importance of these types of simulations in the context of predicting material behavior.« less

Discovering mechanisms relevant for radiation damage evolution

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

Uberuaga, Blas Pedro; Martinez, Enrique Saez; Perez, Danny

he response of a material to irradiation is a consequence of the kinetic evolution of defects produced during energetic damage events. Thus, accurate predictions of radiation damage evolution require knowing the atomic scale mechanisms associated with those defects. Atomistic simulations are a key tool in providing insight into the types of mechanisms possible. Further, by extending the time scale beyond what is achievable with conventional molecular dynamics, even greater insight can be obtained. Here, we provide examples in which such simulations have revealed new kinetic mechanisms that were not obvious before performing the simulations. We also demonstrate, through the couplingmore » with higher level models, how those mechanisms impact experimental observables in irradiated materials. Lastly, we discuss the importance of these types of simulations in the context of predicting material behavior.« less

Mechanical Circulatory Support Devices for Acute Right Ventricular Failure.

PubMed

Kapur, Navin K; Esposito, Michele L; Bader, Yousef; Morine, Kevin J; Kiernan, Michael S; Pham, Duc Thinh; Burkhoff, Daniel

2017-07-18

Right ventricular (RV) failure remains a major cause of global morbidity and mortality for patients with advanced heart failure, pulmonary hypertension, or acute myocardial infarction and after major cardiac surgery. Over the past 2 decades, percutaneously delivered acute mechanical circulatory support pumps specifically designed to support RV failure have been introduced into clinical practice. RV acute mechanical circulatory support now represents an important step in the management of RV failure and provides an opportunity to rapidly stabilize patients with cardiogenic shock involving the RV. As experience with RV devices grows, their role as mechanical therapies for RV failure will depend less on the technical ability to place the device and more on improved algorithms for identifying RV failure, patient monitoring, and weaning protocols for both isolated RV failure and biventricular failure. In this review, we discuss the pathophysiology of acute RV failure and both the mechanism of action and clinical data exploring the utility of existing RV acute mechanical circulatory support devices. © 2017 American Heart Association, Inc.

Damage Mechanisms and Mechanical Properties of High-Strength Multiphase Steels

PubMed Central

Heibel, Sebastian; Dettinger, Thomas; Nester, Winfried; Tekkaya, A. Erman

2018-01-01

The usage of high-strength steels for structural components and reinforcement parts is inevitable for modern car-body manufacture in reaching lightweight design as well as increasing passive safety. Depending on their microstructure these steels show differing damage mechanisms and various mechanical properties which cannot be classified comprehensively via classical uniaxial tensile testing. In this research, damage initiation, evolution and final material failure are characterized for commercially produced complex-phase (CP) and dual-phase (DP) steels in a strength range between 600 and 1000 MPa. Based on these investigations CP steels with their homogeneous microstructure are characterized as damage tolerant and hence less edge-crack sensitive than DP steels. As final fracture occurs after a combination of ductile damage evolution and local shear band localization in ferrite grains at a characteristic thickness strain, this strain measure is introduced as a new parameter for local formability. In terms of global formability DP steels display advantages because of their microstructural composition of soft ferrite matrix including hard martensite particles. Combining true uniform elongation as a measure for global formability with the true thickness strain at fracture for local formability the mechanical material response can be assessed on basis of uniaxial tensile testing incorporating all microstructural characteristics on a macroscopic scale. Based on these findings a new classification scheme for the recently developed high-strength multiphase steels with significantly better formability resulting of complex underlying microstructures is introduced. The scheme overcomes the steel designations using microstructural concepts, which provide no information about design and production properties. PMID:29747417

Damage Mechanisms and Mechanical Properties of High-Strength Multiphase Steels.

PubMed

Heibel, Sebastian; Dettinger, Thomas; Nester, Winfried; Clausmeyer, Till; Tekkaya, A Erman

2018-05-09

The usage of high-strength steels for structural components and reinforcement parts is inevitable for modern car-body manufacture in reaching lightweight design as well as increasing passive safety. Depending on their microstructure these steels show differing damage mechanisms and various mechanical properties which cannot be classified comprehensively via classical uniaxial tensile testing. In this research, damage initiation, evolution and final material failure are characterized for commercially produced complex-phase (CP) and dual-phase (DP) steels in a strength range between 600 and 1000 MPa. Based on these investigations CP steels with their homogeneous microstructure are characterized as damage tolerant and hence less edge-crack sensitive than DP steels. As final fracture occurs after a combination of ductile damage evolution and local shear band localization in ferrite grains at a characteristic thickness strain, this strain measure is introduced as a new parameter for local formability. In terms of global formability DP steels display advantages because of their microstructural composition of soft ferrite matrix including hard martensite particles. Combining true uniform elongation as a measure for global formability with the true thickness strain at fracture for local formability the mechanical material response can be assessed on basis of uniaxial tensile testing incorporating all microstructural characteristics on a macroscopic scale. Based on these findings a new classification scheme for the recently developed high-strength multiphase steels with significantly better formability resulting of complex underlying microstructures is introduced. The scheme overcomes the steel designations using microstructural concepts, which provide no information about design and production properties.

Electron radiation damage mechanisms in 2D MoSe2

NASA Astrophysics Data System (ADS)

Lehnert, T.; Lehtinen, O.; Algara-Siller, G.; Kaiser, U.

2017-01-01

The contributions of different damage mechanisms in single-layer MoSe2 were studied by investigating different MoSe2/graphene heterostructures by the aberration-corrected high-resolution transmission electron microscopy (AC-HRTEM) at 80 keV. The damage cross-sections were determined by direct counting of atoms in the AC-HRTEM images. The contributions of damage mechanisms such as knock-on damage or ionization effects were estimated by comparing the damage rates in different heterostructure configurations, similarly to what has been earlier done with MoS2. The behaviour of MoSe2 was found to be nearly identical to that of MoS2, which is an unexpected result, as the knock-on mechanism should be suppressed in MoSe2 due to the high mass of Se, as compared to S.

[Mechanisms of electromagnetic radiation damaging male reproduction].

PubMed

Xue, Lei; Chen, Hao-Yu; Wang, Shui-Ming

2012-08-01

More and more evidence from over 50 years of researches on the effects of electromagnetic radiation on male reproduction show that a certain dose of electromagnetic radiation obviously damages male reproduction, particularly the structure and function of spermatogenic cells. The mechanisms of the injury may be associated with energy dysmetabolism, lipid peroxidation, abnormal expressions of apoptosis-related genes and proteins, and DNA damage.

Experimental acute alcohol pancreatitis-related liver damage and endotoxemia: synbiotics but not metronidazole have a protective effect.

PubMed

Marotta, F; Barreto, R; Wu, C C; Naito, Y; Gelosa, F; Lorenzetti, A; Yoshioka, M; Fesce, E

2005-01-01

The aim of this study was to test the effect of gut manipulation by either novel synbiotics or by metronidazole on either endotoxemia or the severity of liver damage in the course of acute pancreatitis from alcohol ingestion. Sprague-Dawley rats were fed for 1 week through an intragastric tube a liquid diet with either: (i) 1 mL t.i.d. of a mixture of synbiotics (Lactobacillus acidophilus, Lactobacillus helveticus and Bifidobacterium in an enriched medium); (ii) 20 mg/kg t.i.d. metronidazole; or (iii) standard diet. Then, acute pancreatitis was induced by caerulein and when the disease was full-blown, rats were fed an alcohol-rich diet. Synbiotic and metronidazole treatment was given for a further 2 weeks. Transaminase and endotoxemia levels were measured before treatment, after 6 h, after 24 h and 2 weeks later, at the time the rats were killed. Liver samples were obtained for histological analysis. Synbiotics but not metronidazole improved the acute pancreatitis-induced increase in endotoxemia and transaminase levels. The addition of alcohol worsened these variables to a limited extent in the synbiotic-treated group, while metronidazole had a negative effect on liver damage. Gut flora pretreatment with synbiotics was able to effectively protect against endotoxin/bacterial translocation, as well as liver damage in the course of acute pancreatitis and concomitant heavy alcohol consumption. The beneficial effect of synbiotics on liver histology seems to be correlated with endotoxemia. Metronidazole did not produce such a beneficial effect; in fact, it further worsened liver damage when alcohol was added to the background of ongoing acute pancreatic inflammation.

Preventive mechanisms of agmatine against ischemic acute kidney injury in rats.

PubMed

Sugiura, Takahiro; Kobuchi, Shuhei; Tsutsui, Hidenobu; Takaoka, Masanori; Fujii, Toshihide; Hayashi, Kentaro; Matsumura, Yasuo

2009-01-28

The excitation of renal sympathetic nervous system plays an important role in the development of ischemic acute kidney injury in rats. Recently, we found that agmatine, an adrenaline alpha(2)/imidazoline I(1)-receptor agonist, has preventive effects on ischemic acute kidney injury by suppressing the enhanced renal sympathetic nerve activity during renal ischemia and by decreasing the renal venous norepinephrine overflow after reperfusion. In the present study, we investigated preventive mechanisms of agmatine against ischemic acute kidney injury in rats. Ischemic acute kidney injury was induced by clamping the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after the contralateral nephrectomy. Pretreatment with efaroxan (30 mumol/kg, i.v.), an alpha(2)/I(1)-receptor antagonist, abolished the suppressive effects of agmatine on the enhanced renal sympathetic nerve activity during renal ischemia and on the elevated norepinephrine overflow after reperfusion, and eliminated the preventing effects of agmatine on the ischemia/reperfusion-induced renal dysfunction and histological damage. On the other hand, pretreatment with yohimbine (6 mumol/kg, i.v.), an alpha(2)-receptor antagonist, eliminated the preventing effects of agmatine on the ischemia/reperfusion-induced renal injury and norepinephrine overflow, without affecting the lowering effect of agmatine on renal sympathetic nerve activity. These results indicate that agmatine prevents the ischemic renal injury by sympathoinhibitory effect probably via I(1) receptors in central nervous system and by suppressing the norepinephrine overflow through alpha(2) or I(1) receptors on sympathetic nerve endings.

Mechanisms of free radical-induced damage to DNA.

PubMed

Dizdaroglu, Miral; Jaruga, Pawel

2012-04-01

Endogenous and exogenous sources cause free radical-induced DNA damage in living organisms by a variety of mechanisms. The highly reactive hydroxyl radical reacts with the heterocyclic DNA bases and the sugar moiety near or at diffusion-controlled rates. Hydrated electron and H atom also add to the heterocyclic bases. These reactions lead to adduct radicals, further reactions of which yield numerous products. These include DNA base and sugar products, single- and double-strand breaks, 8,5'-cyclopurine-2'-deoxynucleosides, tandem lesions, clustered sites and DNA-protein cross-links. Reaction conditions and the presence or absence of oxygen profoundly affect the types and yields of the products. There is mounting evidence for an important role of free radical-induced DNA damage in the etiology of numerous diseases including cancer. Further understanding of mechanisms of free radical-induced DNA damage, and cellular repair and biological consequences of DNA damage products will be of outmost importance for disease prevention and treatment.

Acute organo-phosphorus pesticide poisoning in North Karnataka, India: oxidative damage, haemoglobin level and total leukocyte.

PubMed

Hundekari, I A; Suryakar, A N; Rathi, D B

2013-03-01

Pesticide poisoning is an important cause of morbidity and mortality in India. To assess the oxidative damage, hemoglobin level and leukocyte count in acute organophosphorus pesticide poisoning. Plasma cholinesterase was assessed as a toxicity marker. Oxidative damage was assessed by estimating serum malondialdehyde (MDA) levels, plasma total antioxidant capacity (TAC), erythrocyte superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) levels. Progressive and significant decline (p< 0.001) in plasma cholinesterase in correlation with the severity of organophosphorus poisoning was observed. Serum MDA levels significantly increased (p< 0.001) in all grades of organophosphorus poisoning cases as compared to controls. Erythrocyte SOD, CAT and GPx were significantly increased (p< 0.05) in earlier grade and (p< 0.001) in later grades of organophosphorus poisoning cases as compared to controls. While plasma TAC (p<0.001) was significantly decreased in all grades of organophosphorus poisoning cases as compared to controls. Leucocytosis observed in these cases signifies the activation of defense mechanism which could be a positive response for survival. Organophosphorus compounds inhibit cholinesterase action leading to cholinergic hyperactivity. Increased MDA level may lead to peroxidative damages deteriorating the structural and functional integrity of neuronal membrane. Increased erythrocyte SOD, CAT and GPx activities suggest an adaptive measure to tackle the pesticide accumulation. Hence it is concluded that cholinesterase inhibition may initiate cellular dysfunction leading to acetylcholine induced oxidative damage.

Temporal relationship of serum markers and tissue damage during acute intestinal ischemia/reperfusion

PubMed Central

la Garza, Francisco Javier Guzmán-de; Ibarra-Hernández, Juan Manuel; Cordero-Pérez, Paula; Villegas-Quintero, Pablo; Villarreal-Ovalle, Claudia Ivette; Torres-González, Liliana; Oliva-Sosa, Norma Edith; Alarcón-Galván, Gabriela; Fernández-Garza, Nancy Esthela; Muñoz-Espinosa, Linda Elsa; Cámara-Lemarroy, Carlos Rodrigo; Carrillo-Arriaga, José Gerardo

2013-01-01

OBJECTIVE: It is essential to identify a serological marker of injury in order to study the pathophysiology of intestinal ischemia reperfusion. In this work, we studied the evolution of several serological markers after intestinal ischemia reperfusion injury in rats. The markers of non-specific cell damage were aspartate aminotransferase, alanine aminotransaminase, and lactic dehydrogenase, the markers of inflammation were tumor necrosis factor alpha, interleukin-6, and interleukin-1 beta, and the markers of intestinal mucosal damage were intestinal fatty acid binding protein and D-lactate. We used Chiús classification to grade the histopathological damage. METHODS: We studied 35 Wistar rats divided into groups according to reperfusion time. The superior mesenteric artery was clamped for 30 minutes, and blood and biopsies were collected at 1, 3, 6, 12, 24, and 48 hours after reperfusion. We plotted the mean ± standard deviation and compared the baseline and maximum values for each marker using Student's t-test. RESULTS: The maximum values of interleukin-1 beta and lactic dehydrogenase were present before the maximal histopathological damage. The maximum tumor necrosis factor alpha and D-lactate expressions coincided with histopathological damage. Alanine aminotransaminase and aspartate aminotransferase had a maximum expression level that increased following the histopathological damage. The maximum expressions of interluken-6 and intestinal fatty acid binding protein were not significantly different from the Sham treated group. CONCLUSION: For the evaluation of injury secondary to acute intestinal ischemia reperfusion with a 30 minute ischemia period, we recommend performing histopathological grading, quantification of D-lactate, which is synthesized by intestinal bacteria and is considered an indicator of mucosal injury, and quantification of tumor necrosis factor alpha as indicators of acute inflammation three hours after reperfusion. PMID:23917671

Laser damage mechanisms in conductive widegap semiconductor films

DOE PAGES

Yoo, Jae-Hyuck; Menor, Marlon G.; Adams, John J.; ...

2016-07-25

Here, laser damage mechanisms of two conductive wide-bandgap semiconductor films - indium tin oxide (ITO) and silicon doped GaN (Si:GaN) were studied via microscopy, spectroscopy, photoluminescence (PL), and elemental analysis. Nanosecond laser pulse exposures with a laser photon energy (1.03 eV, 1064 nm) smaller than the conductive films bandgaps were applied and radically different film damage morphologies were produced. The laser damaged ITO film exhibited deterministic features of thermal degradation. In contrast, laser damage in the Si:GaN film resulted in highly localized eruptions originating at interfaces. For ITO, thermally driven damage was related to free carrier absorption and, for GaN,more » carbon complexes were proposed as potential damage precursors or markers.« less

SPARC (secreted protein acidic and rich in cysteine) knockdown protects mice from acute liver injury by reducing vascular endothelial cell damage

PubMed Central

Peixoto, E; Atorrasagasti, C; Aquino, JB; Militello, R; Bayo, J; Fiore, E; Piccioni, F; Salvatierra, E; Alaniz, L; García, MG; Bataller, R; Corrales, F; Gidekel, M; Podhajcer, O; Colombo, MI; Mazzolini, G

2015-01-01

Secreted protein, acidic and rich in cysteine (SPARC) is involved in many biological process including liver fibrogenesis, but its role in acute liver damage is unknown. To examine the role of SPARC in acute liver injury, we used SPARC knock-out (SPARC−/−) mice. Two models of acute liver damage were used: concanavalin A (Con A) and the agonistic anti-CD95 antibody Jo2. SPARC expression levels were analyzed in liver samples from patients with acute-on-chronic alcoholic hepatitis (AH). SPARC expression is increased on acute-on-chronic AH patients. Knockdown of SPARC decreased hepatic damage in the two models of liver injury. SPARC−/− mice showed a marked reduction in Con A-induced necroinflammation. Infiltration by CD4+ T cells, expression of tumor necrosis factor-α and interleukin-6 and apoptosis were attenuated in SPARC−/− mice. Sinusoidal endothelial cell monolayer was preserved and was less activated in Con A-treated SPARC−/− mice. SPARC knockdown reduced Con A-induced autophagy of cultured human microvascular endothelial cells (HMEC-1). Hepatic transcriptome analysis revealed several gene networks that may have a role in the attenuated liver damaged found in Con A-treated SPARC−/− mice. SPARC has a significant role in the development of Con A-induced severe liver injury. These results suggest that SPARC could represent a therapeutic target in acute liver injury. PMID:25410742

Acute O3 damage on first year coppice sprouts of aspen and maple sprouts in an open-air experiment

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

Darbah, J.N.; Nagy, J.; Jones, W. S.

2011-10-01

We studied the effect of high ozone (O{sub 3}) concentration (110-490 nmol mol{sup -1}) on regenerating aspen (Populus tremuloides) and maple (Acer saccharum) trees at an open-air O{sub 3} pollution experiment near Rhinelander WI USA. This study is the first of its kind to examine the effects of acute O{sub 3} exposure on aspen and maple sprouts after the parent trees, which were grown under elevated O{sub 3} and/or CO{sub 2} for 12 years, were harvested. Acute O{sub 3} damage was not uniform within the crowns of aspen suckers; it was most severe in the mature, fully expanded photosynthesizing leaves.more » Young expanding leaves showed no visible signs of acute O{sub 3} damage contrary to expectations. Stomatal conductance played a primary role in the severity of acute O{sub 3} damage as it directly controlled O{sub 3} uptake. Maple sprouts, which had lower stomatal conductance, smaller stomatal aperture, higher stomatal density and larger leaf surface area, were tolerant of acute O{sub 3} exposure. Moreover, elevated CO{sub 2} did not ameliorate the adverse effects of acute O{sub 3} dose on aspen and maple sprouts, in contrast to its ability to counteract the effects of long-term chronic exposure to lower O{sub 3} levels.« less

Rat liver mitochondrial damage under acute or chronic carbon tetrachloride-induced intoxication: Protection by melatonin and cranberry flavonoids

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

Cheshchevik, V.T.; Department of Biochemistry, Yanka Kupala Grodno State University, Len. Kom. Blvd. - 50, 230017 Grodno; Lapshina, E.A.

In current societies, the risk of toxic liver damage has markedly increased. The aim of the present work was to carry out further research into the mechanism(s) of liver mitochondrial damage induced by acute (0.8 g/kg body weight, single injection) or chronic (1.6 g/ kg body weight, 30 days, biweekly injections) carbon tetrachloride – induced intoxication and to evaluate the hepatoprotective potential of the antioxidant, melatonin, as well as succinate and cranberry flavonoids in rats. Acute intoxication resulted in considerable impairment of mitochondrial respiratory parameters in the liver. The activity of mitochondrial succinate dehydrogenase (complex II) decreased (by 25%, pmore » < 0.05). Short-term melatonin treatment (10 mg/kg, three times) of rats did not reduce the degree of toxic mitochondrial dysfunction but decreased the enhanced NO production. After 30-day chronic intoxication, no significant change in the respiratory activity of liver mitochondria was observed, despite marked changes in the redox-balance of mitochondria. The activities of the mitochondrial enzymes, succinate dehydrogenase and glutathione peroxidase, as well as that of cytoplasmic catalase in liver cells were inhibited significantly. Mitochondria isolated from the livers of the rats chronically treated with CCl{sub 4} displayed obvious irreversible impairments. Long-term melatonin administration (10 mg/kg, 30 days, daily) to chronically intoxicated rats diminished the toxic effects of CCl{sub 4}, reducing elevated plasma activities of alanine aminotransferase and aspartate aminotransferase and bilirubin concentration, prevented accumulation of membrane lipid peroxidation products in rat liver and resulted in apparent preservation of the mitochondrial ultrastructure. The treatment of the animals by the complex of melatonin (10 mg/kg) plus succinate (50 mg/kg) plus cranberry flavonoids (7 mg/kg) was even more effective in prevention of toxic liver injury and liver mitochondria damage

Hierarchical damage mechanisms in composite materials subjected to fatigue loadings

NASA Astrophysics Data System (ADS)

D'Amore, Alberto; Grassia, Luigi

2018-02-01

The strength degradation of fiber reinforced composites subjected to constant amplitude (CA) fatigue loadings can be described by a two-parameter residual strength model. From the analytical approach it results that under moderate loadings the multiple damage mechanisms develop with different kinetics and manifest their effectiveness at different time scales highlighting the three-Stage hierarchical nature of damage accumulation in composites. The model captures the sequence of damage accumulation mechanisms from diffuse matrix cracking (I), to fiber/matrix interface failure (II) to fiber and ply rupture and delamination (III). Further, by increasing the loading severity it appears that the different mechanisms superpose witnessing their simultaneous co-existence.

[Definition and biomarkers of acute renal damage: new perspectives].

PubMed

Seijas, M; Baccino, C; Nin, N; Lorente, J A

2014-01-01

The RIFLE and AKIN criteria have definitely help out to draw attention to the relationship between a deterioration of renal function that produces a small increase in serum creatinine and a worse outcome. However, the specific clinical utility of using these criteria remains to be well-defined. It is believed that the main use of these criteria is for the design of epidemiological studies and clinical trials to define inclusion criteria and objectives of an intervention. AKI adopting term, re-summoning former ARF terminology, it is appropriate to describe the clinical condition characterized by damage to kidney, in the same way as the term is used to describe acute lung damage where the lung injury situation still has not increased to a situation of organ failure (dysfunction). The serum and urine biomarkers (creatinine, urea, and diuresis) currently in use are not sensitive or specific for detecting kidney damage, limiting treatment options and potentially compromising the outcome. New biomarkers are being studied in order to diagnose an earlier and more specific AKI, with the potential to change the definition criteria of AKI with different stages, currently based in diuresis and serum creatinine. Copyright © 2013 Elsevier España, S.L. and SEMICYUC. All rights reserved.

Glutamate Excitoxicity Is the Key Molecular Mechanism Which Is Influenced by Body Temperature during the Acute Phase of Brain Stroke

PubMed Central

Campos, Francisco; Pérez-Mato, María; Agulla, Jesús; Blanco, Miguel; Barral, David; Almeida, Ángeles; Brea, David; Waeber, Christian; Castillo, José; Ramos-Cabrer, Pedro

2012-01-01

Glutamate excitotoxicity, metabolic rate and inflammatory response have been associated to the deleterious effects of temperature during the acute phase of stroke. So far, the association of temperature with these mechanisms has been studied individually. However, the simultaneous study of the influence of temperature on these mechanisms is necessary to clarify their contributions to temperature-mediated ischemic damage. We used non-invasive Magnetic Resonance Spectroscopy to simultaneously measure temperature, glutamate excitotoxicity and metabolic rate in the brain in animal models of ischemia. The immune response to ischemia was measured through molecular serum markers in peripheral blood. We submitted groups of animals to different experimental conditions (hypothermia at 33°C, normothermia at 37°C and hyperthermia at 39°C), and combined these conditions with pharmacological modulation of glutamate levels in the brain through systemic injections of glutamate and oxaloacetate. We show that pharmacological modulation of glutamate levels can neutralize the deleterious effects of hyperthermia and the beneficial effects of hypothermia, however the analysis of the inflammatory response and metabolic rate, demonstrated that their effects on ischemic damage are less critical than glutamate excitotoxity. We conclude that glutamate excitotoxicity is the key molecular mechanism which is influenced by body temperature during the acute phase of brain stroke. PMID:22952923

Glutamate excitoxicity is the key molecular mechanism which is influenced by body temperature during the acute phase of brain stroke.

PubMed

Campos, Francisco; Pérez-Mato, María; Agulla, Jesús; Blanco, Miguel; Barral, David; Almeida, Angeles; Brea, David; Waeber, Christian; Castillo, José; Ramos-Cabrer, Pedro

2012-01-01

Glutamate excitotoxicity, metabolic rate and inflammatory response have been associated to the deleterious effects of temperature during the acute phase of stroke. So far, the association of temperature with these mechanisms has been studied individually. However, the simultaneous study of the influence of temperature on these mechanisms is necessary to clarify their contributions to temperature-mediated ischemic damage. We used non-invasive Magnetic Resonance Spectroscopy to simultaneously measure temperature, glutamate excitotoxicity and metabolic rate in the brain in animal models of ischemia. The immune response to ischemia was measured through molecular serum markers in peripheral blood. We submitted groups of animals to different experimental conditions (hypothermia at 33°C, normothermia at 37°C and hyperthermia at 39°C), and combined these conditions with pharmacological modulation of glutamate levels in the brain through systemic injections of glutamate and oxaloacetate. We show that pharmacological modulation of glutamate levels can neutralize the deleterious effects of hyperthermia and the beneficial effects of hypothermia, however the analysis of the inflammatory response and metabolic rate, demonstrated that their effects on ischemic damage are less critical than glutamate excitotoxity. We conclude that glutamate excitotoxicity is the key molecular mechanism which is influenced by body temperature during the acute phase of brain stroke.

Mechanisms for microvascular damage induced by ultrasound-activated microbubbles

NASA Astrophysics Data System (ADS)

Chen, Hong; Brayman, Andrew A.; Evan, Andrew P.; Matula, Thomas J.

2012-10-01

To provide insight into the mechanisms of microvascular damage induced by ultrasound-activated microbubbles, experimental studies were performed to correlate microvascular damage to the dynamics of bubble-vessel interactions. High-speed photomicrography was used to record single microbubbles interacting with microvessels in ex vivo tissue, under the exposure of short ultrasound pulses with a center frequency of 1 MHz and peak negative pressures (PNP) ranging from 0.8-4 MPa. Vascular damage associated with observed bubble-vessel interactions was either indicated directly by microbubble extravasation or examined by transmission electron microscopy (TEM) analyses. As observed previously, the high-speed images revealed that ultrasound-activated microbubbles could cause distention and invagination of adjacent vessel walls, and could form liquid jets in microvessels. Vessel distention, invagination, and liquid jets were associated with the damage of microvessels whose diameters were smaller than those of maximally expanded microbubbles. However, vessel invagination appeared to be the dominant mechanism for the damage of relative large microvessels.

Mechanisms for microvascular damage induced by ultrasound-activated microbubbles

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

Chen Hong; Brayman, Andrew A.; Evan, Andrew P.

To provide insight into the mechanisms of microvascular damage induced by ultrasound-activated microbubbles, experimental studies were performed to correlate microvascular damage to the dynamics of bubble-vessel interactions. High-speed photomicrography was used to record single microbubbles interacting with microvessels in ex vivo tissue, under the exposure of short ultrasound pulses with a center frequency of 1 MHz and peak negative pressures (PNP) ranging from 0.8-4 MPa. Vascular damage associated with observed bubble-vessel interactions was either indicated directly by microbubble extravasation or examined by transmission electron microscopy (TEM) analyses. As observed previously, the high-speed images revealed that ultrasound-activated microbubbles could cause distentionmore » and invagination of adjacent vessel walls, and could form liquid jets in microvessels. Vessel distention, invagination, and liquid jets were associated with the damage of microvessels whose diameters were smaller than those of maximally expanded microbubbles. However, vessel invagination appeared to be the dominant mechanism for the damage of relative large microvessels.« less

Non-Fourier based thermal-mechanical tissue damage prediction for thermal ablation.

PubMed

Li, Xin; Zhong, Yongmin; Smith, Julian; Gu, Chengfan

2017-01-02

Prediction of tissue damage under thermal loads plays important role for thermal ablation planning. A new methodology is presented in this paper by combing non-Fourier bio-heat transfer, constitutive elastic mechanics as well as non-rigid motion of dynamics to predict and analyze thermal distribution, thermal-induced mechanical deformation and thermal-mechanical damage of soft tissues under thermal loads. Simulations and comparison analysis demonstrate that the proposed methodology based on the non-Fourier bio-heat transfer can account for the thermal-induced mechanical behaviors of soft tissues and predict tissue thermal damage more accurately than classical Fourier bio-heat transfer based model.

Non-Fourier based thermal-mechanical tissue damage prediction for thermal ablation

PubMed Central

Li, Xin; Zhong, Yongmin; Smith, Julian; Gu, Chengfan

2017-01-01

ABSTRACT Prediction of tissue damage under thermal loads plays important role for thermal ablation planning. A new methodology is presented in this paper by combing non-Fourier bio-heat transfer, constitutive elastic mechanics as well as non-rigid motion of dynamics to predict and analyze thermal distribution, thermal-induced mechanical deformation and thermal-mechanical damage of soft tissues under thermal loads. Simulations and comparison analysis demonstrate that the proposed methodology based on the non-Fourier bio-heat transfer can account for the thermal-induced mechanical behaviors of soft tissues and predict tissue thermal damage more accurately than classical Fourier bio-heat transfer based model. PMID:27690290

Study on Damage Mechanism of Ductile Cast Iron Cooling Stave

NASA Astrophysics Data System (ADS)

Wang, Cui; Zhang, Jianliang; Zuo, Haibin; Dai, Bing

The damage mechanism of ductile cast iron cooling stave applied to No.4 blast furnace of Guofeng steel was analyzed through damage investigation in details, the damage causes: high-temperature gas flow erosion, wear of burden, high-temperature ablation, carburizing damage, improper operation on blast furnace, etc. were given out both in macroscopic and microscopic views. It can be obtained from metallographic diagrams that the diameter of graphite nodules increases, the number per unit area reduces, and roundness declines, successively, from cold to hot surface, which are not conducive to stave longevity. In summary, the material for staves manufacture should be better in comprehensive mechanical properties to prolong the service life, thus making blast furnace long campaign.

Investigation of Laser-Induced Retinal Damage: Wavelength and Pulsewidth Dependent Mechanisms

DTIC Science & Technology

1994-08-31

transformation. Biochim Biophys Acta 1991; 1072:129-57. 2. Artuc M, Ramshad M, Kappus H. Studies on acute toxic effects to keratinocytes induced by...hematoporphyrin derivatives and laser light Arch Dermatol Res 1989;281:491-4. 3. Artuc M, Ramshad M, Reinhold C, Kappus H. DNA damage caused by laser light

Possible GABAergic modulation in the protective effect of zolpidem in acute hypoxic stress-induced behavior alterations and oxidative damage.

PubMed

Kumar, Anil; Goyal, Richa

2008-03-01

Hypoxia is an environmental stressor that is known to elicit alterations in both the autonomic nervous system and endocrine functions. The free radical or oxidative stress theory holds that oxidative reactions are mainly underlying neurodegenerative disorders. In fact among complex metabolic reactions occurring during hypoxia, many could be related to the formation of oxygen derived free radicals, causing a wide spectrum of cell damage. In present study, we investigated possible involvement of GABAergic mechanism in the protective effect of zolpidem against acute hypoxia-induced behavioral modification and biochemical alterations in mice. Mice were subjected to acute hypoxic stress for a period of 2 h. Acute hypoxic stress for 2 h caused significant impairment in locomotor activity, anxiety-like behavior, and antinocioceptive effect in mice. Biochemical analysis revealed a significant increased malondialdehyde, nitrite concentrations and depleted reduced glutathione and catalase levels. Pretreatment with zolpidem (5 and 10 mg/kg, i.p.) significantly improved locomotor activity, anti-anxiety effect, reduced tail flick latency and attenuated oxidative damage (reduced malondialdehyde, nitrite concentration, and restoration of reduced glutathione and catalase levels) as compared to stressed control (hypoxia) (P < 0.05). Besides, protective effect of zolpidem (5 mg/kg) was blocked significantly by picrotoxin (1.0 mg/kg) or flumazenil (2 mg/kg) and potentiated by muscimol (0.05 mg/kg) in hypoxic animals (P < 0.05). These effects were significant as compared to zolpidem (5 mg/kg) per se (P < 0.05). Present study suggest that the possible involvement of GABAergic modulation in the protective effect of zolpidem against hypoxic stress.

Damage Mechanics in the Community Ice Sheet Model

NASA Astrophysics Data System (ADS)

Whitcomb, R.; Cathles, L. M. M., IV; Bassis, J. N.; Lipscomb, W. H.; Price, S. F.

2016-12-01

Half of the mass that floating ice shelves lose to the ocean comes from iceberg calving, which is a difficult process to simulate accurately. This is especially true in the large-scale ice dynamics models that couple changes in the cryosphere to climate projections. Damage mechanics provide a powerful technique with the potential to overcome this obstacle by describing how fractures in ice evolve over time. Here, we demonstrate the application of a damage model to ice shelves that predicts realistic geometries. We incorporated this solver into the Community Ice Sheet Model, a three dimensional ice sheet model developed at Los Alamos National Laboratory. The damage mechanics formulation that we use comes from a first principles-based evolution law for the depth of basal and surface crevasses and depends on the large scale strain rate, stress state, and basal melt. We show that under idealized conditions it produces ice tongue lengths that match well with observations for a selection of natural ice tongues, including Erebus, Drygalski, and Pine Island in Antarctica, as well as Petermann in Greenland. We also apply the model to more generalized ideal ice shelf geometries and show that it produces realistic calving front positions. Although our results are preliminary, the damage mechanics model that we developed provides a promising first principles method for predicting ice shelf extent and how the calving margins of ice shelves respond to climate change.

Huperzine A ameliorates damage induced by acute myocardial infarction in rats through antioxidant, anti-apoptotic and anti-inflammatory mechanisms.

PubMed

Sui, Xizhong; Gao, Changqing

2014-01-01

Huperzine A (HupA), an alkaloid used in traditional Chinese medicine and isolated from Huperzia serrata, has been shown to possess diverse biological activities. The present study was undertaken to evaluate the cardioprotective potential of HupA in myocardial ischemic damage using a rat model of acute myocardial infarction. HupA significantly diminished the infarct size and inhibited the activities of myocardial enzymes, including creatine kinase (CK), the MB isoenzyme of creatine kinase (CK-MB), lactate dehydrogenase (LDH) and cardiac troponin T (cTnT). A significantly reduced activity of malondialdehyde (MDA) and elevated activities of superoxide dismutase (SOD), of the non-enzymatic scavenger enzyme, glutathione (GSH), as well as of glutathione peroxidase (GSH-PX) were found in the HupA-treated groups. Furthermore, decreased protein levels of caspase-3 and Bax, and increased levels of Bcl-2 were observed in the infarcted hearts of the rats treated with various concentrations of HupA. In addition, treatment with HupA markedly inhibited the expression of the nuclear factor-κB (NF-κB) subunit p65, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). These findings suggest that the cardioprotective potential of HupA is associated with its antioxidant, anti-apoptotic and anti-inflammatory properties in acute myocardial infarction in rats.

Acute sun damage and photoprotective responses in whales

PubMed Central

Martinez-Levasseur, Laura M.; Gendron, Diane; Knell, Rob J.; O'Toole, Edel A.; Singh, Manuraj; Acevedo-Whitehouse, Karina

2011-01-01

Rising levels of ultraviolet radiation (UVR) secondary to ozone depletion are an issue of concern for public health. Skin cancers and intraepidermal dysplasia are increasingly observed in individuals that undergo chronic or excessive sun exposure. Such alterations of skin integrity and function are well established for humans and laboratory animals, but remain unexplored for mammalian wildlife. However, effects are unlikely to be negligible, particularly for species such as whales, whose anatomical or life-history traits force them to experience continuous sun exposure. We conducted photographic and histological surveys of three seasonally sympatric whale species to investigate sunburn and photoprotection. We find that lesions commonly associated with acute severe sun damage in humans are widespread and that individuals with fewer melanocytes have more lesions and less apoptotic cells. This suggests that the pathways used to limit and resolve UVR-induced damage in humans are shared by whales and that darker pigmentation is advantageous to them. Furthermore, lesions increased significantly in time, as would be expected under increasing UV irradiance. Apoptosis and melanocyte proliferation mirror this trend, suggesting that whales are capable of quick photoprotective responses. We conclude that the thinning ozone layer may pose a risk to the health of whales and other vulnerable wildlife. PMID:21068035

Vessel Wall Enhancement and Blood-Cerebrospinal Fluid Barrier Disruption After Mechanical Thrombectomy in Acute Ischemic Stroke.

PubMed

Renú, Arturo; Laredo, Carlos; Lopez-Rueda, Antonio; Llull, Laura; Tudela, Raúl; San-Roman, Luis; Urra, Xabier; Blasco, Jordi; Macho, Juan; Oleaga, Laura; Chamorro, Angel; Amaro, Sergio

2017-03-01

Less than half of acute ischemic stroke patients treated with mechanical thrombectomy obtain permanent clinical benefits. Consequently, there is an urgent need to identify mechanisms implicated in the limited efficacy of early reperfusion. We evaluated the predictors and prognostic significance of vessel wall permeability impairment and its association with blood-cerebrospinal fluid barrier (BCSFB) disruption after acute stroke treated with thrombectomy. A prospective cohort of acute stroke patients treated with stent retrievers was analyzed. Vessel wall permeability impairment was identified as gadolinium vessel wall enhancement (GVE) in a 24- to 48-hour follow-up contrast-enhanced magnetic resonance imaging, and severe BCSFB disruption was defined as subarachnoid hemorrhage or gadolinium sulcal enhancement (present across >10 slices). Infarct volume was evaluated in follow-up magnetic resonance imaging, and clinical outcome was evaluated with the modified Rankin Scale at day 90. A total of 60 patients (median National Institutes of Health Stroke Scale score, 18) were analyzed, of whom 28 (47%) received intravenous alteplase before mechanical thrombectomy. Overall, 34 (57%) patients had GVE and 27 (45%) had severe BCSFB disruption. GVE was significantly associated with alteplase use before thrombectomy and with more stent retriever passes, along with the presence of severe BCSFB disruption. GVE was associated with poor clinical outcome, and both GVE and severe BCSFB disruption were associated with increased final infarct volume. These findings may support the clinical relevance of direct vessel damage and BCSFB disruption after acute stroke and reinforce the need for further improvements in reperfusion strategies. Further validation in larger cohorts of patients is warranted. © 2017 American Heart Association, Inc.

The application of continuum damage mechanics to solve problems in geodynamics

NASA Astrophysics Data System (ADS)

Manaker, David Martin

Deformation within the Earth's lithosphere is largely controlled by the rheology of the rock. Ductile behavior in rocks is often associated with plasticity due to dislocation motion or diffusion under high pressures and temperatures. However, ductile behavior can also occur in brittle materials. An example would be cataclastic flow associated with folding at shallow crustal levels, steep subduction zones, and large-scale deformation at plate boundaries. Engineers utilize damage mechanics to model the continuum deformation of brittle materials. We utilize a modified form of damage mechanics where damage represents a reduction in frictional strength and includes a yield stress. We use this empirical approach to simulate the bending of the lithosphere. We use numerical simulations to obtain elastostatic solutions for plate bending and where the stress exceeds a yield stress, we apply damage to reduce the elastic moduli. Damage is calculated at each time step by a power-law relationship of the ratio of the yield stress to stress and the yield strain to the strain. To test our method, we apply our damage rheology to a plate deforming under applied shear, a constant bending moment, and a constant load. We simulate a wide range of behaviors from slow relaxation to instantaneous failure, over timescales that span six orders of magnitude. Stress relaxation produces elastic-perfectly plastic behavior in cases where failure does not occur. For cases of failure, we observe a rapid increase in damage leading to failure. The changes in the rate of damage accumulation in failure cases are similar to the changes in b-values of acoustic emissions observed in triaxial compression tests of fractured rock and b-value changes prior to some large earthquakes. Thus continuum damage mechanics can simulate ductile behavior due to brittle mechanisms as well as observations of laboratory experiments and seismicity.

Anisotropic Damage Mechanics Modeling in Metal Matrix Composites

DTIC Science & Technology

1993-05-15

conducted on a titanium aluminide SiC-reinforced metal matrix composite. Center-cracked plates with laminate layups of (0/90) and (±45). were tested... interfacial damage mechanisms as debonding or delamination. Equations (2.14) and (2.15) represent the damage transformation equations for the stress... titanium aluminide SiC 46 continuous reinforced metal matrix composite. As a means of enforcing quality assurance, all manufacturing and cutting of the

Mechanisms of mutagenesis: DNA replication in the presence of DNA damage

PubMed Central

Liu, Binyan; Xue, Qizhen; Tang, Yong; Cao, Jia; Guengerich, F. Peter; Zhang, Huidong

2017-01-01

Environmental mutagens cause DNA damage that disturbs replication and produces mutations, leading to cancer and other diseases. We discuss mechanisms of mutagenesis resulting from DNA damage, from the level of DNA replication by a single polymerase to the complex DNA replisome of some typical model organisms (including bacteriophage T7, T4, Sulfolobus solfataricus, E. coli, yeast and human). For a single DNA polymerase, DNA damage can affect replication in three major ways: reducing replication fidelity, causing frameshift mutations, and blocking replication. For the DNA replisome, protein interactions and the functions of accessory proteins can yield rather different results even with a single DNA polymerase. The mechanism of mutation during replication performed by the DNA replisome is a long-standing question. Using new methods and techniques, the replisomes of certain organisms and human cell extracts can now be investigated with regard to the bypass of DNA damage. In this review, we consider the molecular mechanism of mutagenesis resulting from DNA damage in replication at the levels of single DNA polymerases and complex DNA replisomes, including translesion DNA synthesis. PMID:27234563

Mechanisms of Severe Acute Respiratory Syndrome Coronavirus-Induced Acute Lung Injury

PubMed Central

Gralinski, Lisa E.; Bankhead, Armand; Jeng, Sophia; Menachery, Vineet D.; Proll, Sean; Belisle, Sarah E.; Matzke, Melissa; Webb-Robertson, Bobbie-Jo M.; Luna, Maria L.; Shukla, Anil K.; Ferris, Martin T.; Bolles, Meagan; Chang, Jean; Aicher, Lauri; Waters, Katrina M.; Smith, Richard D.; Metz, Thomas O.; Law, G. Lynn; Katze, Michael G.; McWeeney, Shannon; Baric, Ralph S.

2013-01-01

ABSTRACT Systems biology offers considerable promise in uncovering novel pathways by which viruses and other microbial pathogens interact with host signaling and expression networks to mediate disease severity. In this study, we have developed an unbiased modeling approach to identify new pathways and network connections mediating acute lung injury, using severe acute respiratory syndrome coronavirus (SARS-CoV) as a model pathogen. We utilized a time course of matched virologic, pathological, and transcriptomic data within a novel methodological framework that can detect pathway enrichment among key highly connected network genes. This unbiased approach produced a high-priority list of 4 genes in one pathway out of over 3,500 genes that were differentially expressed following SARS-CoV infection. With these data, we predicted that the urokinase and other wound repair pathways would regulate lethal versus sublethal disease following SARS-CoV infection in mice. We validated the importance of the urokinase pathway for SARS-CoV disease severity using genetically defined knockout mice, proteomic correlates of pathway activation, and pathological disease severity. The results of these studies demonstrate that a fine balance exists between host coagulation and fibrinolysin pathways regulating pathological disease outcomes, including diffuse alveolar damage and acute lung injury, following infection with highly pathogenic respiratory viruses, such as SARS-CoV. PMID:23919993

Chemotherapy-induced damage to ovary: mechanisms and clinical impact.

PubMed

Bedoschi, Giuliano; Navarro, Paula Andrea; Oktay, Kutluk

2016-10-01

Cancer is a major public health problem around the world. Currently, about 5% of women diagnosed with cancer are of reproductive age. These young survivors may face compromised fertility. The effects of chemotherapeutic agents on ovarian reserve and its clinical consequences are generally inferred from a variety of surrogate markers of ovarian reserve, all aiming to provide prognostic information on fertility or the likelihood of success of infertility treatment. Until recently, the mechanisms that are responsible for chemotherapy-induced ovarian damage were not fully elucidated. The understanding of these mechanisms may lead to targeted treatments to preserve fertility. In this manuscript, we will review the current knowledge on the mechanism of ovarian damage and clinical impact of chemotherapy agents on fertility.

Molecular level detection and localization of mechanical damage in collagen enabled by collagen hybridizing peptides.

PubMed

Zitnay, Jared L; Li, Yang; Qin, Zhao; San, Boi Hoa; Depalle, Baptiste; Reese, Shawn P; Buehler, Markus J; Yu, S Michael; Weiss, Jeffrey A

2017-03-22

Mechanical injury to connective tissue causes changes in collagen structure and material behaviour, but the role and mechanisms of molecular damage have not been established. In the case of mechanical subfailure damage, no apparent macroscale damage can be detected, yet this damage initiates and potentiates in pathological processes. Here, we utilize collagen hybridizing peptide (CHP), which binds unfolded collagen by triple helix formation, to detect molecular level subfailure damage to collagen in mechanically stretched rat tail tendon fascicle. Our results directly reveal that collagen triple helix unfolding occurs during tensile loading of collagenous tissues and thus is an important damage mechanism. Steered molecular dynamics simulations suggest that a likely mechanism for triple helix unfolding is intermolecular shearing of collagen α-chains. Our results elucidate a probable molecular failure mechanism associated with subfailure injuries, and demonstrate the potential of CHP targeting for diagnosis, treatment and monitoring of tissue disease and injury.

A Micro-Mechanism-Based Continuum Corrosion Fatigue Damage Model for Steels

NASA Astrophysics Data System (ADS)

Sun, Bin; Li, Zhaoxia

2018-05-01

A micro-mechanism-based corrosion fatigue damage model is developed for studying the high-cycle corrosion fatigue of steel from multi-scale viewpoint. The developed physical corrosion fatigue damage model establishes micro-macro relationships between macroscopic continuum damage evolution and collective evolution behavior of microscopic pits and cracks, which can be used to describe the multi-scale corrosion fatigue process of steel. As a case study, the model is used to predict continuum damage evolution and number density of the corrosion pit and short crack of steel component in 5% NaCl water under constant stress amplitude at 20 kHz, and the numerical results are compared with experimental results. It shows that the model is effective and can be used to evaluate the continuum macroscopic corrosion fatigue damage and study microscopic corrosion fatigue mechanisms of steel.

A Micro-Mechanism-Based Continuum Corrosion Fatigue Damage Model for Steels

NASA Astrophysics Data System (ADS)

Sun, Bin; Li, Zhaoxia

2018-04-01

A micro-mechanism-based corrosion fatigue damage model is developed for studying the high-cycle corrosion fatigue of steel from multi-scale viewpoint. The developed physical corrosion fatigue damage model establishes micro-macro relationships between macroscopic continuum damage evolution and collective evolution behavior of microscopic pits and cracks, which can be used to describe the multi-scale corrosion fatigue process of steel. As a case study, the model is used to predict continuum damage evolution and number density of the corrosion pit and short crack of steel component in 5% NaCl water under constant stress amplitude at 20 kHz, and the numerical results are compared with experimental results. It shows that the model is effective and can be used to evaluate the continuum macroscopic corrosion fatigue damage and study microscopic corrosion fatigue mechanisms of steel.

Probing multi-scale mechanical damage in connective tissues using X-ray diffraction.

PubMed

Bianchi, Fabio; Hofmann, Felix; Smith, Andrew J; Thompson, Mark S

2016-11-01

The accumulation of microstructural collagen damage following repetitive loading is linked to painful and debilitating tendon injuries. As a hierarchical, semi-crystalline material, collagen mechanics can be studied using X-ray diffraction. The aim of the study was to describe multi-structural changes in tendon collagen following controlled plastic damage (5% permanent strain). We used small angle X-ray scattering (SAXS) to interrogate the spacing of collagen molecules within a fibril, and wide angle X-ray scattering (WAXS) to measure molecular strains under macroscopic loading. Simultaneous recordings of SAXS and WAXS patterns, together with whole-tissue strain in physiologically hydrated rat-tail tendons were made during increments of in situ tensile loading. Results showed that while tissue level modulus was unchanged, fibril modulus decreased significantly, and molecular modulus significantly increased. Further, analysis of higher order SAXS peaks suggested structural changes in the gap and overlap regions, possibly localising the damage to molecular cross-links. Our results provide new insight into the fundamental damage processes at work in collagenous tissues and point to new directions for their mitigation and repair. This article reports the first in situ loading synchrotron studies on mechanical damage in collagenous tissues. We provide new insight into the nano- and micro-structural mechanisms of damage processes. Pre-damaged tendons showed differential alteration of moduli at macro, micro and nano-scales as measured using X-ray scattering techniques. Detailed analysis of higher order diffraction peaks suggested damage is localised to molecular cross-links. The results are consistent with previous X-ray scattering studies of tendons and also with recent thermal stability studies on damaged material. Detailed understanding of damage mechanisms is essential in the development of new therapies promoting tissue repair. Copyright © 2016 Acta Materialia Inc

A damage mechanics based general purpose interface/contact element

NASA Astrophysics Data System (ADS)

Yan, Chengyong

Most of the microelectronics packaging structures consist of layered substrates connected with bonding materials, such as solder or epoxy. Predicting the thermomechanical behavior of these multilayered structures is a challenging task in electronic packaging engineering. In a layered structure the most complex part is always the interfaces between the strates. Simulating the thermo-mechanical behavior of such interfaces, is the main theme of this dissertation. The most commonly used solder material, Pb-Sn alloy, has a very low melting temperature 180sp°C, so that the material demonstrates a highly viscous behavior. And, creep usually dominates the failure mechanism. Hence, the theory of viscoplasticity is adapted to describe the constitutive behavior. In a multilayered assembly each layer has a different coefficient of thermal expansion. Under thermal cycling, due to heat dissipated from circuits, interfaces and interconnects experience low cycle fatigue. Presently, the state-of-the art damage mechanics model used for fatigue life predictions is based on Kachanov (1986) continuum damage model. This model uses plastic strain as a damage criterion. Since plastic strain is a stress path dependent value, the criterion does not yield unique damage values for the same state of stress. In this dissertation a new damage evolution equation based on the second law of thermodynamic is proposed. The new criterion is based on the entropy of the system and it yields unique damage values for all stress paths to the final state of stress. In the electronics industry, there is a strong desire to develop fatigue free interconnections. The proposed interface/contact element can also simulate the behavior of the fatigue free Z-direction thin film interconnections as well as traditional layered interconnects. The proposed interface element can simulate behavior of a bonded interface or unbonded sliding interface, also called contact element. The proposed element was verified against

Edaravone attenuates brain damage in rats after acute CO poisoning through inhibiting apoptosis and oxidative stress.

PubMed

Li, Qin; Bi, Ming Jun; Bi, Wei Kang; Kang, Hai; Yan, Le Jing; Guo, Yun-Liang

2016-03-01

Acute carbon monoxide (CO) poisoning is the most common cause of death from poisoning all over the world and may result in neuropathologic and neurophysiologic changes. Acute brain damage and delayed encephalopathy are the most serious complication, yet their pathogenesis is poorly understood. The present study aimed to evaluate the neuroprotective effects of Edaravone against apoptosis and oxidative stress after acute CO poisoning. The rat model of CO poisoning was established in a hyperbaric oxygen chamber by exposed to CO. Ultrastructure changes were observed by transmission electron microscopy (TEM). TUNEL stain was used to assess apoptosis. Immunohistochemistry and immunofluorescence double stain were used to evaluate the expression levels of heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf-2) protein and their relationship. By dynamically monitored the carboxyhemoglobin (HbCO) level in blood, we successfully established rat model of severe CO poisoning. Ultrastructure changes, including chromatin condensation, cytoplasm dissolution, vacuoles formation, nucleus membrane and cell organelles decomposition, could be observed after CO poisoning. Edaravone could improve the ultrastructure damage. CO poisoning could induce apoptosis. Apoptotic cells were widely distributed in cortex, striatum and hippocampus. Edaravone treatment attenuated neuronal apoptosis as compared with the poisoning group (P < 0.01). Basal expressions of HO-1 and Nrf-2 proteins were found in normal brain tissue. CO poisoning could activate HO-1/Nrf-2 pathway, start oxidative stress response. After the administration of Edaravone, the expression of HO-1 and Nrf-2 significantly increased (P < 0.01). These findings suggest that Edaravone may inhibit apoptosis, activate the Keapl-Nrf/ARE pathway, and thus improve the ultrastructure damage and neurophysiologic changes following acute CO poisoning. © 2014 Wiley Periodicals, Inc.

Zalypsis has in vitro activity in acute myeloid blasts and leukemic progenitor cells through the induction of a DNA damage response

PubMed Central

Colado, Enrique; Paíno, Teresa; Maiso, Patricia; Ocio, Enrique M.; Chen, Xi; Álvarez-Fernández, Stela; Gutiérrez, Norma C.; Martín-Sánchez, Jesús; Flores-Montero, Juan; San Segundo, Laura; Garayoa, Mercedes; Fernández-Lázaro, Diego; Vidriales, Maria-Belen; Galmarini, Carlos M.; Avilés, Pablo; Cuevas, Carmen; Pandiella, Atanasio; San-Miguel, Jesús F.

2011-01-01

Background Although the majority of patients with acute myeloid leukemia initially respond to conventional chemotherapy, relapse is still the leading cause of death, probably because of the presence of leukemic stem cells that are insensitive to current therapies. We investigated the antileukemic activity and mechanism of action of zalypsis, a novel alkaloid of marine origin. Design and Methods The activity of zalypsis was studied in four acute myeloid leukemia cell lines and in freshly isolated blasts taken from patients with acute myeloid leukemia before they started therapy. Zalypsis-induced apoptosis of both malignant and normal cells was measured using flow cytometry techniques. Gene expression profiling and western blot studies were performed to assess the mechanism of action of the alkaloid. Results Zalypsis showed a very potent antileukemic activity in all the cell lines tested and potentiated the effect of conventional antileukemic drugs such as cytarabine, fludarabine and daunorubicin. Interestingly, zalypsis showed remarkable ex vivo potency, including activity against the most immature blast cells (CD34+ CD38− Lin−) which include leukemic stem cells. Zalypsis-induced apoptosis was the result of an important deregulation of genes involved in the recognition of double-strand DNA breaks, such as Fanconi anemia genes and BRCA1, but also genes implicated in the repair of double-strand DNA breaks, such as RAD51 and RAD54. These gene findings were confirmed by an increase in several proteins involved in the pathway (pCHK1, pCHK2 and pH2AX). Conclusions The potent and selective antileukemic effect of zalypsis on DNA damage response mechanisms observed in acute myeloid leukemia cell lines and in patients’ samples provides the rationale for the investigation of this compound in clinical trials. PMID:21330323

Mechanisms of mutagenesis: DNA replication in the presence of DNA damage.

PubMed

Liu, Binyan; Xue, Qizhen; Tang, Yong; Cao, Jia; Guengerich, F Peter; Zhang, Huidong

2016-01-01

Environmental mutagens cause DNA damage that disturbs replication and produces mutations, leading to cancer and other diseases. We discuss mechanisms of mutagenesis resulting from DNA damage, from the level of DNA replication by a single polymerase to the complex DNA replisome of some typical model organisms (including bacteriophage T7, T4, Sulfolobus solfataricus, Escherichia coli, yeast and human). For a single DNA polymerase, DNA damage can affect replication in three major ways: reducing replication fidelity, causing frameshift mutations, and blocking replication. For the DNA replisome, protein interactions and the functions of accessory proteins can yield rather different results even with a single DNA polymerase. The mechanism of mutation during replication performed by the DNA replisome is a long-standing question. Using new methods and techniques, the replisomes of certain organisms and human cell extracts can now be investigated with regard to the bypass of DNA damage. In this review, we consider the molecular mechanism of mutagenesis resulting from DNA damage in replication at the levels of single DNA polymerases and complex DNA replisomes, including translesion DNA synthesis. Copyright © 2016 Elsevier B.V. All rights reserved.

Acute pulmonary allograft rejection. Mechanisms, diagnosis, and management.

PubMed

King-Biggs, M B

1997-06-01

Rejection is a common complication following lung transplantation, and can lead to considerable short- and long-term morbidity. As numbers and survival rates of lung transplant recipients increase, it is apparent that acute rejection can occur months or years after transplantation, and may be resistant to standard therapies. Mechanisms of acute rejection have been well studied in other solid organ transplant recipients, and are beginning to be addressed in the lung recipient. This article addresses some of the common issues of diagnosis and management of acute rejection which arise frequently during the care of lung transplant recipients.

Metyrapone prevents acute glucose hypermetabolism and short-term brain damage induced by intrahippocampal administration of 4-aminopyridine in rats.

PubMed

García-García, Luis; Fernández de la Rosa, Rubén; Delgado, Mercedes; Silván, Ágata; Bascuñana, Pablo; Bankstahl, Jens P; Gomez, Francisca; Pozo, Miguel A

2018-02-01

Intracerebral administration of the potassium channel blocker 4-aminopyridine (4-AP) triggers neuronal depolarization and intense acute seizure activity followed by neuronal damage. We have recently shown that, in the lithium-pilocarpine rat model of status epilepticus (SE), a single administration of metyrapone, an inhibitor of the 11β-hydroxylase enzyme, had protective properties of preventive nature against signs of brain damage and neuroinflammation. Herein, our aim was to investigate to which extent, pretreatment with metyrapone (150 mg/kg, i.p.) was also able to prevent eventual changes in the acute brain metabolism and short-term neuronal damage induced by intrahippocampal injection of 4-AP (7 μg/5 μl). To this end, regional brain metabolism was assessed by 2-deoxy-2-[ 18 F]fluoro-d-glucose ([ 18 F]FDG) positron emission tomography (PET) during the ictal period. Three days later, markers of neuronal death and hippocampal integrity and apoptosis (Nissl staining, NeuN and active caspase-3 immunohistochemistry), neurodegeneration (Fluoro-Jade C labeling), astrogliosis (glial fibrillary acidic protein (GFAP) immunohistochemistry) and microglia-mediated neuroinflammation (in vitro [ 18 F]GE180 autoradiography) were evaluated. 4-AP administration acutely triggered marked brain hypermetabolism within and around the site of injection as well as short-term signs of brain damage and inflammation. Most important, metyrapone pretreatment was able to reduce ictal hypermetabolism as well as all the markers of brain damage except microglia-mediated neuroinflammation. Overall, our study corroborates the neuroprotective effects of metyrapone against multiple signs of brain damage caused by seizures triggered by 4-AP. Ultimately, our data add up to the consistent protective effect of metyrapone pretreatment reported in other models of neurological disorders of different etiology. Copyright © 2017 Elsevier Ltd. All rights reserved.

A Coupled Thermal–Hydrological–Mechanical Damage Model and Its Numerical Simulations of Damage Evolution in APSE

PubMed Central

Wei, Chenhui; Zhu, Wancheng; Chen, Shikuo; Ranjith, Pathegama Gamage

2016-01-01

This paper proposes a coupled thermal–hydrological–mechanical damage (THMD) model for the failure process of rock, in which coupling effects such as thermally induced rock deformation, water flow-induced thermal convection, and rock deformation-induced water flow are considered. The damage is considered to be the key factor that controls the THM coupling process and the heterogeneity of rock is characterized by the Weibull distribution. Next, numerical simulations on excavation-induced damage zones in Äspö pillar stability experiments (APSE) are carried out and the impact of in situ stress conditions on damage zone distribution is analysed. Then, further numerical simulations of damage evolution at the heating stage in APSE are carried out. The impacts of in situ stress state, swelling pressure and water pressure on damage evolution at the heating stage are simulated and analysed, respectively. The simulation results indicate that (1) the v-shaped notch at the sidewall of the pillar is predominantly controlled by the in situ stress trends and magnitude; (2) at the heating stage, the existence of confining pressure can suppress the occurrence of damage, including shear damage and tensile damage; and (3) the presence of water flow and water pressure can promote the occurrence of damage, especially shear damage. PMID:28774001

Biological Signatures of Brain Damage Associated with High Serum Ferritin Levels in Patients with Acute Ischemic Stroke and Thrombolytic Treatment

PubMed Central

Millán, Mónica; Sobrino, Tomás; Arenillas, Juan Francisco; Rodríguez-Yáñez, Manuel; García, María; Nombela, Florentino; Castellanos, Mar; de la Ossa, Natalia Pérez; Cuadras, Patricia; Serena, Joaquín; Castillo, José; Dávalos, Antoni

2008-01-01

Background and purpose: Increased body iron stores have been related to greater oxidative stress and brain injury in clinical and experimental cerebral ischemia and reperfusion. We aimed to investigate the biological signatures of excitotoxicity, inflammation and blood brain barrier disruption potentially associated with high serum ferritin levels-related damage in acute stroke patients treated with i.v. t-PA. Methods: Serum levels of ferritin (as index of increased cellular iron stores), glutamate, interleukin-6, matrix metalloproteinase-9 and cellular fibronectin were determined in 134 patients treated with i.v. t-PA within 3 hours from stroke onset in blood samples obtained before t-PA treatment, at 24 and 72 hours. Results: Serum ferritin levels before t-PA infusion correlated to glutamate (r = 0.59, p < 0.001) and interleukin-6 (r = 0.55, p <0.001) levels at baseline, and with glutamate (r = 0.57,p <0.001), interleukin-6 (r = 0.49,p <0.001), metalloproteinase-9 (r = 0.23, p = 0.007) and cellular fibronectin (r = 0.27, p = 0.002) levels measured at 24 hours and glutamate (r = 0.415, p < 0.001), interleukin-6 (r = 0.359, p < 0.001) and metalloproteinase-9 (r = 0.261, p = 0.004) at 72 hours. The association between ferritin and glutamate levels remained after adjustment for confounding factors in generalized linear models. Conclusions: Brain damage associated with increased iron stores in acute ischemic stroke patients treated with iv. tPA may be mediated by mechanisms linked to excitotoxic damage. The role of inflammation, blood brain barrier disruption and oxidative stress in this condition needs further research. PMID:19096131

Modeling the roles of damage accumulation and mechanical healing on rainfall-induced landslides

NASA Astrophysics Data System (ADS)

Fan, Linfeng; Lehmann, Peter; Or, Dani

2014-05-01

The abrupt release of rainfall-induced shallow landslides is preceded by local failures that may abruptly coalesce and form a continuous failure plane within a hillslope. The mechanical status of hillslopes reflects a competition between the extent of severity of accumulated local damage during prior rainfall events and the rates of mechanically healing (i.e. regaining of strength) by closure of micro-cracks, regrowth of roots, etc. The interplay of these processes affects the initial conditions for landslide modeling and shapes potential failure patterns during future rainfall events. We incorporated these competing mechanical processes in a hydro-mechanical landslide triggering model subjected to a sequence of rainfall scenarios. The model employs the Fiber Bundle Model (FBM) with bonds (fiber bundle) with prescribed threshold linking adjacent soil columns and soil to bedrock. Prior damage was represented by a fraction of broken fibers during previous rainfall events, and the healing of broken fibers was described by strength regaining models for soil and roots at different characteristic time scales. Results show that prior damage and healing introduce highly nonlinear response to landslide triggering. For small prior damage, mechanical bonds at soil-bedrock interface may fail early in next rainfall event but lead to small perturbations onto lateral bonds without triggering a landslide. For more severe damage weakening lateral bonds, excess load due to failure at soil-bedrock interface accumulates at downslope soil columns resulting in early soil failure with patterns strongly correlated with prior damage distribution. Increasing prior damage over the hillslope decreases the volume of first landslide and prolongs the time needed to trigger the second landslide due to mechanical relaxation of the system. The mechanical healing of fibers diminishes effects of prior damage on the time of failure, and shortens waiting time between the first and second landslides

Beyond debuttressing: Mechanics of paraglacial rock slope damage during repeat glacial cycles

NASA Astrophysics Data System (ADS)

Grämiger, Lorenz M.; Moore, Jeffrey R.; Gischig, Valentin S.; Ivy-Ochs, Susan; Loew, Simon

2017-04-01

Cycles of glaciation impose mechanical stresses on underlying bedrock as glaciers advance, erode, and retreat. Fracture initiation and propagation constitute rock mass damage and act as preparatory factors for slope failures; however, the mechanics of paraglacial rock slope damage remain poorly characterized. Using conceptual numerical models closely based on the Aletsch Glacier region of Switzerland, we explore how in situ stress changes associated with fluctuating ice thickness can drive progressive rock mass failure preparing future slope instabilities. Our simulations reveal that glacial cycles as purely mechanical loading and unloading phenomena produce relatively limited new damage. However, ice fluctuations can increase the criticality of fractures in adjacent slopes, which may in turn increase the efficacy of fatigue processes. Bedrock erosion during glaciation promotes significant new damage during first deglaciation. An already weakened rock slope is more susceptible to damage from glacier loading and unloading and may fail completely. We find that damage kinematics are controlled by discontinuity geometry and the relative position of the glacier; ice advance and retreat both generate damage. We correlate model results with mapped landslides around the Great Aletsch Glacier. Our result that most damage occurs during first deglaciation agrees with the relative age of the majority of identified landslides. The kinematics and dimensions of a slope failure produced in our models are also in good agreement with characteristics of instabilities observed in the field. Our results extend simplified assumptions of glacial debuttressing, demonstrating in detail how cycles of ice loading, erosion, and unloading drive paraglacial rock slope damage.

Acutely damaged axons are remyelinated in multiple sclerosis and experimental models of demyelination.

PubMed

Schultz, Verena; van der Meer, Franziska; Wrzos, Claudia; Scheidt, Uta; Bahn, Erik; Stadelmann, Christine; Brück, Wolfgang; Junker, Andreas

2017-08-01

Remyelination is in the center of new therapies for the treatment of multiple sclerosis to resolve and improve disease symptoms and protect axons from further damage. Although remyelination is considered beneficial in the long term, it is not known, whether this is also the case early in lesion formation. Additionally, the precise timing of acute axonal damage and remyelination has not been assessed so far. To shed light onto the interrelation between axons and the myelin sheath during de- and remyelination, we employed cuprizone- and focal lysolecithin-induced demyelination and performed time course experiments assessing the evolution of early and late stage remyelination and axonal damage. We observed damaged axons with signs of remyelination after cuprizone diet cessation and lysolecithin injection. Similar observations were made in early multiple sclerosis lesions. To assess the correlation of remyelination and axonal damage in multiple sclerosis lesions, we took advantage of a cohort of patients with early and late stage remyelinated lesions and assessed the number of APP- and SMI32- positive damaged axons and the density of SMI31-positive and silver impregnated preserved axons. Early de- and remyelinating lesions did not differ with respect to axonal density and axonal damage, but we observed a lower axonal density in late stage demyelinated multiple sclerosis lesions than in remyelinated multiple sclerosis lesions. Our findings suggest that remyelination may not only be protective over a long period of time, but may play an important role in the immediate axonal recuperation after a demyelinating insult. © 2017 The Authors GLIA Published by Wiley Periodicals, Inc.

Distinct effects of acute and chronic sleep loss on DNA damage in rats.

PubMed

Andersen, M L; Ribeiro, D A; Bergamaschi, C T; Alvarenga, T A; Silva, A; Zager, A; Campos, R R; Tufik, S

2009-04-30

The aim of this investigation was to evaluate genetic damage induced in male rats by experimental sleep loss for short-term (24 and 96 h) and long-term (21 days) intervals, as well as their respective recovery periods in peripheral blood, brain, liver and heart tissue by the single cell gel (comet) assay. Rats were paradoxically deprived of sleep (PSD) by the platform technique for 24 or 96 h, or chronically sleep-restricted (SR) for 21 days. We also sought to verify the time course of their recovery after 24 h of rebound sleep. The results showed DNA damage in blood cells of rats submitted to PSD for 96 h. Brain tissue showed extensive genotoxic damage in PSD rats (both 24 and 96 h), though the effect was more pronounced in the 96 h group. Rats allowed to recover from the PSD-96 h and SR-21 days treatments showed DNA damage as compared to negative controls. Liver and heart did not display any genotoxicity activity. Corticosterone concentrations were increased after PSD (24 and 96 h) relative to control rats, whereas these levels were unaffected in the SR group. Collectively, these findings reveal that sleep loss was able to induce genetic damage in blood and brain cells, especially following acute exposure. Since DNA damage is an important step in events leading to genomic instability, this study represents a relevant contribution to the understanding of the potential health risks associated with sleep deprivation.

Effects of hydromechanical loading history and antecedent soil mechanical damage on shallow landslide triggering

NASA Astrophysics Data System (ADS)

Fan, Linfeng; Lehmann, Peter; Or, Dani

2015-10-01

Evidence suggests that the sudden triggering of rainfall-induced shallow landslides is preceded by accumulation of local internal failures in the soil mantle before their abrupt coalescence into a landslide failure plane. The mechanical status of a hillslope at any given time reflects competition between local damage accumulated during antecedent rainfall events and rates of mechanical healing (e.g., rebonding of microcracks and root regrowth). This dynamic interplay between damage accumulation and healing rates determines the initial mechanical state for landslide modeling. We evaluated the roles of these dynamic processes on landslide characteristics and patterns using a hydromechanical landslide-triggering model for a sequence of rainfall scenarios. The progressive nature of soil failure was represented by the fiber bundle model formalism that considers threshold strength of mechanical bonds linking adjacent soil columns and bedrock. The antecedent damage induced by prior rainfall events was expressed by the fraction of broken fibers that gradually regain strength or mechanically heal at rates specific to soil and roots. Results indicate that antecedent damage accelerates landslide initiation relative to pristine (undamaged) hillslopes. The volumes of first triggered landslides increase with increasing antecedent damage; however, for heavily damaged hillslopes, landslide volumes tend to decrease. Elapsed time between rainfall events allows mechanical healing that reduces the effects of antecedent damage. This study proposed a quantitative framework for systematically incorporating hydromechanical loading history and information on precursor events (e.g., such as recorded by acoustic emissions) into shallow landslide hazard assessment.

Necroptosis may be a novel mechanism for cardiomyocyte death in acute myocarditis.

PubMed

Zhou, Fei; Jiang, Xuejun; Teng, Lin; Yang, Jun; Ding, Jiawang; He, Chao

2018-05-01

In this study, we investigated the roles of RIP1/RIP3 mediated cardiomyocyte necroptosis in CVB3-induced acute myocarditis. Serum concentrations of creatinine kinase (CK), CK-MB, and cardiac troponin I were detected using a Hitachi Automatic Biochemical Analyzer in a mouse model of acute VMC. Histological changes in cardiac tissue were observed by light microscope and expression levels of RIP1/RIP3 in the cardiac tissue were detected via Western blot and immunohistochemistry. The data showed that RIP1/RIP3 was highly expressed in cardiomyocytes in the acute VMC mouse model and that the necroptosis pathway specific blocker, Nec-1, dramatically reduced the myocardial damage by downregulating the expression of RIP1/RIP3. These findings provide evidence that necroptosis plays a significant role in cardiomyocyte death and it is a major pathway for cell death in acute VMC. Blocking the necroptosis pathway may serve as a new therapeutic option for the treatment of acute viral myocarditis.

A damage mechanics based approach to structural deterioration and reliability

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

Bhattcharya, B.; Ellingwood, B.

1998-02-01

Structural deterioration often occurs without perceptible manifestation. Continuum damage mechanics defines structural damage in terms of the material microstructure, and relates the damage variable to the macroscopic strength or stiffness of the structure. This enables one to predict the state of damage prior to the initiation of a macroscopic flaw, and allows one to estimate residual strength/service life of an existing structure. The accumulation of damage is a dissipative process that is governed by the laws of thermodynamics. Partial differential equations for damage growth in terms of the Helmholtz free energy are derived from fundamental thermodynamical conditions. Closed-form solutions tomore » the equations are obtained under uniaxial loading for ductile deformation damage as a function of plastic strain, for creep damage as a function of time, and for fatigue damage as function of number of cycles. The proposed damage growth model is extended into the stochastic domain by considering fluctuations in the free energy, and closed-form solutions of the resulting stochastic differential equation are obtained in each of the three cases mentioned above. A reliability analysis of a ring-stiffened cylindrical steel shell subjected to corrosion, accidental pressure, and temperature is performed.« less

Cutaneous exposure to lewisite causes acute kidney injury by invoking DNA damage and autophagic response.

PubMed

Srivastava, Ritesh K; Traylor, Amie M; Li, Changzhao; Feng, Wenguang; Guo, Lingling; Antony, Veena B; Schoeb, Trenton R; Agarwal, Anupam; Athar, Mohammad

2018-06-01

Lewisite (2-chlorovinyldichloroarsine) is an organic arsenical chemical warfare agent that was developed and weaponized during World Wars I/II. Stockpiles of lewisite still exist in many parts of the world and pose potential environmental and human health threat. Exposure to lewisite and similar chemicals causes intense cutaneous inflammatory response. However, morbidity and mortality in the exposed population is not only the result of cutaneous damage but is also a result of systemic injury. Here, we provide data delineating the pathogenesis of acute kidney injury (AKI) following cutaneous exposure to lewisite and its analog phenylarsine oxide (PAO) in a murine model. Both agents caused renal tubular injury, characterized by loss of brush border in proximal tubules and tubular cell apoptosis accompanied by increases in serum creatinine, neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1. Interestingly, lewisite exposure enhanced production of reactive oxygen species (ROS) in the kidney and resulted in the activation of autophagic and DNA damage response (DDR) signaling pathways with increased expression of beclin-1, autophagy-related gene 7, and LC-3A/B-II and increased phosphorylation of γ-H 2 A.X and checkpoint kinase 1/2, respectively. Terminal deoxyribonucleotide-transferase-mediated dUTP nick-end labeling-positive cells were detected in renal tubules along with enhanced proapoptotic BAX/cleaved caspase-3 and reduced antiapoptotic BCL 2 . Scavenging ROS by cutaneous postexposure application of the antioxidant N-acetyl-l-cysteine reduced lewisite-induced autophagy and DNA damage. In summary, we provide evidence that topical exposure to lewisite causes AKI. The molecular mechanism underlying these changes involves ROS-dependent activation of autophagy and DDR pathway associated with the induction of apoptosis.

Navy Enhanced Sierra Mechanics (NESM): Toolbox for predicting Navy shock and damage

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

Moyer, Thomas; Stergiou, Jonathan; Reese, Garth

Here, the US Navy is developing a new suite of computational mechanics tools (Navy Enhanced Sierra Mechanics) for the prediction of ship response, damage, and shock environments transmitted to vital systems during threat weapon encounters. NESM includes fully coupled Euler-Lagrange solvers tailored to ship shock/damage predictions. NESM is optimized to support high-performance computing architectures, providing the physics-based ship response/threat weapon damage predictions needed to support the design and assessment of highly survivable ships. NESM is being employed to support current Navy ship design and acquisition programs while being further developed for future Navy fleet needs.

Navy Enhanced Sierra Mechanics (NESM): Toolbox for predicting Navy shock and damage

DOE PAGES

Moyer, Thomas; Stergiou, Jonathan; Reese, Garth; ...

2016-05-25

Here, the US Navy is developing a new suite of computational mechanics tools (Navy Enhanced Sierra Mechanics) for the prediction of ship response, damage, and shock environments transmitted to vital systems during threat weapon encounters. NESM includes fully coupled Euler-Lagrange solvers tailored to ship shock/damage predictions. NESM is optimized to support high-performance computing architectures, providing the physics-based ship response/threat weapon damage predictions needed to support the design and assessment of highly survivable ships. NESM is being employed to support current Navy ship design and acquisition programs while being further developed for future Navy fleet needs.

Mechanisms of acute myocardial infarction study (MAMIS).

PubMed

Singh, Ram B; Pella, Daniel; Neki, Nirankar S; Chandel, J P; Rastogi, Saurabh; Mori, Heideki; Otsuka, Kuniaki; Gupta, Pankaj

2004-10-01

Acute myocardial infarction (AMI) is a highly dynamic event, which is associated with marked neuroendocrinological dysfunction in addition to cardiac damage. The immediate trigger for AMI is not precisely known. Studies conducted by Lown, Braunwald, Halberg, Otsuka and our group have demonstrated a marked increase in sympathetic activity, oxidative stress, and magnesium and potassium deficiency during AMI. Clinical studies have reported an increased incidence of AMI, sudden death and ischemia during first quarter of the day when there is a rapid withdrawal of vagal activity and increase in sympathetic tone. In one case-control study of 202 patients with AMI, there was a significant (P < 0.02) increase in cardiac events in the second quarter of the day compared to other quarters, respectively (16.8%, 41.0%, 13.8%, 28.2% per quarter). This characteristic remained prevalent in both men and women and among patients with and without known AMI (n = 52), diabetes (n = 53) or hypertension (n = 75). Triggers of AMI were noted among 162 (82.2%) of the patients. Neuropsychological mechanisms were observed as follows: emotional stress (45.5%), sleep deprivation (27.7%), cold climate (29.2%), hot climate (24.7%), large meals (47.5%) and physical exertion (31.2%). These triggering factors are known to enhance sympathetic activity and decrease vagal tone, resulting in an increased secretion of plasma cortisol, noradrenaline, aldosterone, angiotension-converting enzyme (ACE), interleukin (IL)-1, -2, -6, -18, and tumor necrosis factor-alpha (TNF-alpha), all of which are are proinflammatory agents. There is also a deficiency in the serum levels of vitamin A, E, and C and magnesium, potassium, melatonin, and IL-10 (an anti-inflammatory agent). In our study, we found a decrease in magnesium, potassium, vitamin A, E, C and beta carotene combined with an increase in thiobarbituric acid-reactive substances (TBARS), MDA and diene conjugates, TNF-alpha and IL-6, all of which are indicators

Lightning Strike Induced Damage Mechanisms of Carbon Fiber Composites

NASA Astrophysics Data System (ADS)

Kawakami, Hirohide

Composite materials have a wide application in aerospace, automotive, and other transportation industries, because of the superior structural and weight performances. Since carbon fiber reinforced polymer composites possess a much lower electrical conductivity as compared to traditional metallic materials utilized for aircraft structures, serious concern about damage resistance/tolerance against lightning has been rising. Main task of this study is to clarify the lightning damage mechanism of carbon fiber reinforced epoxy polymer composites to help further development of lightning strike protection. The research on lightning damage to carbon fiber reinforced polymer composites is quite challenging, and there has been little study available until now. In order to tackle this issue, building block approach was employed. The research was started with the development of supporting technologies such as a current impulse generator to simulate a lightning strike in a laboratory. Then, fundamental electrical properties and fracture behavior of CFRPs exposed to high and low level current impulse were investigated using simple coupon specimens, followed by extensive parametric investigations in terms of different prepreg materials frequently used in aerospace industry, various stacking sequences, different lightning intensity, and lightning current waveforms. It revealed that the thermal resistance capability of polymer matrix was one of the most influential parameters on lightning damage resistance of CFRPs. Based on the experimental findings, the semi-empirical analysis model for predicting the extent of lightning damage was established. The model was fitted through experimental data to determine empirical parameters and, then, showed a good capability to provide reliable predictions for other test conditions and materials. Finally, structural element level lightning tests were performed to explore more practical situations. Specifically, filled-hole CFRP plates and patch

Chemical characteristics of normal, woolly apple aphid-damaged, and mechanically damaged twigs of six apple cultivars, measured in autumn wood.

PubMed

Zhou, Hong-Xu; Wang, Xi-Cun; Yu, Yi; Tan, Xiu-Mei; Cheng, Zai-Quan; Zhang, An-Sheng; Men, Xing-Yuan; Li-Li, Li

2013-04-01

Chemical characteristics of normal, woolly apple aphid-damaged, and mechanically damaged twigs of six apple cultivars: Red Fuji, Golden Delicious, Qinguan, Zhaojin 108, Starkrimson, and Red General, were examined in autumn wood to provide abetter understanding of factors related to cultivar resistance to the woolly apple aphid, Eriosoma lanigerum (Hausmann). Chemical measures examined included soluble sugars, soluble proteins and amino acids, total phenolics, and polyphenol oxidase (that enhances the resistance of plants to insects) and superoxide dismutase, peroxidase, and catalase (that degrade waste products in plants). Soluble sugar, protein, and amino acid contents in normal (undamaged) twigs of Red Fuji, aphid-susceptible cultivar, were higher than in mechanically damaged and aphid-damaged twigs. Total phenolic compounds, an important group of defensive compounds against aphids, increased by 30.5 and 6.0% in mechanically damaged twigs of Qinguan and Zhaojin 108, respectively, and decreased by 21.7 and 16.1% in aphid-damaged twigs of Red Fuji and Red General, respectively. Compared with normal twigs, in aphid-damaged twigs, superoxide dismutase, peroxidase, and polyphenol activity all decreased in Red Fuji. The resistance of some apple cultivars to woolly apple aphid during the growth of autumn shoots was related to several of the physiological indices we monitored. The thin epidermis of callus tissue over healed wounds showed increased susceptibility to the attack by woolly apple aphid. Apple cultivar Qinguan with the highest level of resistance to woolly apple aphid in autumn had increased in amino acid, total phenolic compound levels, and enzyme activity after aphid feeding.

Personalizing mechanical ventilation for acute respiratory distress syndrome.

PubMed

Berngard, S Clark; Beitler, Jeremy R; Malhotra, Atul

2016-03-01

Lung-protective ventilation with low tidal volumes remains the cornerstone for treating patient with acute respiratory distress syndrome (ARDS). Personalizing such an approach to each patient's unique physiology may improve outcomes further. Many factors should be considered when mechanically ventilating a critically ill patient with ARDS. Estimations of transpulmonary pressures as well as individual's hemodynamics and respiratory mechanics should influence PEEP decisions as well as response to therapy (recruitability). This summary will emphasize the potential role of personalized therapy in mechanical ventilation.

Role of damage control enterostomy in management of children with peritonitis from acute intestinal disease.

PubMed

Ameh, Emmanuel A; Ayeni, Michael A; Kache, Stephen A; Mshelbwala, Philip M

2013-01-01

Intestinal anastomosis in severely ill children with peritonitis from intestinal perforation, intestinal gangrene or anastomotic dehiscence (acute intestinal disease) is associated with high morbidity and mortality. Enterostomy as a damage control measure may be an option to minimize the high morbidity and mortality. This report evaluates the role of damage control enterostomy in the treatment of these patients. A retrospective review of 52 children with acute intestinal disease who had enterostomy as a damage control measure in 12 years. There were 34 (65.4%) boys and 18 (34.6%) girls aged 3 days-13 years (median 9 months), comprising 27 (51.9%) neonates and infants and 25 (48.1%) older children. The primary indication for enterostomy in neonates and infants was intestinal gangrene 25 (92.6%) and perforated typhoid ileitis 22 (88%) in older children. Enterostomy was performed as the initial surgery in 33 (63.5%) patients and as a salvage procedure following anastomotic dehiscence in 19 (36.5%) patients. Enterostomy-related complications occurred in 19 (36.5%) patients, including 11 (21.2%) patients with skin excoriations and eight (15.4%) with hypokalaemia. There were four (7.7%) deaths (aged 19 days, 3 months, 3½ years and 10 years, respectively) directly related to the enterostomy, from hypokalaemia at 4, 12, 20 and 28 days postoperatively, respectively. Twenty other patients died shortly after surgery from their primary disease. Twenty of 28 surviving patients have had their enterostomy closed without complications, while eight are awaiting enterostomy closure. Damage-control enterostomy is useful in management of severely ill children with intestinal perforation or gangrene. Careful and meticulous attention to fluid and electrolyte balance, and stoma care, especially in the first several days following surgery, are important in preventing morbidity and mortality.

Laser-Induced Thermal-Mechanical Damage Characteristics of Cleartran Multispectral Zinc Sulfide with Temperature-Dependent Properties

NASA Astrophysics Data System (ADS)

Peng, Yajing; Jiang, Yanxue; Yang, Yanqiang

2015-01-01

Laser-induced thermal-mechanical damage characteristics of window materials are the focus problems in laser weapon and anti-radiation reinforcement technology. Thermal-mechanical effects and damage characteristics are investigated for cleartran multispectral zinc sulfide (ZnS) thin film window materials irradiated by continuous laser using three-dimensional (3D) thermal-mechanical model. Some temperature-dependent parameters are introduced into the model. The temporal-spatial distributions of temperature and thermal stress are exhibited. The damage mechanism is analyzed. The influences of temperature effect of material parameters and laser intensity on the development of thermal stress and the damage characteristics are examined. The results show, the von Mises equivalent stress along the thickness direction is fluctuant, which originates from the transformation of principal stresses from compressive stress to tensile stress with the increase of depth from irradiated surface. The damage originates from the thermal stress but not the melting. The thermal stress is increased and the damage is accelerated by introducing the temperature effect of parameters or the increasing laser intensity.

Acute and timing effects of beta-hydroxy-beta-methylbutyrate (HMB) on indirect markers of skeletal muscle damage.

PubMed

Wilson, Jacob M; Kim, Jeong-Su; Lee, Sang-Rok; Rathmacher, John A; Dalmau, Brett; Kingsley, J Derek; Koch, Heather; Manninen, Anssi H; Saadat, Raz; Panton, Lynn B

2009-02-04

While chronic β-Hydroxy β-Methylbutyrate (HMB) supplementation (≥ 2 wk) lowers exercise induced muscle damage, its acute or timing effects have not been examined. The purpose of this study was to investigate the acute and timing effects of oral HMB supplementation on serum creatine kinase (CK), lactate dehydrogenase (LDH), muscle soreness, and maximal voluntary contraction (MVC). Sixteen non-resistance trained men (22 ± 2 yrs) were assigned to HMB-Pre or HMB-Post groups. In a crossover design, all subjects performed 55 maximal eccentric knee extension/flexion contractions on 2 occasions on either the right or left leg. HMB-Pre (N = 8) randomly received 3 grams of either a placebo or HMB before and a placebo after exercise. HMB-Post (N = 8) received a placebo before and either 3 grams of HMB or a placebo after exercise. Muscle damage tests were recorded before, at 8, 24, 48, and 72 hrs post exercise. There was a reduction in MVC and an increase in soreness in the quadriceps and hamstrings following exercise (p < 0.001). Although HMB-Pre approached significance in attenuating soreness for the quadriceps (p = 0.07), there was no time x group effect. Serum indices of damage increased, peaking at 48 hrs for CK (773%) (p < 0.001) and 72 hrs for LDH (180%) (p < 0.001). While there were no time x group effects of HMB on CK and LDH, post hoc analysis revealed that only HMB-Pre showed no significant increase in LDH levels following exercise. Our findings suggest no clear acute or timing effects of HMB supplementation. However, consuming HMB before exercise appeared to prevent increases in LDH.

Acute and timing effects of beta-hydroxy-beta-methylbutyrate (HMB) on indirect markers of skeletal muscle damage

PubMed Central

Wilson, Jacob M; Kim, Jeong-su; Lee, Sang-rok; Rathmacher, John A; Dalmau, Brett; Kingsley, J Derek; Koch, Heather; Manninen, Anssi H; Saadat, Raz; Panton, Lynn B

2009-01-01

Background While chronic β-Hydroxy β-Methylbutyrate (HMB) supplementation (≥ 2 wk) lowers exercise induced muscle damage, its acute or timing effects have not been examined. The purpose of this study was to investigate the acute and timing effects of oral HMB supplementation on serum creatine kinase (CK), lactate dehydrogenase (LDH), muscle soreness, and maximal voluntary contraction (MVC). Methods Sixteen non-resistance trained men (22 ± 2 yrs) were assigned to HMB-Pre or HMB-Post groups. In a crossover design, all subjects performed 55 maximal eccentric knee extension/flexion contractions on 2 occasions on either the right or left leg. HMB-Pre (N = 8) randomly received 3 grams of either a placebo or HMB before and a placebo after exercise. HMB-Post (N = 8) received a placebo before and either 3 grams of HMB or a placebo after exercise. Muscle damage tests were recorded before, at 8, 24, 48, and 72 hrs post exercise. Results There was a reduction in MVC and an increase in soreness in the quadriceps and hamstrings following exercise (p < 0.001). Although HMB-Pre approached significance in attenuating soreness for the quadriceps (p = 0.07), there was no time × group effect. Serum indices of damage increased, peaking at 48 hrs for CK (773%) (p < 0.001) and 72 hrs for LDH (180%) (p < 0.001). While there were no time × group effects of HMB on CK and LDH, post hoc analysis revealed that only HMB-Pre showed no significant increase in LDH levels following exercise. Conclusion Our findings suggest no clear acute or timing effects of HMB supplementation. However, consuming HMB before exercise appeared to prevent increases in LDH. PMID:19193206

[Importance of mechanical assist devices in acute circulatory arrest].

PubMed

Ferrari, Markus Wolfgang

2016-03-01

Mechanical assist devices are indicated for hemodynamic stabilization in acute circulatory arrest if conventional means of cardiopulmonary resuscitation are unable to re-establish adequate organ perfusion. Their temporary use facilitates further diagnostic and therapeutic options in selected patients, e.g. coronary angiography followed by revascularization.External thorax compression devices allow sufficient cardiac massage in case of preclinical or in-hospital circulatory arrest, especially under complex transfer conditions. These devices perform standardized thorax compressions at a rate of 80-100 per minute. Invasive mechanical support devices are used in the catheter laboratory or in the intensive care unit. Axial turbine pumps, e.g. the Impella, continuously pump blood from the left ventricle into the aortic root. The Impella can also provide right ventricle support by pumping blood from the vena cava into the pulmonary artery. So-called emergency systems or ECMO devices consist of a centrifugal pump and a membrane oxygenator allowing complete takeover of cardiac and pulmonary functions. Withdrawing blood from the right atrium and vena cava, oxygenated blood is returned to the abdominal aorta. Isolated centrifugal pumps provide left heart support without an oxygenator after transseptal insertion of a venous cannula into the left atrium.Mechanical assist devices are indicated for acute organ protection and hemodynamic stabilization for diagnostic and therapeutic measures as well as bridge to myocardial recovery. Future technical developments and better insights into the pathophysiology of mechanical circulatory support will broaden the spectrum of indications of such devices in acute circulatory arrest.

Brain damage resembling acute necrotizing encephalopathy as a specific manifestation of haemophagocytic lymphohistiocytosis - induced by hypersensitivity.

PubMed

Dai, Dongling; Wen, Feiqiu; Liu, Sixi; Zhou, Shaoming

2016-08-31

Both haemophagocytic lymphohistiocytosis and acute necrotizing encephalopathy are life-threatening condition. It presents major diagnostic difficulties, since it may have a diversity in clinical picture and with many conditions leading to the same clinical presentation. So it is key important to understand the disorders. We report a pediatric case of haemophagocytic lymphohistiocytosis with specific presentation which predominantly featured as acute necrotizing encephalopathy of childhood. We discuss the diagnosis and differential diagnosis, and speculate the etiology of haemophagocytic lymphohistiocytosis is due to hypersensitivity. Haemophagocytic lymphohistiocytosis and brain damage in this case may be induced by hypersensitivity, which have good clinical outcome if diagnosed and treated early.

DNA damage in an animal model of maple syrup urine disease.

PubMed

Scaini, Giselli; Jeremias, Isabela C; Morais, Meline O S; Borges, Gabriela D; Munhoz, Bruna P; Leffa, Daniela D; Andrade, Vanessa M; Schuck, Patrícia F; Ferreira, Gustavo C; Streck, Emilio L

2012-06-01

Maple syrup urine disease is an inborn error of metabolism caused by a severe deficiency of the branched chain alpha-ketoacid dehydrogenase complex. Neurological dysfunction is a common finding in patients with maple syrup urine disease. However, the mechanisms underlying the neuropathology of brain damage in this disorder are poorly understood. In this study, we investigated whether acute or chronic administration of a branched chain amino acid pool (leucine, isoleucine and valine) causes transient DNA damage, as determined by the alkaline comet assay, in the brain and blood of rats during development and whether antioxidant treatment prevented the alterations induced by branched chain amino acids. Our results showed that the acute administration of branched chain amino acids increased the DNA damage frequency and damage index in the hippocampus. However, the chronic administration of branched chain amino acids increased the DNA damage frequency and damage index in both the hippocampus and the striatum, and the antioxidant treatment was able to prevent DNA damage in the hippocampus and striatum. The present study demonstrated that metabolite accumulation in MSUD induces DNA damage in the hippocampus and striatum and that it may be implicated in the neuropathology observed in the affected patients. We demonstrated that the effect of antioxidant treatment (N-acetylcysteine plus deferoxamine) prevented DNA damage, suggesting the involvement of oxidative stress in DNA damage. Copyright © 2012 Elsevier Inc. All rights reserved.

Protective effect of Carica papaya L leaf extract against alcohol induced acute gastric damage and blood oxidative stress in rats.

PubMed

Indran, M; Mahmood, A A; Kuppusamy, U R

2008-09-01

The effects of Carica papaya leaf (CPL) aqueous extract on alcohol induced acute gastric damage and the immediate blood oxidative stress level were studied in rats. The results showed that gastric ulcer index was significantly reduced in rats pretreated with CPL extract as compared with alcohol treated controls. The in vitro studies using 2,2-Diphenyl-1-Picryl-Hydrazyl (DPPH) assay showed strong antioxidant nature of CPL extract. Biochemical analysis indicated that the acute alcohol induced damage is reflected in the alterations of blood oxidative indices and CPL extract offered some protection with reduction in plasma lipid peroxidation level and increased erythrocyte glutathione peroxidase activity. Carica papaya leaf may potentially serve as a good therapeutic agent for protection against gastric ulcer and oxidative stress.

Erythrocyte membrane fluidity and indices of plasmatic oxidative damage after acute physical exercise in humans.

PubMed

Berzosa, C; Gómez-Trullén, E M; Piedrafita, E; Cebrián, I; Martínez-Ballarín, E; Miana-Mena, F J; Fuentes-Broto, L; García, J J

2011-06-01

Optimal levels of membrane fluidity are essential for numerous cell functions including cell growth, solute transport and signal transduction. Since exercise enhances free radical production, our aim was to evaluate in healthy male subjects the effects of an acute bout of maximal and submaximal exercise on the erythrocyte membrane fluidity and its possible relation to the oxidative damage overproduction due to exercise. Subjects (n = 34) performed three cycloergometric tests: a continuous progressive exercise, a strenuous exercise until exhaustion and an acute bout of exercise at an intensity corresponding to 70% of maximal work capacity for 30 min. Venous blood samples were collected before and immediately after these exercises. Erythrocyte membrane fluidity was assessed by fluorescence spectroscopy. Plasma malondialdehyde (MDA) and 4-hydroxyalkenals (4-HDA) concentrations and carbonyl content of plasmatic proteins were used as an index of lipid and protein oxidation, respectively. Exercise produced a dramatic drop in the erythrocyte membrane fluidity as compared to resting time, but this was not accompanied by significant changes in the plasmatic MDA and 4-HDA concentrations. The highest erythrocyte membrane rigidity was detected immediately after strenuous exercise until exhaustion was performed. Protein carbonyl levels were higher after exhaustive exercises than at rest. Continuous progressive and strenuous exercises until exhaustion, but not submaximal workload, resulted in a significant enhanced accumulation of carbonylated proteins in the plasma. These findings are consistent with the idea that exercise exaggerates oxidative damage, which may contribute, at least partially, to explain the rigidity in the membrane of the erythrocytes due to acute exercise.

3D Progressive Damage Modeling for Laminated Composite Based on Crack Band Theory and Continuum Damage Mechanics

NASA Technical Reports Server (NTRS)

Wang, John T.; Pineda, Evan J.; Ranatunga, Vipul; Smeltzer, Stanley S.

2015-01-01

A simple continuum damage mechanics (CDM) based 3D progressive damage analysis (PDA) tool for laminated composites was developed and implemented as a user defined material subroutine to link with a commercially available explicit finite element code. This PDA tool uses linear lamina properties from standard tests, predicts damage initiation with an easy-to-implement Hashin-Rotem failure criteria, and in the damage evolution phase, evaluates the degradation of material properties based on the crack band theory and traction-separation cohesive laws. It follows Matzenmiller et al.'s formulation to incorporate the degrading material properties into the damaged stiffness matrix. Since nonlinear shear and matrix stress-strain relations are not implemented, correction factors are used for slowing the reduction of the damaged shear stiffness terms to reflect the effect of these nonlinearities on the laminate strength predictions. This CDM based PDA tool is implemented as a user defined material (VUMAT) to link with the Abaqus/Explicit code. Strength predictions obtained, using this VUMAT, are correlated with test data for a set of notched specimens under tension and compression loads.

Jinhong Tablet Reduces Damage of Intestinal Mucosal Barrier in Rats with Acute Biliary Infection via Bcl-2/Bax mRNA and Protein Regulation

PubMed Central

Wang, YongQi; Xie, Jinkun; Zhang, Xuelin; Gu, Honggang

2017-01-01

Objective To explore the effects and mechanism of Jinhong Tablet on intestinal mucosal barrier function and SIRS in rats with acute biliary infection. Methods 36 SD male rats were divided into three groups: sham operation (control), acute biliary infection (ABI) model, and Jinhong Tablet (Jinhong) group. Jinhong group were force-fed with Jinhong Tablet, while the other two groups received oral saline. At days 3 and 5, morphological changes of intestinal mucosa were assessed. Serum diamine oxidase (DAO), D-lactate, and endotoxin levels were measured. And the genes bcl-2 and bax in intestinal tissues were tested by real-time PCR and Western blotting. Results Intestinal damage was significantly less severe in Jinhong group compared with ABI group, as indicated by Chiu's scoring, TUNEL analysis, and serum DAO, D-lactic acid, and endotoxin levels. Additionally, the expression of bax mRNA and protein was decreased and the ratio of bcl-2/bax mRNA and protein was increased compared with ABI group. Conclusion Jinhong Tablet had a positive intervention on acute biliary infection through improving inflammation and intestinal mucosal barrier, inhibiting excessive apoptosis of intestinal epithelial cells via bax and bcl-2 gene, and protein regulation. PMID:29234407

Renoprotective effects of combined endothelin-converting enzyme/neutral endopeptidase inhibitor SLV338 in acute and chronic experimental renal damage.

PubMed

Sharkovska, Yuliya; Kalk, Philipp; von Websky, Karoline; Relle, Katharina; Pfab, Thiemo; Alter, Markus; Fischer, Yvan; Hocher, Berthold

2011-01-01

Acute kidney injury (AKI) as well as chronic renal failure are associated with a huge mortality/morbidity. However, so far no drugs have been approved for the treatment of acute kidney failure and only a few for the treatment of chronic kidney disease (CKD). We analysed the effect of SLV338, a neutral endopeptidase (NEP)/endothelin converting enzyme (ECE)-inhibitor in animal models of acute kidney failure as well as chronic renal failure. Acute renal failure was induced in male Wistar rats by uninephrectomy and clamping of the remaining kidney for 55 minutes. SLV338 (total dose: 4.9 mg/kg) or vehicle was continuously infused for 2 hours (starting 20 minutes prior to clamping). Sham operated animals served as controls. Plasma creatinine was measured at baseline and day 2 and 8 after renal ischemia-reperfusion. Hypertensive renal damage was induced in male Sprague Dawley rats by nitric oxide deficiency using L-NAME (50 mg/kg per day, added to drinking water for 4 weeks). One group was treated over the same time period with SLV338 (30 mg/kg per day, mixed with food). Systolic blood pressure was monitored weekly. At study end, urine and blood samples were collected and kidneys were harvested. Acute renal ischemia-reperfusion caused a 5-fold plasma creatinine elevation (day 2), which was significantly attenuated by more than 50% in animals treated with SLV338 (p < 0.05). Renal failure was accompanied by a 67% mortality in vehicle-treated rats, but only 20% after SLV338 treatment (p = 0.03 compared to sham controls). Chronic L-NAME administration caused hypertension, urinary albumin excretion, glomerulosclerosis, renal arterial remodelling, and renal interstitial fibrosis. Treatment with SLV338 did not significantly affect blood pressure, but abolished renal tissue damage (interstitial fibrosis, glomerulosclerosis, renal arterial remodelling (p < 0.05 versus L-NAME group in each case). The dual ECE/NEP inhibitor SLV338 preserves kidney function and reduces mortality in

Hematopoietic Acute Radiation Syndrome (Bone marrow syndrome, Aplastic Anemia): Molecular Mechanisms of Radiation Toxicity.

NASA Astrophysics Data System (ADS)

Popov, Dmitri

Key Words: Aplastic Anemia (AA), Pluripotential Stem Cells (PSC) Introduction: Aplastic Anemia (AA) is a disorder of the pluripotential stem cells involve a decrease in the number of cells of myeloid, erythroid and megakaryotic lineage [Segel et al. 2000 ]. The etiology of AA include idiopathic cases and secondary aplastic anemia after exposure to drugs, toxins, chemicals, viral infections, lympho-proliferative diseases, radiation, genetic causes, myelodisplastic syndromes and hypoplastic anemias, thymomas, lymphomas. [Brodskyet al. 2005.,Modan et al. 1975., Szklo et al. 1975]. Hematopoietic Acute Radiation Syndrome (or Bone marrow syndrome, or Radiation-Acquired Aplastic Anemia) is the acute toxic syndrome which usually occurs with a dose of irradiation between 0.7 and 10 Gy (70- 1000 rads), depending on the species irradiated. [Waselenko et al., 2004]. The etiology of bone morrow damage from high-level radiation exposure results depends on the radiosensitivity of certain bone marrow cell lines. [Waselenko et al. 2004] Aplastic anemia after radiation exposure is a clinical syndrome that results from a marked disorder of bone marrow blood cell production. [Waselenko et al. 2004] Radiation hematotoxicity is mediated via genotoxic and other specific toxic mechanisms, leading to aplasia, cell apoptosis or necrosis, initiation via genetic mechanisms of clonal disorders, in cases such as the acute radiation-acquired form of AA. AA results from radiation injury to pluripotential and multipotential stem cells in the bone marrow. The clinical signs displayed in reticulocytopenia, anemia, granulocytopenia, monocytopenia, and thrombocytopenia. The number of marrow CD34+ cells (multipotential hematopoietic progenitors) and their derivative colony-forming unit{granulocyte-macrophage (CFU-GM) and burst forming unit {erythroid (BFU{E) are reduced markedly in patients with AA. [Guinan 2011, Brodski et al. 2005, Beutler et al.,2000] Cells expressing CD34 (CD34+ cell) are normally

Coexistence of hyperlipidemia and acute cerebral ischemia/reperfusion induces severe liver damage in a rat model

PubMed Central

Gong, Wei-Hong; Zheng, Wen-Xia; Wang, Jun; Chen, Shi-Hui; Pang, Bo; Hu, Xia-Min; Cao, Xiao-Lu

2012-01-01

AIM: To investigate the correlation of hyperlipemia (HL) and acute cerebral ischemia/reperfusion (I/R) injury on liver damage and its mechanism. METHODS: Rats were divided into 4 groups: control, HL, I/R and HL+I/R. After the induction of HL via a high-fat diet for 18 wk, middle cerebral artery occlusion was followed by 24 h of reperfusion to capture I/R. Serum alanine transaminase (ALT) and aspartate aminotransferase (AST) were analyzed as part of liver function tests and liver damage was further assessed by histological examination. Hepatocyte apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. The expression of genes related to apoptosis (caspase-3, bcl-2) was assayed by immunohistochemistry and Western blotting. Serum tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1) and liver mitochondrial superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA) and Ca2+ levels were measured to determine inflammatory and oxidative/antioxidative status respectively. Microsomal hydroxylase activity of the cytochrome P450 2E1 (CYP2E1)-containing enzyme was measured with aniline as the substrate, and CYP2E1 expression in the liver tissue and microsome was determined by immunohistochemistry and Western blotting respectively. RESULTS: HL alone induced by high-fat diet for 18 wk resulted in liver damage, indicated by histopathological analysis, and a considerable increase in serum ALT (25.13 ± 16.90 vs 9.56 ± 1.99, P < 0.01) and AST levels (18.01 ± 10.00 vs 11.33 ± 4.17, P < 0.05) compared with control. Moreover, HL alone induced hepatocyte apoptosis, which was determined by increased TUNEL-positive cells (4.47 ± 0.45 vs 1.5 ± 0.22, P < 0.01), higher caspase-3 and lower bcl-2 expression. Interestingly, compared with those in control, HL or I/R groups, massive increases of serum ALT (93.62 ± 24.00 vs 9.56 ± 1.99, 25.13 ± 16.90 or 12.93 ± 6.14, P < 0.01) and AST (82.32 ± 26.92 vs 11.33 ± 4

Continuum theory of fibrous tissue damage mechanics using bond kinetics: application to cartilage tissue engineering.

PubMed

Nims, Robert J; Durney, Krista M; Cigan, Alexander D; Dusséaux, Antoine; Hung, Clark T; Ateshian, Gerard A

2016-02-06

This study presents a damage mechanics framework that employs observable state variables to describe damage in isotropic or anisotropic fibrous tissues. In this mixture theory framework, damage is tracked by the mass fraction of bonds that have broken. Anisotropic damage is subsumed in the assumption that multiple bond species may coexist in a material, each having its own damage behaviour. This approach recovers the classical damage mechanics formulation for isotropic materials, but does not appeal to a tensorial damage measure for anisotropic materials. In contrast with the classical approach, the use of observable state variables for damage allows direct comparison of model predictions to experimental damage measures, such as biochemical assays or Raman spectroscopy. Investigations of damage in discrete fibre distributions demonstrate that the resilience to damage increases with the number of fibre bundles; idealizing fibrous tissues using continuous fibre distribution models precludes the modelling of damage. This damage framework was used to test and validate the hypothesis that growth of cartilage constructs can lead to damage of the synthesized collagen matrix due to excessive swelling caused by synthesized glycosaminoglycans. Therefore, alternative strategies must be implemented in tissue engineering studies to prevent collagen damage during the growth process.

Acute respiratory failure requiring mechanical ventilation in severe chronic obstructive pulmonary disease (COPD)

PubMed Central

Gadre, Shruti K.; Duggal, Abhijit; Mireles-Cabodevila, Eduardo; Krishnan, Sudhir; Wang, Xiao-Feng; Zell, Katrina; Guzman, Jorge

2018-01-01

Abstract There are limited data on the epidemiology of acute respiratory failure necessitating mechanical ventilation in patients with severe chronic obstructive pulmonary disease (COPD). The prognosis of acute respiratory failure requiring invasive mechanical ventilation is believed to be grim in this population. The purpose of this study was to illustrate the epidemiologic characteristics and outcomes of patients with underlying severe COPD requiring mechanical ventilation. A retrospective study of patients admitted to a quaternary referral medical intensive care unit (ICU) between January 2008 and December 2012 with a diagnosis of severe COPD and requiring invasive mechanical ventilation for acute respiratory failure. We evaluated 670 patients with an established diagnosis of severe COPD requiring mechanical ventilation for acute respiratory failure of whom 47% were male with a mean age of 63.7 ± 12.4 years and Acute physiology and chronic health evaluation (APACHE) III score of 76.3 ± 27.2. Only seventy-nine (12%) were admitted with a COPD exacerbation, 27(4%) had acute respiratory distress syndrome (ARDS), 78 (12%) had pneumonia, 78 (12%) had sepsis, and 312 (47%) had other causes of respiratory failure, including pulmonary embolism, pneumothorax, etc. Eighteen percent of the patients received a trial of noninvasive positive pressure ventilation. The median duration of mechanical ventilation was 3 days (interquartile range IQR 2–7); the median duration for ICU length of stay (LOS) was 5 (IQR 2–9) days and the median duration of hospital LOS was 12 (IQR 7–22) days. The overall ICU mortality was 25%. Patients with COPD exacerbation had a shorter median duration of mechanical ventilation (2 vs 4 days; P = .04), ICU (3 vs 5 days; P = .01), and hospital stay (10 vs 13 days; P = .01). The ICU mortality (9% vs 27%; P < .001), and the hospital mortality (17% vs 32%; P = .004) for mechanically ventilated patients with an acute

Acute respiratory failure requiring mechanical ventilation in severe chronic obstructive pulmonary disease (COPD).

PubMed

Gadre, Shruti K; Duggal, Abhijit; Mireles-Cabodevila, Eduardo; Krishnan, Sudhir; Wang, Xiao-Feng; Zell, Katrina; Guzman, Jorge

2018-04-01

There are limited data on the epidemiology of acute respiratory failure necessitating mechanical ventilation in patients with severe chronic obstructive pulmonary disease (COPD). The prognosis of acute respiratory failure requiring invasive mechanical ventilation is believed to be grim in this population. The purpose of this study was to illustrate the epidemiologic characteristics and outcomes of patients with underlying severe COPD requiring mechanical ventilation.A retrospective study of patients admitted to a quaternary referral medical intensive care unit (ICU) between January 2008 and December 2012 with a diagnosis of severe COPD and requiring invasive mechanical ventilation for acute respiratory failure.We evaluated 670 patients with an established diagnosis of severe COPD requiring mechanical ventilation for acute respiratory failure of whom 47% were male with a mean age of 63.7 ± 12.4 years and Acute physiology and chronic health evaluation (APACHE) III score of 76.3 ± 27.2. Only seventy-nine (12%) were admitted with a COPD exacerbation, 27(4%) had acute respiratory distress syndrome (ARDS), 78 (12%) had pneumonia, 78 (12%) had sepsis, and 312 (47%) had other causes of respiratory failure, including pulmonary embolism, pneumothorax, etc. Eighteen percent of the patients received a trial of noninvasive positive pressure ventilation. The median duration of mechanical ventilation was 3 days (interquartile range IQR 2-7); the median duration for ICU length of stay (LOS) was 5 (IQR 2-9) days and the median duration of hospital LOS was 12 (IQR 7-22) days. The overall ICU mortality was 25%. Patients with COPD exacerbation had a shorter median duration of mechanical ventilation (2 vs 4 days; P = .04), ICU (3 vs 5 days; P = .01), and hospital stay (10 vs 13 days; P = .01). The ICU mortality (9% vs 27%; P < .001), and the hospital mortality (17% vs 32%; P = .004) for mechanically ventilated patients with an acute exacerbation of severe

Monitoring of pulmonary mechanics in acute respiratory distress syndrome to titrate therapy.

PubMed

Gattinoni, Luciano; Eleonora, Carlesso; Caironi, Pietro

2005-06-01

This paper reviews recent findings regarding the respiratory mechanics during acute respiratory distress syndrome as a tool for tailoring its ventilatory management. The pressure-volume curve has been used for many years as a descriptor of the respiratory mechanics in patients affected by acute respiratory distress syndrome. The use of the sigmoidal equation introduced by Venegas for the analysis of the pressure-volume curve seems to be the most rigorous mathematical approach to assessing lung mechanics. Increasing attention has been focused on the deflation limb for titration of positive end-expiratory pressure. Based on physiologic reasoning, a novel parameter, the stress index, has been proposed for tailoring a safe mechanical ventilation, although its clinical impact has still to be proved. Evidence has confirmed that a variety of underlying pathologies may lead to acute respiratory distress syndrome, making unrealistic any attempt to unify the ventilatory approach. Although extensively proposed to tailor mechanical ventilation during acute respiratory distress syndrome, there is no evidence that the pressure-volume curve may be useful in setting a lung-protective strategy in the presence of different potentials for recruitment. The Venegas approach should be the standard analysis of pressure-volume curves. In any patient, the potential for recruitment should be assessed, as a basis for tailoring the most effective mechanical ventilation. Further studies are needed to clarify the potential use of the pressure-volume curve to guide a lung-protective ventilatory strategy.

Anisotropic constitutive model incorporating multiple damage mechanisms for multiscale simulation of dental enamel.

PubMed

Ma, Songyun; Scheider, Ingo; Bargmann, Swantje

2016-09-01

An anisotropic constitutive model is proposed in the framework of finite deformation to capture several damage mechanisms occurring in the microstructure of dental enamel, a hierarchical bio-composite. It provides the basis for a homogenization approach for an efficient multiscale (in this case: multiple hierarchy levels) investigation of the deformation and damage behavior. The influence of tension-compression asymmetry and fiber-matrix interaction on the nonlinear deformation behavior of dental enamel is studied by 3D micromechanical simulations under different loading conditions and fiber lengths. The complex deformation behavior and the characteristics and interaction of three damage mechanisms in the damage process of enamel are well captured. The proposed constitutive model incorporating anisotropic damage is applied to the first hierarchical level of dental enamel and validated by experimental results. The effect of the fiber orientation on the damage behavior and compressive strength is studied by comparing micro-pillar experiments of dental enamel at the first hierarchical level in multiple directions of fiber orientation. A very good agreement between computational and experimental results is found for the damage evolution process of dental enamel. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

[Myocardial mechanical injury in acute ischemia: a pathophysiologic and histopathologic review].

PubMed

Rossi, L; Matturri, L

1986-03-01

The recognition of histopathologic substrates of myocardial contractile damage in human acute ischemia is still very poor, notwithstanding the impressive advances in the inherent clinical diagnostic technology and concepts. The first and foremost inotropic abnormality ensuing ischemia, easily taken for atonic in origin, actually consists of a pathologic contracture of the injured myocardium, depending upon abrupt fall of ATP, and defective extrusion calcium pump with persistence of actomyosin rigor-complexes. In sustained ischemia, further membrane damage exposes the myocell to massive calcium intrusion, with eventual precipitation of it and cell death (reperfusion stone-heart). In case of transient, "hit and run" ischemia, the "stunned" myocardium undergoes prolonged contractile abnormalities. In keeping with fundamentals in pathophysiology of contraction, ischemic myofibrils in human hyperacute infarct, showed spare I bands, accounting for contracture and followed by loss of the regular cross-striation register; then, groups of adjacent sarcomeres were seen to join into true "contraction" bands, with Z lines impinging upon A bands and obliterating the I bands. Coagulative denaturation of contractile proteins follows, presenting as irregular, amorphous degeneration stripes astride irreversibly damaged myocells. As such, these cells can be passively overstretched by the nearby functioning muscle. In turn, the fixed waviness of viable, acutely ischemic myocardium was thought to configure, histologically, the loss of ATP-dependent "plasticity" of myofilaments, in a state of contracture. The "relaxant effect" of inotropic-chronotropic-positive catecholamines, favoring diastole, has been also pointed out. The present microscopic findings are cogent to clinicopathologic problems of coronary ischemia-reperfusion, and sudden death from cardiogenic shock.

Independent mechanisms recruit the cohesin loader protein NIPBL to sites of DNA damage.

PubMed

Bot, Christopher; Pfeiffer, Annika; Giordano, Fosco; Manjeera, Dharani E; Dantuma, Nico P; Ström, Lena

2017-03-15

NIPBL is required to load the cohesin complex on to DNA. While the canonical role of cohesin is to couple replicated sister chromatids together until the onset of mitosis, it also promotes tolerance to DNA damage. Here, we show that NIPBL is recruited to DNA damage throughout the cell cycle via independent mechanisms, influenced by type of damage. First, the heterochromatin protein HP1γ (also known as CBX3) recruits NIPBL to DNA double-strand breaks (DSBs) through the corresponding HP1-binding motif within the N-terminus. By contrast, the C-terminal HEAT repeat domain is unable to recruit NIPBL to DSBs but independently targets NIPBL to laser microirradiation-induced DNA damage. Each mechanism is dependent on the RNF8 and RNF168 ubiquitylation pathway, while the recruitment of the HEAT repeat domain requires further ATM or ATR activity. Thus, NIPBL has evolved a sophisticated response to damaged DNA that is influenced by the form of damage, suggesting a highly dynamic role for NIPBL in maintaining genomic stability. © 2017. Published by The Company of Biologists Ltd.

Inelastic Deformation of Metal Matrix Composites. Part 1; Plasticity and Damage Mechanisms

NASA Technical Reports Server (NTRS)

Majumdar, B. S.; Newaz, G. M.

1992-01-01

The deformation mechanisms of a Ti 15-3/SCS6 (SiC fiber) metal matrix composite (MMC) were investigated using a combination of mechanical measurements and microstructural analysis. The objectives were to evaluate the contributions of plasticity and damage to the overall inelastic response, and to confirm the mechanisms by rigorous microstructural evaluations. The results of room temperature experiments performed on 0 degree and 90 degree systems primarily are reported in this report. Results of experiments performed on other laminate systems and at high temperatures will be provided in a forthcoming report. Inelastic deformation of the 0 degree MMC (fibers parallel to load direction) was dominated by the plasticity of the matrix. In contrast, inelastic deformations of the 90 degree composite (fibers perpendicular to loading direction) occurred by both damage and plasticity. The predictions of a continuum elastic plastic model were compared with experimental data. The model was adequate for predicting the 0 degree response; however, it was inadequate for predicting the 90 degree response largely because it neglected damage. The importance of validating constitutive models using a combination of mechanical measurements and microstructural analysis is pointed out. The deformation mechanisms, and the likely sequence of events associated with the inelastic deformation of MMCs, are indicated in this paper.

Blocking NMDA receptors delays death in rats with acute liver failure by dual protective mechanisms in kidney and brain.

PubMed

Cauli, Omar; González-Usano, Alba; Cabrera-Pastor, Andrea; Gimenez-Garzó, Carla; López-Larrubia, Pilar; Ruiz-Sauri, Amparo; Hernández-Rabaza, Vicente; Duszczyk, Malgorzata; Malek, Michal; Lazarewicz, Jerzy W; Carratalá, Arturo; Urios, Amparo; Miguel, Alfonso; Torregrosa, Isidro; Carda, Carmen; Montoliu, Carmina; Felipo, Vicente

2014-06-01

Treatment of patients with acute liver failure (ALF) is unsatisfactory and mortality remains unacceptably high. Blocking NMDA receptors delays or prevents death of rats with ALF. The underlying mechanisms remain unclear. Clarifying these mechanisms will help to design more efficient treatments to increase patient's survival. The aim of this work was to shed light on the mechanisms by which blocking NMDA receptors delays rat's death in ALF. ALF was induced by galactosamine injection. NMDA receptors were blocked by continuous MK-801 administration. Edema and cerebral blood flow were assessed by magnetic resonance. The time course of ammonia levels in brain, muscle, blood, and urine; of glutamine, lactate, and water content in brain; of glomerular filtration rate and kidney damage; and of hepatic encephalopathy (HE) and intracranial pressure was assessed. ALF reduces kidney glomerular filtration rate (GFR) as reflected by reduced inulin clearance. GFR reduction is due to both reduced renal perfusion and kidney tubular damage as reflected by increased Kim-1 in urine and histological analysis. Blocking NMDA receptors delays kidney damage, allowing transient increased GFR and ammonia elimination which delays hyperammonemia and associated changes in brain. Blocking NMDA receptors does not prevent cerebral edema or blood-brain barrier permeability but reduces or prevents changes in cerebral blood flow and brain lactate. The data show that dual protective effects of MK-801 in kidney and brain delay cerebral alterations, HE, intracranial pressure increase and death. NMDA receptors antagonists may increase survival of patients with ALF by providing additional time for liver transplantation or regeneration.

Prediction of Size Effects in Notched Laminates Using Continuum Damage Mechanics

NASA Technical Reports Server (NTRS)

Camanho, D. P.; Maimi, P.; Davila, C. G.

2007-01-01

This paper examines the use of a continuum damage model to predict strength and size effects in notched carbon-epoxy laminates. The effects of size and the development of a fracture process zone before final failure are identified in an experimental program. The continuum damage model is described and the resulting predictions of size effects are compared with alternative approaches: the point stress and the inherent flaw models, the Linear-Elastic Fracture Mechanics approach, and the strength of materials approach. The results indicate that the continuum damage model is the most accurate technique to predict size effects in composites. Furthermore, the continuum damage model does not require any calibration and it is applicable to general geometries and boundary conditions.

A new look on brain mechanisms of acute illness anorexia.

PubMed

Asarian, Lori; Langhans, Wolfgang

2010-07-14

Bacterial lipopolysaccharide (LPS) and other microbial substances trigger the organism's acute phase response and cause acute illness anorexia. Pro-inflammatory cytokines are major endogenous mediators of acute illness anorexia, but how LPS or cytokines stimulate the brain to inhibit eating is not fully resolved. One emerging mechanism involves the activation of the enzyme cyclooxygenase-2 (COX-2) in blood-brain barrier endothelial cells and the subsequent release of prostaglandin E2 (PGE2). Serotonin neurons in the midbrain raphe are targets of PGE2, and serotonergic projections from the midbrain raphe to the hypothalamus appear to be crucial for LPS anorexia. That is, raphe projections activate (1) the corticotrophin-releasing hormone neurons in the paraventricular nucleus which then elicit the stress response and (2) the pro-opiomelanocortin neurons in the arcuate nucleus which then release alphaMSH and elicit anorexia. Here we review available data to support a role for this brain mechanism in acute illness anorexia by center staging PGE2 signaling pathways that converge on central neural circuits that control normal eating. In addition, we review interactions between gonadal hormones and immune function that lead to sex differences in acute illness anorexia. The paper represents an invited review by a symposium, award winner or keynote speaker at the Society for the Study of Ingestive Behavior [SSIB] Annual Meeting in Portland, July 2009. 2010 Elsevier Inc. All rights reserved.

Molecular mechanisms of cisplatin cytotoxicity in acute promyelocytic leukemia cells.

PubMed

Kumar, Sanjay; Tchounwou, Paul B

2015-12-01

Cis-diamminedichloroplatinum (II) (cisplatin) is a widely used anti-tumor drug for the treatment of a broad range of human malignancies with successful therapeutic outcomes for head and neck, ovarian, and testicular cancers. It has been found to inhibit cell cycle progression and to induce oxidative stress and apoptosis in acute promyelocytic leukemia (APL) cells. However, its molecular mechanisms of cytotoxic action are poorly understood. We hypothesized that cisplatin induces cytotoxicity through DNA adduct formation, oxidative stress, transcriptional factors (p53 and AP-1), cell cycle regulation, stress signaling and apoptosis in APL cells. We used the APL cell line as a model, and applied a variety of molecular tools to elucidate the cytotoxic mode of action of cisplatin. We found that cisplatin inhibited cell proliferation by a cytotoxicity, characterized by DNA damage and modulation of oxidative stress. Cisplatin also activated p53 and phosphorylated activator protein (AP-1) component, c-Jun at serine (63, 73) residue simultaneously leading to cell cycle arrest through stimulation of p21 and down regulation of cyclins and cyclin dependent kinases in APL cell lines. It strongly activated the intrinsic pathway of apoptosis through alteration of the mitochondrial membrane potential, release of cytochrome C, and up-regulation of caspase 3 activity. It also down regulated the p38MAPK pathway. Overall, this study highlights the molecular mechanisms that underline cisplatin toxicity to APL cells, and provides insights into selection of novel targets and/or design of therapeutic agents to treat APL.

Continuum theory of fibrous tissue damage mechanics using bond kinetics: application to cartilage tissue engineering

PubMed Central

Nims, Robert J.; Durney, Krista M.; Cigan, Alexander D.; Hung, Clark T.; Ateshian, Gerard A.

2016-01-01

This study presents a damage mechanics framework that employs observable state variables to describe damage in isotropic or anisotropic fibrous tissues. In this mixture theory framework, damage is tracked by the mass fraction of bonds that have broken. Anisotropic damage is subsumed in the assumption that multiple bond species may coexist in a material, each having its own damage behaviour. This approach recovers the classical damage mechanics formulation for isotropic materials, but does not appeal to a tensorial damage measure for anisotropic materials. In contrast with the classical approach, the use of observable state variables for damage allows direct comparison of model predictions to experimental damage measures, such as biochemical assays or Raman spectroscopy. Investigations of damage in discrete fibre distributions demonstrate that the resilience to damage increases with the number of fibre bundles; idealizing fibrous tissues using continuous fibre distribution models precludes the modelling of damage. This damage framework was used to test and validate the hypothesis that growth of cartilage constructs can lead to damage of the synthesized collagen matrix due to excessive swelling caused by synthesized glycosaminoglycans. Therefore, alternative strategies must be implemented in tissue engineering studies to prevent collagen damage during the growth process. PMID:26855751

Acute Mitral Valve Dysfunction Due to Escape of Prosthetic Mechanical Leaflet and Peripheral Leaftlet Embolization.

PubMed

Calik, Eyup Serhat; Limandal, Husnu Kamil; Arslan, Umit; Tort, Mehmet; Yildiz, Ziya; Bayram, Ednan; Dag, Ozgur; Kaygin, Mehmet Ali; Erkut, Bilgehan

2015-12-14

Leaflet escape of prosthetic valve is rare but potentially life threatening. Early diagnosis is essential on account of avoiding mortality, and emergency surgical correction is compulsory. This complication has previously been reported for both monoleaflet and bileaflet valve models. A 30-year-old man who had undergone mitral valve replacement with a bileaflet valve 8 years prior at another center was admitted with acute-onset with cardiogenic shock as an emergency case. Transthoracic echocardiograms showed acute-starting severe mitral regurgitation associated with prosthetic mitral valve. There was a suspicious finding of a single prosthetic mitral leaflet. But the problem related with the valve wasn't specifically determined. The patient underwent emergent surgery for replacement of the damaged prosthetic valves immediately. There was no tissue impingement and thrombosis, one of the two leaflets was absent, and there were no signs of endocarditis or pannus formation in the prosthetic valve. The missing leaflet could not be found within the cardiac cavity. The abdominal fluoroscopic study and plain radiography were unable to detect the escaped leaflet during surgery. The damaged valve was removed and a replacement 29 mm bileaflet mechanical valve was inserted by right lateral thoracotomy. After post-operative week one, the abdominal computed tomography scan and the ultrasound showed the escaped leaflet in the left femoral artery. Fifteen days after the surgery the escaped leaflet was removed safely from the left femoral artery and the patient made a complete recovery. The escaped leaflet showed a fracture of one of the pivot systems caused by structural failure. Early cardiac surgery should be applied because of life-threatening problems.

Mechanical Damage Detection of Indonesia Local Citrus Based on Fluorescence Imaging

NASA Astrophysics Data System (ADS)

Siregar, T. H.; Ahmad, U.; Sutrisno; Maddu, A.

2018-05-01

Citrus experienced physical damage in peel will produce essential oils that contain polymethoxylated flavone. Polymethoxylated flavone is fluorescence substance; thus can be detected by fluorescence imaging. This study aims to study the fluorescence spectra characteristic and to determine the damage region in citrus peel based on fluorescence image. Pulung citrus from Batu district, East Java, as a famous citrus production area in Indonesia, was used in the experiment. It was observed that the image processing could detect the mechanical damage region. Fluorescence imaging can be used to classify the citrus into two categories, sound and defect citruses.

Targeting HDAC3, a new partner protein of AKT in the reversal of chemoresistance in acute myeloid leukemia via DNA damage response.

PubMed

Long, J; Fang, W Y; Chang, L; Gao, W H; Shen, Y; Jia, M Y; Zhang, Y X; Wang, Y; Dou, H B; Zhang, W J; Zhu, J; Liang, A B; Li, J M; Hu, Jiong

2017-12-01

Resistance to cytotoxic chemotherapy drugs remains as the major cause of treatment failure in acute myeloid leukemia. Histone deacetylases (HDAC) are important regulators to maintain chromatin structure and control DNA damage; nevertheless, how each HDAC regulates genome stability remains unclear, especially under genome stress conditions. Here, we identified a mechanism by which HDAC3 regulates DNA damage repair and mediates resistance to chemotherapy drugs. In addition to inducing DNA damage, chemotherapy drugs trigger upregulation of HDAC3 expression in leukemia cells. Using genetic and pharmacological approaches, we show that HDAC3 contributes to chemotherapy resistance by regulating the activation of AKT, a well-documented factor in drug resistance development. HDAC3 binds to AKT and deacetylates it at the site Lys20, thereby promoting the phosphorylation of AKT. Chemotherapy drug exposure enhances the interaction between HDAC3 and AKT, resulting in decrease in AKT acetylation and increase in AKT phosphorylation. Whereas HDAC3 depletion or inhibition abrogates these responses and meanwhile sensitizes leukemia cells to chemotoxicity-induced apoptosis. Importantly, in vivo HDAC3 suppression reduces leukemia progression and sensitizes MLL-AF9 + leukemia to chemotherapy. Our findings suggest that combination therapy with HDAC3 inhibitor and genotoxic agents may constitute a successful strategy for overcoming chemotherapy resistance.

Damage Tolerance and Mechanics of Interfaces in Nanostructured Metals

NASA Astrophysics Data System (ADS)

Foley, Daniel J.

The concept of interface driven properties in crystalline metals has been one of the most intensely discussed topics in materials science for decades. Since the 1980s researchers have been exploring the concept of grain boundary engineering as route for tuning properties such as fracture toughness and irradiation resistance. This is especially true in ultra-fine grained and nanocrystalline materials where grain boundary mediated properties become dominant. More recently, materials composed of hierarchical nanostructures, such as amorphous-crystalline nanolaminates, have attracted considerable attention due to their favorable properties, ease of manufacture and highly tunable microstructure. While both grain boundary engineering and hierarchical nanostructures have shown promise there are still questions remaining regarding the role of specific attributes of the microstructure (such as grain boundaries, grain/layer size and inter/intralayer morphology) in determining material properties. This thesis attempts to address these questions by using atomistic simulations to perform deformation and damage loading studies on a series of nanolaminate and bicrystalline structures. During the course of this thesis the roles of layer thickness, interlayer structure and interlayer chemistry on the mechanical properties of Ni-NiX amorphous-crystalline nanolaminates were explored using atomistic simulations. This thesis found that layer thickness/thickness ratio and amorphous layer chemistry play a crucial role in yield strength and Young's modulus. Analysis of the deformation mechanisms at the atomic scale revealed that structures containing single crystalline, crystalline layers undergo plastic deformation when shear transformation zones form in the amorphous layer and impinge on the amorphous-crystalline interface, leading to dislocation emission. However, structures containing nanocrystalline, crystalline layers (both equiaxed and columnar nanocrystalline) undergo plastic

Experimental verification of a progressive damage model for composite laminates based on continuum damage mechanics. M.S. Thesis Final Report

NASA Technical Reports Server (NTRS)

Coats, Timothy William

1994-01-01

Progressive failure is a crucial concern when using laminated composites in structural design. Therefore the ability to model damage and predict the life of laminated composites is vital. The purpose of this research was to experimentally verify the application of the continuum damage model, a progressive failure theory utilizing continuum damage mechanics, to a toughened material system. Damage due to tension-tension fatigue was documented for the IM7/5260 composite laminates. Crack density and delamination surface area were used to calculate matrix cracking and delamination internal state variables, respectively, to predict stiffness loss. A damage dependent finite element code qualitatively predicted trends in transverse matrix cracking, axial splits and local stress-strain distributions for notched quasi-isotropic laminates. The predictions were similar to the experimental data and it was concluded that the continuum damage model provided a good prediction of stiffness loss while qualitatively predicting damage growth in notched laminates.

Antioxidant and hepatoprotective effects of A. cerana honey against acute alcohol-induced liver damage in mice.

PubMed

Zhao, Haoan; Cheng, Ni; He, Liangliang; Peng, Guoxia; Xue, Xiaofeng; Wu, Liming; Cao, Wei

2017-11-01

A. cerana honey, gathered from Apis cerana Fabricius (A. cerana), has not been fully studied. Samples of honey originating from six geographical regions (mainly in the Qinling Mountains of China) were investigated to determine their antioxidant and hepatoprotective effects against acute alcohol-induced liver damage. The results showed that A. cerana honeys from the Qinling Mountains had high total phenolic contents (345.1-502.1mgGAkg -1 ), ascorbic acid contents (153.8-368.4mgkg -1 ), and strong antioxidant activities in DPPH radical scavenging activity assays (87.5-136.2IC50mgmL -1 ), ferric reducing antioxidant powers (191.8-317.4mgTroloxkg -1 ), and ferrous ion-chelating activities (27.5-35.5mgNa 2 EDTAkg -1 ). Pretreatment with A. cerana honey (Qinling Mountains) at 5, 10, or 20gkg -1 twice daily for 12weeks significantly inhibited serum lipoprotein oxidation and increased serum radical absorbance capacity (ORAC) (P<0.05). Moreover, A. cerana honey inhibited acute alcohol-induced increases in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum (P<0.05), reduced the production of hepatic malondialdehyde (MDA) (P<0.05), and promoted superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities (P<0.05). More importantly, it also remarkably inhibited the level of TGF-β1 in the serum and liver (P<0.05). The results of this study indicate that administration of A. cerana honey prevents acute alcohol-induced liver damage likely because of its antioxidant properties and ability to prevent oxidative stress. Copyright © 2017 Elsevier Ltd. All rights reserved.

DNA Repair Mechanisms and the Bypass of DNA Damage in Saccharomyces cerevisiae

PubMed Central

Boiteux, Serge; Jinks-Robertson, Sue

2013-01-01

DNA repair mechanisms are critical for maintaining the integrity of genomic DNA, and their loss is associated with cancer predisposition syndromes. Studies in Saccharomyces cerevisiae have played a central role in elucidating the highly conserved mechanisms that promote eukaryotic genome stability. This review will focus on repair mechanisms that involve excision of a single strand from duplex DNA with the intact, complementary strand serving as a template to fill the resulting gap. These mechanisms are of two general types: those that remove damage from DNA and those that repair errors made during DNA synthesis. The major DNA-damage repair pathways are base excision repair and nucleotide excision repair, which, in the most simple terms, are distinguished by the extent of single-strand DNA removed together with the lesion. Mistakes made by DNA polymerases are corrected by the mismatch repair pathway, which also corrects mismatches generated when single strands of non-identical duplexes are exchanged during homologous recombination. In addition to the true repair pathways, the postreplication repair pathway allows lesions or structural aberrations that block replicative DNA polymerases to be tolerated. There are two bypass mechanisms: an error-free mechanism that involves a switch to an undamaged template for synthesis past the lesion and an error-prone mechanism that utilizes specialized translesion synthesis DNA polymerases to directly synthesize DNA across the lesion. A high level of functional redundancy exists among the pathways that deal with lesions, which minimizes the detrimental effects of endogenous and exogenous DNA damage. PMID:23547164

Hygrothermal damage mechanisms in graphite-epoxy composites

NASA Technical Reports Server (NTRS)

Crossman, F. W.; Mauri, R. E.; Warren, W. J.

1979-01-01

T300/5209 and T300/5208 graphite epoxy laminates were studied experimentally and analytically in order to: (1) determine the coupling between applied stress, internal residual stress, and moisture sorption kinetics; (2) examine the microscopic damage mechanisms due to hygrothermal cycling; (3) evaluate the effect of absorbed moisture and hygrothermal cycling on inplane shear response; (4) determine the permanent loss of interfacial bond strength after moisture absorption and drying; and (5) evaluate the three dimensional stress state in laminates under a combination of hygroscopic, thermal, and mechanical loads. Specimens were conditioned to equilibrium moisture content under steady exposure to 55% or 95% RH at 70 C or 93 C. Some specimens were tested subsequent to moisture conditioning and 100 cycles between -54 C and either 70 C or 93 C.

Simulation of fatigue damage in ferroelectric polycrystals under mechanical/electrical loading

NASA Astrophysics Data System (ADS)

Kozinov, S.; Kuna, M.

2018-07-01

The reliability of smart-structures made of ferroelectric ceramics is essentially reduced by the formation of cracks under the action of external electrical and/or mechanical loading. In the current research a numerical model for low-cycle fatigue in ferroelectric mesostructures is proposed. In the finite element simulations a combination of two user element routines is utilized. The first one is used to model a micromechanical ferroelectric domain switching behavior inside the grains. The second one is used to simulate fatigue damage of grain boundaries by a cohesive zone model (EMCCZM) based on an electromechanical cyclic traction-separation law (TSL). For numerical simulations a scanning electron microscope image of the ceramic's grain structure was digitalized and meshed. The response of this mesostructure to cyclic electrical or mechanical loading is systematically analyzed. As a result of the simulations, the distribution of electric potential, field, displacement and polarization as well as mechanical stresses and deformations inside the grains are obtained. At the grain boundaries, the formation and evolution of damage are analyzed until final failure and induced degradation of electric permittivity. It is found that the proposed model correctly mimics polycrystalline behavior during poling processes and progressive damage under cyclic electromechanical loading. To the authors' knowledge, it is the first model and numerical analysis of ferroelectric polycrystals taking into account both domain reorientation and cohesive modeling of intergranular fracture. It can help to understand failure mechanisms taking place in ferroelectrics during fatigue processes.

Mechanical Blood Trauma in Assisted Circulation: Sublethal RBC Damage Preceding Hemolysis

PubMed Central

Olia, Salim E.; Maul, Timothy M.; Antaki, James F.; Kameneva, Marina V.

2016-01-01

After many decades of improvements in mechanical circulatory assist devices (CADs), blood damage remains a serious problem during support contributing to variety of adverse events, and consequently affecting patient survival and quality of life. The mechanisms of cumulative cell damage in continuous-flow blood pumps are still not fully understood despite numerous in vitro, in vivo, and in silico studies of blood trauma. Previous investigations have almost exclusively focused on lethal blood damage, namely hemolysis, which is typically negligible during normal operation of current generation CADs. The measurement of plasma free hemoglobin (plfHb) concentration to characterize hemolysis is straightforward, however sublethal trauma is more difficult to detect and quantify since no simple direct test exists. Similarly, while multiple studies have focused on thrombosis within blood pumps and accessories, sublethal blood trauma and its sequelae have yet to be adequately documented or characterized. This review summarizes the current understanding of sublethal trauma to red blood cells (RBCs) produced by exposure of blood to flow parameters and conditions similar to those within CADs. It also suggests potential strategies to reduce and/or prevent RBC sublethal damage in a clinically-relevant context, and encourages new research into this relatively uncharted territory. PMID:27034320

Mechanical properties of silicon in subsurface damage layer from nano-grinding studied by atomistic simulation

NASA Astrophysics Data System (ADS)

Zhang, Zhiwei; Chen, Pei; Qin, Fei; An, Tong; Yu, Huiping

2018-05-01

Ultra-thin silicon wafer is highly demanded by semi-conductor industry. During wafer thinning process, the grinding technology will inevitably induce damage to the surface and subsurface of silicon wafer. To understand the mechanism of subsurface damage (SSD) layer formation and mechanical properties of SSD layer, atomistic simulation is the effective tool to perform the study, since the SSD layer is in the scale of nanometer and hardly to be separated from underneath undamaged silicon. This paper is devoted to understand the formation of SSD layer, and the difference between mechanical properties of damaged silicon in SSD layer and ideal silicon. With the atomistic model, the nano-grinding process could be performed between a silicon workpiece and diamond tool under different grinding speed. To reach a thinnest SSD layer, nano-grinding speed will be optimized in the range of 50-400 m/s. Mechanical properties of six damaged silicon workpieces with different depths of cut will be studied. The SSD layer from each workpiece will be isolated, and a quasi-static tensile test is simulated to perform on the isolated SSD layer. The obtained stress-strain curve is an illustration of overall mechanical properties of SSD layer. By comparing the stress-strain curves of damaged silicon and ideal silicon, a degradation of Young's modulus, ultimate tensile strength (UTS), and strain at fracture is observed.

Preemptive mechanical ventilation can block progressive acute lung injury.

PubMed

Sadowitz, Benjamin; Jain, Sumeet; Kollisch-Singule, Michaela; Satalin, Joshua; Andrews, Penny; Habashi, Nader; Gatto, Louis A; Nieman, Gary

2016-02-04

Mortality from acute respiratory distress syndrome (ARDS) remains unacceptable, approaching 45% in certain high-risk patient populations. Treating fulminant ARDS is currently relegated to supportive care measures only. Thus, the best treatment for ARDS may lie with preventing this syndrome from ever occurring. Clinical studies were examined to determine why ARDS has remained resistant to treatment over the past several decades. In addition, both basic science and clinical studies were examined to determine the impact that early, protective mechanical ventilation may have on preventing the development of ARDS in at-risk patients. Fulminant ARDS is highly resistant to both pharmacologic treatment and methods of mechanical ventilation. However, ARDS is a progressive disease with an early treatment window that can be exploited. In particular, protective mechanical ventilation initiated before the onset of lung injury can prevent the progression to ARDS. Airway pressure release ventilation (APRV) is a novel mechanical ventilation strategy for delivering a protective breath that has been shown to block progressive acute lung injury (ALI) and prevent ALI from progressing to ARDS. ARDS mortality currently remains as high as 45% in some studies. As ARDS is a progressive disease, the key to treatment lies with preventing the disease from ever occurring while it remains subclinical. Early protective mechanical ventilation with APRV appears to offer substantial benefit in this regard and may be the prophylactic treatment of choice for preventing ARDS.

DNA Damage Response in Cisplatin-Induced Nephrotoxicity

PubMed Central

Zhu, Shiyao; Pabla, Navjotsingh; Tang, Chengyuan; He, Liyu; Dong, Zheng

2015-01-01

Cisplatin and its derivatives are widely used chemotherapeutic drugs for cancer treatment. However, they have debilitating side-effects in normal tissues and induce ototoxicity, neurotoxicity, and nephrotoxicity. In kidneys, cisplatin preferentially accumulates in renal tubular cells causing tubular cell injury and death, resulting in acute kidney injury (AKI). Recent studies have suggested that DNA damage and the associated DNA damage response (DDR) is an important pathogenic mechanism of AKI following cisplatin treatment. Activation of DDR may lead to cell cycle arrest and DNA repair for cell survival or, in the presence of severe injury, kidney cell death. Modulation of DDR may provide novel renoprotective strategies for cancer patients undergoing cisplatin chemotherapy. PMID:26564230

Microcavitation as a Neuronal Damage Mechanism in Blast Traumatic Brain Injury

NASA Astrophysics Data System (ADS)

Franck, Christian; Estrada, Jonathan

2015-11-01

Blast traumatic brain injury (bTBI) is a leading cause of injury in the armed forces. Diffuse axonal injury, the hallmark feature of blunt TBI, has been investigated in direct mechanical loading conditions. However, recent evidence suggests inertial cavitation as a possible bTBI mechanism, particularly in the case of exposure to blasts. Cavitation damage to free surfaces has been well-studied, but bubble interactions within confined 3D environments, in particular their stress and strain signatures are not well understood. The structural damage due to cavitation in living tissues - particularly at the cellular level - are incompletely understood, in part due to the rapid bubble formation and deformation strain rates of up to ~ 105-106 s-1. This project aims to characterize material damage in 2D and 3D cell culture environments by utilizing a novel high-speed red-blue diffraction assisted image correlation method at speeds of up to 106 frames per second. We gratefully acknowledge funding from the Office of Naval Research (POC: Dr. Tim Bentley).

The Crucial Role of Early Mitochondrial Injury in L-Lysine-Induced Acute Pancreatitis

PubMed Central

Biczó, György; Hegyi, Péter; Dósa, Sándor; Shalbuyeva, Natalia; Berczi, Sándor; Sinervirta, Riitta; Hracskó, Zsuzsanna; Siska, Andrea; Kukor, Zoltán; Jármay, Katalin; Venglovecz, Viktória; Varga, Ilona S.; Iványi, Béla; Alhonen, Leena; Wittmann, Tibor; Gukovskaya, Anna; Takács, Tamás

2011-01-01

Abstract Aims Large doses of intraperitoneally injected basic amino acids, L-arginine, or L-ornithine, induce acute pancreatitis in rodents, although the mechanisms mediating pancreatic toxicity remain unknown. Another basic amino acid, L-lysine, was also shown to cause pancreatic acinar cell injury. The aim of the study was to get insight into the mechanisms through which L-lysine damages the rat exocrine pancreas, in particular to characterize the kinetics of L-lysine-induced mitochondrial injury, as well as the pathologic responses (including alteration of antioxidant systems) characteristic of acute pancreatitis. Results We showed that intraperitoneal administration of 2 g/kg L-lysine induced severe acute necrotizing pancreatitis. L-lysine administration caused early pancreatic mitochondrial damage that preceded the activation of trypsinogen and the proinflammatory transcription factor nuclear factor-κB (NF-κB), which are commonly thought to play an important role in the development of acute pancreatitis. Our data demonstrate that L-lysine impairs adenosine triphosphate synthase activity of isolated pancreatic, but not liver, mitochondria. Innovation and Conclusion Taken together, early mitochondrial injury caused by large doses of L-lysine may lead to the development of acute pancreatitis independently of pancreatic trypsinogen and NF-κB activation. PMID:21644850

Damage Mechanics Approach to Penetration of Water-filled Surface Crevasses

NASA Astrophysics Data System (ADS)

Duddu, R.; Jimenez, S. K.; Bassis, J. N.

2017-12-01

Iceberg calving is a natural process that occurs when crevasses penetrate the entire thickness of an ice shelf or a glacier leading to the detachment (birth) of icebergs. Calving from marine-terminating glaciers and floating ice shelves accounts for nearly 50% of the mass lost from both the Greenland and Antarctic ice sheets, which can directly or indirectly contribute to sealevel rise. A widely-accepted hypothesis is that crevasses in ice form due to brittle mode I fracture under the action of tensile stresses. Existing theoretical approaches for modeling crevasse propagation based on the above hypothesis include the Nye zero stress and fracture mechanics approaches. These theoretical approaches assume idealized geometry and boundary conditions, and ignore the effects of viscous creep deformations in ice over longer time scales; however, they still produced interesting results that matched well with sparse field observations available. An alternative is to use the continuum damage mechanics approach for modeling crevasse propagation, which is more easily incorporated into numerical ice sheet models that consider realistic geometries, boundary conditions and viscous creep effects. In this presentation, we describe the damage mechanics approach to penetration of dry and water-filled surface crevasses using the principles of poromechanics and compare our results with those from existing theoretical approaches. We investigate the upper limits on crevasse penetration depth in relation to ice thickness, water depth in the surface crevasse, seawater depth at the ice terminus and ice rheology (i.e., elastic vs. viscous). Our studies on idealized glaciers show that the damage mechanics approach is consistent with the fracture mechanics approach when the seawater depth at the ice terminus is low, but is inconsistent with the theoretical approaches when the seawater depth at the ice terminus is high (i.e., near floatation). Our studies also indicate that the upper limit on

The Reactivity, Distribution and Abundance of Non-Astrocytic Inner Retinal Glial (NIRG) Cells Are Regulated by Microglia, Acute Damage, and IGF1

PubMed Central

Zelinka, Christopher P.; Scott, Melissa A.; Volkov, Leo; Fischer, Andy J.

2012-01-01

Recent studies have described a novel type of glial cell that is scattered across the inner layers of the avian retina and possibly the retinas of primates. These cells have been termed Non-astrocytic Inner Retinal Glial (NIRG) cells. These cells are stimulated by insulin-like growth factor 1 (IGF1) to proliferate, migrate distally into the retina, and become reactive. These changes in glial activity correlate with increased susceptibility of retinal neurons and Müller glia to excitotoxic damage. The purpose of this study was to further study the NIRG cells in retinas treated with IGF1 or acute damage. In response to IGF1, the reactivity, proliferation and migration of NIRG cells persists through 3 days after treatment. At 7 days after treatment, the numbers and distribution of NIRG cells returns to normal, suggesting that homeostatic mechanisms are in place within the retina to maintain the numbers and distribution of these glial cells. By comparison, IGF1-induced microglial reactivity persists for at least 7 days after treatment. In damaged retinas, we find a transient accumulation of NIRG cells, which parallels the accumulation of reactive microglia, suggesting that the reactivity of NIRG cells and microglia are linked. When the microglia are selectively ablated by the combination of interleukin 6 and clodronate-liposomes, the NIRG cells down-regulate transitin and perish within the following week, suggesting that the survival and phenotype of NIRG cells are somehow linked to the microglia. We conclude that the abundance, reactivity and retinal distribution of NIRG cells can be dynamic, are regulated by homoestatic mechanisms and are tethered to the microglia. PMID:22973454

Surface Damage Mechanism of Monocrystalline Si Under Mechanical Loading

NASA Astrophysics Data System (ADS)

Zhao, Qingliang; Zhang, Quanli; To, Suet; Guo, Bing

2017-03-01

Single-point diamond scratching and nanoindentation on monocrystalline silicon wafer were performed to investigate the surface damage mechanism of Si under the contact loading. The results showed that three typical stages of material removal appeared during dynamic scratching, and a chemical reaction of Si with the diamond indenter and oxygen occurred under the high temperature. In addition, the Raman spectra of the various points in the scratching groove indicated that the Si-I to β-Sn structure (Si-II) and the following β-Sn structure (Si-II) to amorphous Si transformation appeared under the rapid loading/unloading condition of the diamond grit, and the volume change induced by the phase transformation resulted in a critical depth (ductile-brittle transition) of cut (˜60 nm ± 15 nm) much lower than the theoretical calculated results (˜387 nm). Moreover, it also led to abnormal load-displacement curves in the nanoindentation tests, resulting in the appearance of elbow and pop-out effects (˜270 nm at 20 s, 50 mN), which were highly dependent on the loading/unloading conditions. In summary, phase transformation of Si promoted surface deformation and fracture under both static and dynamic mechanical loading.

The acute response of pericytes to muscle-damaging eccentric contraction and protein supplementation in human skeletal muscle.

PubMed

De Lisio, Michael; Farup, Jean; Sukiennik, Richard A; Clevenger, Nicole; Nallabelli, Julian; Nelson, Brett; Ryan, Kelly; Rahbek, Stine K; de Paoli, Frank; Vissing, Kristian; Boppart, Marni D

2015-10-15

Skeletal muscle pericytes increase in quantity following eccentric exercise (ECC) and contribute to myofiber repair and adaptation in mice. The purpose of the present investigation was to examine pericyte quantity in response to muscle-damaging ECC and protein supplementation in human skeletal muscle. Male subjects were divided into protein supplement (WHY; n = 12) or isocaloric placebo (CHO; n = 12) groups and completed ECC using an isokinetic dynamometer. Supplements were consumed 3 times/day throughout the experimental time course. Biopsies were collected prior to (PRE) and 3, 24, 48, and 168 h following ECC. Reflective of the damaging protocol, integrin subunits, including α7, β1A, and β1D, increased (3.8-fold, 3.6-fold and 3.9-fold, respectively, P < 0.01) 24 h post-ECC with no difference between supplements. Pericyte quantity did not change post-ECC. WHY resulted in a small, but significant, decrease in ALP(+) pericytes when expressed as a percentage of myonuclei (CHO 6.8 ± 0.3% vs. WHY 5.8 ± 0.3%, P < 0.05) or per myofiber (CHO 0.119 ± 0.01 vs. WHY 0.098 ± 0.01, P < 0.05). The quantity of myonuclei expressing serum response factor and the number of pericytes expressing serum response factor, did not differ as a function of time post-ECC or supplement. These data demonstrate that acute muscle-damaging ECC increases α7β1 integrin content in human muscle, yet pericyte quantity is largely unaltered. Future studies should focus on the capacity for ECC to influence pericyte function, specifically paracrine factor release as a mechanism toward pericyte contribution to repair and adaptation postexercise. Copyright © 2015 the American Physiological Society.

Acute kidney failure

MedlinePlus

Kidney failure; Renal failure; Renal failure - acute; ARF; Kidney injury - acute ... There are many possible causes of kidney damage. They include: ... cholesterol (cholesterol emboli) Decreased blood flow due to very ...

Contribution of neutrophils to acute lung injury.

PubMed

Grommes, Jochen; Soehnlein, Oliver

2011-01-01

Treatment of acute lung injury (ALI) and its most severe form, acute respiratory distress syndrome (ARDS), remain unsolved problems of intensive care medicine. ALI/ARDS are characterized by lung edema due to increased permeability of the alveolar-capillary barrier and subsequent impairment of arterial oxygenation. Lung edema, endothelial and epithelial injury are accompanied by an influx of neutrophils into the interstitium and broncheoalveolar space. Hence, activation and recruitment of neutrophils are regarded to play a key role in progression of ALI/ARDS. Neutrophils are the first cells to be recruited to the site of inflammation and have a potent antimicrobial armour that includes oxidants, proteinases and cationic peptides. Under pathological circumstances, however, unregulated release of these microbicidal compounds into the extracellular space paradoxically can damage host tissues. This review focuses on the mechanisms of neutrophil recruitment into the lung and on the contribution of neutrophils to tissue damage in ALI.

Low-Cost, Full-Field Surface Profiling Tool for Mechanical Damage Evaluation

DOT National Transportation Integrated Search

2010-03-03

In this project, Intelligent Optical Systems (IOS) developed an inexpensive, full-field, surfaceprofiling tool for mechanical damage evaluation based on the processing of a single digital image. Little operator training is required for acquiring the ...

Preemptive mechanical ventilation can block progressive acute lung injury

PubMed Central

Sadowitz, Benjamin; Jain, Sumeet; Kollisch-Singule, Michaela; Satalin, Joshua; Andrews, Penny; Habashi, Nader; Gatto, Louis A; Nieman, Gary

2016-01-01

Mortality from acute respiratory distress syndrome (ARDS) remains unacceptable, approaching 45% in certain high-risk patient populations. Treating fulminant ARDS is currently relegated to supportive care measures only. Thus, the best treatment for ARDS may lie with preventing this syndrome from ever occurring. Clinical studies were examined to determine why ARDS has remained resistant to treatment over the past several decades. In addition, both basic science and clinical studies were examined to determine the impact that early, protective mechanical ventilation may have on preventing the development of ARDS in at-risk patients. Fulminant ARDS is highly resistant to both pharmacologic treatment and methods of mechanical ventilation. However, ARDS is a progressive disease with an early treatment window that can be exploited. In particular, protective mechanical ventilation initiated before the onset of lung injury can prevent the progression to ARDS. Airway pressure release ventilation (APRV) is a novel mechanical ventilation strategy for delivering a protective breath that has been shown to block progressive acute lung injury (ALI) and prevent ALI from progressing to ARDS. ARDS mortality currently remains as high as 45% in some studies. As ARDS is a progressive disease, the key to treatment lies with preventing the disease from ever occurring while it remains subclinical. Early protective mechanical ventilation with APRV appears to offer substantial benefit in this regard and may be the prophylactic treatment of choice for preventing ARDS. PMID:26855896

A fracture mechanics analysis of impact damage in a thick composite laminate

NASA Technical Reports Server (NTRS)

Poe, C. C., Jr.

1985-01-01

Graphite/epoxy filament-wound cases (FWC) for the solid rocket motors of the space shuttle are being made by NASA. The FWC cases are wound with AS4W graphite fiber impregnated with an epoxy resin and are about 1.4 inches or more thick. Graphite-epoxy composite laminates, unlike metals, can be damaged easily by low velocity impacts of objects like dropped tools. The residual tension strength of the FWC laminate, after impact, is being studied at Langley Research Center. The conditions that give minimum visual evidence of damage are being emphasized. A fracture mechanics analysis was developed to predict the residual strength, after impact, using radiographs to measure the size of the damage and an equivalent surface crack to represent the damage.

A physically-based continuum damage mechanics model for numerical prediction of damage growth in laminated composite plates

NASA Astrophysics Data System (ADS)

Williams, Kevin Vaughan

Rapid growth in use of composite materials in structural applications drives the need for a more detailed understanding of damage tolerant and damage resistant design. Current analytical techniques provide sufficient understanding and predictive capabilities for application in preliminary design, but current numerical models applicable to composites are few and far between and their development into well tested, rigorous material models is currently one of the most challenging fields in composite materials. The present work focuses on the development, implementation, and verification of a plane-stress continuum damage mechanics based model for composite materials. A physical treatment of damage growth based on the extensive body of experimental literature on the subject is combined with the mathematical rigour of a continuum damage mechanics description to form the foundation of the model. The model has been implemented in the LS-DYNA3D commercial finite element hydrocode and the results of the application of the model are shown to be physically meaningful and accurate. Furthermore it is demonstrated that the material characterization parameters can be extracted from the results of standard test methodologies for which a large body of published data already exists for many materials. Two case studies are undertaken to verify the model by comparison with measured experimental data. The first series of analyses demonstrate the ability of the model to predict the extent and growth of damage in T800/3900-2 carbon fibre reinforced polymer (CFRP) plates subjected to normal impacts over a range of impact energy levels. The predicted force-time and force-displacement response of the panels compare well with experimental measurements. The damage growth and stiffness reduction properties of the T800/3900-2 CFRP are derived using published data from a variety of sources without the need for parametric studies. To further demonstrate the physical nature of the model, a IM6

Damage mechanisms of MoN/SiN multilayer optics for next-generation pulsed XUV light sources.

PubMed

Sobierajski, R; Bruijn, S; Khorsand, A R; Louis, E; van de Kruijs, R W E; Burian, T; Chalupsky, J; Cihelka, J; Gleeson, A; Grzonka, J; Gullikson, E M; Hajkova, V; Hau-Riege, S; Juha, L; Jurek, M; Klinger, D; Krzywinski, J; London, R; Pelka, J B; Płociński, T; Rasiński, M; Tiedtke, K; Toleikis, S; Vysin, L; Wabnitz, H; Bijkerk, F

2011-01-03

We investigated the damage mechanism of MoN/SiN multilayer XUV optics under two extreme conditions: thermal annealing and irradiation with single shot intense XUV pulses from the free-electron laser facility in Hamburg - FLASH. The damage was studied "post-mortem" by means of X-ray diffraction, interference-polarizing optical microscopy, atomic force microscopy, and scanning transmission electron microscopy. Although the timescale of the damage processes and the damage threshold temperatures were different (in the case of annealing it was the dissociation temperature of Mo2N and in the case of XUV irradiation it was the melting temperature of MoN) the main damage mechanism is very similar: molecular dissociation and the formation of N2, leading to bubbles inside the multilayer structure.

Impaired Facilitatory Mechanisms of Auditory Attention After Damage of the Lateral Prefrontal Cortex.

PubMed

Bidet-Caulet, Aurélie; Buchanan, Kelly G; Viswanath, Humsini; Black, Jessica; Scabini, Donatella; Bonnet-Brilhault, Frédérique; Knight, Robert T

2015-11-01

There is growing evidence that auditory selective attention operates via distinct facilitatory and inhibitory mechanisms enabling selective enhancement and suppression of sound processing, respectively. The lateral prefrontal cortex (LPFC) plays a crucial role in the top-down control of selective attention. However, whether the LPFC controls facilitatory, inhibitory, or both attentional mechanisms is unclear. Facilitatory and inhibitory mechanisms were assessed, in patients with LPFC damage, by comparing event-related potentials (ERPs) to attended and ignored sounds with ERPs to these same sounds when attention was equally distributed to all sounds. In control subjects, we observed 2 late frontally distributed ERP components: a transient facilitatory component occurring from 150 to 250 ms after sound onset; and an inhibitory component onsetting at 250 ms. Only the facilitatory component was affected in patients with LPFC damage: this component was absent when attending to sounds delivered in the ear contralateral to the lesion, with the most prominent decreases observed over the damaged brain regions. These findings have 2 important implications: (i) they provide evidence for functionally distinct facilitatory and inhibitory mechanisms supporting late auditory selective attention; (ii) they show that the LPFC is involved in the control of the facilitatory mechanisms of auditory attention. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Matrix Fatigue Cracking Mechanisms of Alpha(2) TMC for Hypersonic Applications

NASA Technical Reports Server (NTRS)

Gabb, Timothy P.; Gayda, John

1994-01-01

The objective of this work was to understand matrix cracking mechanisms in a unidirectional alpha(sub 2) TMC in possible hypersonic applications. A (0)(sub 8) SCS-6/Ti-24Al-11Nb (at. percent) TMC was first subjected to a variety of simple isothermal and nonisothermal fatigue cycles to evaluate the damage mechanisms in simple conditions. A modified ascent mission cycle test was then performed to evaluate the combined effects of loading modes. This cycle mixes mechanical cycling at 150 and 483 C, sustained loads, and a slow thermal cycle to 815 C. At low cyclic stresses and strains more common in hypersonic applications, environment-assisted surface cracking limited fatigue resistance. This damage mechanism was most acute for out-of-phase nonisothermal cycles having extended cycle periods and the ascent mission cycle. A simple linear fraction damage model was employed to help understand this damage mechanism. Time-dependent environmental damage was found to strongly influence out-of-phase and mission life, with mechanical cycling damage due to the combination of external loading and CTE mismatch stresses playing a smaller role. The mechanical cycling and sustained loads in the mission cycle also had a smaller role.

Model-Based Fatigue Prognosis of Fiber-Reinforced Laminates Exhibiting Concurrent Damage Mechanisms

NASA Technical Reports Server (NTRS)

Corbetta, M.; Sbarufatti, C.; Saxena, A.; Giglio, M.; Goebel, K.

2016-01-01

Prognostics of large composite structures is a topic of increasing interest in the field of structural health monitoring for aerospace, civil, and mechanical systems. Along with recent advancements in real-time structural health data acquisition and processing for damage detection and characterization, model-based stochastic methods for life prediction are showing promising results in the literature. Among various model-based approaches, particle-filtering algorithms are particularly capable in coping with uncertainties associated with the process. These include uncertainties about information on the damage extent and the inherent uncertainties of the damage propagation process. Some efforts have shown successful applications of particle filtering-based frameworks for predicting the matrix crack evolution and structural stiffness degradation caused by repetitive fatigue loads. Effects of other damage modes such as delamination, however, are not incorporated in these works. It is well established that delamination and matrix cracks not only co-exist in most laminate structures during the fatigue degradation process but also affect each other's progression. Furthermore, delamination significantly alters the stress-state in the laminates and accelerates the material degradation leading to catastrophic failure. Therefore, the work presented herein proposes a particle filtering-based framework for predicting a structure's remaining useful life with consideration of multiple co-existing damage-mechanisms. The framework uses an energy-based model from the composite modeling literature. The multiple damage-mode model has been shown to suitably estimate the energy release rate of cross-ply laminates as affected by matrix cracks and delamination modes. The model is also able to estimate the reduction in stiffness of the damaged laminate. This information is then used in the algorithms for life prediction capabilities. First, a brief summary of the energy-based damage model

Histologic damage of lung allografts according to magnitude of acute rejection in the re-isotransplant model.

PubMed

Marui, Tsutomu; Iwata, Hisashi; Shirahashi, Koyo; Matsumoto, Shinsuke; Mizuno, Yoshimasa; Matsui, Masafumi; Takemura, Hirofumi

2008-06-01

Graft damage due to acute rejection has been reported as one of the risk factors in the chronic stage of cardiac and renal allografts. This study was designed to elucidate the histologic changes of grafts after ongoing acute allograft rejection was discontinued in models of lung re-isotransplantation. WKAH rat lungs were orthotopically transplanted into F344 recipients. Three days (3A group) and 5 days (5A group) after the first allotransplantation, the grafts were re-isotransplanted back into the WKAH rats (3RA and 5RA groups, respectively). Five days (5I group) after the first isotransplantation, the grafts were re-isotransplanted back into the WKAH rats (5RI group). The grafts were removed 30 and 60 days after re-isotransplantation and assessed histologically. Typical acute allograft rejection developed in the 3A and 5A groups, and the changes were reduced after re-isotransplantation, although they remained significantly greater in the 5RA group than in the 3RA and 5RI groups. For intimal hyperplasia, the graft score 60 days after re-isotransplantation in the 5RA group was significantly higher than in the 5RI and 3RA groups. The changes in airway inflammation were significantly greater in the 5RA group than in the 3RA and 5RI groups at 60 days. Peribronchiolar fibrosis was significantly more frequent in the 5RA and 3RA groups than in the 5RI group. Acute rejection and airway inflammation corresponded to the magnitude of rejection before retransplantation. Significant intimal hyperplasia developed in severe acute rejection, and peribronchiolar fibrosis occurred after the first acute rejection.

Mechanical Properties of Shock-Damaged Rocks

NASA Technical Reports Server (NTRS)

He, Hongliang; Ahrens, T. J.

1994-01-01

Stress-strain tests were performed both on shock-damaged gabbro and limestone. The effective Young's modulus decreases with increasing initial damage parameter value, and an apparent work-softening process occurs prior to failure. To further characterize shock-induced microcracks, the longitudinal elastic wave velocity behavior of shock-damaged gabbro in the direction of compression up to failure was measured using an acoustic transmission technique under uniaxial loading. A dramatic increase in velocity was observed for the static compressive stress range of 0-50 MPa. Above that stress range, the velocity behavior of lightly damaged (D(sub 0) less than 0.1) gabbro is almost equal to unshocked gabbro. The failure strength of heavily-damaged (D(sub 0) greater than 0.1) gabbro is approx. 100-150 MPa, much lower than that of lightly damaged and unshocked gabbros (approx. 230-260 MPa). Following Nur's theory, the crack shape distribution was analyzed. The shock-induced cracks in gabbro appear to be largely thin penny-shaped cracks with c/a values below 5 x 10(exp -4). Moreover, the applicability of Ashby and Sammis's theory relating failure strength and damage parameter of shock-damaged rocks was examined and was found to yield a good estimate of the relation of shock-induced deficit in elastic modulus with the deficit in compressive strength.

Experimental approach to IGF-1 therapy in CCl4-induced acute liver damage in healthy controls and mice with partial IGF-1 deficiency.

PubMed

Morales-Garza, Luis A; Puche, Juan E; Aguirre, Gabriel A; Muñoz, Úrsula; García-Magariño, Mariano; De la Garza, Rocío G; Castilla-Cortazar, Inma

2017-05-04

Cell necrosis, oxidative damage, and fibrogenesis are involved in cirrhosis development, a condition in which insulin-like growth factor 1 (IGF-1) levels are diminished. This study evaluates whether the exogenous administration of low doses of IGF-1 can induce hepatoprotection in acute carbon tetrachloride (CCl 4 )-induced liver damage compared to healthy controls (Wt Igf +/+ ). Additionally, the impact of IGF-1 deficiency on a damaged liver was investigated in mice with a partial deficit of this hormone (Hz Igf1 +/- ). Three groups of 25 ± 5-week-old healthy male mice (Wt Igf +/+ ) were included in the protocol: untreated controls (Wt). Controls that received CCl 4 (Wt + CCl 4 ) and Wt + CCl 4 were treated subcutaneously with IGF-1 (2 µg/100 g body weight/day) for 10 days (Wt + CCl 4  + IGF1). In parallel, three IGF-1-deficient mice (Hz Igf1 +/- ) groups were studied: untreated Hz, Hz + CCl 4 , and Hz + CCl 4  + IGF-1. Microarray and real-time quantitative polymerase chain reaction (RT-qPCR) analyses, serum aminotransferases levels, liver histology, and malondialdehyde (MDA) levels were assessed at the end of the treatment in all groups. All data represent mean ± SEM. An altered gene coding expression pattern for proteins of the extracellular matrix, fibrosis, and cellular protection were found, as compared to healthy controls, in which IGF-1 therapy normalized in the series including healthy mice. Liver histology showed that Wt + CCl 4  + IGF1 mice had less oxidative damage, fibrosis, lymphocytic infiltrate, and cellular changes when compared to the Wt + CCl 4 . Moreover, there was a correlation between MDA levels and the histological damage score (Pearson's r = 0.858). In the IGF-1-deficient mice series, similar findings were identified, denoting a much more vulnerable hepatic parenchyma. IGF1 treatment improved the biochemistry, histology, and genetic expression of pro-regenerative and cytoprotective factors in both series

DNA Damage and Repair in Human Cancer: Molecular Mechanisms and Contribution to Therapy-Related Leukemias

PubMed Central

Casorelli, Ida; Bossa, Cecilia; Bignami, Margherita

2012-01-01

Most antitumour therapies damage tumour cell DNA either directly or indirectly. Without repair, damage can result in genetic instability and eventually cancer. The strong association between the lack of DNA damage repair, mutations and cancer is dramatically demonstrated by a number of cancer-prone human syndromes, such as xeroderma pigmentosum, ataxia-telangiectasia and Fanconi anemia. Notably, DNA damage responses, and particularly DNA repair, influence the outcome of therapy. Because DNA repair normally excises lethal DNA lesions, it is intuitive that efficient repair will contribute to intrinsic drug resistance. Unexpectedly, a paradoxical relationship between DNA mismatch repair and drug sensitivity has been revealed by model studies in cell lines. This suggests that connections between DNA repair mechanism efficiency and tumour therapy might be more complex. Here, we review the evidence for the contribution of carcinogenic properties of several drugs as well as of alterations in specific mechanisms involved in drug-induced DNA damage response and repair in the pathogenesis of therapy-related cancers. PMID:23066388

Combining Functional and Tubular Damage Biomarkers Improves Diagnostic Precision for Acute Kidney Injury After Cardiac Surgery

PubMed Central

Basu, Rajit K.; Wong, Hector R.; Krawczeski, Catherine D.; Wheeler, Derek S.; Manning, Peter B.; Chawla, Lakhmir S.; Devarajan, Prasad; Goldstein, Stuart L.

2015-01-01

BACKGROUND Increases in serum creatinine (ΔSCr) from baseline signify acute kidney injury (AKI) but offer little granular information regarding its characteristics. The 10th Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) suggested that combining AKI biomarkers would provide better precision for AKI course prognostication. OBJECTIVES This study investigated the value of combining a functional damage biomarker (plasma cystatin C [pCysC]) with a tubular damage biomarker (urine neutrophil gelatinase-associated lipocalin [uNGAL]), forming a composite biomarker for prediction of discrete characteristics of AKI. METHODS Data from 345 children after cardiopulmonary bypass (CPB) were analyzed. Severe AKI was defined as Kidney Disease Global Outcomes Initiative stages 2 to 3 (>100% ΔSCr) within 7 days of CPB. Persistent AKI lasted >2 days. SCr in reversible AKI returned to baseline ≤48 h after CPB. The composite of uNGAL (>200 ng/mg urine Cr = positive [+]) and pCysC (>0.8 mg/l = positive [+]), uNGAL+/pCysC+, measured 2 h after CPB initiation, was compared to ΔSCr increases of ≤50% for correlation with AKI characteristics by using predictive probabilities, likelihood ratios (LR), and area under the curve receiver operating curve (AUC-ROC) values. RESULTS Severe AKI occurred in 18% of patients. The composite uNGAL+/pCysC+ demonstrated a greater likelihood than ΔSCr for severe AKI (+LR: 34.2 [13.0:94.0] vs. 3.8 [1.9:7.2]) and persistent AKI (+LR: 15.6 [8.8:27.5] versus 4.5 [2.3:8.8]). In AKI patients, the uNGAL−/pCysC+ composite was superior to ΔSCr for prediction of transient AKI. Biomarker composites carried greater probability for specific outcomes than ΔSCr strata. CONCLUSIONS Composites of functional and tubular damage biomarkers are superior to ΔSCr for predicting discrete characteristics of AKI. PMID:25541128

Flavocoxid, a dual inhibitor of cyclooxygenase-2 and 5-lipoxygenase, reduces pancreatic damage in an experimental model of acute pancreatitis

PubMed Central

Polito, F; Bitto, A; Irrera, N; Squadrito, F; Fazzari, C; Minutoli, L; Altavilla, D

2010-01-01

BACKGROUND AND PURPOSE Acute pancreatitis is an autodigestive process resulting in acute inflammation of the pancreas. Accumulating evidence indicates the essential contribution of cyclooxygenase (COX)-2 and 5-lipoxygenase (5-LOX) to acute pancreatitis. We studied the effects of flavocoxid, a plant-derived dual inhibitor of COX-2 and 5-LOX, in a model of caerulein (CER)-induced acute pancreatitis. EXPERIMENTAL APPROACH Rats were given CER (80 µg·kg−1 for each of four injections at hourly intervals) or vehicle (Sham-CER). Animals were then randomized to receive flavocoxid (20 mg·kg−1 i.p.) or vehicle, 30 min after the first CER injection. Two hours after the last CER injection, we evaluated damage to the pancreas by histological methods; serum levels of amylase, lipase, leukotriene (LT)B4 and prostaglandin (PG)E2; pancreatic expression of COX-2 and 5-LOX and tumour necrosis factor-α (TNF-α) gene expression by real-time polymerase chain reaction. KEY RESULTS Caerulein induced inflammatory changes in the pancreas and raised values of the other variables measured. In CER-treated animals, but not in those given saline, flavocoxid inhibited COX-2 and 5-LOX expression, reduced serum levels of lipase and amylase and the degree of pancreatic oedema. Treatment with flavocoxid blunted the increased pancreatic TNF-α mRNA expression, serum leukotriene B4 and prostaglandin E2 levels, and protected against histological damage in terms of vacuolization and leukocyte infiltration. CONCLUSIONS AND IMPLICATIONS Our results confirm the key role of both COX-2 and 5-LOX in the inflammatory response to acute pancreatitis. Flavocoxid may provide a potential therapeutic approach to the treatment of patients at high risk of developing this life-threatening condition. PMID:20977452

Flavocoxid, a dual inhibitor of cyclooxygenase-2 and 5-lipoxygenase, reduces pancreatic damage in an experimental model of acute pancreatitis.

PubMed

Polito, F; Bitto, A; Irrera, N; Squadrito, F; Fazzari, C; Minutoli, L; Altavilla, D

2010-11-01

Acute pancreatitis is an autodigestive process resulting in acute inflammation of the pancreas. Accumulating evidence indicates the essential contribution of cyclooxygenase (COX)-2 and 5-lipoxygenase (5-LOX) to acute pancreatitis. We studied the effects of flavocoxid, a plant-derived dual inhibitor of COX-2 and 5-LOX, in a model of caerulein (CER)-induced acute pancreatitis. Rats were given CER (80 µg·kg⁻¹ for each of four injections at hourly intervals) or vehicle (Sham-CER). Animals were then randomized to receive flavocoxid (20 mg·kg⁻¹ i.p.) or vehicle, 30 min after the first CER injection. Two hours after the last CER injection, we evaluated damage to the pancreas by histological methods; serum levels of amylase, lipase, leukotriene (LT)B₄ and prostaglandin (PG)E₂ ; pancreatic expression of COX-2 and 5-LOX and tumour necrosis factor-α (TNF-α) gene expression by real-time polymerase chain reaction. Caerulein induced inflammatory changes in the pancreas and raised values of the other variables measured. In CER-treated animals, but not in those given saline, flavocoxid inhibited COX-2 and 5-LOX expression, reduced serum levels of lipase and amylase and the degree of pancreatic oedema. Treatment with flavocoxid blunted the increased pancreatic TNF-α mRNA expression, serum leukotriene B₄ and prostaglandin E₂ levels, and protected against histological damage in terms of vacuolization and leukocyte infiltration. Our results confirm the key role of both COX-2 and 5-LOX in the inflammatory response to acute pancreatitis. Flavocoxid may provide a potential therapeutic approach to the treatment of patients at high risk of developing this life-threatening condition. © 2010 The Authors. British Journal of Pharmacology © 2010 The British Pharmacological Society.

Trimetazidine protects retinal ganglion cells from acute glaucoma via the Nrf2/Ho-1 pathway.

PubMed

Wan, Peixing; Su, Wenru; Zhang, Yingying; Li, Zhidong; Deng, Caibin; Zhuo, Yehong

2017-09-15

Acute glaucoma is one of the leading causes of irreversible vision impairment characterized by the rapid elevation of intraocular pressure (IOP) and consequent retinal ganglion cell (RGC) death. Oxidative stress and neuroinflammation have been considered critical for the pathogenesis of RGC death in acute glaucoma. Trimetazidine (TMZ), an anti-ischemic drug, possesses antioxidative and anti-inflammatory properties, contributing to its therapeutic potential in tissue damage. However, the role of TMZ in acute glaucoma and the underlying molecular mechanisms remain elusive. Here, we report that treatment with TMZ significantly attenuated retinal damage and RGC death in mice with acute glaucoma, with a significant decrease in reactive oxygen species (ROS) and inflammatory cytokine production in the retina. Furthermore, TMZ treatment directly decreased ROS production and rebalanced the intracellular redox state, thus contributing to the survival of RGCs in vitro TMZ treatment also reduced the production of inflammatory cytokines in vitro Mechanistically, the TMZ-mediated inhibition of apoptosis and inflammatory cytokine production in RGCs occurred via the regulation of the nuclear factor erythroid 2-related factor 2/heme oxygenase 1/caspase-8 pathway. Moreover, the TMZ-mediated neuroprotection in acute glaucoma was abrogated when an HO-1 inhibitor, SnPP, was used. Our findings identify potential mechanisms of RGC apoptosis and propose a novel therapeutic agent, TMZ, which exerts a precise neuroprotective effect against acute glaucoma. © 2017 The Author(s).

Socioeconomic disparities in the utilization of mechanical thrombectomy for acute ischemic stroke in US hospitals.

PubMed

Brinjikji, W; Rabinstein, A A; McDonald, J S; Cloft, H J

2014-03-01

Previous studies have demonstrated that socioeconomic disparities in the treatment of cerebrovascular diseases exist. We studied a large administrative data base to study disparities in the utilization of mechanical thrombectomy for acute ischemic stroke. With the utilization of the Perspective data base, we studied disparities in mechanical thrombectomy utilization between patient race and insurance status in 1) all patients presenting with acute ischemic stroke and 2) patients presenting with acute ischemic stroke at centers that performed mechanical thrombectomy. We examined utilization rates of mechanical thrombectomy by race/ethnicity (white, black, and Hispanic) and insurance status (Medicare, Medicaid, self-pay, and private). Multivariate logistic regression analysis adjusting for potential confounding variables was performed to study the association between race/insurance status and mechanical thrombectomy utilization. The overall mechanical thrombectomy utilization rate was 0.15% (371/249,336); utilization rate at centers that performed mechanical thrombectomy was 1.0% (371/35,376). In the sample of all patients with acute ischemic stroke, multivariate logistic regression analysis demonstrated that uninsured patients had significantly lower odds of mechanical thrombectomy utilization compared with privately insured patients (OR = 0.52, 95% CI = 0.25-0.95, P = .03), as did Medicare patients (OR = 0.53, 95% CI = 0.41-0.70, P < .0001). Blacks had significantly lower odds of mechanical thrombectomy utilization compared with whites (OR = 0.35, 95% CI = 0.23-0.51, P < .0001). When considering only patients treated at centers performing mechanical thrombectomy, multivariate logistic regression analysis demonstrated that insurance was not associated with significant disparities in mechanical thrombectomy utilization; however, black patients had significantly lower odds of mechanical thrombectomy utilization compared with whites (OR = 0.41, 95% CI = 0.27-0.60, P

Vinpocetine ameliorates acute hepatic damage caused by administration of carbon tetrachloride in rats.

PubMed

Abdel Salam, O M E; Oraby, Fatma Hassan; Hassan, Nabila S

2007-12-01

Vinpocetine is a widely used drug for the treatment of cerebrovascular and memory disorders. This study aimed to investigate the effect of vinpocetine on the acute hepatic injury caused in the rat by the administration of CCl4 in vivo. Vinpocetine (2.1, 4.2, 8.4 mg/kg) or silymarin (30 mg/kg) was given once daily orally simultaneously with CCl4 and for 15 days thereafter. Liver damage was assessed by determining serum enzyme activities and hepatic histopathology. Stained sections were subjected to morphometric evaluation using computerized image analyzer. The results showed that vinpocetine administered to CCl4-treated rats decreased the elevated alanine aminotransferase (ALT) by 49.3, 58.1 and 63.6%, aspartate aminotransferase (AST) by 10.5, 22.6 and 27.2% and alkaline phosphatase (ALP) by 52.5, 59.6 and 64.9%, respectively, and in a dose-dependent manner. Meanwhile, silymarin reduced elevated ALT, AST and ALP levels by 53.1, 26.9 and 66%, respectively. Histological examination of liver specimens revealed a marked reduction in liver cell necrosis in vinpocetine and silymarin-treated rats compared with vehicle-treated CCl4-treated rats. Quantitative analysis of the area of damage showed 85.3% reduction in the area of damage after silymarin and 72.2, 78.9 and 82.6% reduction after vinpocetine treatment at 2.1, 4.2, 8.4 mg/kg, respectively. It is concluded that administration of vinpocetine in a model of CCl4-induced liver injury in rats reduced liver damage. The reduction obtained by 4.2 mg/kg of vinpocetine was similar to that obtained by 30 mg/kg silymarin. Therefore, it is suggested that vinpocetine might be a good pharmacological agent in the treatment of liver disease besides its neuroprotective effects.

Characteristics and mechanism of laser-induced surface damage initiated by metal contaminants

NASA Astrophysics Data System (ADS)

Shi, Shuang; Sun, Mingying; Shi, Shuaixu; Li, Zhaoyan; Zhang, Ya-nan; Liu, Zhigang

2015-08-01

In high power laser facility, contaminants on optics surfaces reduce damage resistance of optical elements and then decrease their lifetime. By damage test experiments, laser damage induced by typical metal particles such as stainless steel 304 is studied. Optics samples with metal particles of different sizes on surfaces are prepared artificially based on the file and sieve. Damage test is implemented in air using a 1-on-1 mode. Results show that damage morphology and mechanism caused by particulate contamination on the incident and exit surfaces are quite different. Contaminants on the incident surface absorb laser energy and generate high temperature plasma during laser irradiation which can ablate optical surface. Metal particles melt and then the molten nano-particles redeposit around the initial particles. Central region of the damaged area bears the same outline as the initial particle because of the shielding effect. However, particles on the exit surface absorb a mass of energy, generate plasma and splash lots of smaller particles, only a few of them redeposit at the particle coverage area on the exit surface. Most of the laser energy is deposited at the interface of the metal particle and the sample surface, and thus damage size on the exit surface is larger than that on the incident surface. The areas covered by the metal particle are strongly damaged. And the damage sites are more serious than that on the incident surface. Besides damage phenomenon also depends on coating and substrate materials.

Noninvasive Mechanical Ventilation in Acute Ventilatory Failure: Rationale and Current Applications.

PubMed

Esquinas, Antonio M; Benhamou, Maly Oron; Glossop, Alastair J; Mina, Bushra

2017-12-01

Noninvasive ventilation plays a pivotal role in acute ventilator failure and has been shown, in certain disease processes such as acute exacerbation of chronic obstructive pulmonary disease, to prevent and shorten the duration of invasive mechanical ventilation, reducing the risks and complications associated with it. The application of noninvasive ventilation is relatively simple and well tolerated by patients and in the right setting can change the course of their illness. Copyright © 2017 Elsevier Inc. All rights reserved.

A micromechanical study of the damage mechanics of acrylic particulate composites under thermomechanical loading

NASA Astrophysics Data System (ADS)

Nie, Shihua

The main aim of this dissertation was to characterize the damage mechanism and fatigue behavior of the acrylic particulate composite. This dissertation also investigated how the failure mechanism is influenced by changes in certain parameters including the volume fraction of particle, the interfacial bonding strength, the stiffness and thickness of the interphase, and the CTE mismatch between the particle and the matrix. Monotonic uniaxial tensile and compressive testing under various temperatures and strain rates, isothermal low-cycle mechanical testing and thermal cycling of a plate with a cutout were performed. The influence of the interfacial bonding strength between the particle and the matrix on the failure mechanism of the ATH filled PMMA was investigated using in situ observations under uniaxial loading conditions. For composites with weak interfacial bonding, the debonding is the major damage mode. For composites with strong interfacial bonding, the breakage of the agglomerate of particles is the major damage mode. Experimental studies also demonstrated the significant influence of interfacial bonding strength on the fatigue life of the ATH filled PMMA. The damage was characterized in terms of the elastic modulus degradation, the load-drop parameter, the plastic strain range and the hysteresis dissipation. Identifying the internal state variables that quantify material degradation under thermomechanical loading is an active research field. In this dissertation, the entropy production, which is a measure of the irreversibility of the thermodynamic system, is used as the metric for damage. The close correlation between the damage measured in terms of elastic modulus degradation and that obtained from the finite element simulation results validates the entropy based damage evolution function. A micromechanical model for acrylic particulate composites with imperfect interfacial bonds was proposed. Acrylic particulate composites are treated as three

Regional Availability of Mechanical Embolectomy for Acute Ischemic Stroke in California, 2009 to 2010

PubMed Central

Choi, Jay Chol; Hsia, Renee Y.

2015-01-01

Background and Purpose— We sought to assess the geographic proximity of patients with stroke in California to centers that performed specific threshold volumes of mechanical embolectomy procedures each year. Methods— We identified all patients who were hospitalized for acute ischemic stroke at all nonfederal acute care hospitals in California from 2009 to 2010, and all hospitals that performed any mechanical embolectomy procedures by case volume during the same period, using nonpublic data from the Office of Statewide Health Planning and Development. We computed geographic service areas around each hospital on the basis of prespecified ground transport distance thresholds. We then calculated the proportion of hospitalized patients with stroke who lived within service areas for centers that performed a low volume and high volume of mechanical embolectomy procedures each year. Results— During the 2-year study period, 15% (53/360) of hospitals performed at least 1 mechanical embolectomy for acute stroke, but only 19% (10/53) performed >10 cases per year. Most hospitalized patients with stroke (94%) lived within a 2-hour transport time (65 miles) to a hospital that performed ≥1 procedure during the 2-year period. Approximately 93% of the patients with stroke who received mechanical embolectomy lived within 20 miles from an embolectomy-capable hospital compared with 7% of those who lived >20 miles. Conclusions— In California, most patients with stroke lived within reasonable ground transport distances from centers that performed ≥1 mechanical embolectomy in a 2-year period. The probability of receiving mechanical embolectomy for acute ischemic stroke was associated with living in close geographic proximity to these hospitals. PMID:25657180

Fisetin Protects DNA Against Oxidative Damage and Its Possible Mechanism.

PubMed

Wang, Tingting; Lin, Huajuan; Tu, Qian; Liu, Jingjing; Li, Xican

2016-06-01

The paper tries to assess the protective effect of fisetin against •OH-induced DNA damage, then to investigate the possible mechanism. The protective effect was evaluated based on the content of malondialdehyde (MDA). The possible mechanism was analyzed using various antioxidant methods in vitro, including •OH scavenging (deoxyribose degradation), •O2 (-) scavenging (pyrogallol autoxidation), DPPH• scavenging, ABTS•(+) scavenging, and Cu(2+)-reducing power assays. Fisetin increased dose-dependently its protective percentages against •OH-induced DNA damage (IC50 value =1535.00±29.60 µM). It also increased its radical-scavenging percentages in a dose-dependent manner in various antioxidants assays. Its IC50 values in •OH scavenging, •O2(-) scavenging, DPPH• scavenging, ABTS•(+) scavenging, and Cu(2+)-reducing power assays, were 47.41±4.50 µM, 34.05±0.87 µM, 9.69±0.53 µM, 2.43±0.14 µM, and 1.49±0.16 µM, respectively. Fisetin can effectively protect DNA against •OH-induced oxidative damage possibly via reactive oxygen species (ROS) scavenging approach, which is assumed to be hydrogen atom (H•) and/or single electron (e) donation (HAT/SET) pathways. In the HAT pathway, the 3',4'-dihydroxyl moiety in B ring of fisetin is thought to play an important role, because it can be ultimately oxidized to a stable ortho-benzoquinone form.

Fisetin Protects DNA Against Oxidative Damage and Its Possible Mechanism

PubMed Central

Wang, Tingting; Lin, Huajuan; Tu, Qian; Liu, Jingjing; Li, Xican

2016-01-01

Purpose: The paper tries to assess the protective effect of fisetin against •OH-induced DNA damage, then to investigate the possible mechanism. Methods: The protective effect was evaluated based on the content of malondialdehyde (MDA). The possible mechanism was analyzed using various antioxidant methods in vitro, including •OH scavenging (deoxyribose degradation), •O2- scavenging (pyrogallol autoxidation), DPPH• scavenging, ABTS•+ scavenging, and Cu2+-reducing power assays. Results: Fisetin increased dose-dependently its protective percentages against •OH-induced DNA damage (IC50 value =1535.00±29.60 µM). It also increased its radical-scavenging percentages in a dose-dependent manner in various antioxidants assays. Its IC50 values in •OH scavenging, •O2- scavenging, DPPH• scavenging, ABTS•+ scavenging, and Cu2+-reducing power assays, were 47.41±4.50 µM, 34.05±0.87 µM, 9.69±0.53 µM, 2.43±0.14 µM, and 1.49±0.16 µM, respectively. Conclusion: Fisetin can effectively protect DNA against •OH-induced oxidative damage possibly via reactive oxygen species (ROS) scavenging approach, which is assumed to be hydrogen atom (H•) and/or single electron (e) donation (HAT/SET) pathways. In the HAT pathway, the 3’,4’-dihydroxyl moiety in B ring of fisetin is thought to play an important role, because it can be ultimately oxidized to a stable ortho-benzoquinone form. PMID:27478791

Determination on Damage Mechanism of the Planet Gear of Heavy Vehicle Final Drive

NASA Astrophysics Data System (ADS)

Ramdan, RD; Setiawan, R.; Sasmita, F.; Suratman, R.; Taufiqulloh

2018-02-01

The works focus on the investigation of damage mechanism of fractured in the form of spalling of the planet gears from the final drive assembly of 160-ton heavy vehicles. The objective of this work is to clearly understand the mechanism of damage. The work is the first stage of the on-going research on the remaining life estimation of such gears. The understanding of the damage mechanism is critical in order to provide accurate estimate of the gear’s remaining life with observed initial damage. The analysis was performed based on the metallurgy laboratory works, including visual observation, macro-micro fractography by optical stereo and optical microscope and micro-vickers hardness test. From visual observation it was observed pitting that form lining defect at common position, which is at gear flank position. From spalling sample it was observed ratchet mark at the boundary between macro pitting and the edge of fractured parts. Further observation on the cross-section of the samples by optical microscope confirm that initial micro pitting occur without spalling of the case hardened surface. Spalling occur when pitting achieve certain critical size, and occur at multiple initiation site of crack propagation. From the present research it was concluded that pitting was resulted due to repeated contact fatigue. In addition, development of micro to macro pitting as well as spalling occur at certain direction towards the top of the gear teeth.

Oxidative Damage and Cellular Defense Mechanisms in Sea Urchin Models of Aging

PubMed Central

Du, Colin; Anderson, Arielle; Lortie, Mae; Parsons, Rachel; Bodnar, Andrea

2013-01-01

The free radical or oxidative stress theory of aging proposes that the accumulation of oxidative cellular damage is a major contributor to the aging process and a key determinant of species longevity. This study investigates the oxidative stress theory in a novel model for aging research, the sea urchin. Sea urchins present a unique model for the study of aging due to the existence of species with tremendously different natural life spans including some species with extraordinary longevity and negligible senescence. Cellular oxidative damage, antioxidant capacity and proteasome enzyme activities were measured in the tissues of three sea urchin species: short-lived Lytechinus variegatus, long-lived Strongylocentrotus franciscanus and Strongylocentrotus purpuratus which has an intermediate lifespan. Levels of protein carbonyls and 4-hydroxynonenal (HNE) measured in tissues (muscle, nerve, esophagus, gonad, coelomocytes, ampullae) and 8-hydroxy-2’-deoxyguanosine (8-OHdG) measured in cell-free coelomic fluid showed no general increase with age. The fluorescent age-pigment lipofuscin measured in muscle, nerve and esophagus, increased with age however it appeared to be predominantly extracellular. Antioxidant mechanisms (total antioxidant capacity, superoxide dismutase) and proteasome enzyme activities were maintained with age. In some instances, levels of oxidative damage were lower and antioxidant activity higher in cells or tissues of the long-lived species compared to the short-lived species, however further studies are required to determine the relationship between oxidative damage and longevity in these animals. Consistent with the predictions of the oxidative stress theory of aging, the results suggest that negligible senescence is accompanied by a lack of accumulation of cellular oxidative damage with age and maintenance of antioxidant capacity and proteasome enzyme activities may be important mechanisms to mitigate damage. PMID:23707327

Oxidative damage and cellular defense mechanisms in sea urchin models of aging.

PubMed

Du, Colin; Anderson, Arielle; Lortie, Mae; Parsons, Rachel; Bodnar, Andrea

2013-10-01

The free radical, or oxidative stress, theory of aging proposes that the accumulation of oxidative cellular damage is a major contributor to the aging process and a key determinant of species longevity. This study investigates the oxidative stress theory in a novel model for aging research, the sea urchin. Sea urchins present a unique model for the study of aging because of the existence of species with tremendously different natural life spans, including some species with extraordinary longevity and negligible senescence. Cellular oxidative damage, antioxidant capacity, and proteasome enzyme activities were measured in the tissues of three sea urchin species: short-lived Lytechinus variegatus, long-lived Strongylocentrotus franciscanus, and Strongylocentrotus purpuratus, which has an intermediate life span. Levels of protein carbonyls and 4-hydroxynonenal measured in tissues (muscle, nerve, esophagus, gonad, coelomocytes, ampullae) and 8-hydroxy-2'-deoxyguanosine measured in cell-free coelomic fluid showed no general increase with age. The fluorescent age pigment lipofuscin, measured in muscle, nerve, and esophagus, increased with age; however, it appeared to be predominantly extracellular. Antioxidant mechanisms (total antioxidant capacity, superoxide dismutase) and proteasome enzyme activities were maintained with age. In some instances, levels of oxidative damage were lower and antioxidant activity higher in cells or tissues of the long-lived species compared to the short-lived species; however, further studies are required to determine the relationship between oxidative damage and longevity in these animals. Consistent with the predictions of the oxidative stress theory of aging, the results suggest that negligible senescence is accompanied by a lack of accumulation of cellular oxidative damage with age, and maintenance of antioxidant capacity and proteasome enzyme activities may be important mechanisms to mitigate damage. Copyright © 2013 Elsevier Inc. All

Genotoxic Evaluation of Mikania laevigata Extract on DNA Damage Caused by Acute Coal Dust Exposure

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

Freitas, T.P.; Heuser, V.D.; Tavares, P.

2009-06-15

We report data on the possible antigenotoxic activity of Mikania laevigata extract (MLE) after acute intratracheal instillation of coal dust using the comet assay in peripheral blood, bone marrow, and liver cells and the micronucleus test in peripheral blood of Wistar rats. The animals were pretreated for 2 weeks with saline solution (groups 1 and 2) or MLE (100 mg/kg) (groups 3 and 4). On day 15, the animals were anesthetized with ketamine (80 mg/kg) and xylazine (20 mg/kg), and gross mineral coal dust (3 mg/0.3 mL saline) (groups 2 and 4) or saline solution (0.3 mL) (groups 1 andmore » 3) was administered directly in the lung by intratracheal administration. Fifteen days after coal dust or saline instillation, the animals were sacrificed, and the femur, liver, and peripheral blood were removed. The results showed a general increase in the DNA damage values at 8 hours for all treatment groups, probably related to surgical procedures that had stressed the animals. Also, liver cells from rats treated with coal dust, pretreated or not with MLE, showed statistically higher comet assay values compared to the control group at 14 days after exposure. These results could be expected because the liver metabolizes a variety of organic compounds to more polar by-products. On the other hand, the micronucleus assay results did not show significant differences among groups. Therefore, our data do not support the antimutagenic activity of M. laevigata as a modulator of DNA damage after acute coal dust instillation.« less

Outrunning damage: Electrons vs X-rays-timescales and mechanisms.

PubMed

Spence, John C H

2017-07-01

Toward the end of his career, Zewail developed strong interest in fast electron spectroscopy and imaging, a field to which he made important contributions toward his aim of making molecular movies free of radiation damage. We therefore compare here the atomistic mechanisms leading to destruction of protein samples in diffract-and-destroy experiments for the cases of high-energy electron beam irradiation and X-ray laser pulses. The damage processes and their time-scales are compared and relevant elastic, inelastic, and photoelectron cross sections are given. Inelastic mean-free paths for ejected electrons at very low energies in insulators are compared with the bioparticle size. The dose rate and structural damage rate for electrons are found to be much lower, allowing longer pulses, reduced beam current, and Coulomb interactions for the formation of smaller probes. High-angle electron scattering from the nucleus, which has no parallel in the X-ray case, tracks the slowly moving nuclei during the explosion, just as the gain of the XFEL (X-ray free-electron laser) has no parallel in the electron case. Despite reduced damage and much larger elastic scattering cross sections in the electron case, leading to not dissimilar elastic scattering rates (when account is taken of the greatly increased incident XFEL fluence), progress for single-particle electron diffraction is seen to depend on the effort to reduce emittance growth due to Coulomb interactions, and so allow formation of intense sub-micron beams no larger than a virus.

Outrunning damage: Electrons vs X-rays—timescales and mechanisms

PubMed Central

Spence, John C. H.

2017-01-01

Toward the end of his career, Zewail developed strong interest in fast electron spectroscopy and imaging, a field to which he made important contributions toward his aim of making molecular movies free of radiation damage. We therefore compare here the atomistic mechanisms leading to destruction of protein samples in diffract-and-destroy experiments for the cases of high-energy electron beam irradiation and X-ray laser pulses. The damage processes and their time-scales are compared and relevant elastic, inelastic, and photoelectron cross sections are given. Inelastic mean-free paths for ejected electrons at very low energies in insulators are compared with the bioparticle size. The dose rate and structural damage rate for electrons are found to be much lower, allowing longer pulses, reduced beam current, and Coulomb interactions for the formation of smaller probes. High-angle electron scattering from the nucleus, which has no parallel in the X-ray case, tracks the slowly moving nuclei during the explosion, just as the gain of the XFEL (X-ray free-electron laser) has no parallel in the electron case. Despite reduced damage and much larger elastic scattering cross sections in the electron case, leading to not dissimilar elastic scattering rates (when account is taken of the greatly increased incident XFEL fluence), progress for single-particle electron diffraction is seen to depend on the effort to reduce emittance growth due to Coulomb interactions, and so allow formation of intense sub-micron beams no larger than a virus. PMID:28653018

A psychodynamic model of behavior after acute central nervous system damage.

PubMed

Groswasser, Z; Stern, M J

1998-02-01

This article describes a conceptual psychodynamic model for understanding the neurobehavioral manifestations of acute central nervous system damage (ACNSD) displayed by patients during the rehabilitation process. According to the proposed model, patientsO behavioral responses are viewed as their only means of emotional expression and therefore may not be considered entirely abnormal when viewed from the perspective of patientsO interpersonal contexts. An improved understanding of the dynamic processes through which recovering patients with ACNSD journey may lead to better interaction between the patient and the therapeutic environment, the interdisciplinary team, and family members. Combining this proposed psychodynamic model with an emerging understanding of the neurobehavioral foundations of aggression and depression may also lead to a more rational approach to intervention with various psychopharmacologic agents. During the rehabilitation process, understanding patients' cognitive deficits, motivational drives, and emotional needs and proper implementation of medical and environmental treatment can ultimately lead to a better psychosocial outcome.

Surface-structure dependence of healing radiation-damage mechanism in nanoporous tungsten

NASA Astrophysics Data System (ADS)

Duan, Guohua; Li, Xiangyan; Sun, Jingjing; Hao, Congyu; Xu, Yichun; Zhang, Yange; Liu, Wei; Liu, C. S.

2018-01-01

Under nuclear fusion environments, displacement damage in tungsten (W) is usually caused by neutrons irradiation through producing large quantities of vacancies (Vs) and self-interstitial atoms (SIAs). These defects not only affect the mechanical properties of W, but also act as the trap sites for implanted hydrogen isotopes and helium. Nano-porous (NP) W with a high fraction of free surfaces has been developed to mitigate the radiation damage. However, the mechanism of the surface reducing defects accumulation is not well understood. By using multi-scale simulation methods, we investigated the interaction of the SIA and V with different surfaces on across length and time scales. We found that, at a typical operation temperature of 1000 K, surface (1 1 0) preferentially heals radiation damage of W compared with surface (1 0 0) and boundary (3 1 0). On surface (1 1 0), the diffusion barrier for the SIA is only 0.68 eV. The annihilation of the SIA-V happens via the coupled motion of the V segregation towards the surface from the bulk and the two-dimensional diffusion of the SIA on the surface. Such mechanism makes the surface (1 1 0) owe better healing capability. On surface (1 0 0), the diffusion energy barrier for the SIA is 2.48 eV, higher than the diffusion energy barrier of the V in bulk. The annihilation of the SIA-V occurs via the V segregation and recombination. The SIA was found to migrate one-dimensionally along a boundary (3 1 0) with a barrier of 0.21 eV, leading to a lower healing efficiency in the boundary. This study suggested that the on-surface process plays an important role in healing radiation damage of NP W in addition to surface-enhanced diffusion and annihilation near the surface. A certain surface structure renders nano-structured W more radiation-tolerant.

Damage evolution and mechanical response of cross-ply ceramic composite laminates

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

Weitsman, Y.; Yu, N.; Zhu, H.

1995-12-31

A mechanistic model for the damage evolution and mechanical response of cross-ply ceramic composite laminates under monotonically increasing uniaxial tension is presented. The model accounts for a variety of damage mechanisms evolving in cross-ply ceramic composite laminates, such as fiber-bridged matrix cracks in 0{degrees}-plies, transversely oriented matrix cracks in 90{degrees}-plies, and slips at 0{degrees}/90{degrees} ply interfaces as well as at the fiber/matrix interfaces. Energy criteria are developed to determine the creation and progression of matrix cracks and slip zones. The model predicts that the crack density in 0{degrees}-plies becomes higher than that within the 90{degrees}-plies as the applied load ismore » incrementally increased, which agrees with the experimental observation. It is also shown that the model provides a reasonable prediction for the nonlinear stress-strain behavior of crossply SiC/CAS ceramic composites.« less

Collagen insulated from tensile damage by domains that unfold reversibly: in situ X-ray investigation of mechanical yield and damage repair in the mussel byssus

PubMed Central

Harrington, Matthew J.; Gupta, Himadri S.; Fratzl, Peter; Waite, J. Herbert

2009-01-01

The byssal threads of the California mussel, Mytilus californianus, are highly hysteretic, elastomeric fibers that collectively perform a holdfast function in wave-swept rocky seashore habitats. Following cyclic loading past the mechanical yield point, threads exhibit a damage-dependent reduction in mechanical performance. However, the distal portion of the byssal thread is capable of recovering initial material properties through a time-dependent healing process in the absence of active cellular metabolism. Byssal threads are composed almost exclusively of multi-domain hybrid collagens known as preCols, which largely determine the mechanical properties of the thread. Here, the structure-property relationships that govern thread mechanical performance are further probed. The molecular rearrangements that occur during yield and damage repair were investigated using time-resolved in situ wide angle X-ray diffraction (WAXD) coupled with cyclic tensile loading of threads and through thermally enhanced damage-repair studies. Results indicate that the collagen domains in byssal preCols are mechanically protected by the unfolding of sacrificial non-collagenous domains that refold on a slower time-scale. Time-dependent healing is primarily attributed to stochastic recoupling of broken histidine-metal coordination complexes. PMID:19275941

Damage tolerance assessment handbook. Volume 1 : introduction, fracture mechanics, fatigue crack propagation

DOT National Transportation Integrated Search

1999-02-01

The handbook is presented in two volumes. This volume, Volume I, introduces the damage tolerance concept with an historical perspective followed by the fundamentals of fracture mechanics and fatigue crack propagation. Various fracture criteria and cr...

Mechanical Thrombectomy in Patients With Acute Ischemic Stroke: A Health Technology Assessment

PubMed Central

2016-01-01

Background In Ontario, current treatment for eligible patients who have an acute ischemic stroke is intravenous thrombolysis (IVT). However, there are some limitations and contraindications to IVT, and outcomes may not be favourable for patients with stroke caused by a proximal intracranial occlusion. An alternative is mechanical thrombectomy with newer devices, and a number of recent studies have suggested that this treatment is more effective for improving functional independence and clinical outcomes. The objective of this health technology assessment was to evaluate the clinical effectiveness and cost-effectiveness of new-generation mechanical thrombectomy devices (with or without IVT) compared to IVT alone (if eligible) in patients with acute ischemic stroke. Methods We conducted a systematic review of the literature, limited to randomized controlled trials that examined the effectiveness of mechanical thrombectomy using stent retrievers and thromboaspiration devices for patients with acute ischemic stroke. We assessed the quality of the evidence using the GRADE approach. We developed a Markov decision-analytic model to assess the cost-effectiveness of mechanical thrombectomy (with or without IVT) versus IVT alone (if eligible), calculated incremental cost-effectiveness ratios using a 5-year time horizon, and conducted sensitivity analyses to examine the robustness of the estimates. Results There was a substantial, statistically significant difference in rate of functional independence (GRADE: high quality) between those who received mechanical thrombectomy (with or without IVT) and IVT alone (odds ratio [OR] 2.39, 95% confidence interval [CI] 1.88–3.04). We did not observe a difference in mortality (GRADE: moderate quality) (OR 0.80, 95% CI 0.60–1.07) or symptomatic intracerebral hemorrhage (GRADE: moderate quality) (OR 1.11, 95% CI 0.66–1.87). In the base-case cost-utility analysis, which had a 5 year time horizon, the costs and effectiveness for

Fracture-Based Mesh Size Requirements for Matrix Cracks in Continuum Damage Mechanics Models

NASA Technical Reports Server (NTRS)

Leone, Frank A.; Davila, Carlos G.; Mabson, Gerald E.; Ramnath, Madhavadas; Hyder, Imran

2017-01-01

This paper evaluates the ability of progressive damage analysis (PDA) finite element (FE) models to predict transverse matrix cracks in unidirectional composites. The results of the analyses are compared to closed-form linear elastic fracture mechanics (LEFM) solutions. Matrix cracks in fiber-reinforced composite materials subjected to mode I and mode II loading are studied using continuum damage mechanics and zero-thickness cohesive zone modeling approaches. The FE models used in this study are built parametrically so as to investigate several model input variables and the limits associated with matching the upper-bound LEFM solutions. Specifically, the sensitivity of the PDA FE model results to changes in strength and element size are investigated.

Acute carbon tetrachloride induced lysosomal membrane damage and the membrane protecting effect of a new dihydroquinoline-type antioxidant.

PubMed

Toncsev, H; Pollák, Z; Kiss, A; Sréter, L; Fehér, J

1982-01-01

The authors examined the damage of lysosomal membrane caused by acute CCl4 intoxication by in vitro methods. They measured the acid phosphatase as well as beta-glucuronidase enzyme levels and determined the rate of release of these two enzymes. The in vivo changes in enzyme activity were extrapolated from the in vitro results. The CCl4 causes a significant increase in the permeability and rigidity of the lysosomal membrane. By oral and/or intraperitoneal administration of MTDQ the state of permeability can be improved or even corrected. On the basis of their results, the authors conclude that the lysosomal damage caused by CCl4 is mediated by peroxidation of lipids and the lysosomal membrane can be stabilised by MTDQ.

[Non-invasive mechanical ventilation in the treatment of acute heart failure].

PubMed

Alfonso Megido, Joaquín; González Franco, Alvaro

2014-03-01

When acute heart failure progresses and there is acute cardiogenic pulmonary edema, routine therapeutic measures should be accompanied by other measures that help to correct oxygenation of the patient. The final and most drastic step is mechanical ventilation. Non-invasive ventilation has been developed in the last few years as a method that attempts to improve oxygenation without the need for intubation, thus, in theory, reducing morbidity and mortality in these patients. The present article describes the controversies surrounding the results of this technique and discusses its indications. The article also discusses how to start non-invasive ventilation in patients with acute pulmonary edema from a practical point of view. Copyright © 2014 Elsevier España, S.L. All rights reserved.

Multiscale Fiber Kinking: Computational Micromechanics and a Mesoscale Continuum Damage Mechanics Models

NASA Technical Reports Server (NTRS)

Herraez, Miguel; Bergan, Andrew C.; Gonzalez, Carlos; Lopes, Claudio S.

2017-01-01

In this work, the fiber kinking phenomenon, which is known as the failure mechanism that takes place when a fiber reinforced polymer is loaded under longitudinal compression, is studied. A computational micromechanics model is employed to interrogate the assumptions of a recently developed mesoscale continuum damage mechanics (CDM) model for fiber kinking based on the deformation gradient decomposition (DGD) and the LaRC04 failure criteria.

Effect of stacking angles on mechanical properties and damage propagation of plain woven carbon fiber laminates

NASA Astrophysics Data System (ADS)

Zhuang, Weimin; Ao, Wenhong

2018-03-01

Damage propagation induced failure is a predominant damage mechanism. This study is aimed at assessing the damage state and damage propagation induced failure with different stacking angles, of woven carbon fiber/epoxy laminates subjected to quasi-static tensile and bending load. Different stages of damage processing and damage behavior under the bending load are investigated by Scanning Electron Microscopy (SEM). The woven carbon fiber/epoxy laminates which are stacked at six different angles (0°, 15°, 30°, 45°, 60°, 75°) with eight plies have been analyzed: [0]8, [15]8, [30]8, [45]8, [60]8, [75]8. Three-point bending test and quasi-static tensile test are used in validating the woven carbon fiber/epoxy laminates’ mechanical properties. Furthermore, the damage propagation and failure modes observed under flexural loading is correlated with flexural force and load-displacement behaviour respectively for the laminates. The experimental results have indicated that [45]8 laminate exhibits the best flexural performance in terms of energy absorption duo to its pseudo-ductile behaviour but the tensile strength and flexural strength drastically decreased compared to [0]8 laminate. Finally, SEM micrographs of specimens and fracture surfaces are used to reveal the different types of damage of the laminates with different stacking angles.

Dissecting the Molecular Mechanism of Ionizing Radiation-Induced Tissue Damage in the Feather Follicle

PubMed Central

Chen, Xi; Liao, Chunyan; Chu, Qiqi; Zhou, Guixuan; Lin, Xiang; Li, Xiaobo; Lu, Haijie; Xu, Benhua; Yue, Zhicao

2014-01-01

Ionizing radiation (IR) is a common therapeutic agent in cancer therapy. It damages normal tissue and causes side effects including dermatitis and mucositis. Here we use the feather follicle as a model to investigate the mechanism of IR-induced tissue damage, because any perturbation of feather growth will be clearly recorded in its regular yet complex morphology. We find that IR induces defects in feather formation in a dose-dependent manner. No abnormality was observed at 5 Gy. A transient, reversible perturbation of feather growth was induced at 10 Gy, leading to defects in the feather structure. This perturbation became irreversible at 20 Gy. Molecular and cellular analysis revealed P53 activation, DNA damage and repair, cell cycle arrest and apoptosis in the pathobiology. IR also induces patterning defects in feather formation, with disrupted branching morphogenesis. This perturbation is mediated by cytokine production and Stat1 activation, as manipulation of cytokine levels or ectopic Stat1 over-expression also led to irregular feather branching. Furthermore, AG-490, a chemical inhibitor of Stat1 signaling, can partially rescue IR-induced tissue damage. Our results suggest that the feather follicle could serve as a useful model to address the in vivo impact of the many mechanisms of IR-induced tissue damage. PMID:24586618

Diffuse Alveolar Damage: A Common Phenomenon in Progressive Interstitial Lung Disorders

PubMed Central

Kaarteenaho, Riitta; Kinnula, Vuokko L.

2011-01-01

It has become obvious that several interstitial lung diseases, and even viral lung infections, can progress rapidly, and exhibit similar features in their lung morphology. The final histopathological feature, common in these lung disorders, is diffuse alveolar damage (DAD). The histopathology of DAD is considered to represent end stage phenomenon in acutely behaving interstitial pneumonias, such as acute interstitial pneumonia (AIP) and acute exacerbations of idiopathic pulmonary fibrosis (IPF). Acute worsening and DAD may occur also in patients with nonspecific interstitial pneumonias (NSIPs), and even in severe viral lung infections where there is DAD histopathology in the lung. A better understanding of the mechanisms underlying the DAD reaction is needed to clarify the treatment for these serious lung diseases. There is an urgent need for international efforts for studying DAD-associated lung diseases, since the prognosis of these patients has been and is still dismal. PMID:21637367

Neuroinflammation markers and methyl alcohol induced toxic brain damage.

PubMed

Zakharov, Sergey; Hlusicka, Jiri; Nurieva, Olga; Kotikova, Katerina; Lischkova, Lucie; Kacer, Petr; Kacerova, Tereza; Urban, Pavel; Vaneckova, Manuela; Seidl, Zdenek; Diblik, Pavel; Kuthan, Pavel; Heissigerova, Jarmila; Lesovsky, Jiri; Rulisek, Jan; Vojtova, Lucie; Hubacek, Jaroslav A; Navratil, Tomas

2018-05-04

Methyl alcohol intoxication is a global problem with high mortality and long-term visual sequelae and severe brain damage in survivors. The role of neuroinflammation in the mechanisms of methyl alcohol-induced toxic brain damage has not been well studied. We measured the acute concentrations and dynamics of lipoxins LxA4 and LxB4 and the interleukins IL-4, IL-5, IL-9, IL-10, and IL-13 in the serum of patients treated with methyl alcohol poisoning and the follow-up concentrations in survivors two years after discharge from the hospital. A series of acute measurements was performed in 28 hospitalized patients (mean age 54.2 ± 5.2 years, mean observation time 88 ± 20 h) and the follow-up measurements were performed in 36 subjects who survived poisoning (including 12/28 survivors from the acute group). Visual evoked potentials (VEP) and magnetic resonance imaging of the brain (MRI) were performed to detect long-term visual and brain sequelae of intoxication. The acute concentrations of inflammatory mediators were higher than the follow-up concentrations: LxA4, 62.0 ± 6.0 vs. 30.0 ± 5.0 pg/mL; LxB4, 64.0 ± 7.0 vs. 34.0 ± 4.0 pg/mL; IL-4, 29.0 ± 4.0 vs. 15.0 ± 1.0 pg/mL; IL-5, 30.0 ± 4.0 vs. 13.0 ± 1.0 pg/mL; IL-9, 30.0 ± 4.0 vs. 13.0 ± 1.0 pg/mL; IL-10, 38.0 ± 5.0 vs. 16.0 ± 1.0 pg/mL; IL-13, 35.0 ± 4.0 vs. 14.0 ± 1.0 pg/mL (all p < 0.001). The patients with higher follow-up IL-5 concentration had prolonged latency P1 (r = 0.413; p = 0.033) and lower amplitude N1P1 (r = -0.498; p = 0.010) of VEP. The higher follow-up IL-10 concentration was associated with MRI signs of brain necrotic damage (r = 0.533; p = 0.001) and brain hemorrhage (r = 0.396; p = 0.020). Our findings suggest that neuroinflammation plays an important role in the mechanisms of toxic brain damage in acute methyl alcohol intoxication. Copyright © 2018 Elsevier B.V. All

Strategies for the evaluation of DNA damage and repair mechanisms in cancer.

PubMed

Figueroa-González, Gabriela; Pérez-Plasencia, Carlos

2017-06-01

DNA lesions and the repair mechanisms that maintain the integrity of genomic DNA are important in preventing carcinogenesis and its progression. Notably, mutations in DNA repair mechanisms are associated with cancer predisposition syndromes. Additionally, these mechanisms maintain the genomic integrity of cancer cells. The majority of therapies established to treat cancer are genotoxic agents that induce DNA damage, promoting cancer cells to undergo apoptotic death. Effective methods currently exist to evaluate the diverse effects of genotoxic agents and the underlying molecular mechanisms that repair DNA lesions. The current study provides an overview of a number of methods that are available for the detection, analysis and quantification of underlying DNA repair mechanisms.

Maltol, a Food Flavoring Agent, Attenuates Acute Alcohol-Induced Oxidative Damage in Mice

PubMed Central

Han, Ye; Xu, Qi; Hu, Jiang-ning; Han, Xin-yue; Li, Wei; Zhao, Li-chun

2015-01-01

The purpose of this study was to evaluate the hepatoprotective effect of maltol, a food-flavoring agent, on alcohol-induced acute oxidative damage in mice. Maltol used in this study was isolated from red ginseng (Panax ginseng C.A Meyer) and analyzed by high performance liquid chromatography (HPLC) and mass spectrometry. For hepatoprotective activity in vivo, pretreatment with maltol (12.5, 25 and 50 mg/kg; 15 days) drastically prevented the elevated activities of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and triglyceride (TG) in serum and the levels of malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) in liver tissue (p < 0.05). Meanwhile, the levels of hepatic antioxidant, such as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) were elevated by maltol pretreatment, compared to the alcohol group (p < 0.05). Histopathological examination revealed that maltol pretreatment significantly inhibited alcohol-induced hepatocyte apoptosis and fatty degeneration. Interestingly, pretreatment of maltol effectively relieved alcohol-induced oxidative damage in a dose-dependent manner. Maltol appeared to possess promising anti-oxidative and anti-inflammatory capacities. It was suggested that the hepatoprotective effect exhibited by maltol on alcohol-induced liver oxidative injury may be due to its potent antioxidant properties. PMID:25608939

Organ protection possibilities in acute heart failure.

PubMed

Montero-Pérez-Barquero, M; Morales-Rull, J L

2016-04-01

Unlike chronic heart failure (HF), the treatment for acute HF has not changed over the last decade. The drugs employed have shown their ability to control symptoms but have not achieved organ protection or managed to reduce medium to long-term morbidity and mortality. Advances in our understanding of the pathophysiology of acute HF suggest that treatment should be directed not only towards correcting the haemodynamic disorders and achieving symptomatic relief but also towards preventing organ damage, thereby counteracting myocardial remodelling and cardiac and extracardiac disorders. Compounds that exert vasodilatory and anti-inflammatory action in the acute phase of HF and can stop cell death, thereby boosting repair mechanisms, could have an essential role in organ protection. Copyright © 2016 Elsevier España, S.L.U. y Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Chromosomal bands affected by acute oil exposure and DNA repair errors.

PubMed

Monyarch, Gemma; de Castro Reis, Fernanda; Zock, Jan-Paul; Giraldo, Jesús; Pozo-Rodríguez, Francisco; Espinosa, Ana; Rodríguez-Trigo, Gema; Verea, Hector; Castaño-Vinyals, Gemma; Gómez, Federico P; Antó, Josep M; Coll, Maria Dolors; Barberà, Joan Albert; Fuster, Carme

2013-01-01

In a previous study, we showed that individuals who had participated in oil clean-up tasks after the wreckage of the Prestige presented an increase of structural chromosomal alterations two years after the acute exposure had occurred. Other studies have also reported the presence of DNA damage during acute oil exposure, but little is known about the long term persistence of chromosomal alterations, which can be considered as a marker of cancer risk. We analyzed whether the breakpoints involved in chromosomal damage can help to assess the risk of cancer as well as to investigate their possible association with DNA repair efficiency. Cytogenetic analyses were carried out on the same individuals of our previous study and DNA repair errors were assessed in cultures with aphidicolin. Three chromosomal bands, 2q21, 3q27 and 5q31, were most affected by acute oil exposure. The dysfunction in DNA repair mechanisms, expressed as chromosomal damage, was significantly higher in exposed-oil participants than in those not exposed (p= 0.016). The present study shows that breaks in 2q21, 3q27 and 5q31 chromosomal bands, which are commonly involved in hematological cancer, could be considered useful genotoxic oil biomarkers. Moreover, breakages in these bands could induce chromosomal instability, which can explain the increased risk of cancer (leukemia and lymphomas) reported in chronically benzene-exposed individuals. In addition, it has been determined that the individuals who participated in clean-up of the oil spill presented an alteration of their DNA repair mechanisms two years after exposure.

Hypogonadotrophism fails to prevent severe testicular damage induced by total body irradiation in a patient with beta-thalassaemia major and acute lymphoblastic leukaemia.

PubMed

Chatterjee, R; Kottaridis, P D; McGarrigle, H H; Papatryphonos, A; Goldstone, A H

2001-11-01

Radiation and chemotherapeutic drugs for cancer produce prolonged and often irreversible gonadal damage. To determine whether total body irradiation (TBI)-induced gonadal damage can be prevented by suppression of pituitary gonadotrophin levels, we studied a patient with transfusion dependent homozygous beta-thalassaemia and acute lymphoblastic leukaemia (ALL) who underwent one-antigen mismatched related bone marrow transplantation (BMT). Our data showed that despite having hypogonadotrophic hypogonadism (HH) prior to BMT, the patient developed primary testicular failure following the procedure, indicating that hypogonadotrophism failed to offer protection against TBI-induced testicular damage in this patient. Although this is an interesting case report, no firm conclusions can be drawn from a single patient.

Anisotropic mechanical properties of zircon and the effect of radiation damage

NASA Astrophysics Data System (ADS)

Beirau, Tobias; Nix, William D.; Bismayer, Ulrich; Boatner, Lynn A.; Isaacson, Scott G.; Ewing, Rodney C.

2016-10-01

This study provides new insights into the relationship between radiation-dose-dependent structural damage due to natural U and Th impurities and the anisotropic mechanical properties (Poisson's ratio, elastic modulus and hardness) of zircon. Natural zircon samples from Sri Lanka (see Muarakami et al. in Am Mineral 76:1510-1532, 1991) and synthetic samples, covering a dose range of zero up to 6.8 × 1018 α-decays/g, have been studied by nanoindentation. Measurements along the [100] crystallographic direction and calculations, based on elastic stiffness constants determined by Özkan (J Appl Phys 47:4772-4779, 1976), revealed a general radiation-induced decrease in stiffness (~54 %) and hardness (~48 %) and an increase in the Poisson's ratio (~54 %) with increasing dose. Additional indentations on selected samples along the [001] allowed one to follow the amorphization process to the point that the mechanical properties are isotropic. This work shows that the radiation-dose-dependent changes of the mechanical properties of zircon can be directly correlated with the amorphous fraction as determined by previous investigations with local and global probes (Ríos et al. in J Phys Condens Matter 12:2401-2412, 2000a; Farnan and Salje in J Appl Phys 89:2084-2090, 2001; Zhang and Salje in J Phys Condens Matter 13:3057-3071, 2001). The excellent agreement, revealed by the different methods, indicates a large influence of structural and even local phenomena on the macroscopic mechanical properties. Therefore, this study indicates the importance of acquiring better knowledge about the mechanical long-term stability of radiation-damaged materials.

Mechanical Ventilation–associated Lung Fibrosis in Acute Respiratory Distress Syndrome A Significant Contributor to Poor Outcome

PubMed Central

Cabrera-Benitez, Nuria E.; Laffey, John G.; Parotto, Matteo; Spieth, Peter M.; Villar, Jesús; Zhang, Haibo; Slutsky, Arthur S.

2016-01-01

One of the most challenging problems in critical care medicine is the management of patients with the acute respiratory distress syndrome. Increasing evidence from experimental and clinical studies suggests that mechanical ventilation, which is necessary for life support in patients with acute respiratory distress syndrome, can cause lung fibrosis, which may significantly contribute to morbidity and mortality. The role of mechanical stress as an inciting factor for lung fibrosis versus its role in lung homeostasis and the restoration of normal pulmonary parenchymal architecture is poorly understood. In this review, the authors explore recent advances in the field of pulmonary fibrosis in the context of acute respiratory distress syndrome, concentrating on its relevance to the practice of mechanical ventilation, as commonly applied by anesthetists and intensivists. The authors focus the discussion on the thesis that mechanical ventilation—or more specifically, that ventilator-induced lung injury—may be a major contributor to lung fibrosis. The authors critically appraise possible mechanisms underlying the mechanical stress–induced lung fibrosis and highlight potential therapeutic strategies to mitigate this fibrosis. PMID:24732023

Mechanical ventilation-associated lung fibrosis in acute respiratory distress syndrome: a significant contributor to poor outcome.

PubMed

Cabrera-Benitez, Nuria E; Laffey, John G; Parotto, Matteo; Spieth, Peter M; Villar, Jesús; Zhang, Haibo; Slutsky, Arthur S

2014-07-01

One of the most challenging problems in critical care medicine is the management of patients with the acute respiratory distress syndrome. Increasing evidence from experimental and clinical studies suggests that mechanical ventilation, which is necessary for life support in patients with acute respiratory distress syndrome, can cause lung fibrosis, which may significantly contribute to morbidity and mortality. The role of mechanical stress as an inciting factor for lung fibrosis versus its role in lung homeostasis and the restoration of normal pulmonary parenchymal architecture is poorly understood. In this review, the authors explore recent advances in the field of pulmonary fibrosis in the context of acute respiratory distress syndrome, concentrating on its relevance to the practice of mechanical ventilation, as commonly applied by anesthetists and intensivists. The authors focus the discussion on the thesis that mechanical ventilation-or more specifically, that ventilator-induced lung injury-may be a major contributor to lung fibrosis. The authors critically appraise possible mechanisms underlying the mechanical stress-induced lung fibrosis and highlight potential therapeutic strategies to mitigate this fibrosis.

DNA DAMAGE REPAIR AND CELL CYCLE CONTROL: A NATURAL BIO-DEFENSE MECHANISM

EPA Science Inventory

DNA DAMAGE REPAIR AND CELL CYCLE CONTROL: A natural bio-defense mechanism
Anuradha Mudipalli.

Maintenance of genetic information, including the correct sequence of nucleotides in DNA, is essential for replication, gene expression, and protein synthesis. DNA lesions onto...

Ultraviolet-B-induced DNA damage and ultraviolet-B tolerance mechanisms in species with different functional groups coexisting in subalpine moorlands.

PubMed

Wang, Qing-Wei; Kamiyama, Chiho; Hidema, Jun; Hikosaka, Kouki

2016-08-01

High doses of ultraviolet-B (UV-B; 280-315 nm) radiation can have detrimental effects on plants, and especially damage their DNA. Plants have DNA repair and protection mechanisms to prevent UV-B damage. However, it remains unclear how DNA damage and tolerance mechanisms vary among field species. We studied DNA damage and tolerance mechanisms in 26 species with different functional groups coexisting in two moorlands at two elevations. We collected current-year leaves in July and August, and determined accumulation of cyclobutane pyrimidine dimer (CPD) as UV-B damage and photorepair activity (PRA) and concentrations of UV-absorbing compounds (UACs) and carotenoids (CARs) as UV-B tolerance mechanisms. DNA damage was greater in dicot than in monocot species, and higher in herbaceous than in woody species. Evergreen species accumulated more CPDs than deciduous species. PRA was higher in Poaceae than in species of other families. UACs were significantly higher in woody than in herbaceous species. The CPD level was not explained by the mechanisms across species, but was significantly related to PRA and UACs when we ignored species with low CPD, PRA and UACs, implying the presence of another effective tolerance mechanism. UACs were correlated negatively with PRA and positively with CARs. Our results revealed that UV-induced DNA damage significantly varies among native species, and this variation is related to functional groups. DNA repair, rather than UV-B protection, dominates in UV-B tolerance in the field. Our findings also suggest that UV-B tolerance mechanisms vary among species under evolutionary trade-off and synergism.

The role of melatonin in pancreatic protection: could melatonin be used in the treatment of acute pancreatitis?

PubMed

Jaworek, Jolanta; Leja-Szpak, Anna; Kot, Michalina; Jaworek, Andrzej; Nawrot-Porbka, Katarzyna; Bonior, Joanna; Szklarczyk, Joanna

2014-01-01

Acute pancreatitis is a disease, which could be manifested as either a mild edematous form or a more severe necrotizing pancreatitis which has a poor prognosis. The etiology and pathogenesis of this ailment is not completely clear. Melatonin is an indoleamine which is produced from L-tryptophan in the pineal gland and in the other tissue including gastrointestinal tract. Both melatonin and its precursor have been demonstrated to protect the pancreas against acute pancreatitis and to attenuate pancreatic tissue damage. In the pancreas melatonin and L-tryptophan activate complex mechanisms which involve direct scavenging of the radical oxygen and nitrogen species, activation of antioxidant enzymes (catalase, superoxide dysmutase, glutation peroxidase), reduction of pro-inflammatory cytokines and prostaglandins, activation of heat shock protein, and a decrease of necrosis and increase of regeneration in the pancreas. There are several arguments for the idea that endogenous melatonin produced in the pineal gland and in the gastrointestinal system could be the part of a native mechanisms for protecting the pancreas against acute damage: 1/ the melatonin precursor L-tryptophan exerts similar protective effect as melatonin, 2/ application of the melatonin receptor antagonist, luzindole aggravates acute pancreatitis, 3/ pinealectomy results in the exacerbation of acute pancreatitis, 4/ low melatonin plasma levels are associated with an increased risk of severe acute pancreatitis. These observations leads to the idea that perhaps melatonin could be used in clinical trials as supportive therapy in acute pancreatitis.

Mechanical instability after an acute lateral ankle sprain.

PubMed

Hubbard, Tricia J; Cordova, Mitchell

2009-07-01

To examine the natural recovery of mechanical laxity after an ankle sprain over an 8-week period. Prospective cohort study. Biodynamics research laboratory. Subjects with an acute lateral ankle sprain (n=16; 7 men, 9 women; age, 19.5+/-0.7y; mass, 64.6+/-8.1 kg; height, 171.9+/-9.6 cm) and healthy controls (n=16; 7 men, 9 women; age, 20.4+/-1.7y; mass, 76.9+/-11.1 kg; height, 176.5+/-11.1 cm) participated. Not applicable. Subjects with acute ankle sprains were tested 3 days after injury and again 8 weeks later. Anterior and posterior displacement (mm) and inversion and eversion rotation ( degrees ) were measured with an instrumented arthrometer. For each dependent variable, a 2 x 2 x 2 repeated-measures multivariate analysis of variance was performed. A significant interaction was found between group, time, and side for anterior translation (F=4.24, P=.05). There were also significant main effects for group. There was significantly more anterior displacement at day 3 (F=19.52, P=.001) and at week 8 (F=8.45, P=.010) in the injured group compared with the healthy group. There was also significantly more inversion rotation at day 3 (F=2.70, P=.002) and at week 8 (F=5.4, P=.033) in the injured group compared with the healthy group. The lack of significant differences in mechanical laxity over an 8-week period suggests that natural recovery of laxity takes longer than 8 weeks. Further research needs to be conducted to examine how long this laxity persists and the role ankle rehabilitation plays in mechanical stability restoration.

Combining functional and tubular damage biomarkers improves diagnostic precision for acute kidney injury after cardiac surgery.

PubMed

Basu, Rajit K; Wong, Hector R; Krawczeski, Catherine D; Wheeler, Derek S; Manning, Peter B; Chawla, Lakhmir S; Devarajan, Prasad; Goldstein, Stuart L

2014-12-30

Increases in serum creatinine (ΔSCr) from baseline signify acute kidney injury (AKI) but offer little granular information regarding its characteristics. The 10th Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) suggested that combining AKI biomarkers would provide better precision for AKI course prognostication. This study investigated the value of combining a functional damage biomarker (plasma cystatin C [pCysC]) with a tubular damage biomarker (urine neutrophil gelatinase-associated lipocalin [uNGAL]), forming a composite biomarker for prediction of discrete characteristics of AKI. Data from 345 children after cardiopulmonary bypass (CPB) were analyzed. Severe AKI was defined as Kidney Disease Global Outcomes Initiative stages 2 to 3 (≥100% ΔSCr) within 7 days of CPB. Persistent AKI lasted >2 days. SCr in reversible AKI returned to baseline ≤48 h after CPB. The composite of uNGAL (>200 ng/mg urine Cr = positive [+]) and pCysC (>0.8 mg/l = positive [+]), uNGAL+/pCysC+, measured 2 h after CPB initiation, was compared to ΔSCr increases of ≥50% for correlation with AKI characteristics by using predictive probabilities, likelihood ratios (LR), and area under the curve receiver operating curve (AUC-ROC) values [Corrected]. Severe AKI occurred in 18% of patients. The composite uNGAL+/pCysC+ demonstrated a greater likelihood than ΔSCr for severe AKI (+LR: 34.2 [13.0:94.0] vs. 3.8 [1.9:7.2]) and persistent AKI (+LR: 15.6 [8.8:27.5] versus 4.5 [2.3:8.8]). In AKI patients, the uNGAL-/pCysC+ composite was superior to ΔSCr for prediction of transient AKI. Biomarker composites carried greater probability for specific outcomes than ΔSCr strata. Composites of functional and tubular damage biomarkers are superior to ΔSCr for predicting discrete characteristics of AKI. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Impact of mechanical stress induced in silica vacuum windows on laser-induced damage.

PubMed

Gingreau, Clémence; Lanternier, Thomas; Lamaignère, Laurent; Donval, Thierry; Courchinoux, Roger; Leymarie, Christophe; Néauport, Jérôme

2018-04-15

At the interface between vacuum and air, optical windows must keep their optical properties, despite being subjected to mechanical stress. In this Letter, we investigate the impact of such stress on the laser-induced damage of fused silica windows at the wavelength of 351 nm in the nanosecond regime. Different stress values, from 1 to 30 MPa, both tensile and compressive, were applied. No effect of the stress on the laser-induced damage was evidenced.

Acute Exacerbation in Interstitial Lung Disease

PubMed Central

Leuschner, Gabriela; Behr, Jürgen

2017-01-01

Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) has been defined as an acute, clinically significant deterioration that develops within less than 1 month without obvious clinical cause like fluid overload, left heart failure, or pulmonary embolism. Pathophysiologically, damage of the alveoli is the predominant feature of AE-IPF which manifests histopathologically as diffuse alveolar damage and radiologically as diffuse, bilateral ground-glass opacification on high-resolution computed tomography. A growing body of literature now focuses on acute exacerbations of interstitial lung disease (AE-ILD) other than idiopathic pulmonary fibrosis. Based on a shared pathophysiology it is generally accepted that AE-ILD can affect all patients with interstitial lung disease (ILD) but apparently occurs more frequently in patients with an underlying usual interstitial pneumonia pattern. The etiology of AE-ILD is not fully understood, but there are distinct risk factors and triggers like infection, mechanical stress, and microaspiration. In general, AE-ILD has a poor prognosis and is associated with a high mortality within 6–12 months. Although there is a lack of evidence based data, in clinical practice, AE-ILD is often treated with a high dose corticosteroid therapy and antibiotics. This article aims to provide a summary of the clinical features, diagnosis, management, and prognosis of AE-ILD as well as an update on the current developments in the field. PMID:29109947

Corneal Confocal Microscopy Detects Corneal Nerve Damage in Patients Admitted With Acute Ischemic Stroke.

PubMed

Khan, Adnan; Akhtar, Naveed; Kamran, Saadat; Ponirakis, Georgios; Petropoulos, Ioannis N; Tunio, Nahel A; Dargham, Soha R; Imam, Yahia; Sartaj, Faheem; Parray, Aijaz; Bourke, Paula; Khan, Rabia; Santos, Mark; Joseph, Sujatha; Shuaib, Ashfaq; Malik, Rayaz A

2017-11-01

Corneal confocal microscopy can identify corneal nerve damage in patients with peripheral and central neurodegeneration. However, the use of corneal confocal microscopy in patients presenting with acute ischemic stroke is unknown. One hundred thirty patients (57 without diabetes mellitus [normal glucose tolerance], 32 with impaired glucose tolerance, and 41 with type 2 diabetes mellitus) admitted with acute ischemic stroke, and 28 age-matched healthy control participants underwent corneal confocal microscopy to quantify corneal nerve fiber density, corneal nerve branch density, and corneal nerve fiber length. There was a significant reduction in corneal nerve fiber density, corneal nerve branch density, and corneal nerve fiber length in stroke patients with normal glucose tolerance ( P <0.001, P <0.001, P <0.001), impaired glucose tolerance ( P =0.004, P <0.001, P =0.002), and type 2 diabetes mellitus ( P <0.001, P <0.001, P <0.001) compared with controls. HbA1c and triglycerides correlated with corneal nerve fiber density ( r =-0.187, P =0.03; r =-0.229 P =0.01), corneal nerve fiber length ( r =-0.228, P =0.009; r =-0.285; P =0.001), and corneal nerve branch density ( r =-0.187, P =0.033; r =-0.229, P =0.01). Multiple linear regression showed no independent associations between corneal nerve fiber density, corneal nerve branch density, and corneal nerve fiber length and relevant risk factors for stroke. Corneal confocal microscopy is a rapid noninvasive ophthalmic imaging technique that identifies corneal nerve fiber loss in patients with acute ischemic stroke. © 2017 American Heart Association, Inc.

A Continuum Damage Mechanics Model for the Static and Cyclic Fatigue of Cellular Composites

PubMed Central

Huber, Otto

2017-01-01

The fatigue behavior of a cellular composite with an epoxy matrix and glass foam granules is analyzed and modeled by means of continuum damage mechanics. The investigated cellular composite is a particular type of composite foam, and is very similar to syntactic foams. In contrast to conventional syntactic foams constituted by hollow spherical particles (balloons), cellular glass, mineral, or metal place holders are combined with the matrix material (metal or polymer) in the case of cellular composites. A microstructural investigation of the damage behavior is performed using scanning electron microscopy. For the modeling of the fatigue behavior, the damage is separated into pure static and pure cyclic damage and described in terms of the stiffness loss of the material using damage models for cyclic and creep damage. Both models incorporate nonlinear accumulation and interaction of damage. A cycle jumping procedure is developed, which allows for a fast and accurate calculation of the damage evolution for constant load frequencies. The damage model is applied to examine the mean stress effect for cyclic fatigue and to investigate the frequency effect and the influence of the signal form in the case of static and cyclic damage interaction. The calculated lifetimes are in very good agreement with experimental results. PMID:28809806

Preventive Effects of Poloxamer 188 on Muscle Cell Damage Mechanics Under Oxidative Stress.

PubMed

Wong, Sing Wan; Yao, Yifei; Hong, Ye; Ma, Zhiyao; Kok, Stanton H L; Sun, Shan; Cho, Michael; Lee, Kenneth K H; Mak, Arthur F T

2017-04-01

High oxidative stress can occur during ischemic reperfusion and chronic inflammation. It has been hypothesized that such oxidative challenges could contribute to clinical risks such as deep tissue pressure ulcers. Skeletal muscles can be challenged by inflammation-induced or reperfusion-induced oxidative stress. Oxidative stress reportedly can lower the compressive damage threshold of skeletal muscles cells, causing actin filament depolymerization, and reduce membrane sealing ability. Skeletal muscles thus become easier to be damaged by mechanical loading under prolonged oxidative exposure. In this study, we investigated the preventive effect of poloxamer 188 (P188) on skeletal muscle cells against extrinsic oxidative challenges (H 2 O 2 ). It was found that with 1 mM P188 pre-treatment for 1 h, skeletal muscle cells could maintain their compressive damage threshold. The actin polymerization dynamics largely remained stable in term of the expression of cofilin, thymosin beta 4 and profilin. Laser photoporation demonstrated that membrane sealing ability was preserved even as the cells were challenged by H 2 O 2 . These findings suggest that P188 pre-treatment can help skeletal muscle cells retain their normal mechanical integrity in oxidative environments, adding a potential clinical use of P188 against the combined challenge of mechanical-oxidative stresses. Such effect may help to prevent deep tissue ulcer development.

Multiaxial Fatigue Life Prediction Based on Nonlinear Continuum Damage Mechanics and Critical Plane Method

NASA Astrophysics Data System (ADS)

Wu, Z. R.; Li, X.; Fang, L.; Song, Y. D.

2018-04-01

A new multiaxial fatigue life prediction model has been proposed in this paper. The concepts of nonlinear continuum damage mechanics and critical plane criteria were incorporated in the proposed model. The shear strain-based damage control parameter was chosen to account for multiaxial fatigue damage under constant amplitude loading. Fatigue tests were conducted on nickel-based superalloy GH4169 tubular specimens at the temperature of 400 °C under proportional and nonproportional loading. The proposed method was checked against the multiaxial fatigue test data of GH4169. Most of prediction results are within a factor of two scatter band of the test results.

A Novel Therapy to Attenuate Acute Kidney Injury and Ischemic Allograft Damage after Allogenic Kidney Transplantation in Mice

PubMed Central

Gueler, Faikah; Shushakova, Nelli; Mengel, Michael; Hueper, Katja; Chen, Rongjun; Liu, Xiaokun; Park, Joon-Keun; Haller, Hermann

2015-01-01

Ischemia followed by reperfusion contributes to the initial damage to allografts after kidney transplantation (ktx). In this study we tested the hypothesis that a tetrapeptide EA-230 (AQGV), might improve survival and attenuate loss of kidney function in a mouse model of renal ischemia/reperfusion injury (IRI) and ischemia-induced delayed graft function after allogenic kidney transplantation. IRI was induced in male C57Bl/6N mice by transient bilateral renal pedicle clamping for 35 min. Treatment with EA-230 (20–50mg/kg twice daily i.p. for four consecutive days) was initiated 24 hours after IRI when acute kidney injury (AKI) was already established. The treatment resulted in markedly improved survival in a dose dependent manner. Acute tubular injury two days after IRI was diminished and tubular epithelial cell proliferation was significantly enhanced by EA-230 treatment. Furthermore, CTGF up-regulation, a marker of post-ischemic fibrosis, at four weeks after IRI was significantly less in EA-230 treated renal tissue. To learn more about these effects, we measured renal blood flow (RBF) and glomerular filtration rate (GFR) at 28 hours after IRI. EA-230 improved both GFR and RBF significantly. Next, EA-230 treatment was tested in a model of ischemia-induced delayed graft function after allogenic kidney transplantation. The recipients were treated with EA-230 (50 mg/kg) twice daily i.p. which improved renal function and allograft survival by attenuating ischemic allograft damage. In conclusion, EA-230 is a novel and promising therapeutic agent for treating acute kidney injury and preventing IRI-induced post-transplant ischemic allograft injury. Its beneficial effect is associated with improved renal perfusion after IRI and enhanced regeneration of tubular epithelial cells. PMID:25617900

A novel therapy to attenuate acute kidney injury and ischemic allograft damage after allogenic kidney transplantation in mice.

PubMed

Gueler, Faikah; Shushakova, Nelli; Mengel, Michael; Hueper, Katja; Chen, Rongjun; Liu, Xiaokun; Park, Joon-Keun; Haller, Hermann; Wensvoort, Gert; Rong, Song

2015-01-01

Ischemia followed by reperfusion contributes to the initial damage to allografts after kidney transplantation (ktx). In this study we tested the hypothesis that a tetrapeptide EA-230 (AQGV), might improve survival and attenuate loss of kidney function in a mouse model of renal ischemia/reperfusion injury (IRI) and ischemia-induced delayed graft function after allogenic kidney transplantation. IRI was induced in male C57Bl/6N mice by transient bilateral renal pedicle clamping for 35 min. Treatment with EA-230 (20-50mg/kg twice daily i.p. for four consecutive days) was initiated 24 hours after IRI when acute kidney injury (AKI) was already established. The treatment resulted in markedly improved survival in a dose dependent manner. Acute tubular injury two days after IRI was diminished and tubular epithelial cell proliferation was significantly enhanced by EA-230 treatment. Furthermore, CTGF up-regulation, a marker of post-ischemic fibrosis, at four weeks after IRI was significantly less in EA-230 treated renal tissue. To learn more about these effects, we measured renal blood flow (RBF) and glomerular filtration rate (GFR) at 28 hours after IRI. EA-230 improved both GFR and RBF significantly. Next, EA-230 treatment was tested in a model of ischemia-induced delayed graft function after allogenic kidney transplantation. The recipients were treated with EA-230 (50 mg/kg) twice daily i.p. which improved renal function and allograft survival by attenuating ischemic allograft damage. In conclusion, EA-230 is a novel and promising therapeutic agent for treating acute kidney injury and preventing IRI-induced post-transplant ischemic allograft injury. Its beneficial effect is associated with improved renal perfusion after IRI and enhanced regeneration of tubular epithelial cells.

Damage Patterns at the Head-Stem Taper Junction Helps Understand the Mechanisms of Material Loss.

PubMed

Hothi, Harry S; Panagiotopoulos, Andreas C; Whittaker, Robert K; Bills, Paul J; McMillan, Rebecca A; Skinner, John A; Hart, Alister J

2017-01-01

Material loss at the taper junction of metal-on-metal total hip arthroplasties has been implicated in their early failure. The mechanisms of material loss are not fully understood; analysis of the patterns of damage at the taper can help us better understand why material loss occurs at this junction. We mapped the patterns of material loss in a series of 155 metal-on-metal total hip arthroplasties received at our center by scanning the taper surface using a roundness-measuring machine. We examined these material loss maps to develop a 5-tier classification system based on visual differences between different patterns. We correlated these patterns to surgical, implant, and patient factors known to be important for head-stem taper damage. We found that 63 implants had "minimal damage" at the taper (material loss <1 mm 3 ), and the remaining 92 implants could be categorized by 4 distinct patterns of taper material loss. We found that (1) head diameter and (2) time to revision were key significant variables separating the groups. These material loss maps allow us to suggest different mechanisms that dominate the cause of the material loss in each pattern: (1) corrosion, (2) mechanically assisted corrosion, or (3) intraoperative damage or poor size tolerances leading to toggling of trunnion in taper. Copyright © 2016 Elsevier Inc. All rights reserved.

Deciphering neuronal population codes for acute thermal pain

NASA Astrophysics Data System (ADS)

Chen, Zhe; Zhang, Qiaosheng; Phuong Sieu Tong, Ai; Manders, Toby R.; Wang, Jing

2017-06-01

Objective. Pain is defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage. Current pain research mostly focuses on molecular and synaptic changes at the spinal and peripheral levels. However, a complete understanding of pain mechanisms requires the physiological study of the neocortex. Our goal is to apply a neural decoding approach to read out the onset of acute thermal pain signals, which can be used for brain-machine interface. Approach. We used micro wire arrays to record ensemble neuronal activities from the primary somatosensory cortex (S1) and anterior cingulate cortex (ACC) in freely behaving rats. We further investigated neural codes for acute thermal pain at both single-cell and population levels. To detect the onset of acute thermal pain signals, we developed a novel latent state-space framework to decipher the sorted or unsorted S1 and ACC ensemble spike activities, which reveal information about the onset of pain signals. Main results. The state space analysis allows us to uncover a latent state process that drives the observed ensemble spike activity, and to further detect the ‘neuronal threshold’ for acute thermal pain on a single-trial basis. Our method achieved good detection performance in sensitivity and specificity. In addition, our results suggested that an optimal strategy for detecting the onset of acute thermal pain signals may be based on combined evidence from S1 and ACC population codes. Significance. Our study is the first to detect the onset of acute pain signals based on neuronal ensemble spike activity. It is important from a mechanistic viewpoint as it relates to the significance of S1 and ACC activities in the regulation of the acute pain onset.

Epithelial and endothelial damage induced by mechanical ventilation modes.

PubMed

Suki, Béla; Hubmayr, Rolf

2014-02-01

The adult respiratory distress syndrome (ARDS) is a common cause of respiratory failure with substantial impact on public health. Patients with ARDS generally require mechanical ventilation, which risks further lung damage. Recent improvements in ARDS outcomes have been attributed to reductions in deforming stress associated with lung protective mechanical ventilation modes and settings. The following review details the mechanics of the lung parenchyma at different spatial scales and the response of its resident cells to deforming stress in order to provide the biologic underpinnings of lung protective care. Although lung injury is typically viewed through the lens of altered barrier properties and mechanical ventilation-associated immune responses, in this review, we call attention to the importance of heterogeneity and the physical failure of the load bearing cell and tissue elements in the pathogenesis of ARDS. Specifically, we introduce a simple elastic network model to better understand the deformations of lung regions, intra-acinar alveoli and cells within a single alveolus, and consider the role of regional distension and interfacial stress-related injury for various ventilation modes. Heterogeneity of stiffness and intercellular and intracellular stress failure are fundamental components of ARDS and their development also depends on the ventilation mode.

The DNA damage response during mitosis.

PubMed

Heijink, Anne Margriet; Krajewska, Małgorzata; van Vugt, Marcel A T M

2013-10-01

Cells are equipped with a cell-intrinsic signaling network called the DNA damage response (DDR). This signaling network recognizes DNA lesions and initiates various downstream pathways to coordinate a cell cycle arrest with the repair of the damaged DNA. Alternatively, the DDR can mediate clearance of affected cells that are beyond repair through apoptosis or senescence. The DDR can be activated in response to DNA damage throughout the cell cycle, although the extent of DDR signaling is different in each cell cycle phase. Especially in response to DNA double strand breaks, only a very marginal response was observed during mitosis. Early on it was recognized that cells which are irradiated during mitosis continued division without repairing broken chromosomes. Although these initial observations indicated diminished DNA repair and lack of an acute DNA damage-induced cell cycle arrest, insight into the mechanistic re-wiring of DDR signaling during mitosis was only recently provided. Different mechanisms appear to be at play to inactivate specific signaling axes of the DDR network in mitosis. Importantly, mitotic cells not simply inactivate the entire DDR, but appear to mark their DNA damage for repair after mitotic exit. Since the treatment of cancer frequently involves agents that induce DNA damage as well as agents that block mitotic progression, it is clinically relevant to obtain a better understanding of how cancer cells deal with DNA damage during interphase versus mitosis. In this review, the molecular details concerning DDR signaling during mitosis as well as the consequences of encountering DNA damage during mitosis for cellular fate are discussed. Copyright © 2013 Elsevier B.V. All rights reserved.

Failure Mechanisms and Damage Model of Ductile Cast Iron Under Low-Cycle Fatigue Conditions

NASA Astrophysics Data System (ADS)

Wu, Xijia; Quan, Guangchun; MacNeil, Ryan; Zhang, Zhong; Sloss, Clayton

2014-10-01

Strain-controlled low-cycle fatigue (LCF) tests were conducted on ductile cast iron (DCI) at strain rates of 0.02, 0.002, and 0.0002/s in the temperature range from room temperature to 1073 K (800 °C). A constitutive-damage model was developed within the integrated creep-fatigue theory (ICFT) framework on the premise of strain decomposition into rate-independent plasticity and time-dependent creep. Four major damage mechanisms: (i) plasticity-induced fatigue, (ii) intergranular embrittlement (IE), (iii) creep, and (iv) oxidation were considered in a nonlinear creep-fatigue interaction model which represents the overall damage accumulation process consisting of oxidation-assisted fatigue crack nucleation and propagation in coalescence with internally distributed damage ( e.g., IE and creep), leading to final fracture. The model was found to agree with the experimental observations of the complex DCI-LCF phenomena, for which the linear damage summation rule would fail.

Optimal support techniques when providing mechanical ventilation to patients with acute respiratory distress syndrome.

PubMed

Parissopoulos, Stelios; Mpouzika, Meropi DA; Timmins, Fiona

2017-01-01

Adult respiratory distress syndrome (ARDS) is a type of acute diffuse lung injury characterized by severe inflammation, increased pulmonary vascular permeability and a loss of aerated lung tissue. The effects of high fraction of inspired oxygen (FiO 2 ) include oxygen toxicity manifested by damage to the lung parenchyma in the acute phase of lung injury. There is still a high mortality rate among this group of patients, so clinically sensitive evidence-based interventions are paramount to maximize survival chances during critical care. The aim of this article is to explore the current opinion concerning optimal mechanical ventilation support techniques for patients with acute respiratory distress syndrome. A literature search of clinical trials and observation studies, reviews, discussion papers, meta-analyses and clinical guidelines written in English up to 2015, derived from the databases of Scopus, CINAHL, Cochrane Library databases and PubMed was conducted. Low tidal volume, pressure limitation and prone positioning in severe ARDS patients appear to be of some benefit. More research is required and further development and use of standardized protocols is an important strategy for reducing practice variations across disciplines, as well as giving clear guidelines to nurses practising in critical care. There is also evidence that this syndrome is under-diagnosed and the utilization of lung protective ventilation is still variable. It is important that nurses have underlying knowledge of both aetiology of ARDS and ventilation management, and that they monitor patients very closely. The adoption of a low tidal ventilation protocol, which is based on quality evidence guidelines, the value of rescue therapies and patient observation practices in the overall patient management, and the need to place emphasis on long-term patient outcomes, all these emerge as key factors for consideration and future research. However, there is also a need for more research that would

Mechanisms of neurotoxicity induced in the developing brain of mice and rats by DNA-damaging chemicals.

PubMed

Doi, Kunio

2011-01-01

It is not widely known how the developing brain responds to extrinsic damage, although the developing brain is considered to be sensitive to diverse environmental factors including DNA-damaging agents. This paper reviews the mechanisms of neurotoxicity induced in the developing brain of mice and rats by six chemicals (ethylnitrosourea, hydroxyurea, 5-azacytidine, cytosine arabinoside, 6-mercaptopurine and etoposide), which cause DNA damage in different ways, especially from the viewpoints of apoptosis and cell cycle arrest in neural progenitor cells. In addition, this paper also reviews the repair process following damage in the developing brain.

Comparison between conventional protective mechanical ventilation and high-frequency oscillatory ventilation associated with the prone position.

PubMed

Fioretto, José Roberto; Klefens, Susiane Oliveira; Pires, Rafaelle Fernandes; Kurokawa, Cilmery Suemi; Carpi, Mario Ferreira; Bonatto, Rossano César; Moraes, Marcos Aurélio; Ronchi, Carlos Fernando

2017-01-01

To compare the effects of high-frequency oscillatory ventilation and conventional protective mechanical ventilation associated with the prone position on oxygenation, histology and pulmonary oxidative damage in an experimental model of acute lung injury. Forty-five rabbits with tracheostomy and vascular access were underwent mechanical ventilation. Acute lung injury was induced by tracheal infusion of warm saline. Three experimental groups were formed: healthy animals + conventional protective mechanical ventilation, supine position (Control Group; n = 15); animals with acute lung injury + conventional protective mechanical ventilation, prone position (CMVG; n = 15); and animals with acute lung injury + high-frequency oscillatory ventilation, prone position (HFOG; n = 15). Ten minutes after the beginning of the specific ventilation of each group, arterial gasometry was collected, with this timepoint being called time zero, after which the animal was placed in prone position and remained in this position for 4 hours. Oxidative stress was evaluated by the total antioxidant performance assay. Pulmonary tissue injury was determined by histopathological score. The level of significance was 5%. Both groups with acute lung injury showed worsening of oxygenation after induction of injury compared with the Control Group. After 4 hours, there was a significant improvement in oxygenation in the HFOG group compared with CMVG. Analysis of total antioxidant performance in plasma showed greater protection in HFOG. HFOG had a lower histopathological lesion score in lung tissue than CMVG. High-frequency oscillatory ventilation, associated with prone position, improves oxygenation and attenuates oxidative damage and histopathological lung injury compared with conventional protective mechanical ventilation.

Comparison between conventional protective mechanical ventilation and high-frequency oscillatory ventilation associated with the prone position

PubMed Central

Fioretto, José Roberto; Klefens, Susiane Oliveira; Pires, Rafaelle Fernandes; Kurokawa, Cilmery Suemi; Carpi, Mario Ferreira; Bonatto, Rossano César; Moraes, Marcos Aurélio; Ronchi, Carlos Fernando

2017-01-01

Objective To compare the effects of high-frequency oscillatory ventilation and conventional protective mechanical ventilation associated with the prone position on oxygenation, histology and pulmonary oxidative damage in an experimental model of acute lung injury. Methods Forty-five rabbits with tracheostomy and vascular access were underwent mechanical ventilation. Acute lung injury was induced by tracheal infusion of warm saline. Three experimental groups were formed: healthy animals + conventional protective mechanical ventilation, supine position (Control Group; n = 15); animals with acute lung injury + conventional protective mechanical ventilation, prone position (CMVG; n = 15); and animals with acute lung injury + high-frequency oscillatory ventilation, prone position (HFOG; n = 15). Ten minutes after the beginning of the specific ventilation of each group, arterial gasometry was collected, with this timepoint being called time zero, after which the animal was placed in prone position and remained in this position for 4 hours. Oxidative stress was evaluated by the total antioxidant performance assay. Pulmonary tissue injury was determined by histopathological score. The level of significance was 5%. Results Both groups with acute lung injury showed worsening of oxygenation after induction of injury compared with the Control Group. After 4 hours, there was a significant improvement in oxygenation in the HFOG group compared with CMVG. Analysis of total antioxidant performance in plasma showed greater protection in HFOG. HFOG had a lower histopathological lesion score in lung tissue than CMVG. Conclusion High-frequency oscillatory ventilation, associated with prone position, improves oxygenation and attenuates oxidative damage and histopathological lung injury compared with conventional protective mechanical ventilation. PMID:29236845

Bayesian inference of the lung alveolar spatial model for the identification of alveolar mechanics associated with acute respiratory distress syndrome

NASA Astrophysics Data System (ADS)

Christley, Scott; Emr, Bryanna; Ghosh, Auyon; Satalin, Josh; Gatto, Louis; Vodovotz, Yoram; Nieman, Gary F.; An, Gary

2013-06-01

Acute respiratory distress syndrome (ARDS) is acute lung failure secondary to severe systemic inflammation, resulting in a derangement of alveolar mechanics (i.e. the dynamic change in alveolar size and shape during tidal ventilation), leading to alveolar instability that can cause further damage to the pulmonary parenchyma. Mechanical ventilation is a mainstay in the treatment of ARDS, but may induce mechano-physical stresses on unstable alveoli, which can paradoxically propagate the cellular and molecular processes exacerbating ARDS pathology. This phenomenon is called ventilator induced lung injury (VILI), and plays a significant role in morbidity and mortality associated with ARDS. In order to identify optimal ventilation strategies to limit VILI and treat ARDS, it is necessary to understand the complex interplay between biological and physical mechanisms of VILI, first at the alveolar level, and then in aggregate at the whole-lung level. Since there is no current consensus about the underlying dynamics of alveolar mechanics, as an initial step we investigate the ventilatory dynamics of an alveolar sac (AS) with the lung alveolar spatial model (LASM), a 3D spatial biomechanical representation of the AS and its interaction with airflow pressure and the surface tension effects of pulmonary surfactant. We use the LASM to identify the mechanical ramifications of alveolar dynamics associated with ARDS. Using graphical processing unit parallel algorithms, we perform Bayesian inference on the model parameters using experimental data from rat lung under control and Tween-induced ARDS conditions. Our results provide two plausible models that recapitulate two fundamental hypotheses about volume change at the alveolar level: (1) increase in alveolar size through isotropic volume change, or (2) minimal change in AS radius with primary expansion of the mouth of the AS, with the implication that the majority of change in lung volume during the respiratory cycle occurs in the

Understanding Magnetic Flux Leakage (MFL) Signals from Mechanical Damage in Pipelines - Phase I

DOT National Transportation Integrated Search

2007-09-18

Pipeline inspection tools based on Magnetic Flux Leakage (MFL) principles represent the most cost-effective method for in-line detection and monitoring of pipeline corrosion defects. Mechanical damage also produces MFL signals, but as yet these signa...

Low-damage direct patterning of silicon oxide mask by mechanical processing

PubMed Central

2014-01-01

To realize the nanofabrication of silicon surfaces using atomic force microscopy (AFM), we investigated the etching of mechanically processed oxide masks using potassium hydroxide (KOH) solution. The dependence of the KOH solution etching rate on the load and scanning density of the mechanical pre-processing was evaluated. Particular load ranges were found to increase the etching rate, and the silicon etching rate also increased with removal of the natural oxide layer by diamond tip sliding. In contrast, the local oxide pattern formed (due to mechanochemical reaction of the silicon) by tip sliding at higher load was found to have higher etching resistance than that of unprocessed areas. The profile changes caused by the etching of the mechanically pre-processed areas with the KOH solution were also investigated. First, protuberances were processed by diamond tip sliding at lower and higher stresses than that of the shearing strength. Mechanical processing at low load and scanning density to remove the natural oxide layer was then performed. The KOH solution selectively etched the low load and scanning density processed area first and then etched the unprocessed silicon area. In contrast, the protuberances pre-processed at higher load were hardly etched. The etching resistance of plastic deformed layers was decreased, and their etching rate was increased because of surface damage induced by the pre-processing. These results show that etching depth can be controlled by controlling the etching time through natural oxide layer removal and mechanochemical oxide layer formation. These oxide layer removal and formation processes can be exploited to realize low-damage mask patterns. PMID:24948891

Ligamentous Injuries and the Risk of Associated Tissue Damage in Acute Ankle Sprains in Athletes: A Cross-sectional MRI Study.

PubMed

Roemer, Frank W; Jomaah, Nabil; Niu, Jingbo; Almusa, Emad; Roger, Bernard; D'Hooghe, Pieter; Geertsema, Celeste; Tol, Johannes L; Khan, Karim; Guermazi, Ali

2014-07-01

Ankle joint injuries are extremely common sports injuries, with the anterior talofibular ligament involved in the majority of ankle sprains. There have been only a few large magnetic resonance imaging (MRI) studies on associated structural injuries after ankle sprains. To describe the injury pattern in athletes who were referred to MRI for the assessment of an acute ankle sprain and to assess the risk of associated traumatic tissue damage including lateral and syndesmotic ligament involvement. Cross-sectional study; Level of evidence, 3. A total of 261 ankle MRI scans of athletes with acute ankle sprains were evaluated for: lateral and syndesmotic ligament injury; concomitant injuries to the deltoid and spring ligaments and sinus tarsi; peroneal, flexor, and extensor retinacula and tendons; traumatic and nontraumatic osteochondral and osseous changes; and joint effusion. Patients were on average 22.5 years old, and the average time from injury to MRI was 5.7 days. Six exclusive injury patterns were defined based on lateral and syndesmotic ligament involvement. The risk for associated injuries was assessed by logistic regression using ankles with no or only low-grade lateral ligament injuries and no syndesmotic ligament damage as the reference. With regard to the injury pattern, there were 103 ankles (39.5%) with complete anterior talofibular ligament disruption and no syndesmotic injury, and 53 ankles (20.3%) had a syndesmotic injury with or without lateral ligament damage. Acute osteochondral lesions of the lateral talar dome were seen in 20 ankles (7.7%). The percentage of chronic lateral osteochondral lesions was 1.1%. The risk for talar bone contusions increased more than 3-fold for ankles with complete lateral ligament ruptures (adjusted odds ratio [aOR], 3.43; 95% CI, 1.72-6.85) but not for ankles with syndesmotic involvement. The risk for associated deltoid ligament injuries increased for ankles with complete lateral ligament injuries (aOR, 4.04; 95% CI, 1

Anesthesia Technique and Outcomes of Mechanical Thrombectomy in Patients With Acute Ischemic Stroke.

PubMed

Bekelis, Kimon; Missios, Symeon; MacKenzie, Todd A; Tjoumakaris, Stavropoula; Jabbour, Pascal

2017-02-01

The impact of anesthesia technique on the outcomes of mechanical thrombectomy for acute ischemic stroke remains an issue of debate. We investigated the association of general anesthesia with outcomes in patients undergoing mechanical thrombectomy for ischemic stroke. We performed a cohort study involving patients undergoing mechanical thrombectomy for ischemic stroke from 2009 to 2013, who were registered in the New York Statewide Planning and Research Cooperative System database. An instrumental variable (hospital rate of general anesthesia) analysis was used to simulate the effects of randomization and investigate the association of anesthesia technique with case-fatality and length of stay. Among 1174 patients, 441 (37.6%) underwent general anesthesia and 733 (62.4%) underwent conscious sedation. Using an instrumental variable analysis, we identified that general anesthesia was associated with a 6.4% increased case-fatality (95% confidence interval, 1.9%-11.0%) and 8.4 days longer length of stay (95% confidence interval, 2.9-14.0) in comparison to conscious sedation. This corresponded to 15 patients needing to be treated with conscious sedation to prevent 1 death. Our results were robust in sensitivity analysis with mixed effects regression and propensity score-adjusted regression models. Using a comprehensive all-payer cohort of acute ischemic stroke patients undergoing mechanical thrombectomy in New York State, we identified an association of general anesthesia with increased case-fatality and length of stay. These considerations should be taken into account when standardizing acute stroke care. © 2017 American Heart Association, Inc.

Interaction between endogenous carbon monoxide and hydrogen sulfide in the mechanism of gastroprotection against acute aspirin-induced gastric damage.

PubMed

Magierowski, Marcin; Magierowska, Katarzyna; Hubalewska-Mazgaj, Magdalena; Adamski, Juliusz; Bakalarz, Dominik; Sliwowski, Zbigniew; Pajdo, Robert; Kwiecien, Slawomir; Brzozowski, Tomasz

2016-12-01

Acetylsalicylic acid (ASA) is mainly recognized as painkiller or anti-inflammatory drug. However, ASA causes serious side effects towards gastrointestinal (GI) tract which limits its usefulness. Carbon monoxide (CO) and hydrogen sulfide (H 2 S) have been described to act as important endogenous messengers and mediators of gastroprotection but whether they can interact in gastroprotection against acute ASA-induced gastric damage remains unknown. In this study male Wistar rats were pretreated with 1) vehicle (saline, i.g.), 2) tricarbonyldichlororuthenium (II) dimer (CORM-2, 5mg/kg i.g.), 3) sodium hydrosulfide (NaHS, 5mg/kg i.g.), 4) zinc protoporphyrin (ZnPP, 10mg/kg i.p.), 5) D,L-propargylglycine (PAG, 30mg/kg i.g.), 6) ZnPP combined with NaHS, 7) PAG combined with CORM-2 or 8) 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10mg/kg i.p.) combined with CORM-2 or NaHS and 30min later ASA was administered i.g. in a single dose of 125mg/kg. After 1h, gastric blood flow (GBF) was determined by H 2 gas clearance technique and gastric lesions were assessed by planimetry and histology. CO content in gastric mucosa and COHb concentration in blood were determined by gas chromatography and H 2 S production was assessed in gastric mucosa using methylene blue method. Protein and/or mRNA expression for cystathionine-γ-lyase (CSE), cystathionine-β-synthase (CBS), 3-mercaptopyruvate sulfurtransferase (3-MST), heme oxygenase (HO)-1, HO-2, hypoxia inducible factor-alpha (HIF)-1α, nuclear factor (erythroid-derived 2)-like 2 (Nrf-2), cyclooxygenase (COX)-1 and COX-2, inducible nitric oxide synthase (iNOS) and interleukin (IL)-1β were determined by Western blot or real-time PCR, respectively. ASA caused hemorrhagic gastric mucosal damage and significantly decreased GBF, H 2 S production, CO content, mRNA or protein expression for CSE, 3-MST, HO-2 and increased mRNA and/or protein expression for CBS, HO-1, Nrf-2, HIF-1α, iNOS, IL-1β, COX-2 in gastric mucosa and COHb

The effect of vitamin A on renal damage following acute pyelonephritis in children: a meta-analysis of randomized controlled trials.

PubMed

Zhang, Guo-Qiang; Chen, Jin-Liang; Zhao, Yong

2016-03-01

Renal scarring after acute pyelonephritis (APN) in children is of concern and in the worst cases leads to long-term cardiovascular morbidity. There are reports that vitamin A may alleviate renal damage following APN. We conducted a meta-analysis to investigate the role of vitamin A in the alleviation of renal damage. We searched PubMed, EMBASE, the Cochrane Central Register of Controlled trials (CENTRAL, the Cochrane Library) and the Wang Fang database (Chinese) from their inception to February 3, 2015 for randomized controlled trials (RCTs) investigating vitamin A and renal damage. Primary outcome was number of patients/kidneys with renal damage, defined as persistence of photopenic lesions based on technetium-99m dimercaptosuccinic acid renal scintigraphy. We calculated pooled relative risks for renal damage in the vitamin A group. Four RCTs, involving a total of 248 patients aged 1-144 months (120 in experimental group, 128 in control group), were included in the meta-analysis. Vitamin A was inversely associated with renal damage (relative risk 0.53, 95 % confidence interval 0.43, 0.67) when compared with placebo group after an average follow-up of 5 months. Current evidence indicates that vitamin A may exert a preventive effect on renal damage in children with APN. However, this finding largely relies on a few studies of low methodological quality, i.e., high risk of selection bias, performance bias and attrition bias. Hence, high-quality and adequately powered RCTs are warranted.

Mechanical Ventilation in Acute Hypoxemic Respiratory Failure: A Review of New Strategies for the Practicing Hospitalist

PubMed Central

Wilson, Jennifer G.; Matthay, Michael A.

2014-01-01

BACKGROUND The goal of mechanical ventilation in acute hypoxemic respiratory failure is to support adequate gas exchange without harming the lungs. How patients are mechanically ventilated can significantly impact their ultimate outcomes. METHODS This review focuses on emerging evidence regarding strategies for mechanical ventilation in patients with acute hypoxemic respiratory failure including: low tidal volume ventilation in the acute respiratory distress syndrome (ARDS), novel ventilator modes as alternatives to low tidal volume ventilation, adjunctive strategies that may enhance recovery in ARDS, the use of lung-protective strategies in patients without ARDS, rescue therapies in refractory hypoxemia, and an evidence-based approach to weaning from mechanical ventilation. RESULTS Once a patient is intubated and mechanically ventilated, low tidal volume ventilation remains the best strategy in ARDS. Adjunctive therapies in ARDS include a conservative fluid management strategy, as well as neuromuscular blockade and prone positioning in moderate-to-severe disease. There is also emerging evidence that a lung-protective strategy may benefit non-ARDS patients. For patients with refractory hypoxemia, extracorporeal membrane oxygenation should be considered. Once the patient demonstrates signs of recovery, the best approach to liberation from mechanical ventilation involves daily spontaneous breathing trials and protocolized assessment of readiness for extubation. CONCLUSIONS Prompt recognition of ARDS and use of lung-protective ventilation, as well as evidence-based adjunctive therapies, remain the cornerstones of caring for patients with acute hypoxemic respiratory failure. In the absence of contraindications, it is reasonable to consider lung-protective ventilation in non-ARDS patients as well, though the evidence supporting this practice is less conclusive. PMID:24733692

Transcription factor Nrf2 hyperactivation in early-phase renal ischemia-reperfusion injury prevents tubular damage progression.

PubMed

Nezu, Masahiro; Souma, Tomokazu; Yu, Lei; Suzuki, Takafumi; Saigusa, Daisuke; Ito, Sadayoshi; Suzuki, Norio; Yamamoto, Masayuki

2017-02-01

Acute kidney injury is a devastating disease with high morbidity in hospitalized patients and contributes to the pathogenesis of chronic kidney disease. An underlying mechanism of acute kidney injury involves ischemia-reperfusion injury which, in turn, induces oxidative stress and provokes organ damage. Nrf2 is a master transcription factor that regulates the cellular response to oxidative stress. Here, we examined the role of Nrf2 in the progression of ischemia-reperfusion injury-induced kidney damage in mice using genetic and pharmacological approaches. Both global and tubular-specific Nrf2 activation enhanced gene expression of antioxidant and NADPH synthesis enzymes, including glucose-6-phosphate dehydrogenase, and ameliorated both the initiation of injury in the outer medulla and the progression of tubular damage in the cortex. Myeloid-specific Nrf2 activation was ineffective. Short-term administration of the Nrf2 inducer CDDO during the initial phase of injury ameliorated the late phase of tubular damage. This inducer effectively protected the human proximal tubular cell line HK-2 from oxidative stress-mediated cell death while glucose-6-phosphate dehydrogenase knockdown increased intracellular reactive oxygen species. These findings demonstrate that tubular hyperactivation of Nrf2 in the initial phase of injury prevents the progression of reactive oxygen species-mediated tubular damage by inducing antioxidant enzymes and NADPH synthesis. Thus, Nrf2 may be a promising therapeutic target for preventing acute kidney injury to chronic kidney disease transition. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

{Linking permeability and mechanical damage for basalt from Mt Etna Volcano, Italy}

NASA Astrophysics Data System (ADS)

Faoro, I.; Vinciguerra, S.; Marone, C.; Elsworth, D.

2009-04-01

Volcanic edifices, such as Mt. Etna volcano (Italy), are affected from repeated episodes of pressurisation due to magma emplacement from deep reservoirs to shallow depths. This mechanism pressurizes the large aquifers within the edifice and increases the level of crack damage within the rocks of the edifice over extended periods of times. In order to improve our understanding of the complex coupling between circulating fluids and the development of crack damage, we performed flow-through tests using cylindrical cores of Etna Basalt (Etna, Italy) to evaluate permeabilty changes as a function of approach to failure under non-hydrostatic stresses at confining pressures from 5 to 60 MPa. Samples were loaded to failure by increasing increments of axial stress or by cyclic stresses of increasing amplitude. Both intact samples and pre-drilled samples (1.18mm) were tested. Under hydrostatic stresses, the permeability values of the intact sample decrease linearly with the increments of pressure and range between 5.2*10-17 m2and 1.5*10-17m2Under non-hydrostatic conditions, at low deviatoric stresses from (up to 18 MPa), the permeability values ranged between 5.5*10-17 m2and 4*10-17m2 and tended to completely recover the initial value each time the sample was unloaded, indicating an elastic regime. At higher deviatoric stresses (up to 60 MPa) the permeability values range between 2*10-17 m2 and 0.6*10-17m2. We hypothesize that from 5MPa to 40MPa axial stress, anelastic deformation mechanisms start to occur, with progressive pore collapse and opening of microfractures, resulting in a change of permeability. Under incremental uniaxial cyclic loading up to peak stresses of 160 MPa permeability decreases up to 2 orders of magnitude from initial values of 1*10-15 m2 to 2*10-14m2 Higher initial permeability values are related to the presence of an open fracture in the sample. We interpreted the reduction as a result of progressive closure of the voids space, as the axial load is

Recent Advances in Methamphetamine Neurotoxicity Mechanisms and Its Molecular Pathophysiology

PubMed Central

Yu, Shaobin; Zhu, Ling; Shen, Qiang; Bai, Xue; Di, Xuhui

2015-01-01

Methamphetamine (METH) is a sympathomimetic amine that belongs to phenethylamine and amphetamine class of psychoactive drugs, which are widely abused for their stimulant, euphoric, empathogenic, and hallucinogenic properties. Many of these effects result from acute increases in dopamine and serotonin neurotransmission. Subsequent to these acute effects, METH produces persistent damage to dopamine and serotonin release in nerve terminals, gliosis, and apoptosis. This review summarized the numerous interdependent mechanisms including excessive dopamine, ubiquitin-proteasome system dysfunction, protein nitration, endoplasmic reticulum stress, p53 expression, inflammatory molecular, D3 receptor, microtubule deacetylation, and HIV-1 Tat protein that have been demonstrated to contribute to this damage. In addition, the feasible therapeutic strategies according to recent studies were also summarized ranging from drug and protein to gene level. PMID:25861156

Continuum Damage Mechanics Models for the Analysis of Progressive Failure in Open-Hole Tension Laminates

NASA Technical Reports Server (NTRS)

Song, Kyonchan; Li, Yingyong; Rose, Cheryl A.

2011-01-01

The performance of a state-of-the-art continuum damage mechanics model for interlaminar damage, coupled with a cohesive zone model for delamination is examined for failure prediction of quasi-isotropic open-hole tension laminates. Limitations of continuum representations of intra-ply damage and the effect of mesh orientation on the analysis predictions are discussed. It is shown that accurate prediction of matrix crack paths and stress redistribution after cracking requires a mesh aligned with the fiber orientation. Based on these results, an aligned mesh is proposed for analysis of the open-hole tension specimens consisting of different meshes within the individual plies, such that the element edges are aligned with the ply fiber direction. The modeling approach is assessed by comparison of analysis predictions to experimental data for specimen configurations in which failure is dominated by complex interactions between matrix cracks and delaminations. It is shown that the different failure mechanisms observed in the tests are well predicted. In addition, the modeling approach is demonstrated to predict proper trends in the effect of scaling on strength and failure mechanisms of quasi-isotropic open-hole tension laminates.

Protective mechanisms of p53-p21-pRb proteins against DNA damage-induced cell death.

PubMed

Garner, Elizabeth; Raj, Kenneth

2008-02-01

There have been innumerate demonstrations of p53's activity as a tumour suppressor protein with the ability to stimulate cell signalling that can lead to cell cycle arrest and cell death in the event of DNA damage. Despite the solid body of evidence to support these properties of p53, reports have emerged that suggest a role for p53 in protecting cells from cell death. Our recent report highlighted a mechanism by which p53 activity can promote cell survival in the event of DNA damage. Here we present the various mechanisms that are activated by p53 signalling that can confer protection to cells with damaged DNA and emphasise the practical and clinical implications of a more balanced and context-dependent understanding of p53's pro-apoptotic and pro-survival activities.

Stevia Prevents Acute and Chronic Liver Injury Induced by Carbon Tetrachloride by Blocking Oxidative Stress through Nrf2 Upregulation

PubMed Central

Ramos-Tovar, Erika; Hernández-Aquino, Erika; Casas-Grajales, Sael; Buendia-Montaño, Laura D.; Tsutsumi, Víctor

2018-01-01

The effect of stevia on liver cirrhosis has not been previously investigated. In the present study, the antioxidant and anti-inflammatory properties of stevia leaves were studied in male Wistar rats with carbon tetrachloride- (CCl4-) induced acute and chronic liver damage. Acute and chronic liver damage induced oxidative stress, necrosis, and cholestasis, which were significantly ameliorated by stevia. Chronic CCl4 treatment resulted in liver cirrhosis, as evidenced by nodules of hepatocytes surrounded by thick bands of collagen and distortion of the hepatic architecture, and stevia significantly prevented these alterations. Subsequently, the underlying mechanism of action of the plant was analyzed. Our study for the first time shows that stevia upregulated Nrf2, thereby counteracting oxidative stress, and prevented necrosis and cholestasis through modulation of the main proinflammatory cytokines via NF-κB inhibition. These multitarget mechanisms led to the prevention of experimental cirrhosis. Given the reasonable safety profile of stevia, our results indicated that it may be useful for the clinical treatment of acute and chronic liver diseases. PMID:29849889

Inelastic deformation of metal matrix composites: Plasticity and damage mechanisms, part 2

NASA Technical Reports Server (NTRS)

Majumdar, B. S.; Newaz, G. M.

1992-01-01

The inelastic deformation mechanisms for the SiC (SCS-6)/Ti-15-3 system were studied at 538 C (1000 F) using a combination of mechanical measurements and detailed microstructural examinations. The objectives were to evaluate the contributions of plasticity and damage to the overall MMC response, and to compare the room temperature and elevated temperature deformation behaviors. Four different laminates were studied: (0)8, (90)8,(+ or -45)2s, and (0/90)2s, with the primary emphasis on the unidirectional (0)8, and (90)8 systems. The elevated temperature responses were similar to those at room temperature, involving a two-stage elastic-plastic type of response for the (0)8 system, and a characteristic three-stage deformation response for the (90)8 and (+ or -45)2s systems. The primary effects of elevated temperatures included: (1) reduction in the 'yield' and failure strengths; (2) plasticity through diffused slip rather than concentrated planar slip (which occurred at room temperature); and (3) time-dependent deformation. The inelastic deformation mechanism for the (0)8 MMC was dominated by plasticity at both temperatures. For the (90)8 and (+ or -45)2s MMCs, a combination of damage and plasticity contributed to the deformation at both temperatures.

Effects of tissue mechanical properties on susceptibility to histotripsy-induced tissue damage

NASA Astrophysics Data System (ADS)

Vlaisavljevich, Eli; Kim, Yohan; Owens, Gabe; Roberts, William; Cain, Charles; Xu, Zhen

2014-01-01

Histotripsy is a non-invasive tissue ablation method capable of fractionating tissue by controlling acoustic cavitation. To determine the fractionation susceptibility of various tissues, we investigated histotripsy-induced damage on tissue phantoms and ex vivo tissues with different mechanical strengths. A histotripsy bubble cloud was formed at tissue phantom surfaces using 5-cycle long ultrasound pulses with peak negative pressure of 18 MPa and PRFs of 10, 100, and 1000 Hz. Results showed significantly smaller lesions were generated in tissue phantoms of higher mechanical strength. Histotripsy was also applied to 43 different ex vivo porcine tissues with a wide range of mechanical properties. Gross morphology demonstrated stronger tissues with higher ultimate stress, higher density, and lower water content were more resistant to histotripsy damage in comparison to weaker tissues. Based on these results, a self-limiting vessel-sparing treatment strategy was developed in an attempt to preserve major vessels while fractionating the surrounding target tissue. This strategy was tested in porcine liver in vivo. After treatment, major hepatic blood vessels and bile ducts remained intact within a completely fractionated liver volume. These results identify varying susceptibilities of tissues to histotripsy therapy and provide a rational basis to optimize histotripsy parameters for treatment of specific tissues.

Effect of acute kidney injury on weaning from mechanical ventilation in critically ill patients.

PubMed

Vieira, José M; Castro, Isac; Curvello-Neto, Américo; Demarzo, Sérgio; Caruso, Pedro; Pastore, Laerte; Imanishe, Marina H; Abdulkader, Regina C R M; Deheinzelin, Daniel

2007-01-01

Acute kidney injury (AKI) worsens outcome in various scenarios. We sought to investigate whether the occurrence of AKI has any effect on weaning from mechanical ventilation. Observational, retrospective study in a 23-bed medical/surgical intensive care unit (ICU) in a cancer hospital from January to December 2003. The inclusion criterion was invasive mechanical ventilation for > or =48 hrs. AKI was defined as at least one measurement of serum creatinine of > or =1.5 mg/dL during the ICU stay. Patients were then separated into AKI and non-AKI patients (control group). The criterion for weaning was the combination of positive end-expiratory pressure of < or =8 cm H2O, pressure support of < or =10 cm H2O, and Fio2 of < or =0.4, with spontaneous breathing. The primary end point was duration of weaning and the secondary end points were rate of weaning failure, total length of mechanical ventilation, length of stay in the ICU, and ICU mortality. A total of 140 patients were studied: 93 with AKI and 47 controls. The groups were similar in regard to age, sex, and type of tumor. Diagnosis of acute lung injury/acute respiratory distress syndrome as cause of respiratory failure and Simplified Acute Physiology Score II at admission did not differ between groups. During ICU stay, AKI patients had markers of more severe disease: increased occurrence of severe sepsis or septic shock, higher number of antibiotics, and longer use of vasoactive drugs. The median (interquartile range) duration of mechanical ventilation (10 [6-17] vs. 7 [2-12] days, p = .017) and duration of weaning from mechanical ventilation (41 [16-97] vs. 21 [7-33.5] hrs, p = .018) were longer in AKI patients compared with control patients. Cox regression analysis demonstrated that a > or =85% increase in baseline serum creatinine (hazard rate, 2.30; 95% confidence interval, 1.30-4.08), oliguria (hazard rate, 2.51; 95% confidence interval, 1.24-5.08), and the number of antibiotics (hazard rate, 2.64; 95

Serum biochemical markers of central nerve system damage in children with acute elemental mercury intoxicatıon.

PubMed

Yılmaz, F M; Yılmaz, H; Tutkun, E; Uysal, S; Carman, K B; Dılber, C; Ercan, M

2014-01-01

Acute mercury intoxication among children can occur through unintentional exposure, and neurotoxicity is one of the main findings in acute exposures. In this study, we aimed to study the central nerve system markers, namely neuron-specific enolase (NSE), S100B, and glutamate receptor (GRIA 1) levels and discuss the mechanisms of central nerve system damage and whether these parameters could be used as markers of acute elemental mercury intoxication neurotoxicity. This is a case-control study which includes 169 children with acute elemental mercury intoxication, who were exposed to mercury in the school laboratory from a broken jar, and 45 sex- and age-matched controls without mercury exposure. Patient group were divided into three subgroups according to the neurological examination performed during the admission. Neuropathy Group included the children with neurological symptoms including peripheral neuropathy and decreased muscle strength (n = 39) (with or without dilated pupils). Dilated Pupil Group included the children who had mid-dilated/dilated pupils (n = 52). Asymptomatic Exposure Group included the children who did not have any neurological symptoms (n = 78). Serum NSE, S100B, GRIA 1, blood, and urine mercury levels were determined. NSE, S100B, GRIA 1, and blood mercury levels were significantly higher in exposed group than the nonexposed subjects (Median values NSE 22.4 ng/mL, 17.2 ng/mL; S100B 0.09 ng/mL, 0.08 ng/mL; GRIA 1 70.6 pg/mL, 54.1 pg/mL, and blood mercury 15.2 μg/L, 0.23 μg/L for exposed and nonexposed groups, respectively). GRIA 1 levels found to differ between exposed and nonexposed groups and it has also been found to be increased in the subgroups with positive neurological findings compared to that in neurological finding negative groups. S100B levels were found to be increased in exposed and having neurological symptom groups. There was not a significant difference between exposed-not having neurological symptom patients and control group

Acute oral dose of sodium nitrite induces redox imbalance, DNA damage, metabolic and histological changes in rat intestine.

PubMed

Ansari, Fariheen Aisha; Ali, Shaikh Nisar; Arif, Hussain; Khan, Aijaz Ahmed; Mahmood, Riaz

2017-01-01

Industrialization and unchecked use of nitrate/nitrite salts for various purposes has increased human exposure to high levels of sodium nitrite (NaNO2) which can act as a pro-oxidant and pro-carcinogen. Oral exposure makes the gastrointestinal tract particularly susceptible to nitrite toxicity. In this work, the effect of administration of a single acute oral dose of NaNO2 on rat intestine was studied. Animals were randomly divided into four groups and given single doses of 20, 40, 60 and 75 mg NaNO2/kg body weight. Untreated animals served as the control group. An NaNO2 dose-dependent decline in the activities of brush border membrane enzymes, increase in lipid peroxidation, protein oxidation, hydrogen peroxide levels and decreased thiol content was observed in all treated groups. The activities of various metabolic and antioxidant defense enzymes were also altered. NaNO2 induced a dose-dependent increase in DNA damage and DNA-protein crosslinking. Histopathological studies showed marked morphological damage in intestinal cells. The intestinal damage might be due to nitrite-induced oxidative stress, direct action of nitrite anion or chemical modification by reaction intermediates.

Mechanisms of fibrosis in acute liver failure.

PubMed

He, Yingli; Jin, Li; Wang, Jing; Yan, Zhi; Chen, Tianyan; Zhao, Yingren

2015-07-01

Acute liver failure (ALF) is a condition with high mortality and morbidity. Fibrosis in chronic liver disease was extensively researched, whereas fibrosis and underlying mechanism in acute liver failure remains unclear. Hepatitis B virus related ALF patients were recruited to investigate if there was ongoing fibrosis by liver histology and liver stiffness measurement(LSM) analysis as well as fibrosis markers assay. Sera HMGB1 were kinetically detected in progression and remission stage of ALF. Hepatic stellate cell(HSC) activation by HMGB1 was explored by testing mRNA and protein level of α-SMA and collagen 1a1 by using qPCR and western blot. Autophagy induction by HMGB1 was explored by LC3-II conversion, autophagy flux and fluorescence. Firstly, ongoing fibrosis in progression stage of ALF was confirmed by histological analysis, LS measurement as well as fibrosis markers detection. HSC activation and autophagy induction in explanted liver tissue also revealed. Next, kinetic monitoring sera HMGB1 revealed elevated HMGB1 in progression stage of ALF vs HBsAg carrier, and drop back to base level in remission stage. Thirdly, rHMGB1 dose dependently activated HSCs, as indicated by increased mRNA and proteins level in α-SMA and collagen 1a1. Moreover, autophagy was induced in HSC treated with rHMGB1, as illustrated by increased LC3 lipidation, elevated autophagy flux and GFP-LC3 puncta. Acute liver failure is accompanied by ongoing fibrosis, HSC activation and autophagy induction. Increased HMGB1 activates HSC via autophagy induction. Those findings integrate HMGB1, HSCs activation, autophagy into a common framework that underlies the fibrosis in ALF. © 2014 The Authors. Liver International Published by John Wiley & Sons Ltd.

Mesenchymal Stem Cells From Bone Marrow, Adipose Tissue, and Lung Tissue Differentially Mitigate Lung and Distal Organ Damage in Experimental Acute Respiratory Distress Syndrome.

PubMed

Silva, Johnatas D; Lopes-Pacheco, Miquéias; Paz, Ana H R; Cruz, Fernanda F; Melo, Elga B; de Oliveira, Milena V; Xisto, Débora G; Capelozzi, Vera L; Morales, Marcelo M; Pelosi, Paolo; Cirne-Lima, Elizabeth; Rocco, Patricia R M

2018-02-01

Mesenchymal stem cells-based therapies have shown promising effects in experimental acute respiratory distress syndrome. Different mesenchymal stem cells sources may result in diverse effects in respiratory diseases; however, there is no information regarding the best source of mesenchymal stem cells to treat pulmonary acute respiratory distress syndrome. We tested the hypothesis that mesenchymal stem cells derived from bone marrow, adipose tissue, and lung tissue would lead to different beneficial effects on lung and distal organ damage in experimental pulmonary acute respiratory distress syndrome. Animal study and primary cell culture. Laboratory investigation. Seventy-five Wistar rats. Wistar rats received saline (control) or Escherichia coli lipopolysaccharide (acute respiratory distress syndrome) intratracheally. On day 2, acute respiratory distress syndrome animals were further randomized to receive saline or bone marrow, adipose tissue, or lung tissue mesenchymal stem cells (1 × 10 cells) IV. Lung mechanics, histology, and protein levels of inflammatory mediators and growth factors were analyzed 5 days after mesenchymal stem cells administration. RAW 264.7 cells (a macrophage cell line) were incubated with lipopolysaccharide followed by coculture or not with bone marrow, adipose tissue, and lung tissue mesenchymal stem cells (10 cells/mL medium). Regardless of mesenchymal stem cells source, cells administration improved lung function and reduced alveolar collapse, tissue cellularity, collagen, and elastic fiber content in lung tissue, as well as decreased apoptotic cell counts in liver. Bone marrow and adipose tissue mesenchymal stem cells administration also reduced levels of tumor necrosis factor-α, interleukin-1β, keratinocyte-derived chemokine, transforming growth factor-β, and vascular endothelial growth factor, as well as apoptotic cell counts in lung and kidney, while increasing expression of keratinocyte growth factor in lung tissue

Rotational 3D printing of damage-tolerant composites with programmable mechanics

PubMed Central

Raney, Jordan R.; Compton, Brett G.; Ober, Thomas J.; Shea, Kristina; Lewis, Jennifer A.

2018-01-01

Natural composites exhibit exceptional mechanical performance that often arises from complex fiber arrangements within continuous matrices. Inspired by these natural systems, we developed a rotational 3D printing method that enables spatially controlled orientation of short fibers in polymer matrices solely by varying the nozzle rotation speed relative to the printing speed. Using this method, we fabricated carbon fiber–epoxy composites composed of volume elements (voxels) with programmably defined fiber arrangements, including adjacent regions with orthogonally and helically oriented fibers that lead to nonuniform strain and failure as well as those with purely helical fiber orientations akin to natural composites that exhibit enhanced damage tolerance. Our approach broadens the design, microstructural complexity, and performance space for fiber-reinforced composites through site-specific optimization of their fiber orientation, strain, failure, and damage tolerance. PMID:29348206

Generation of plate tectonics via grain-damage and pinning

NASA Astrophysics Data System (ADS)

Bercovici, D.; Ricard, Y. R.

2012-12-01

-parallel to plate motion), oblique subduction and highly localized, weak and long lived acute plate-boundary junctions such as at the Aleution-Kurile intersection. The grain-damage and pinning theory therefore readily satisfies key plate-tectonic metrics of localized toroidal motion and plate-boundary inheritance, and thus provides a predictive theory for the generation of plate tectonics on Earth and other planets. References: Bercovici, D., Ricard, Y., 2012. Mechanisms for the generation of plate tectonics by two-phase grain-damage and pinning. Phys. Earth Planet. Int. 202-203, 27--55.

A sneaky surgical emergency: Acute compartment syndrome. Retrospective analysis of 66 closed claims, medico-legal pitfalls and damages evaluation.

PubMed

Marchesi, M; Marchesi, A; Calori, G M; Cireni, L V; Sileo, G; Merzagora, I; Zoia, R; Vaienti, L; Morini, O

2014-12-01

Acute compartment syndrome (ACS) is a clinical condition with potentially dramatic consequences, therefore, it is important to recognise and treat it early. Good management of ACS minimises or avoids the sequelae associated with a late diagnosis, and may also reduce the risk of malpractice claims. The aim of this article was to evaluate different errors ascribed to the surgeon and to identify how the damage was evaluated. A total of 66 completed and closed ACS cases were selected. The following were analysed for each case: clinical management before and after diagnosis of ACS, imputed errors, professional fault, damage evaluation and quantification. Particular attention was paid to distinguishing between impairment because of primary injury and iatrogenic impairment. Statistical analyses were performed using Fisher's exact test and Pearson's correlation. The most common presenting symptom was pain. Delay in the diagnosis, and hence delay in decompression, was common in the study. A total of 48 out of 66 cases resolved with the verdict of iatrogenic damage, which varied from 12% to 75% of global capability of the person. A total of $394,780 out of $574,680 (average payment) derived from a medical error. ACS is a clinical emergency that requires continuous clinical surveillance from both medical and nursing staff. The related damage should be evaluated in two parts: damage deriving from the trauma, so that it is considered inevitable and independent from the surgeon's conduct, and damage deriving from a surgeon's error, which is eligible for an indemnity payment. Copyright © 2014 Elsevier Ltd. All rights reserved.

Computational Simulation of Damage Progression of Composite Thin Shells Subjected to Mechanical Loads

NASA Technical Reports Server (NTRS)

Gotsis, P. K.; Chamis, C. C.; Minnetyan, L.

1996-01-01

Defect-free and defected composite thin shells with ply orientation (90/0/+/-75) made of graphite/epoxy are simulated for damage progression and fracture due to internal pressure and axial loading. The thin shells have a cylindrical geometry with one end fixed and the other free. The applied load consists of an internal pressure in conjunction with an axial load at the free end, the cure temperature was 177 C (350 F) and the operational temperature was 21 C (70 F). The residual stresses due to the processing are taken into account. Shells with defect and without defects were examined by using CODSTRAN an integrated computer code that couples composite mechanics, finite element and account for all possible failure modes inherent in composites. CODSTRAN traces damage initiation, growth, accumulation, damage propagation and the final fracture of the structure. The results show that damage initiation started with matrix failure while damage/fracture progression occurred due to additional matrix failure and fiber fracture. The burst pressure of the (90/0/+/- 75) defected shell was 0.092% of that of the free defect. Finally the results of the damage progression of the (90/0/+/- 75), defective composite shell was compared with the (90/0/+/- theta, where theta = 45 and 60, layup configurations. It was shown that the examined laminate (90/0/+/- 75) has the least damage tolerant of the two compared defective shells with the (90/0/+/- theta), theta = 45 and 60 laminates.

Adrenocorticotropic hormone ameliorates acute kidney injury by steroidogenic-dependent and -independent mechanisms

PubMed Central

Si, Jin; Ge, Yan; Zhuang, Shougang; Juan Wang, Li; Chen, Shan; Gong, Rujun

2013-01-01

Adrenocorticotropic hormone (ACTH) has a renoprotective effect in chronic kidney disease; however, its effect on acute kidney injury (AKI) remains unknown. In a rat model of tumor necrosis factor (TNF)–induced AKI, we found that ACTH gel prevented kidney injury, corrected acute renal dysfunction, and improved survival. Morphologically, ACTH gel ameliorated TNF-induced acute tubular necrosis, associated with a reduction in tubular apoptosis. While the steroidogenic response to ACTH gel plateaued, the kidney-protective effect continued to increase at even higher doses, suggesting steroid-independent mechanisms. Of note, ACTH also acts as a key agonist of the melanocortin system, with its cognate melanocortin 1 receptor (MC1R) abundantly expressed in renal tubules. In TNF-injured tubular epithelial cells in vitro, ACTH reinstated cellular viability and eliminated apoptosis. This beneficial effect was blunted in MC1R-silenced cells, suggesting that this receptor mediates the anti-apoptotic signaling of ACTH. Moreover, ACTH gel protected mice against cecal ligation puncture–induced septic AKI better than α-melanocyte-stimulating hormone: a protein equal in biological activity to ACTH except for steroidogenesis. Thus, ACTH has additive renoprotective actions achieved by both steroid-dependent mechanisms and MC1R-directed anti-apoptosis. ACTH may represent a novel therapeutic strategy to prevent or treat AKI. PMID:23325074

Single shot damage mechanism of Mo/Si multilayer optics under intense pulsed XUV-exposure.

PubMed

Khorsand, A R; Sobierajski, R; Louis, E; Bruijn, S; van Hattum, E D; van de Kruijs, R W E; Jurek, M; Klinger, D; Pelka, J B; Juha, L; Burian, T; Chalupsky, J; Cihelka, J; Hajkova, V; Vysin, L; Jastrow, U; Stojanovic, N; Toleikis, S; Wabnitz, H; Tiedtke, K; Sokolowski-Tinten, K; Shymanovich, U; Krzywinski, J; Hau-Riege, S; London, R; Gleeson, A; Gullikson, E M; Bijkerk, F

2010-01-18

We investigated single shot damage of Mo/Si multilayer coatings exposed to the intense fs XUV radiation at the Free-electron LASer facility in Hamburg - FLASH. The interaction process was studied in situ by XUV reflectometry, time resolved optical microscopy, and "post-mortem" by interference-polarizing optical microscopy (with Nomarski contrast), atomic force microscopy, and scanning transmission electron microcopy. An ultrafast molybdenum silicide formation due to enhanced atomic diffusion in melted silicon has been determined to be the key process in the damage mechanism. The influence of the energy diffusion on the damage process was estimated. The results are of significance for the design of multilayer optics for a new generation of pulsed (from atto- to nanosecond) XUV sources.

Damage-Resistant Composites Using Electrospun Nanofibers: A Multiscale Analysis of the Toughening Mechanisms.

PubMed

Daelemans, Lode; van der Heijden, Sam; De Baere, Ives; Rahier, Hubert; Van Paepegem, Wim; De Clerck, Karen

2016-05-11

Today, fiber-reinforced polymer composites are a standard material in applications where a high stiffness and strength are required at minimal weight, such as aerospace structures, ultralight vehicles, or even flywheels for highly efficient power storage systems. Although fiber-reinforced polymer composites show many advantages compared to other materials, delamination between reinforcing plies remains a major problem limiting further breakthrough. Traditional solutions that have been proposed to toughen the interlaminar region between reinforcing plies have already reached their limit or have important disadvantages such as a high cost or the need for adapted production processes. Recently, electrospun nanofibers have been suggested as a more viable interlaminar toughening method. Although the expected benefits are numerous, the research on composite laminates enhanced with electrospun nanofibrous veils is still very limited. The work that has been done so far is almost exclusively focused on interlaminar fracture toughness tests with different kinds of nanofibers, where typically a trial and error approach has been used. A thorough understanding of the micromechanical fracture mechanisms and the parameters to obtain toughened composites has not been reported as of yet, but it is crucial to advance the research and design highly damage-resistant composites. This article provides such insight by analyzing the nanofiber toughening effect on three different levels for several nanofiber types. Only by combining the results from different levels, a thorough understanding can be obtained. These levels correspond to the hierarchical nature of a composite: the laminate, the interlaminar region, and the matrix resin. It is found that each level corresponds to certain mechanisms that result in a toughening effect. The bridging of microcracks by electrospun nanofibers is the main toughening mechanism resulting in damage resistance. Nevertheless, the way in which the

355 nm and 1064 nm-pulse mixing to identify the laser-induced damage mechanisms in KDP

NASA Astrophysics Data System (ADS)

Reyné, Stéphane; Duchateau, Guillaume; Natoli, Jean-Yves; Lamaignère, Laurent

2011-02-01

Nanosecond laser-induced damage (LID) in potassium dihydrogen phosphate (KH2PO4 or KDP) remains an issue for light-frequency converters in large-aperture lasers such as NIF (National Ignition Facility, in USA) LMJ (Laser MegaJoule, in France). In the final optic assembly, converters are simultaneously illuminated by multiple wavelengths during the frequency conversion. In this configuration, the damage resistance of the KDP crystals becomes a crucial problem and has to be improved. In this study, we propose a refined investigation about the LID mechanisms involved in the case of a multiple wavelengths combination. Experiments based on an original pump-pump set-up have been carried out in the nanosecond regime on a KDP crystal. In particular, the impact of a simultaneous mixing of 355 nm and 1064 nm pulses has been experimentally studied and compared to a model based on heat transfer, the Mie theory and a Drude model. This study sheds light on the physical processes implied in the KDP laser damage. In particular, a three-photon ionization mechanism is shown to be responsible for laser damage in KDP.

Evaluation of deterioration of structural concrete due to chloride intrusion and other damaging mechanisms.

DOT National Transportation Integrated Search

2015-09-01

Kentucky's bridges continue to age and experience distress. The intrusion of chlorides into : concrete remains the primary mechanism for deterioration. It leads to reinforcing steel corrosion : that damages the adjoining concrete structure. This stud...

Iron-Induced Damage in Cardiomyopathy: Oxidative-Dependent and Independent Mechanisms

PubMed Central

Gammella, Elena; Recalcati, Stefania; Rybinska, Ilona; Buratti, Paolo; Cairo, Gaetano

2015-01-01

The high incidence of cardiomyopathy in patients with hemosiderosis, particularly in transfusional iron overload, strongly indicates that iron accumulation in the heart plays a major role in the process leading to heart failure. In this context, iron-mediated generation of noxious reactive oxygen species is believed to be the most important pathogenetic mechanism determining cardiomyocyte damage, the initiating event of a pathologic progression involving apoptosis, fibrosis, and ultimately cardiac dysfunction. However, recent findings suggest that additional mechanisms involving subcellular organelles and inflammatory mediators are important factors in the development of this disease. Moreover, excess iron can amplify the cardiotoxic effect of other agents or events. Finally, subcellular misdistribution of iron within cardiomyocytes may represent an additional pathway leading to cardiac injury. Recent advances in imaging techniques and chelators development remarkably improved cardiac iron overload detection and treatment, respectively. However, increased understanding of the pathogenic mechanisms of iron overload cardiomyopathy is needed to pave the way for the development of improved therapeutic strategies. PMID:25878762

Fatigue damage mechanics of notched graphite-epoxy laminates

NASA Astrophysics Data System (ADS)

Spearing, Mark; Beaumont, Peter W. R.; Ashby, Michael F.

A modeling approach is presented that recognizes that the residual properties of composite laminates after any form of loading depend on the damage state. Therefore, in the case of cyclic loading, it is necessary to first derive a damage growth law and then relate the residual properties to the accumulated damage. The propagation of fatigue damage in notched laminates is investigated. A power law relationship between damage growth and the strain energy release rate is developed. The material constants used in the model have been determined in independent experiments and are invariant for all the layups investigated. The strain energy release rates are calculated using a simple finite element representation of the damaged specimen. The model is used to predict the effect of tension-tension cyclic loading on laminates of the T300/914C carbon-fiber epoxy system. The extent of damage propagation is successfully predicted in a number of cross-ply laminates.

Kinetic theory approach to modeling of cellular repair mechanisms under genome stress.

PubMed

Qi, Jinpeng; Ding, Yongsheng; Zhu, Ying; Wu, Yizhi

2011-01-01

Under acute perturbations from outer environment, a normal cell can trigger cellular self-defense mechanism in response to genome stress. To investigate the kinetics of cellular self-repair process at single cell level further, a model of DNA damage generating and repair is proposed under acute Ion Radiation (IR) by using mathematical framework of kinetic theory of active particles (KTAP). Firstly, we focus on illustrating the profile of Cellular Repair System (CRS) instituted by two sub-populations, each of which is made up of the active particles with different discrete states. Then, we implement the mathematical framework of cellular self-repair mechanism, and illustrate the dynamic processes of Double Strand Breaks (DSBs) and Repair Protein (RP) generating, DSB-protein complexes (DSBCs) synthesizing, and toxins accumulating. Finally, we roughly analyze the capability of cellular self-repair mechanism, cellular activity of transferring DNA damage, and genome stability, especially the different fates of a certain cell before and after the time thresholds of IR perturbations that a cell can tolerate maximally under different IR perturbation circumstances.

Neglect severity after left and right brain damage.

PubMed

Suchan, Julia; Rorden, Chris; Karnath, Hans-Otto

2012-05-01

While unilateral spatial neglect after left brain damage is undoubtedly less common than spatial neglect after a right hemisphere lesion, it is also assumed to be less severe. Here we directly test this latter hypothesis using a continuous measure of neglect severity: the so-called Center of Cancellation (CoC). Rorden and Karnath (2010) recently validated this index for right brain damaged neglect patients. A first aim of the present study was to evaluate this new measure for spatial neglect after left brain damage. In a group of 48 left-sided stroke patients with and without neglect, a score greater than -0.086 on the Bells Test and greater than -0.024 on the Letter Cancellation Task turned out to indicate neglect behavior for acute left brain damaged patients. A second aim was to directly compare the severity of spatial neglect after left versus right brain injury by using the new CoC measure. While neglect is less frequent following left than right hemisphere injury, we found that when this symptom occurs it is of similar severity in acute left brain injury as in patients after acute right brain injury. Copyright © 2012 Elsevier Ltd. All rights reserved.

Ultrashort Laser Retinal Damage Threshold Mechanisms

DTIC Science & Technology

2010-01-15

epithelium . Below one nanosecond both stress-confinement in melanosomes and self-focusing reduce the threshold for damage as measured in corneal radiant... epithelium (RPE). Below 1 ns, both stress confinement in melanosomes and self-focusing reduce the threshold for damage as measured in corneal radiant...collimated laser light is focused to a very small spot on the retina. The retinal pigment epithelium (RPE) contains melanosomes, which are the primary

Duration of emission of volatile organic compounds from mechanically damaged plant leaves.

PubMed

Smith, Lincoln; Beck, John J

2015-09-01

Classical biological control of invasive alien weeds depends on the use of arthropod herbivores that are sufficiently host specific to avoid risk of injuring nontarget plants. Host plant specificity is usually evaluated by using a combination of behavioral and developmental experiments under choice, no-choice and field conditions. Secondary plant compounds are likely to have an important influence on host plant specificity. However, relatively little is known about the volatile organic compounds (VOCs) that are emitted by target and nontarget plants, and how environmental conditions may affect their emission. Previous studies have shown that mechanical damage of leaves increases the composition and content of VOCs emitted. In this study we measured the VOC emissions of five species of plants in the subtribe Centaureinae (Asteraceae)--Carthamus tinctorius, Centaurea cineraria, Centaurea melitensis, Centaurea rothrockii, and Centaurea solstitialis--that have previously been used in host specificity experiments for a prospective biological control agent of yellow starthistle (C. solstitialis). Leaves of each plant were punctured with a needle and the VOCs were collected by solid-phase microextraction (SPME) periodically over 48 h and analyzed by GC-MS. A total of 49 compounds were detected. Damage caused an immediate increase of 200-600% in the composition of VOCs emitted from each plant species, and the amounts generally remained high for at least 48 h. The results indicate that a very unspecific mechanical damage can cause a prolonged change in the VOC profile of plants. Published by Elsevier GmbH.

Corrosion Damage and Wear Mechanisms in Long-Term Retrieved CoCr Femoral Components for Total Knee Arthroplasty.

PubMed

Arnholt, Christina M; MacDonald, Daniel W; Malkani, Arthur L; Klein, Gregg R; Rimnac, Clare M; Kurtz, Steven M; Kocagoz, Sevi B; Gilbert, Jeremy L

2016-12-01

Metal debris and ion release has raised concerns in joint arthroplasty. The purpose of this study was to characterize the sources of metallic ions and particulate debris released from long-term (in vivo >15 years) total knee arthroplasty femoral components. A total of 52 CoCr femoral condyles were identified as having been implanted for more than 15 years. The femoral components were examined for incidence of 5 types of damage (metal-on-metal wear due to historical polyethylene insert failure, mechanically assisted crevice corrosion at taper interfaces, cement interface corrosion, third-body abrasive wear, and inflammatory cell-induced corrosion [ICIC]). Third-body abrasive wear was evaluated using the Hood method for polyethylene components and a similar method quantifying surface damage of the femoral condyle was used. The total area damaged by ICIC was quantified using digital photogrammetry. Surface damage associated with corrosion and/or CoCr debris release was identified in 51 (98%) CoCr femoral components. Five types of damage were identified: 98% of femoral components exhibited third-body abrasive wear (mostly observed as scratching, n = 51/52), 29% of femoral components exhibited ICIC damage (n = 15/52), 41% exhibited cement interface damage (n = 11/27), 17% exhibited metal-on-metal wear after wear-through of the polyethylene insert (n = 9/52), and 50% of the modular femoral components exhibited mechanically assisted crevice corrosion taper damage (n = 2/4). The total ICIC-damaged area was an average of 0.11 ± 0.12 mm 2 (range: 0.01-0.46 mm 2 ). Although implant damage in total knee arthroplasty is typically reported with regard to the polyethylene insert, the results of this study demonstrate that abrasive and corrosive damage occurs on the CoCr femoral condyle in vivo. Copyright © 2016 Elsevier Inc. All rights reserved.

Acute respiratory distress syndrome in combat casualties: military medicine and advances in mechanical ventilation.

PubMed

Morris, Michael James

2006-11-01

Military medicine has made numerous enduring contributions to the advancement of pulmonary medicine. Acute respiratory distress syndrome was first recognized as a complication in battlefield casualties in World War I and continued to play a significant role in the treatment of casualties through the Vietnam War. Innovative surgeons during World War II devised methods to assist their patients with positive pressure breathing. This concept was later adopted and applied to the development of mechanical ventilation in the late 1940s and early 1950s. The continued treatment of acute respiratory distress syndrome in combat casualties by military physicians has provided a major impetus for advances in modern mechanical ventilation and intensive care unit medicine.

Urocortin Treatment Improves Acute Hemodynamic Instability and Reduces Myocardial Damage in Post-Cardiac Arrest Myocardial Dysfunction

PubMed Central

Huang, Chien-Hua; Wang, Chih-Hung; Tsai, Min-Shan; Hsu, Nai-Tan; Chiang, Chih-Yen; Wang, Tzung-Dau; Chang, Wei-Tien; Chen, Huei-Wen; Chen, Wen-Jone

2016-01-01

Aims Hemodynamic instability occurs following cardiac arrest and is associated with high mortality during the post-cardiac period. Urocortin is a novel peptide and a member of the corticotrophin-releasing factor family. Urocortin has the potential to improve acute cardiac dysfunction, as well as to reduce the myocardial damage sustained after ischemia reperfusion injury. The effects of urocortin in post-cardiac arrest myocardial dysfunction remain unclear. Methods and Results We developed a preclinical cardiac arrest model and investigated the effects of urocortin. After cardiac arrest induced by 6.5 min asphyxia, male Wistar rats were resuscitated and randomized to either the urocortin treatment group or the control group. Urocortin (10 μg/kg) was administrated intravenously upon onset of resuscitation in the experimental group. The rate of return of spontaneous circulation (ROSC) was similar between the urocortin group (76%) and the control group (72%) after resuscitation. The left ventricular systolic (dP/dt40) and diastolic (maximal negative dP/dt) functions, and cardiac output, were ameliorated within 4 h after ROSC in the urocortin-treated group compared to the control group (P<0.01). The neurological function of surviving animals was better at 6 h after ROSC in the urocortin-treated group (p = 0.023). The 72-h survival rate was greater in the urocortin-treated group compared to the control group (p = 0.044 by log-rank test). Cardiomyocyte apoptosis was lower in the urocortin-treated group (39.9±8.6 vs. 17.5±4.6% of TUNEL positive nuclei, P<0.05) with significantly increased Akt, ERK and STAT-3 activation and phosphorylation in the myocardium (P<0.05). Conclusions Urocortin treatment can improve acute hemodynamic instability as well as reducing myocardial damage in post-cardiac arrest myocardial dysfunction. PMID:27832152

Acute high-intensity interval running increases markers of gastrointestinal damage and permeability but not gastrointestinal symptoms.

PubMed

Pugh, Jamie N; Impey, Samuel G; Doran, Dominic A; Fleming, Simon C; Morton, James P; Close, Graeme L

2017-09-01

The purpose of this study was to investigate the effects of high-intensity interval running on markers of gastrointestinal (GI) damage and permeability alongside subjective symptoms of GI discomfort. Eleven male runners completed an acute bout of high-intensity interval training (HIIT) (eighteen 400-m runs at 120% maximal oxygen uptake) where markers of GI permeability, intestinal damage, and GI discomfort symptoms were assessed and compared with resting conditions. Compared with rest, HIIT significantly increased serum lactulose/rhamnose ratio (0.051 ± 0.016 vs. 0.031 ± 0.021, p = 0.0047; 95% confidence interval (CI) = 0.006 to 0.036) and sucrose concentrations (0.388 ± 0.217 vs. 0.137 ± 0.148 mg·L -1 ; p < 0.001; 95% CI = 0.152 to 0.350). In contrast, urinary lactulose/rhamnose (0.032 ± 0.005 vs. 0.030 ± 0.005; p = 0.3; 95% CI = -0.012 to 0.009) or sucrose concentrations (0.169% ± 0.168% vs. 0.123% ± 0.120%; p = 0.54; 95% CI = -0.199 to 0.108) did not differ between HIIT and resting conditions. Plasma intestinal-fatty acid binding protein (I-FABP) was significantly increased (p < 0.001) during and in the recovery period from HIIT whereas no changes were observed during rest. Mild symptoms of GI discomfort were reported immediately and at 24 h post-HIIT, although these symptoms did not correlate to GI permeability or I-FABP. In conclusion, acute HIIT increased GI permeability and intestinal I-FABP release, although these do not correlate with symptoms of GI discomfort. Furthermore, by using serum sampling, we provide data showing that it is possible to detect changes in intestinal permeability that is not observed using urinary sampling over a shorter time-period.

Mechanisms of Retinal Damage from Chronic Laser Radiation.

DTIC Science & Technology

1981-07-01

culture. The pigment epithelium is deter- mined to be almost equally susceptible to damage in vitro as in vivo and the same action spectrum is similar in...92 -97 D. Experiment III. Light Damage in Culture of Bovine Retinal Pigment Epithelium 1. Methodology a. Collection of Cells... epithelium : Mild form of damage. Figure 18 Inner segments severely damaged. Figure 19 : Cone pedicle after exposure. Figure 20 Outer plexiform layer

Review: Wind impacts on plant growth, mechanics and damage.

PubMed

Gardiner, Barry; Berry, Peter; Moulia, Bruno

2016-04-01

Land plants have adapted to survive under a range of wind climates and this involve changes in chemical composition, physical structure and morphology at all scales from the cell to the whole plant. Under strong winds plants can re-orientate themselves, reconfigure their canopies, or shed needles, leaves and branches in order to reduce the drag. If the wind is too strong the plants oscillate until the roots or stem fail. The mechanisms of root and stem failure are very similar in different plants although the exact details of the failure may be different. Cereals and other herbaceous crops can often recover after wind damage and even woody plants can partially recovery if there is sufficient access to water and nutrients. Wind damage can have major economic impacts on crops, forests and urban trees. This can be reduced by management that is sensitive to the local site and climatic conditions and accounts for the ability of plants to acclimate to their local wind climate. Wind is also a major disturbance in many plant ecosystems and can play a crucial role in plant regeneration and the change of successional stage. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Effect of thermal and mechanical parameter’s damage numerical simulation cycling effects on defects in hot metal forming processes

NASA Astrophysics Data System (ADS)

El Amri, Abdelouahid; el yakhloufi Haddou, Mounir; Khamlichi, Abdellatif

2017-10-01

Damage mechanisms in hot metal forming processes are accelerated by mechanical stresses arising during Thermal and mechanical properties variations, because it consists of the materials with different thermal and mechanical loadings and swelling coefficients. In this work, 3D finite element models (FEM) are developed to simulate the effect of Temperature and the stresses on the model development, using a general purpose FE software ABAQUS. Explicit dynamic analysis with coupled Temperature displacement procedure is used for a model. The purpose of this research was to study the thermomechanical damage mechanics in hot forming processes. The important process variables and the main characteristics of various hot forming processes will also be discussed.

Combined meso-scale modeling and experimental investigation of the effect of mechanical damage on the transport properties of cementitious composites

NASA Astrophysics Data System (ADS)

Raghavan, Balaji; Niknezhad, Davood; Bernard, Fabrice; Kamali-Bernard, Siham

2016-09-01

The transport properties of cementitious composites such as concrete are important indicators of their durability, and are known to be heavily influenced by mechanical loading. In the current work, we use meso-scale hygro-mechanical modeling with a morphological 3D two phase mortar-aggregate model, in conjunction with experimentally obtained properties, to investigate the coupling between mechanical loading and damage and the permeability of the composite. The increase in permeability of a cylindrical test specimen at 28% aggregate fraction during a uniaxial displacement-controlled compression test at 85% of the peak load was measured using a gas permeameter. The mortar's mechanical behavior is assumed to follow the well-known compression damaged plasticity (CDP) model with isotropic damage, at varying thresholds, and obtained from different envelope curves. The damaged intrinsic permeability of the mortar evolves according to a logarithmic matching law with progressive loading. We fit the matching law parameters to the experimental result for the test specimen by inverse identification using our meso-scale model. We then subject a series of virtual composite specimens to quasi-static uniaxial compressive loading with varying boundary conditions to obtain the simulated damage and strain evolutions, and use the damage data and the previously identified parameters to determine the evolution of the macroscopic permeability tensor for the specimens, using a network model. We conduct a full parameter study by varying aggregate volume fraction, granulometric distribution, loading/boundary conditions and "matching law" parameters, as well as for different strain-damage thresholds and uniaxial loading envelope curves. Based on this study, we propose Avrami equation-based upper and lower bounds for the evolution of the damaged permeability of the composite.

Platelet-derived CXCL4 regulates neutrophil infiltration and tissue damage in severe acute pancreatitis.

PubMed

Wetterholm, Erik; Linders, Johan; Merza, Mohammed; Regner, Sara; Thorlacius, Henrik

2016-10-01

Platelets are known to play an important role in acute pancreatitis (AP) via promotion of neutrophil accumulation, although mechanisms behind platelet-dependent accumulation of neutrophils in the pancreas remain elusive. Platelets contain a wide spectrum of different pro-inflammatory compounds, such as chemokines. CXCL4 (platelet factor 4) is one of the most abundant chemokine in platelets, and we hypothesized that CXCL4 might be involved in platelet-dependent accumulation of neutrophils in the inflamed pancreas. The aim of this study was to examine the role of CXCL4 in severe AP. Pancreatitis was provoked by infusion of taurocholate into the pancreatic duct or by intraperitoneal administration of L-arginine in C57BL/6 mice. Animals were treated with an antibody against platelets or CXCL4 before induction of pancreatitis. Plasma and lung levels of CXCL2, CXCL4, and interleukin (IL)-6 were determined by use of enzyme-linked immunosorbent assay. Flow cytometry was used to examine surface expression of macrophage-1 (Mac-1) on neutrophils. Plasma was obtained from healthy individuals (controls) and patients with AP. Challenge with taurocholate increased plasma levels of CXCL4, and depletion of platelets markedly reduced plasma levels of CXCL4 indicating that circulating levels of CXCL4 are mainly derived from platelets in AP. Inhibition of CXCL4 reduced taurocholate-induced neutrophil recruitment, IL-6 secretion, edema formation, amylase release, and tissue damage in the pancreas. However, immunoneutralization of CXCL4 had no effect on CXCL2-evoked neutrophil expression of Mac-1 or chemotaxis in vitro, suggesting an indirect effect of CXCL4 on neutrophil recruitment in AP. Targeting CXCL4 significantly attenuated plasma and lung levels of CXCL2, which is a potent neutrophil chemoattractant, and inhibition of the CXCL2 receptor attenuated neutrophil infiltration and tissue damage in the inflamed pancreas. A significant role of CXCL4 was confirmed in an alternate model

Mice Lacking RIP3 Kinase are not Protected from Acute Radiation Syndrome.

PubMed

Castle, Katherine D; Daniel, Andrea R; Moding, Everett J; Luo, Lixia; Lee, Chang-Lung; Kirsch, David G

2018-06-01

Exposure to high doses of ionizing radiation can cause lethal injury to normal tissue, thus inducing acute radiation syndrome. Acute radiation syndrome is caused by depletion of bone marrow cells (hematopoietic syndrome) and irreparable damage to the epithelial cells in the gastrointestinal tract (gastrointestinal syndrome). Although radiation initiates apoptosis in the hematopoietic and gastrointestinal compartments within the first few hours after exposure, alternative mechanisms of cell death may contribute to injury in these radiosensitive tissues. In this study, we utilized mice lacking a critical regulator of necroptosis, receptor interacting protein 3 (RIP3) kinase, to characterize the role of RIP3 in normal tissue toxicity after irradiation. Our results suggest that RIP3-mediated signaling is not a critical driver of acute radiation syndrome.

Rotational 3D printing of damage-tolerant composites with programmable mechanics.

PubMed

Raney, Jordan R; Compton, Brett G; Mueller, Jochen; Ober, Thomas J; Shea, Kristina; Lewis, Jennifer A

2018-02-06

Natural composites exhibit exceptional mechanical performance that often arises from complex fiber arrangements within continuous matrices. Inspired by these natural systems, we developed a rotational 3D printing method that enables spatially controlled orientation of short fibers in polymer matrices solely by varying the nozzle rotation speed relative to the printing speed. Using this method, we fabricated carbon fiber-epoxy composites composed of volume elements (voxels) with programmably defined fiber arrangements, including adjacent regions with orthogonally and helically oriented fibers that lead to nonuniform strain and failure as well as those with purely helical fiber orientations akin to natural composites that exhibit enhanced damage tolerance. Our approach broadens the design, microstructural complexity, and performance space for fiber-reinforced composites through site-specific optimization of their fiber orientation, strain, failure, and damage tolerance. Copyright © 2018 the Author(s). Published by PNAS.

Cell Death and DAMPs in Acute Pancreatitis

PubMed Central

Kang, Rui; Lotze, Michael T; Zeh, Herbert J; Billiar, Timothy R; Tang, Daolin

2014-01-01

Cell death and inflammation are key pathologic responses of acute pancreatitis (AP), the leading cause of hospital admissions for gastrointestinal disorders. It is becoming increasingly clear that damage-associated molecular pattern molecules (DAMPs) play an important role in the pathogenesis of AP by linking local tissue damage to systemic inflammation syndrome. Endogenous DAMPs released from dead, dying or injured cells initiate and extend sterile inflammation via specific pattern recognition receptors. Inhibition of the release and activity of DAMPs (for example, high mobility group box 1, DNA, histones and adenosine triphosphate) provides significant protection against experimental AP. Moreover, increased serum levels of DAMPs in patients with AP correlate with disease severity. These findings provide novel insight into the mechanism, diagnosis and management of AP. DAMPs might be an attractive therapeutic target in AP. PMID:25105302

Development of dual field magnetic flux leakage (MFL) inspection technology to detect mechanical damage.

DOT National Transportation Integrated Search

2013-03-01

This report details the development and testing of a dual magnetization in-line inspection (ILI) : tool for detecting mechanical damage in operating pipelines, including the first field trials of a : fully operational dual-field magnetic flux leakage...

Characteristics and mechanisms of acrylate polymer damage to maize seedlings.

PubMed

Chen, Xian; Mao, Xiaoyun; Lu, Qin; Liao, Zongwen; He, Zhenli

2016-07-01

Superabsorbent acrylate polymers (SAPs) have been widely used to maintain soil moisture in agricultural management, but they may cause damage to plants, and the mechanisms are not well understood. In this study, seed germination, soil pot culture, hydroponic experiments, and SAPs degradation were conducted to investigate damage characteristics and mechanisms associated with SAPs application. The Results showed that SAPs inhibited maize growth and altered root morphology (irregular and loose arrangement of cells and breakage of cortex parenchyma), and the inhibitory effects were enhanced at higher SAPs rates. After 1h SAP hydrogels treatment, root malondialdehyde (MDA) content was significantly increased, while superoxide dismutase (SOD) and catalase (CAT) content were significantly decreased. Hydroponics experiment indicated that root and shoot growth was inhibited at 2.5mgL(-1) acrylic acid (AA), and the inhibition was enhanced with increasing AA rates. This effect was exacerbated by the presence of Na(+) at a high concentration in the hydrogels. Release and degradation of AA were enhanced at higher soil moisture levels. A complete degradation of AA occurred between 15 and 20 days after incubation (DAI), but it took longer for Na(+) concentration to decrease to a safe level. These results indicate that high concentration of both AA and Na(+) present in the SAPs inhibits plant growth. The finding of this study may provide a guideline for appropriate application of SAPs in agriculture. Copyright © 2016 Elsevier Inc. All rights reserved.

A multistep damage recognition mechanism for global genomic nucleotide excision repair

PubMed Central

Sugasawa, Kaoru; Okamoto, Tomoko; Shimizu, Yuichiro; Masutani, Chikahide; Iwai, Shigenori; Hanaoka, Fumio

2001-01-01

A mammalian nucleotide excision repair (NER) factor, the XPC–HR23B complex, can specifically bind to certain DNA lesions and initiate the cell-free repair reaction. Here we describe a detailed analysis of its binding specificity using various DNA substrates, each containing a single defined lesion. A highly sensitive gel mobility shift assay revealed that XPC–HR23B specifically binds a small bubble structure with or without damaged bases, whereas dual incision takes place only when damage is present in the bubble. This is evidence that damage recognition for NER is accomplished through at least two steps; XPC–HR23B first binds to a site that has a DNA helix distortion, and then the presence of injured bases is verified prior to dual incision. Cyclobutane pyrimidine dimers (CPDs) were hardly recognized by XPC–HR23B, suggesting that additional factors may be required for CPD recognition. Although the presence of mismatched bases opposite a CPD potentiated XPC–HR23B binding, probably due to enhancement of the helix distortion, cell-free excision of such compound lesions was much more efficient than expected from the observed affinity for XPC–HR23B. This also suggests that additional factors and steps are required for the recognition of some types of lesions. A multistep mechanism of this sort may provide a molecular basis for ensuring the high level of damage discrimination that is required for global genomic NER. PMID:11238373

A multistep damage recognition mechanism for global genomic nucleotide excision repair.

PubMed

Sugasawa, K; Okamoto, T; Shimizu, Y; Masutani, C; Iwai, S; Hanaoka, F

2001-03-01

A mammalian nucleotide excision repair (NER) factor, the XPC-HR23B complex, can specifically bind to certain DNA lesions and initiate the cell-free repair reaction. Here we describe a detailed analysis of its binding specificity using various DNA substrates, each containing a single defined lesion. A highly sensitive gel mobility shift assay revealed that XPC-HR23B specifically binds a small bubble structure with or without damaged bases, whereas dual incision takes place only when damage is present in the bubble. This is evidence that damage recognition for NER is accomplished through at least two steps; XPC-HR23B first binds to a site that has a DNA helix distortion, and then the presence of injured bases is verified prior to dual incision. Cyclobutane pyrimidine dimers (CPDs) were hardly recognized by XPC-HR23B, suggesting that additional factors may be required for CPD recognition. Although the presence of mismatched bases opposite a CPD potentiated XPC-HR23B binding, probably due to enhancement of the helix distortion, cell-free excision of such compound lesions was much more efficient than expected from the observed affinity for XPC-HR23B. This also suggests that additional factors and steps are required for the recognition of some types of lesions. A multistep mechanism of this sort may provide a molecular basis for ensuring the high level of damage discrimination that is required for global genomic NER.

Mechanisms of bee venom-induced acute renal failure.

PubMed

Grisotto, Luciana S D; Mendes, Glória E; Castro, Isac; Baptista, Maria A S F; Alves, Venancio A; Yu, Luis; Burdmann, Emmanuel A

2006-07-01

The spread of Africanized bees in the American continent has increased the number of severe envenomation after swarm attacks. Acute renal failure (ARF) is one of the major hazards in surviving patients. To assess the mechanisms of bee venom-induced ARF, rats were evaluated before, up to 70 min and 24h after 0.5mg/kg of venom injection. Control rats received saline. Bee venom caused an early and significant reduction in glomerular filtration rate (GFR, inulin clearance, 0.84+/-0.05 to 0.40+/-0.08 ml/min/100g, p<0.0001) and renal blood flow (RBF, laser Doppler flowmetry), which was more severe in the cortical (-72%) than in the medullary area (-48%), without systemic blood pressure decrease. Creatine phosphokinase, lactic dehydrogenase (LDH) and serum glutamic oxaloacetic transaminase increased significantly, pointing to rhabdomyolysis, whereas serum glutamic pyruvic transaminase and hematocrit remained stable. Twenty-four hours after venom, RBF recovered but GFR remained significantly impaired. Renal histology showed acute tubular injury and a massive tubular deposition of myoglobin. Venom was added to isolated rat proximal tubules (PT) suspension subjected to normoxia and hypoxia/reoxygenation (H/R) for direct nephrotoxicity evaluation. After 60 min of incubation, 0.1, 2 and 10 microg of venom induced significant increases in LDH release: 47%, 64% and 86%, respectively, vs. 21% in control PT while 2 microg of venom enhanced H/R injury (85% vs. 55%, p<0.01). These results indicate that vasoconstriction, direct nephrotoxicity and rhabdomyolysis are important mechanisms in the installation of bee venom-induced ARF that may occur even without hemolysis or hypotension.

Uncoupling and oxidative stress in liver mitochondria isolated from rats with acute iron overload.

PubMed

Pardo Andreu, G L; Inada, N M; Vercesi, A E; Curti, C

2009-01-01

One hypothesis for the etiology of cell damage arising from iron overload is that its excess selectively affects mitochondria. Here we tested the effects of acute iron overload on liver mitochondria isolated from rats subjected to a single dose of i.p. 500 mg/kg iron-dextran. The treatment increased the levels of iron in mitochondria (from 21 +/- 4 to 130 +/- 7 nmol/mg protein) and caused both lipid peroxidation and glutathione oxidation. The mitochondria of iron-treated rats showed lower respiratory control ratio in association with higher resting respiration. The mitochondrial uncoupling elicited by iron-treatment did not affect the phosphorylation efficiency or the ATP levels, suggesting that uncoupling is a mitochondrial protective mechanism against acute iron overload. Therefore, the reactive oxygen species (ROS)/H+ leak couple, functioning as a mitochondrial redox homeostatic mechanism could play a protective role in the acutely iron-loaded mitochondria.

Acute damage threshold for infrared neural stimulation of the cochlea: functional and histological evaluation.

PubMed

Goyal, Vinay; Rajguru, Suhrud; Matic, Agnella I; Stock, Stuart R; Richter, Claus-Peter

2012-11-01

This article provides a mini review of the current state of infrared neural stimulation (INS), and new experimental results concerning INS damage thresholds. INS promises to be an attractive alternative for neural interfaces. With this method, one can attain spatially selective neural stimulation that is not possible with electrical stimulation. INS is based on the delivery of short laser pulses that result in a transient temperature increase in the tissue and depolarize the neurons. At a high stimulation rate and/or high pulse energy, the method bears the risk of thermal damage to the tissue from the instantaneous temperature increase or from potential accumulation of thermal energy. With the present study, we determined the injury thresholds in guinea pig cochleae for acute INS using functional measurements (compound action potentials) and histological evaluation. The selected laser parameters for INS were the wavelength (λ = 1,869 nm), the pulse duration (100 μs), the pulse repetition rate (250 Hz), and the radiant energy (0-127 μJ/pulse). For up to 5 hr of continuous irradiation at 250 Hz and at radiant energies up to 25 μJ/pulse, we did not observe any functional or histological damage in the cochlea. Functional loss was observed for energies above 25 μJ/pulse and the probability of injury to the target tissue resulting in functional loss increased with increasing radiant energy. Corresponding cochlear histology from control animals and animals exposed to 98 or 127 μJ/pulse at 250 Hz pulse repetition rate did not show a loss of spiral ganglion cells, hair cells, or other soft tissue structures of the organ of Corti. Light microscopy did not reveal any structural changes in the soft tissue either. Additionally, microcomputed tomography was used to visualize the placement of the optical fiber within the cochlea. Copyright © 2012 Wiley Periodicals, Inc.

Antihepatotoxic activity of Rosmarinus tomentosus in a model of acute hepatic damage induced by thioacetamide.

PubMed

Galisteo, M; Suárez, A; del Pilar Montilla, M; del Pilar Utrilla, M; Jiménez, J; Gil, A; Faus, M J; Navarro, M

2000-11-01

R. tomentosus is a vegetal species closely related to the culinary rosemary (R. officinalis), a plant reported to contain antihepatotoxic agents. A dried ethanol extract of the aerial parts of Rosmarinus tomentosus (Lamiaceae) and its major fraction separated by column chromatography (fraction F19) were evaluated for antihepatotoxic activity in rats with acute liver damage induced by a single oral dose of thioacetamide. Silymarin was used as a reference antihepatotoxic substance. Pre-treatment with R. tomentosus ethanol extract, fraction F19 or silymarin significantly reduced the impact of thioacetamide toxicity on plasma protein and urea levels as well as on plasma aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase and gamma-glutamyl transpeptidase activities compared with thioacetamide-treated animals (group T). Pre-treatment with R. tomentosus ethanol extract significantly reduced the impact of thioacetamide damage on alkaline phosphatase and gamma-glutamyl transpeptidase activities compared with group T. Silymarin administration significantly reduced alkaline phosphatase and gamma-glutamyl transpeptidase activities compared with group T. Fraction F19 administration reduced only alkaline phosphatase activity compared with group T. According to these data, R. tomentosus extract shows promising antihepatotoxic activity, suggesting the need to isolate the chemical principles responsible for this activity and to study this activity in a model of thioacetamide-induced cirrhosis. Copyright 2000 John Wiley & Sons, Ltd.

The effect of acute exposure to hyperbaric oxygen on respiratory system mechanics in the rat.

PubMed

Rubini, Alessandro; Porzionato, Andrea; Zara, Susi; Cataldi, Amelia; Garetto, Giacomo; Bosco, Gerardo

2013-10-01

This study was designed to investigate the possible effects of acute hyperbaric hyperoxia on respiratory mechanics of anaesthetised, positive-pressure ventilated rats. We measured respiratory mechanics by the end-inflation occlusion method in nine rats previously acutely exposed to hyperbaric hyperoxia in a standard fashion. The method allows the measurements of respiratory system elastance and of both the "ohmic" and of the viscoelastic components of airway resistance, which respectively depend on the newtonian pressure dissipation due to the ohmic airway resistance to air flow, and on the viscoelastic pressure dissipation caused by respiratory system tissues stress-relaxation. The activities of inducible and endothelial NO-synthase in the lung's tissues (iNOS and eNOS respectively) also were investigated. Data were compared with those obtained in control animals. We found that the exposure to hyperbaric hyperoxia increased respiratory system elastance and both the "ohmic" and viscoelastic components of inspiratory resistances. These changes were accompanied by increased iNOS but not eNOS activities. Hyperbaric hyperoxia was shown to acutely induce detrimental effects on respiratory mechanics. A possible causative role was suggested for increased nitrogen reactive species production because of increased iNOS activity.

Obatoclax potentiates the cytotoxic effect of cytarabine on acute myeloid leukemia cells by enhancing DNA damage.

PubMed

Xie, Chengzhi; Edwards, Holly; Caldwell, J Timothy; Wang, Guan; Taub, Jeffrey W; Ge, Yubin

2015-02-01

Resistance to cytarabine and anthracycline-based chemotherapy is a major cause of treatment failure for acute myeloid leukemia (AML) patients. Overexpression of Bcl-2, Bcl-xL, and/or Mcl-1 has been associated with chemoresistance in AML cell lines and with poor clinical outcome of AML patients. Thus, inhibitors of anti-apoptotic Bcl-2 family proteins could be novel therapeutic agents. In this study, we investigated how clinically achievable concentrations of obatoclax, a pan-Bcl-2 inhibitor, potentiate the antileukemic activity of cytarabine in AML cells. MTT assays in AML cell lines and diagnostic blasts, as well as flow cytometry analyses in AML cell lines revealed synergistic antileukemic activity between cytarabine and obatoclax. Bax activation was detected in the combined, but not the individual, drug treatments. This was accompanied by significantly increased loss of mitochondrial membrane potential. Most importantly, in AML cells treated with the combination, enhanced early induction of DNA double-strand breaks (DSBs) preceded a decrease of Mcl-1 levels, nuclear translocation of Bcl-2, Bcl-xL, and Mcl-1, and apoptosis. These results indicate that obatoclax enhances cytarabine-induced apoptosis by enhancing DNA DSBs. This novel mechanism provides compelling evidence for the clinical use of BH3 mimetics in combination with DNA-damaging agents in AML and possibly a broader range of malignancies. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Underlying chronic inflammation alters the profile and mechanisms of acute neutrophil recruitment.

PubMed

Ma, Bin; Whiteford, James R; Nourshargh, Sussan; Woodfin, Abigail

2016-11-01

Chronically inflamed tissues show altered characteristics that include persistent populations of inflammatory leukocytes and remodelling of the vascular network. As the majority of studies on leukocyte recruitment have been carried out in normal healthy tissues, the impact of underlying chronic inflammation on ongoing leukocyte recruitment is largely unknown. Here, we investigate the profile and mechanisms of acute inflammatory responses in chronically inflamed and angiogenic tissues, and consider the implications for chronic inflammatory disorders. We have developed a novel model of chronic ischaemia of the mouse cremaster muscle that is characterized by a persistent population of monocyte-derived cells (MDCs), and capillary angiogenesis. These tissues also show elevated acute neutrophil recruitment in response to locally administered inflammatory stimuli. We determined that Gr1 low MDCs, which are widely considered to have anti-inflammatory and reparative functions, amplified acute inflammatory reactions via the generation of additional proinflammatory signals, changing both the profile and magnitude of the tissue response. Similar vascular and inflammatory responses, including activation of MDCs by transient ischaemia-reperfusion, were observed in mouse hindlimbs subjected to chronic ischaemia. This response demonstrates the relevance of the findings to peripheral arterial disease, in which patients experience transient exercise-induced ischaemia known as claudication.These findings demonstrate that chronically inflamed tissues show an altered profile and altered mechanisms of acute inflammatory responses, and identify tissue-resident MDCs as potential therapeutic targets. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Molecular and sensory mechanisms to mitigate sunlight-induced DNA damage in treefrog tadpoles.

PubMed

Schuch, André P; Lipinski, Victor M; Santos, Mauricio B; Santos, Caroline P; Jardim, Sinara S; Cechin, Sonia Z; Loreto, Elgion L S

2015-10-01

The increased incidence of solar ultraviolet B (UVB) radiation has been proposed as an environmental stressor, which may help to explain the enigmatic decline of amphibian populations worldwide. Despite growing knowledge regarding the UV-induced biological effects in several amphibian models, little is known about the efficacy of DNA repair pathways. In addition, little attention has been given to the interplay between these molecular mechanisms with other physiological strategies that avoid the damage induced by sunlight. Here, DNA lesions induced by environmental doses of solar UVB and UVA radiation were detected in genomic DNA samples of treefrog tadpoles (Hypsiboas pulchellus) and their DNA repair activity was evaluated. These data were complemented by monitoring the induction of apoptosis in blood cells and tadpole survival. Furthermore, the tadpoles' ability to perceive and escape from UV wavelengths was evaluated as an additional strategy of photoprotection. The results show that tadpoles are very sensitive to UVB light, which could be explained by the slow DNA repair rates for both cyclobutane pyrimidine dimers (CPDs) and pyrimidine (6,4) pyrimidone photoproducts (6,4PPs). However, they were resistant to UVA, probably as a result of the activation of photolyases during UVA irradiation. Surprisingly, a sensory mechanism that triggers their escape from UVB and UVA light avoids the generation of DNA damage and helps to maintain the genomic integrity. This work demonstrates the genotoxic impact of both UVB and UVA radiation on tadpoles and emphasizes the importance of the interplay between molecular and sensory mechanisms to minimize the damage caused by sunlight. © 2015. Published by The Company of Biologists Ltd.

[Contrast-induced acute kidney injury in cardiology].

PubMed

Genovesi, Eugenio; Romanello, Mattia; De Caterina, Raffaele

2016-12-01

The intravascular administration of contrast media is an important tool in cardiovascular imaging, especially in percutaneous coronary interventions (PCI). Owing to the widespread use of these procedures, contrast-induced acute kidney injury (CI-AKI) has become one of the most common types of acute renal failures. CI-AKI is mainly mediated by mechanisms of oxidative damage, and its onset is associated with prolonged hospitalization and significant morbidity and mortality. Preexisting chronic kidney disease, diabetes, age, heart failure, and characteristics related to the procedure (primary or elective PCI, type and amount of contrast medium) are the most important risk factors for the development of post-PCI CI-AKI.For this serious complication, prevention is more important than treatment, and various preventive measures have been widely tested in recent years. However, none of the strategies so far evaluated, with the exception of pre-procedural hydration with isotonic saline, has been shown to effectively prevent CI-AKI in randomized trials in large populations. In this review, we discuss the incidence, risk factors, main pathogenetic mechanisms and current strategies for the prevention of CI-AKI.

Myocardial changes in acute Trypanosoma cruzi infection. Ultrastructural evidence of immune damage and the role of microangiopathy.

PubMed Central

Andrade, Z. A.; Andrade, S. G.; Correa, R.; Sadigursky, M.; Ferrans, V. J.

1994-01-01

Histological and ultrastructural studies of the hearts of dogs sacrificed 18 to 26 days after intraperitoneal inoculation with 4 x 10(5) blood forms of the 12 SF strain of Trypanosoma cruzi/kg of body weight disclosed myocarditis characterized by parasitic invasion of some myocytes, damage and necrosis of nonparasitized myocytes, and interstitial infiltration by mononuclear cells. Nonparasitized myocytes showed alterations ranging from mild edema to severe myocytolysis. These changes often were accompanied by contacts of myocytes with lymphocytes (both granular and agranular) and macrophages. These contacts were characterized by focal loss of the myocyte basement membrane and close approximation of the plasma membranes of the two cells. Contacts between lymphocytes and capillary endothelial cells were also frequent. Platelet aggregates and fibrin microthrombi were observed in some capillaries. Our findings suggest that immune effector cells play a major role in the pathogenesis of the myocyte damage and the microangiopathy in acute Chagas' disease. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 PMID:8203476

An enhanced version of a bone-remodelling model based on the continuum damage mechanics theory.

PubMed

Mengoni, M; Ponthot, J P

2015-01-01

The purpose of this work was to propose an enhancement of Doblaré and García's internal bone remodelling model based on the continuum damage mechanics (CDM) theory. In their paper, they stated that the evolution of the internal variables of the bone microstructure, and its incidence on the modification of the elastic constitutive parameters, may be formulated following the principles of CDM, although no actual damage was considered. The resorption and apposition criteria (similar to the damage criterion) were expressed in terms of a mechanical stimulus. However, the resorption criterion is lacking a dimensional consistency with the remodelling rate. We propose here an enhancement to this resorption criterion, insuring the dimensional consistency while retaining the physical properties of the original remodelling model. We then analyse the change in the resorption criterion hypersurface in the stress space for a two-dimensional (2D) analysis. We finally apply the new formulation to analyse the structural evolution of a 2D femur. This analysis gives results consistent with the original model but with a faster and more stable convergence rate.

Ultraviolet Radiations: Skin Defense-Damage Mechanism.

PubMed

Mohania, Dheeraj; Chandel, Shikha; Kumar, Parveen; Verma, Vivek; Digvijay, Kumar; Tripathi, Deepika; Choudhury, Khushboo; Mitten, Sandeep Kumar; Shah, Dilip

2017-01-01

UV-radiations are the invisible part of light spectra having a wavelength between visible rays and X-rays. Based on wavelength, UV rays are subdivided into UV-A (320-400 nm), UV-B (280-320 nm) and UV-C (200-280 nm). Ultraviolet rays can have both harmful and beneficial effects. UV-C has the property of ionization thus acting as a strong mutagen, which can cause immune-mediated disease and cancer in adverse cases. Numbers of genetic factors have been identified in human involved in inducing skin cancer from UV-radiations. Certain heredity diseases have been found susceptible to UV-induced skin cancer. UV radiations activate the cutaneous immune system, which led to an inflammatory response by different mechanisms. The first line of defense mechanism against UV radiation is melanin (an epidermal pigment), and UV absorbing pigment of skin, which dissipate UV radiation as heat. Cell surface death receptor (e.g. Fas) of keratinocytes responds to UV-induced injury and elicits apoptosis to avoid malignant transformation. In addition to the formation of photo-dimers in the genome, UV also can induce mutation by generating ROS and nucleotides are highly susceptible to these free radical injuries. Melanocortin 1 receptor (MC1R) has been known to be implicated in different UV-induced damages such as pigmentation, adaptive tanning, and skin cancer. UV-B induces the formation of pre-vitamin D3 in the epidermal layer of skin. UV-induced tans act as a photoprotection by providing a sun protection factor (SPF) of 3-4 and epidermal hyperplasia. There is a need to prevent the harmful effects and harness the useful effects of UV radiations.

Coagulopathy in patients with acute pulmonary embolism: a pilot study of whole blood coagulation and markers of endothelial damage.

PubMed

Lehnert, Per; Johansson, Pär I; Ostrowski, Sisse R; Møller, Christian H; Bang, Lia E; Olsen, Peter Skov; Carlsen, Jørn

2017-02-01

Whole blood coagulation and markers of endothelial damage were studied in patients with acute pulmonary embolism (PE), and evaluated in relation to PE severity. Twenty-five patients were enrolled prospectively each having viscoelastical analysis of whole blood done using thrombelastography (TEG) and Multiplate aggregometry. Fourteen of these patients were investigated for endothelial damage by ELISA measurements of Syndecan-1 (endothelial glycocalyx degradation), soluble endothelial Selectin (endothelial cell activation), soluble Thrombomodulin (endothelial cell injury) and Histone Complexed DNA fragments (endothelial cytotoxic histones). The mean values of TEG and Multiplate parameters were all within the reference levels, but a significant difference between patients with high and intermediate risk PE was observed for Ly30 (lytic activity) 1.5% [0-10] vs. 0.2% [0-2.2] p = .04, and ADP (platelet reactivity) 92 U [20-145] vs. 59 U [20-111] p = .03. A similar difference was indicated for functional fibrinogen 21 mm [17-29] vs. 18 mm [3-23] p = .05. Analysis of endothelial markers identified a significant difference in circulating levels between high and intermediate risk PE patients for Syndecan-1 118.6 ng/mL [76-133] vs. 36.3 ng/mL [11.8-102.9] p = .008. In conclusion, patients with acute PE had normal whole blood coagulation, but high risk PE patients had signs of increased activity of the haemostatic system and significantly increased level of endothelial glycocalyx degradation.

Acute transient cognitive dysfunction and acute brain injury induced by systemic inflammation occur by dissociable IL-1-dependent mechanisms.

PubMed

Skelly, Donal T; Griffin, Éadaoin W; Murray, Carol L; Harney, Sarah; O'Boyle, Conor; Hennessy, Edel; Dansereau, Marc-Andre; Nazmi, Arshed; Tortorelli, Lucas; Rawlins, J Nicholas; Bannerman, David M; Cunningham, Colm

2018-06-06

Systemic inflammation can impair cognition with relevance to dementia, delirium and post-operative cognitive dysfunction. Episodes of delirium also contribute to rates of long-term cognitive decline, implying that these acute events induce injury. Whether systemic inflammation-induced acute dysfunction and acute brain injury occur by overlapping or discrete mechanisms remains unexplored. Here we show that systemic inflammation, induced by bacterial LPS, produces both working-memory deficits and acute brain injury in the degenerating brain and that these occur by dissociable IL-1-dependent processes. In normal C57BL/6 mice, LPS (100 µg/kg) did not affect working memory but impaired long-term memory consoliodation. However prior hippocampal synaptic loss left mice selectively vulnerable to LPS-induced working memory deficits. Systemically administered IL-1 receptor antagonist (IL-1RA) was protective against, and systemic IL-1β replicated, these working memory deficits. Dexamethasone abolished systemic cytokine synthesis and was protective against working memory deficits, without blocking brain IL-1β synthesis. Direct application of IL-1β to ex vivo hippocampal slices induced non-synaptic depolarisation and irrevesible loss of membrane potential in CA1 neurons from diseased animals and systemic LPS increased apoptosis in the degenerating brain, in an IL-1RI -/- -dependent fashion. The data suggest that LPS induces working memory dysfunction via circulating IL-1β but direct hippocampal action of IL-1β causes neuronal dysfunction and may drive neuronal death. The data suggest that acute systemic inflammation produces both reversible cognitive deficits, resembling delirium, and acute brain injury contributing to long-term cognitive impairment but that these events are mechanistically dissociable. These data have significant implications for management of cognitive dysfunction during acute illness.

Mechanisms of decreased intestinal epithelial proliferation and increased apoptosis in murine acute lung injury.

PubMed

Husain, Kareem D; Stromberg, Paul E; Woolsey, Cheryl A; Turnbull, Isaiah R; Dunne, W Michael; Javadi, Pardis; Buchman, Timothy G; Karl, Irene E; Hotchkiss, Richard S; Coopersmith, Craig M

2005-10-01

The aim of this study was to determine the effects of acute lung injury on the gut epithelium and examine mechanisms underlying changes in crypt proliferation and apoptosis. The relationship between severity and timing of lung injury to intestinal pathology was also examined. Randomized, controlled study. University research laboratory. Genetically inbred mice. Following induction of acute lung injury, gut epithelial proliferation and apoptosis were assessed in a) C3H/HeN wild-type and C3H/HeJ mice, which lack functional Toll-like receptor 4 (n = 17); b) C57Bl/6 mice that received monoclonal anti-tumor necrosis factor-alpha or control antibody (n = 22); and c) C57Bl/6 wild-type and transgenic mice that overexpress Bcl-2 in their gut epithelium (n = 21). Intestinal epithelial proliferation and death were also examined in animals with differing degrees of lung inflammation (n = 24) as well as in a time course analysis following a fixed injury (n = 18). Acute lung injury caused decreased proliferation and increased apoptosis in crypt epithelial cells in all animals studied. C3H/HeJ mice had higher levels of proliferation than C3H/HeN animals without additional changes in apoptosis. Anti-tumor necrosis factor-alpha antibody had no effect on gut epithelial proliferation or death. Overexpression of Bcl-2 did not change proliferation despite decreasing gut apoptosis. Proliferation and apoptosis were not correlated to severity of lung injury, as gut alterations were lost in mice with more severe acute lung injury. Changes in both gut epithelial proliferation and death were apparent within 12 hrs, but proliferation was decreased 36 hrs following acute lung injury while apoptosis returned to normal. Acute lung injury causes disparate effects on crypt proliferation and apoptosis, which occur, at least in part, through differing mechanisms involving Toll-like receptor 4 and Bcl-2. Severity of lung injury does not correlate with perturbations in proliferation or death in the

Acute and chronic nociceptive phases observed in a rat hind paw ischemia/reperfusion model depend on different mechanisms.

PubMed

Klafke, J Z; da Silva, M A; Rossato, M F; de Prá, S Dal Toé; Rigo, F K; Walker, C I B; Bochi, G V; Moresco, R N; Ferreira, J; Trevisan, G

2016-02-01

Complex regional pain syndrome type 1 (CRPS1) may be evoked by ischemia/reperfusion, eliciting acute and chronic pain that is difficult to treat. Despite this, the underlying mechanism of CRPS1 has not been fully elucidated. Therefore, the goal of this study is to evaluate the involvement of inflammation, oxidative stress, and the transient receptor potential ankyrin 1 (TRPA1) channel, a chemosensor of inflammation and oxidative substances, in an animal model of chronic post-ischemia pain (CPIP). Male Wistar rats were subjected to 3 h hind paw ischemia/reperfusion (CPIP model). Different parameters of nociception, inflammation, ischemia, and oxidative stress were evaluated at 1 (acute) and 14 (chronic) days after CPIP. The effect of a TRPA1 antagonist and the TRPA1 immunoreactivity were also observed after CPIP. In the CPIP acute phase, we observed mechanical and cold allodynia; increased levels of tumor necrosis factor-α (hind paw), ischemia-modified albumin (IMA) (serum), protein carbonyl (hind paw and spinal cord), lactate (serum), and 4-hydroxy-2-nonenal (4-HNE, hind paw and spinal cord); and higher myeloperoxidase (MPO) and N-acetyl-β-D-glucosaminidase (NAGase) activities (hind paw). In the CPIP chronic phase, we detected mechanical and cold allodynia and increased levels of IMA (serum), protein carbonyl (hind paw and spinal cord), and 4-HNE (hind paw and spinal cord). TRPA1 antagonism reduced mechanical and cold allodynia 1 and 14 days after CPIP, but no change in TRPA1 immunoreactivity was observed. Different mechanisms underlie acute (inflammation and oxidative stress) and chronic (oxidative stress) phases of CPIP. TRPA1 activation may be relevant for CRPS1/CPIP-induced acute and chronic pain.

Towards mechanism-based simulation of impact damage using exascale computing

NASA Astrophysics Data System (ADS)

Shterenlikht, Anton; Margetts, Lee; McDonald, Samuel; Bourne, Neil K.

2017-01-01

Over the past 60 years, the finite element method has been very successful in modelling deformation in engineering structures. However the method requires the definition of constitutive models that represent the response of the material to applied loads. There are two issues. Firstly, the models are often difficult to define. Secondly, there is often no physical connection between the models and the mechanisms that accommodate deformation. In this paper, we present a potentially disruptive two-level strategy which couples the finite element method at the macroscale with cellular automata at the mesoscale. The cellular automata are used to simulate mechanisms, such as crack propagation. The stress-strain relationship emerges as a continuum mechanics scale interpretation of changes at the micro- and meso-scales. Iterative two-way updating between the cellular automata and finite elements drives the simulation forward as the material undergoes progressive damage at high strain rates. The strategy is particularly attractive on large-scale computing platforms as both methods scale well on tens of thousands of CPUs.

Gold nanoparticles induce DNA damage in the blood and liver of rats

NASA Astrophysics Data System (ADS)

Cardoso, Eria; Londero, Eduardo; Ferreira, Gabriela Kozuchovski; Rezin, Gislaine Tezza; Zanoni, Elton Torres; de Souza Notoya, Frederico; Leffa, Daniela Dimer; Damiani, Adriani Paganini; Daumann, Francine; Rohr, Paula; da Silva, Luciano; Andrade, Vanessa M.; da Silva Paula, Marcos Marques

2014-11-01

The potential of gold nanoparticles (GNPs) for use in different biological applications has led to a strong interest in the study of their possible deleterious effects in biological systems and how these effects may be mitigated. This study was undertaken to investigate the effects of the acute and chronic administration of GNPs with mean diameters of 10 and 30 nm on deoxyribonucleic acid (DNA) damage in the blood and liver of adult rats. For the acute administration, Wistar adult rats received a single intraperitoneal injection of either GNPs or a saline solution. For the chronic administration, Wistar adult rats received a daily single injection of the same GNPs or saline solution for 28 days. Twenty-four hours after either the single (acute) or final injection (chronic), the rats were euthanised by decapitation, and the blood and liver were isolated for the evaluation of DNA damage. In this study, we demonstrated that the acute and chronic administration of GNPs 10 and 30 nm in size increased the frequency of DNA damage and the damage index in the blood and liver of adult rats. These findings suggest that the DNA damage may be caused by oxidative stress, which occurred regardless of the type of administration and GNP size.

Acute versus chronic phase mechanisms in a rat model of CRPS.

PubMed

Wei, Tzuping; Guo, Tian-Zhi; Li, Wen-Wu; Kingery, Wade S; Clark, John David

2016-01-19

Tibia fracture followed by cast immobilization in rats evokes nociceptive, vascular, epidermal, and bone changes resembling complex regional pain syndrome (CRPS). In most cases, CRPS has three stages. Over time, this acute picture, allodynia, warmth, and edema observed at 4 weeks, gives way to a cold, dystrophic but still painful limb. In the acute phase (at 4 weeks post fracture), cutaneous immunological and NK1-receptor signaling mechanisms underlying CRPS have been discovered; however, the mechanisms responsible for the chronic phase are still unknown. The purpose of this study is to understand the mechanisms responsible for the chronic phases of CRPS (at 16 weeks post fracture) at both the peripheral and central levels. We used rat tibial fracture/cast immobilization model of CRPS to study molecular, vascular, and nociceptive changes at 4 and 16 weeks post fracture. Immunoassays and Western blotting were carried out to monitor changes in inflammatory response and NK1-receptor signaling in the skin and spinal cord. Skin temperature and thickness were measured to elucidate vascular changes, whereas von Frey testing and unweighting were carried out to study nociceptive changes. All data were analyzed by one-way analysis of variance (ANOVA) followed by Neuman-Keuls multiple comparison test to compare among all cohorts. In the acute phase (at 4 weeks post fracture), hindpaw allodynia, unweighting, warmth, edema, and/or epidermal thickening were observed among 90 % fracture rats, though by 16 weeks (chronic phase), only the nociceptive changes persisted. The expression of the neuropeptide signaling molecule substance P (SP), NK1 receptor, inflammatory mediators TNFα, IL-1β, and IL-6 and nerve growth factor (NGF) were elevated at 4 weeks in sciatic nerve and/or skin, returning to normal levels by 16 weeks post fracture. The systemic administration of a peripherally restricted IL-1 receptor antagonist (anakinra) or of anti-NGF inhibited nociceptive behaviors at 4

Chemo-mechanics of salt damage in stone.

PubMed

Flatt, Robert J; Caruso, Francesco; Sanchez, Asel Maria Aguilar; Scherer, George W

2014-09-11

Many porous materials are damaged by pressure exerted by salt crystals growing in their pores. This is a serious issue in conservation science, geomorphology, geotechnical engineering and concrete materials science. In all cases, a central question is whether crystallization pressure will cause damage. Here we present an experiment in which the crystallization pressure and the pore saturation are varied in a controlled way. We demonstrate that a strain energy failure criterion can be used to predict when damage will occur. The experiment considered is the most widely used means to study the susceptibility to salt crystallization, so quantification of this test has far-reaching implications.

Early Blood-Brain Barrier Disruption after Mechanical Thrombectomy in Acute Ischemic Stroke.

PubMed

Shi, Zhong-Song; Duckwiler, Gary R; Jahan, Reza; Tateshima, Satoshi; Szeder, Viktor; Saver, Jeffrey L; Kim, Doojin; Sharma, Latisha K; Vespa, Paul M; Salamon, Noriko; Villablanca, J Pablo; Viñuela, Fernando; Feng, Lei; Loh, Yince; Liebeskind, David S

2018-05-01

The impact of blood-brain barrier (BBB) disruption can be detected by intraparenchymal hyperdense lesion on the computed tomography (CT) scan after endovascular stroke therapy. The purpose of this study was to determine whether early BBB disruption predicts intracranial hemorrhage and poor outcome in patients with acute ischemic stroke treated with mechanical thrombectomy. We analyzed patients with anterior circulation stroke treated with mechanical thrombectomy and identified BBB disruption on the noncontrast CT images immediately after endovascular treatment. Follow-up CT or magnetic resonance imaging scan was performed at 24 hours to assess intracranial hemorrhage. We dichotomized patients into those with moderate BBB disruption versus those with minor BBB disruption and no BBB disruption. We evaluated the association of moderate BBB disruption after mechanical thrombectomy with intracranial hemorrhage and clinical outcomes. Moderate BBB disruption after mechanical thrombectomy was found in 56 of 210 patients (26.7%). Moderate BBB disruption was independently associated with higher rates of hemorrhagic transformation (OR 25.33; 95% CI 9.93-64.65; P < .001), parenchymal hematoma (OR 20.57; 95% CI 5.64-74.99; P < .001), and poor outcome at discharge (OR 2.35; 95% CI 1.09-5.07; P = .03). The association of BBB disruption with intracranial hemorrhage remained in patients with successful reperfusion after mechanical thrombectomy. The location of BBB disruption was not associated with intracranial hemorrhage and poor outcome. Moderate BBB disruption is common after mechanical thrombectomy in a quarter of patients with acute ischemic stroke and increases the risk of intracranial hemorrhage and poor outcome. Copyright © 2018 by the American Society of Neuroimaging.

Wild chrysanthemum extract prevents UVB radiation-induced acute cell death and photoaging.

PubMed

Sun, Sujiao; Jiang, Ping; Su, Weiting; Xiang, Yang; Li, Jian; Zeng, Lin; Yang, Shuangjuan

2016-03-01

Wild chrysanthemum (Chrysanthemum indicum L.) is traditionally used in folk medicine as an anti-inflammatory agent. It is also used in the southwest plateau region of China to prevent ultraviolet-induced skin damage. However, the role and mechanism by which wild chrysanthemum prevents UV-induced skin damage and photoaging have never been investigated in vitro. In the present study, we found that aqueous extracts from wild chrysanthemum strongly reduced high-dose UVB-induced acute cell death of human immortalized keratinocytic HaCat cells. Wild chrysanthemum extract was also demonstrated to reduce low-dose UVB-induced expression of the photoaging-related matrix metalloproteinases MMP-2 and MMP-9. The ROS level elevated by UVB irradiation was strongly attenuated by wild chrysanthemum extract. Further study revealed that wild chrysanthemum extract reduced UVB-triggered ERK1/2 and p38 MAPK phosphorylation and their protective role, which is partially dependent on inhibiting p38 activation. These results suggest that wild chrysanthemum extract can protect the skin from UVB-induced acute skin damage and photoaging by reducing the intracellular reactive oxygen species (ROS) level and inhibiting p38 MAPK phosphorylation. The present study confirmed the protective role of wild chrysanthemum against UV-induced skin disorders in vitro and indicated the possible mechanism. Further study to identify the active components in wild chrysanthemum extract would be useful for developing new drugs for preventing and treating skin diseases, including skin cancer and photoaging, induced by UV irradiation.

Obesity in patients with acute lymphoblastic leukemia in childhood

PubMed Central

2012-01-01

Acute lymphoblastic leukemia is the most common malignancy in childhood. Continuous progress in risk-adapted treatment for childhood acute lymphoblastic leukemia has secured 5-year event-free survival rates of approximately 80% and 8-year survival rates approaching 90%. Almost 75% of survivors, however, have a chronic health condition negatively impacting on cardiovascular morbidity and mortality. Obesity can be considered one of the most important health chronic conditions in the general population, with an increasing incidence in patients treated for childhood cancers and especially in acute lymphoblastic leukemia survivors who are, at the same time, more at risk of experiencing precocious cardiovascular and metabolic co-morbidities. The hypothalamic-pituitary axis damage secondary to cancer therapies (cranial irradiation and chemotherapy) or to primary tumor together with lifestyle modifications and genetic factors could affect long-term outcomes. Nevertheless, the etiology of obesity in acute lymphoblastic leukemia is not yet fully understood. The present review has the aim of summarizing the published data and examining the most accepted mechanisms and main predisposing factors related to weight gain in this particular population. PMID:22284631

White Matter Hyperintensity Volume and Outcome of Mechanical Thrombectomy With Stentriever in Acute Ischemic Stroke.

PubMed

Atchaneeyasakul, Kunakorn; Leslie-Mazwi, Thabele; Donahue, Kathleen; Giese, Anne-Katrin; Rost, Natalia S

2017-10-01

Finding of white matter hyperintensity (WMH) has been associated with an increased risk of parenchymal hematoma and poor clinical outcomes after mechanical thrombectomy using old-generation endovascular devices. Currently, no data exist with regard to the risk of mechanical thrombectomy using stentriever devices in patients with significant WMH. We hypothesized that WMH volume will not affect the hemorrhagic and clinical outcome in patients with acute ischemic stroke undergoing thrombectomy using new-generation devices. A retrospective cohort of consecutive acute ischemic stroke patients >18-year-old receiving mechanical thrombectomy with stentriever devices at a single academic center was examined. WMH volume was assessed by a semiautomated volumetric analysis on T2 fluid attenuated inversion recovery-magnetic resonance imaging. Outcomes included the rate of any intracerebral hemorrhage, 90-day modified Rankin Score (mRS), the rate of good outcome (discharge mRS ≤2), and the rate of successful reperfusion (thrombolysis in cerebral ischemia score 2b or 3). Between June 2012 and December 2015, 56 patients with acute ischemic stroke met the study criteria. Median WMH volume was 6.76 cm 3 (4.84-16.09 cm 3 ). Increasing WMH volume did not significantly affect the odds of good outcome (odds ratio [OR], 0.811; 95% confidence interval [CI], 0.456-1.442), intracerebral hemorrhage (OR, 1.055; 95% CI, 0.595-1.871), parenchymal hematoma (OR, 0.353; 95% CI, 0.061-2.057), successful recanalization (OR, 1.295; 95% CI, 0.704-2.383), or death (OR, 1.583; 95% CI, 0.84-2.98). Mechanical thrombectomy using stentrievers seems to be safe in selected patients with acute ischemic stroke with large vessel occlusion, nonwithstanding the severity of WMH burden in this population. Larger prospective studies are warranted to validate these findings. © 2017 American Heart Association, Inc.

Lung protective mechanical ventilation and two year survival in patients with acute lung injury: prospective cohort study.

PubMed

Needham, Dale M; Colantuoni, Elizabeth; Mendez-Tellez, Pedro A; Dinglas, Victor D; Sevransky, Jonathan E; Dennison Himmelfarb, Cheryl R; Desai, Sanjay V; Shanholtz, Carl; Brower, Roy G; Pronovost, Peter J

2012-04-05

To evaluate the association of volume limited and pressure limited (lung protective) mechanical ventilation with two year survival in patients with acute lung injury. Prospective cohort study. 13 intensive care units at four hospitals in Baltimore, Maryland, USA. 485 consecutive mechanically ventilated patients with acute lung injury. Two year survival after onset of acute lung injury. 485 patients contributed data for 6240 eligible ventilator settings, as measured twice daily (median of eight eligible ventilator settings per patient; 41% of which adhered to lung protective ventilation). Of these patients, 311 (64%) died within two years. After adjusting for the total duration of ventilation and other relevant covariates, each additional ventilator setting adherent to lung protective ventilation was associated with a 3% decrease in the risk of mortality over two years (hazard ratio 0.97, 95% confidence interval 0.95 to 0.99, P=0.002). Compared with no adherence, the estimated absolute risk reduction in two year mortality for a prototypical patient with 50% adherence to lung protective ventilation was 4.0% (0.8% to 7.2%, P=0.012) and with 100% adherence was 7.8% (1.6% to 14.0%, P=0.011). Lung protective mechanical ventilation was associated with a substantial long term survival benefit for patients with acute lung injury. Greater use of lung protective ventilation in routine clinical practice could reduce long term mortality in patients with acute lung injury. Clinicaltrials.gov NCT00300248.

Lung-protective mechanical ventilation does not protect against acute kidney injury in patients without lung injury at onset of mechanical ventilation.

PubMed

Cortjens, Bart; Royakkers, Annick A N M; Determann, Rogier M; van Suijlen, Jeroen D E; Kamphuis, Stephan S; Foppen, Jannetje; de Boer, Anita; Wieland, Cathrien W; Spronk, Peter E; Schultz, Marcus J; Bouman, Catherine S C

2012-06-01

Preclinical and clinical studies suggest that mechanical ventilation contributes to the development of acute kidney injury (AKI), particularly in the setting of lung-injurious ventilator strategies. To determine whether ventilator settings in critically ill patients without acute lung injury (ALI) at onset of mechanical ventilation affect the development of AKI. Secondary analysis of a randomized controlled trial (N = 150), comparing conventional tidal volume (V(T), 10 mL/kg) with low tidal volume (V(T), 6 mL/kg) mechanical ventilation in critically ill patients without ALI at randomization. During the first 5 days of mechanical ventilation, the RIFLE class was determined daily, whereas neutrophil gelatinase-associated lipocalin and cystatin C levels were measured in plasma collected on days 0, 2, and 4. Eighty-six patients had no AKI at inclusion, and 18 patients (21%) subsequently developed AKI, but without significant difference between ventilation strategies. (Cumulative hazard, 0.26 vs 0.23; P = .88.) The courses of neutrophil gelatinase-associated lipocalin and cystatin C plasma levels did not differ significantly between randomization groups. In the present study in critically patients without ALI at onset of mechanical ventilation, lower tidal volume ventilation did not reduce the development or worsening of AKI compared with conventional tidal volume ventilation. Copyright © 2012 Elsevier Inc. All rights reserved.

Cellular characterization of compression induced-damage in live biological samples

NASA Astrophysics Data System (ADS)

Bo, Chiara; Balzer, Jens; Hahnel, Mark; Rankin, Sara M.; Brown, Katherine A.; Proud, William G.

2011-06-01

Understanding the dysfunctions that high-intensity compression waves induce in human tissues is critical to impact on acute-phase treatments and requires the development of experimental models of traumatic damage in biological samples. In this study we have developed an experimental system to directly assess the impact of dynamic loading conditions on cellular function at the molecular level. Here we present a confinement chamber designed to subject live cell cultures in liquid environment to compression waves in the range of tens of MPa using a split Hopkinson pressure bars system. Recording the loading history and collecting the samples post-impact without external contamination allow the definition of parameters such as pressure and duration of the stimulus that can be related to the cellular damage. The compression experiments are conducted on Mesenchymal Stem Cells from BALB/c mice and the damage analysis are compared to two control groups. Changes in Stem cell viability, phenotype and function are assessed flow cytometry and with in vitro bioassays at two different time points. Identifying the cellular and molecular mechanisms underlying the damage caused by dynamic loading in live biological samples could enable the development of new treatments for traumatic injuries.

Neural Mechanisms Underlying 5-HTTLPR Related Sensitivity to Acute Stress

PubMed Central

Drabant, Emily M; Ramel, Wiveka; Edge, Michael D; Hyde, Luke W; Kuo, Janice R; Goldin, Philippe R; Hariri, Ahmad R; Gross, James J

2013-01-01

Objective Many studies have shown that 5-HTTLPR genotype interacts with exposure to stress in conferring risk for psychopathology. However, the specific neural mechanisms through which this gene-by-environment interaction confers risk remain largely unknown, and no study to date has directly examined the modulatory effects of the 5-HTTLPR on corticolimbic circuit responses during exposure to acute stress. Methods An acute laboratory stressor was administered to 51 healthy women during BOLD fMRI scanning. In this task, electric shocks of uncertain intensity were threatened and unpredictably delivered to the wrist after a long anticipatory cue period of unpredictable duration. Results Relative to those carrying the L allele, SS homozygotes showed enhanced activation during threat anticipation in a network of regions including amygdala, hippocampus, anterior insula, thalamus, pulvinar, caudate, precuneus, anterior cingulate cortex, and medial prefrontal cortex. SS homozygotes also displayed enhanced positive coupling between medial prefrontal cortex activation and anxiety experience, whereas individuals carrying the L allele displayed enhanced negative coupling between insula activation and perceived success at regulating anxiety. Conclusions The present findings suggest that, when exposed to stress, SS homozygotes may preferentially engage neural systems which enhance fear and arousal, modulate attention toward threat, and perseverate on emotional salience of the threat. This may be one mechanism underlying risk for psychopathology conferred by the S allele upon exposure to life stressors. PMID:22362395

Multiscale Modeling of Damage Processes in Aluminum Alloys: Grain-Scale Mechanisms

NASA Technical Reports Server (NTRS)

Hochhalter, J. D.; Veilleux, M. G.; Bozek, J. E.; Glaessgen, E. H.; Ingraffea, A. R.

2008-01-01

This paper has two goals related to the development of a physically-grounded methodology for modeling the initial stages of fatigue crack growth in an aluminum alloy. The aluminum alloy, AA 7075-T651, is susceptible to fatigue cracking that nucleates from cracked second phase iron-bearing particles. Thus, the first goal of the paper is to validate an existing framework for the prediction of the conditions under which the particles crack. The observed statistics of particle cracking (defined as incubation for this alloy) must be accurately predicted to simulate the stochastic nature of microstructurally small fatigue crack (MSFC) formation. Also, only by simulating incubation of damage in a statistically accurate manner can subsequent stages of crack growth be accurately predicted. To maintain fidelity and computational efficiency, a filtering procedure was developed to eliminate particles that were unlikely to crack. The particle filter considers the distributions of particle sizes and shapes, grain texture, and the configuration of the surrounding grains. This filter helps substantially reduce the number of particles that need to be included in the microstructural models and forms the basis of the future work on the subsequent stages of MSFC, crack nucleation and microstructurally small crack propagation. A physics-based approach to simulating fracture should ultimately begin at nanometer length scale, in which atomistic simulation is used to predict the fundamental damage mechanisms of MSFC. These mechanisms include dislocation formation and interaction, interstitial void formation, and atomic diffusion. However, atomistic simulations quickly become computationally intractable as the system size increases, especially when directly linking to the already large microstructural models. Therefore, the second goal of this paper is to propose a method that will incorporate atomistic simulation and small-scale experimental characterization into the existing multiscale

Acute coagulopathy of trauma: balancing progressive catecholamine induced endothelial activation and damage by fluid phase anticoagulation.

PubMed

Johansson, P I; Ostrowski, S R

2010-12-01

Acute coagulopathy of trauma predicts a poor clinical outcome. Tissue trauma activates the sympathoadrenal system resulting in high circulating levels of catecholamines that influence hemostasis dose-dependently through immediate effects on the two major compartments of hemostasis, i.e., the circulating blood and the vascular endothelium. There appears to be a dose-dependency with regards to injury severity and the hemostatic response to trauma evaluated in whole blood by viscoelastic assays like thrombelastography (TEG), changing from normal to hypercoagulable, to hypocoagulable and finally hyperfibrinolytic in severely injured patients. Since high catecholamine levels may directly damage the endothelium and thereby promote systemic coagulation activation, we hypothesize that the progressive hypocoagulability and ultimate hyperfibrinolysis observed in whole blood with increasing injury severity, is an evolutionary developed response that counterbalances the injury and catecholamine induced endothelial activation and damage. Given this, the rise in circulating catecholamines in trauma patients may favor a switch from hyper- to hypocoagulability in the blood to keep the progressively more procoagulant microvasculature open. The hypothesis delineated in the present paper thus infers that the state of the fluid phase, including its cellular elements, is a consequence of the degree of the tissue injury and importantly, critically related to the degree of endothelial damage, with a progressively more procoagulant endothelium inducing a gradient of increasing anticoagulation towards the fluid phase. The implications of this hypothesis may include targeted treatment strategies according to the degree of sympathoadrenal response as evaluated by whole blood viscoelastical hemostatic assays in trauma patients. Copyright © 2010 Elsevier Ltd. All rights reserved.

Mechanisms of CNS invasion and damage by parasites.

PubMed

Kristensson, Krister; Masocha, Willias; Bentivoglio, Marina

2013-01-01

Invasion of the central nervous system (CNS) is a most devastating complication of a parasitic infection. Several physical and immunological barriers provide obstacles to such an invasion. In this broad overview focus is given to the physical barriers to neuroinvasion of parasites provided at the portal of entry of the parasites, i.e., the skin and epithelial cells of the gastrointestinal tract, and between the blood and the brain parenchyma, i.e., the blood-brain barrier (BBB). A description is given on how human pathogenic parasites can reach the CNS via the bloodstream either as free-living or extracellular parasites, by embolization of eggs, or within red or white blood cells when adapted to intracellular life. Molecular mechanisms are discussed by which parasites can interact with or pass across the BBB. The possible targeting of the circumventricular organs by parasites, as well as the parasites' direct entry to the brain from the nasal cavity through the olfactory nerve pathway, is also highlighted. Finally, examples are given which illustrate different mechanisms by which parasites can cause dysfunction or damage in the CNS related to toxic effects of parasite-derived molecules or to immune responses to the infection. Copyright © 2013 Elsevier B.V. All rights reserved.

[Copeptin and ischemia modified albumin in early diagnosis and prognosis of myocardial damage in acute organic phosphorus pesticide poisoning].

PubMed

Li, Jing; Zhang, Jianjun; Li, Na; Li, Jia; Liu, Juan; Liu, Qian

2015-03-01

To assess the value of combined detection of copeptin and ischemia modified albumin (IMA) in early diagnosis and prognostic evaluation of myocardial damage in patients with acute organic phosphorus pesticide poisoning (AOPP). A total of 126 AOPP patients were examined for blood copepin and IMA levels and myocardial injury markers within 1 h after admission. Copeptin and IMA levels significantly increased in patients with AOPP compared with those in the control subjects. Copeptin and IMA levels were significantly higher in severe AOPP cases than in mild to moderate cases (P<0.05). Logistic regression analysis showed that increased copeptin and IMA levels and severe complications of AOPP were associated with an increased risk of cardiovascular events. Early detection of copeptin and IMA levels has important clinical value in early diagnosis and prognostic evaluation of myocardial damage in patients with AOPP, and their levels are positively correlated with the severity of the condition.

APTO-253 Stabilizes G-quadruplex DNA, Inhibits MYC Expression, and Induces DNA Damage in Acute Myeloid Leukemia Cells.

PubMed

Local, Andrea; Zhang, Hongying; Benbatoul, Khalid D; Folger, Peter; Sheng, Xia; Tsai, Cheng-Yu; Howell, Stephen B; Rice, William G

2018-06-01

APTO-253 is a phase I clinical stage small molecule that selectively induces CDKN1A (p21), promotes G 0 -G 1 cell-cycle arrest, and triggers apoptosis in acute myeloid leukemia (AML) cells without producing myelosuppression in various animal species and humans. Differential gene expression analysis identified a pharmacodynamic effect on MYC expression, as well as induction of DNA repair and stress response pathways. APTO-253 was found to elicit a concentration- and time-dependent reduction in MYC mRNA expression and protein levels. Gene ontogeny and structural informatic analyses suggested a mechanism involving G-quadruplex (G4) stabilization. Intracellular pharmacokinetic studies in AML cells revealed that APTO-253 is converted intracellularly from a monomer to a ferrous complex [Fe(253) 3 ]. FRET assays demonstrated that both monomeric APTO-253 and Fe(253) 3 stabilize G4 structures from telomeres, MYC, and KIT promoters but do not bind to non-G4 double-stranded DNA. Although APTO-253 exerts a host of mechanistic sequelae, the effect of APTO-253 on MYC expression and its downstream target genes, on cell-cycle arrest, DNA damage, and stress responses can be explained by the action of Fe(253) 3 and APTO-253 on G-quadruplex DNA motifs. Mol Cancer Ther; 17(6); 1177-86. ©2018 AACR . ©2018 American Association for Cancer Research.

Kinetic gating mechanism of DNA damage recognition by Rad4/XPC

NASA Astrophysics Data System (ADS)

Chen, Xuejing; Velmurugu, Yogambigai; Zheng, Guanqun; Park, Beomseok; Shim, Yoonjung; Kim, Youngchang; Liu, Lili; van Houten, Bennett; He, Chuan; Ansari, Anjum; Min, Jung-Hyun

2015-01-01

The xeroderma pigmentosum C (XPC) complex initiates nucleotide excision repair by recognizing DNA lesions before recruiting downstream factors. How XPC detects structurally diverse lesions embedded within normal DNA is unknown. Here we present a crystal structure that captures the yeast XPC orthologue (Rad4) on a single register of undamaged DNA. The structure shows that a disulphide-tethered Rad4 flips out normal nucleotides and adopts a conformation similar to that seen with damaged DNA. Contrary to many DNA repair enzymes that can directly reject non-target sites as structural misfits, our results suggest that Rad4/XPC uses a kinetic gating mechanism whereby lesion selectivity arises from the kinetic competition between DNA opening and the residence time of Rad4/XPC per site. This mechanism is further supported by measurements of Rad4-induced lesion-opening times using temperature-jump perturbation spectroscopy. Kinetic gating may be a general mechanism used by site-specific DNA-binding proteins to minimize time-consuming interrogations of non-target sites.

[Effect of thalidomide in a mouse model of paraquat-induced acute lung injury and the underlying mechanisms].

PubMed

Li, Dong; Xu, Li-yan; Chang, Zi-juan; Zhao, Guang-ju; Nan, Chao; Lu, Zhong-qiu

2013-03-01

-κB p65. The observation of pathological changes showed that the paraquat poisoning group had the most marked lung tissue damage at 3 d after poisoning, and the lung tissue damage was lessened in the thalidomide treatment groups. Thalidomide can reduce paraquat-induced acute lung injury and lung edema. The mechanism may include inhibition of NF-κB activation and expression and downregulation of TNF-α, IL-1β, and IL-6.

Thermomechanical Fatigue Damage/Failure Mechanisms in SCS-6/Timetal 21S [0/90](Sub S) Composite

NASA Technical Reports Server (NTRS)

Castelli, Michael G.

1994-01-01

The thermomechanical fatigue (TMF) deformation, damage, and life behaviors of SCS6/Timetal 21S (0/90)s were investigated under zero-tension conditions. In-phase (IP) and out-of-phase (OP) loadings were investigated with a temperature cycle from 150 to 650 deg C. An advanced TMF test technique was used to quantify mechanically damage progression. The technique incorporated explicit measurements of the macroscopic (1) isothermal static moduli at the temperature extremes of the TMF cycle and (2) coefficient of thermal expansion (CTE) as functions of the TMF cycles. The importance of thermal property degradation and its relevance to accurate post-test data analysis and interpretation is briefly addressed. Extensive fractography and metallography were conducted on specimens from failed and interrupted tests to characterize the extent of damage at the microstructure level. Fatigue life results indicated trends analogous to those established for similar unidirectional(0) reinforced titanium matrix composite systems. High stress IP and mid to low stress OP loading conditions were life-limiting in comparison to maximum temperature isothermal conditions. Dominant damage mechanisms changed with cycle type. Damage resulting from IP TMF conditions produced measurable decreases in static moduli but only minimal changes in the CTE. Metallography on interrupted and failed specimens revealed extensive (0) fiber cracking with sparse matrix damage. No surface initiated matrix cracks were present. Comparable OP TMF conditions initiated environment enhanced surface cracking and matrix cracking initiated at (90) fiber/matrix (F/M) interfaces. Notable static moduli and CTE degradations were measured. Fractography and metallography revealed that the transverse cracks originating from the surface and (90) F/M interfaces tended to converge and coalesce at the (0) fibers.

Preferential type II muscle fiber damage from plyometric exercise.

PubMed

Macaluso, Filippo; Isaacs, Ashwin W; Myburgh, Kathryn H

2012-01-01

Plyometric training has been successfully used in different sporting contexts. Studies that investigated the effect of plyometric training on muscle morphology are limited, and results are controversial with regard to which muscle fiber type is mainly affected. To analyze the skeletal muscle structural and ultrastructural change induced by an acute bout of plyometric exercise to determine which type of muscle fibers is predominantly damaged. Descriptive laboratory study. Research laboratory. Eight healthy, untrained individuals (age = 22 ± 1 years, height = 179.2 ± 6.4 cm, weight = 78.9 ± 5.9 kg). Participants completed an acute bout of plyometric exercise (10 sets of 10 squat-jumps with a 1-minute rest between sets). Blood samples were collected 9 days and immediately before and 6 hours and 1, 2, and 3 days after the acute intervention. Muscle samples were collected 9 days before and 3 days after the exercise intervention. Blood samples were analyzed for creatine kinase activity. Muscle biopsies were analyzed for damage using fluorescent and electron transmission microscopy. Creatine kinase activity peaked 1 day after the exercise bout (529.0 ± 317.8 U/L). Immunofluorescence revealed sarcolemmal damage in 155 of 1616 fibers analyzed. Mainly fast-twitch fibers were damaged. Within subgroups, 7.6% of type I fibers, 10.3% of type IIa fibers, and 14.3% of type IIx fibers were damaged as assessed by losses in dystrophin staining. Similar damage was prevalent in IIx and IIa fibers. Electron microscopy revealed clearly distinguishable moderate and severe sarcomere damage, with damage quantifiably predominant in type II muscle fibers of both the glycolytic and oxidative subtypes (86% and 84%, respectively, versus only 27% of slow-twitch fibers). We provide direct evidence that a single bout of plyometric exercise affected mainly type II muscle fibers.

High-resolution computed tomography findings of acute respiratory distress syndrome, acute interstitial pneumonia, and acute exacerbation of idiopathic pulmonary fibrosis.

PubMed

Ichikado, Kazuya

2014-02-01

Diffuse alveolar damage (DAD) is the pathologic feature of rapidly progressive lung diseases, including acute respiratory distress syndrome, acute interstitial pneumonia, and acute exacerbation of idiopathic pulmonary fibrosis. The clinical significance and limitation of high-resolution computed tomography (HRCT) findings in these diseases were reviewed. The HRCT findings correlate well with pathologic phases (exudative, proliferative, and fibrotic) of DAD, although it cannot detect early exudative phase. Traction bronchiolectasis or bronchiectasis within areas of increased attenuation on HRCT scan is a sign of progression from the exudative to the proliferative and fibrotic phase of DAD. Extensive abnormalities seen on HRCT scans, which are indicative of fibroproliferative changes, were independently predictive of poor prognosis in patients with clinically early acute respiratory distress syndrome, acute interstitial pneumonia, and acute exacerbation of idiopathic pulmonary fibrosis. © 2013 Published by Elsevier Inc.

A Contemporary Assessment of Acute Mechanical Ventilation in Beijing: Description, Costs, and Outcomes.

PubMed

Ye, Yanping; Zhu, Bo; Jiang, Li; Jiang, Qi; Wang, Meiping; Hua, Lin; Xi, Xiuming

2017-07-01

To evaluate the contemporary practice, outcomes, and costs related to mechanical ventilation among ICUs in China. A prospective observational cohort study. Fourteen ICUs among 13 hospitals in Beijing, China. Seven hundred ninety-three patients who received at least 24 hours of mechanical ventilation within the first 48 hours of ICU stay. None. The mean age was 64 years. Sixty-three percent were male. New acute respiratory failure accounted for 85.5% of mechanical ventilation cases. Only 4.7% of the patients received mechanical ventilation for acute exacerbation of chronic obstructive pulmonary disease. The most widely used ventilation mode was the combination of synchronized intermittent mandatory ventilation and pressure support (43.6%). Use of lung-protective ventilation is widespread with tidal volumes of 7.1 mL/kg (2.1 mL/kg). The ICU/hospital mortality was 27.6%/29.3%, respectively (8.5%/9.7% for surgical patients and 41.3%/43.2% for medical patients, respectively). The mean level of ICU/hospital cost per patient was $15,271 (18,940)/$22,946 (25,575), respectively. The mean daily ICU cost per patient was $1,212. For the first time, we obtained a preliminary epidemiology data of mechanical ventilation in Beijing, China, through the study. Compared with the other nations, our patients are older, predominantly male, and treated according to prevailing international guidelines yet at a relatively high cost and high mortality. The expanding elderly population predicts increase demand for mechanical ventilation that must be met by continuous improvement in quality and efficiency of critical care services.

Antithrombin III is associated with acute liver failure in patients with end-stage heart failure undergoing mechanical circulatory support.

PubMed

Hoefer, Judith; Ulmer, Hanno; Kilo, Juliane; Margreiter, Raimund; Grimm, Michael; Mair, Peter; Ruttmann, Elfriede

2017-06-01

There are few data on the role of liver dysfunction in patients with end-stage heart failure supported by mechanical circulatory support. The aim of our study was to investigate predictors for acute liver failure in patients with end-stage heart failure undergoing mechanical circulatory support. A consecutive 164 patients with heart failure with New York Heart Association class IV undergoing mechanical circulatory support were investigated for acute liver failure using the King's College criteria. Clinical characteristics of heart failure together with hemodynamic and laboratory values were analyzed by logistic regression. A total of 45 patients (27.4%) with heart failure developed subsequent acute liver failure with a hospital mortality of 88.9%. Duration of heart failure, cause, cardiopulmonary resuscitation, use of vasopressors, central venous pressure, pulmonary capillary wedge pressure, pulmonary pulsatility index, cardiac index, and transaminases were not significantly associated with acute liver failure. Repeated decompensation, atrial fibrillation (P < .001) and the use of inotropes (P = .007), mean arterial (P = .005) and pulmonary pressures (P = .042), cholinesterase, international normalized ratio, bilirubin, lactate, and pH (P < .001) were predictive of acute liver failure in univariate analysis only. In multivariable analysis, decreased antithrombin III was the strongest single measurement indicating acute liver failure (relative risk per %, 0.84; 95% confidence interval, 0.77-0.93; P = .001) and remained an independent predictor when adjustment for the Model for End-Stage Liver Disease score was performed (relative risk per %, 0.89; 95% confidence interval, 0.80-0.99; P = .031). Antithrombin III less than 59.5% was identified as a cutoff value to predict acute liver failure with a corresponding sensitivity of 81% and specificity of 87%. In addition to the Model for End-Stage Liver Disease score, decreased antithrombin III activity tends

Mechanical behavior, damage tolerance and durability of fiber metal laminates for aircraft structures

NASA Astrophysics Data System (ADS)

Wu, Guocai

This study systematically explores the mechanical behavior, damage tolerance and durability of fiber metal laminates, a promising candidate materials system for next generation aerospace structures. The experimental results indicated that GLARE laminates exhibited a bilinear deformation behavior under static in-plane loading. Both an analytical constitutive model based on a modified classical lamination theory which incorporates the elasto-plastic behavior of aluminum alloy and a numerical simulation based on finite element modeling are used to predict the nonlinear stress-strain response and deformation behavior of GLARE laminates. The blunt notched strength of GLARE laminates increased with decreasing specimen width and decreasing hole diameter. The notched strength of GLARE laminates was evaluated based on a modified point stress criterion. A computer simulation based on finite element method was performed to study stress concentration and distribution around the notch and verify the analytical and experimental results of notched strength. Good agreement is obtained between the model predictions and experimental results. Experimental results also indicate that GLARE laminates exhibited superior impact properties to those of monolithic 2024-T3 aluminum alloy at low velocity impact loading. The GLARE 5-2/1 laminate with 0°/90°/90°/0° fiber configuration exhibits a better impact resistance than the GLARE 4-3/2 laminate with 0°/90°/0° fiber orientation. The characteristic impact energies, the damage area, and the permanent deflection of laminates are used to evaluate the impact damage resistance. The post-impact residual tensile strength under various damage states ranging from the plastic dent, barely visible impact damage (BVID), clearly visible impact damage (CVID) up to the complete perforation was also measured and compared. The post-impact fatigue behavior under various stress levels and impact damage states was extensively explored. The damage

Laser-induced damage threshold of camera sensors and micro-opto-electro-mechanical systems

NASA Astrophysics Data System (ADS)

Schwarz, Bastian; Ritt, Gunnar; Körber, Michael; Eberle, Bernd

2016-10-01

The continuous development of laser systems towards more compact and efficient devices constitutes an increasing threat to electro-optical imaging sensors such as complementary metal-oxide-semiconductors (CMOS) and charge-coupled devices (CCD). These types of electronic sensors are used in day-to-day life but also in military or civil security applications. In camera systems dedicated to specific tasks, also micro-opto-electro-mechanical systems (MOEMS) like a digital micromirror device (DMD) are part of the optical setup. In such systems, the DMD can be located at an intermediate focal plane of the optics and it is also susceptible to laser damage. The goal of our work is to enhance the knowledge of damaging effects on such devices exposed to laser light. The experimental setup for the investigation of laser-induced damage is described in detail. As laser sources both pulsed lasers and continuous-wave (CW) lasers are used. The laser-induced damage threshold (LIDT) is determined by the single-shot method by increasing the pulse energy from pulse to pulse or in the case of CW-lasers, by increasing the laser power. Furthermore, we investigate the morphology of laser-induced damage patterns and the dependence of the number of destructed device elements on the laser pulse energy or laser power. In addition to the destruction of single pixels, we observe aftereffects like persisting dead columns or rows of pixels in the sensor image.

Acute injuries in recreational and competitive surfers: incidence, severity, location, type, and mechanism.

PubMed

Furness, James; Hing, Wayne; Walsh, Joe; Abbott, Allan; Sheppard, Jeremy M; Climstein, Mike

2015-05-01

There are an estimated 37 million surfers worldwide, with 2.5 million recreational surfers in Australia. The recreational activity and sport of surfing has grown dramatically since the 1960s, but scientific research has been poorly mirrored in comparison with most other mainstream sports. To identify the incidence, severity, location, type, and mechanism of acute injuries in recreational and competitive surfers over a 12-month period. Descriptive epidemiology study. An online survey using an open-source survey application was utilized. The survey consisted of 2 primary sections: Section 1 included demographic information and participation levels (age, height, weight, hours surfed, competitive level); section 2 incorporated injury type, mechanism, severity, and injury management. A total of 1348 participants (91.3% males; 43.1% competitive surfers) were included in data analysis. A total of 512 acute injuries were classified as major, providing an incidence proportion of 0.38 (CI, 0.35-0.41) acute injuries per year. The incidence rate was calculated to be 1.79 (CI, 1.67-1.92) major injuries per 1000 hours of surfing. The shoulder, ankle, and head/face regions had the highest frequencies of acute injury, representing 16.4%, 14.6%, and 13.3%, respectively. Injuries were predominantly of muscular, joint, and skin origin, representing 30.3%, 27.7%, and 18.9%, respectively. Skin injuries were primarily a result of direct trauma, while joint and muscular injuries were mainly a result of maneuvers performed and repetitive actions. Key risk factors that increased the incidence of sustaining an acute injury included competitive status, hours surfed (>6.5 hours/week), and the ability to perform aerial maneuvers. The incidence proportion for surfers completing aerial maneuvers was calculated to be 0.48 (CI, 0.39-0.58) major injuries per year, this being the highest incidence proportion irrespective of competitive status. This is the largest surfing-specific survey that

Identification of substrates for transglutaminase in Physarum polycephalum, an acellular slime mold, upon cellular mechanical damage.

PubMed

Wada, Fumitaka; Hasegawa, Hiroki; Nakamura, Akio; Sugimura, Yoshiaki; Kawai, Yoshiki; Sasaki, Narie; Shibata, Hideki; Maki, Masatoshi; Hitomi, Kiyotaka

2007-06-01

Transglutaminases are Ca(2+)-dependent enzymes that post-translationally modify proteins by crosslinking or polyamination at specific polypeptide-bound glutamine residues. Physarum polycephalum, an acellular slime mold, is the evolutionarily lowest organism expressing a transglutimase whose primary structure is similar to that of mammalian transglutimases. We observed transglutimase reaction products at injured sites in Physarum macroplasmodia upon mechanical damage. With use of a biotin-labeled primary amine, three major proteins constituting possible transglutimase substrates were affinity-purified from the damaged slime mold. The purified proteins were Physarum actin, a 40 kDa Ca(2+)-binding protein with four EF-hand motifs (CBP40), and a novel 33 kDa protein highly homologous to the eukaryotic adenine nucleotide translocator, which is expressed in mitochondria. Immunochemical analysis of extracts from the damaged macroplasmodia indicated that CBP40 is partly dimerized, whereas the other proteins migrated as monomers on SDS/PAGE. Of the three proteins, CBP40 accumulated most significantly around injured areas, as observed by immunofluoresence. These results suggested that transglutimase reactions function in the response to mechanical injury.

Delayed Consequences of Acute Kidney Injury

PubMed Central

Parr, Sharidan K; Siew, Edward D

2016-01-01

Acute kidney injury (AKI) is an increasingly common complication of hospitalization and acute illness. Experimental data indicate that AKI may cause permanent kidney damage through tubulointerstitial fibrosis and progressive nephron loss, while also lowering the threshold for subsequent injury. Furthermore, preclinical data suggest that AKI may also cause distant organ dysfunction. The extension of these findings to human studies suggests long-term consequences of AKI including, but not limited to recurrent AKI, progressive kidney disease, elevated blood pressure, cardiovascular events, and mortality. As the number of AKI survivors increases, the need to better understand the mechanisms driving these processes becomes paramount. Optimizing care for AKI survivors will require understanding the short- and long-term risks associated with AKI, identifying patients at highest risk for poor outcomes, and testing interventions that target modifiable risk factors. In this review, we examine the literature describing the association between AKI and long-term outcomes and highlight opportunities for further research and potential intervention. PMID:27113695

The Sequelae of Acute Purulent Meningitis in Childhood

PubMed Central

Hutchison, Patricia A.; Kovacs, Michael C.

1963-01-01

Of a series of 122 children suffering from acute purulent meningitis at the Children's Hospital, Winnipeg, in the years 1952-56, 12 (9.8%) succumbed, all deaths occurring in those 12 months of age or less. Fortyone of the survivors were re-studied 2.5 to 7.5 years after their acute illness to assess the nature and incidence of sequelae, the relationship of sequelae to the severity of the acute illness, and the correlation between the various methods of identifying sequelae. Five children exhibited psychiatric evidence of organic brain damage; seven, neurological abnormality; 11, electroencephalographic abnormality. Three had defective intelligence and nine psychological test evidence of organic brain damage. Children with sequelae tended to have several abnormal test results, the total number with neuropsychiatric and/or psychological sequelae being 11 (26%). There was a positive correlation between the severity of the acute illness and the presence of neuropsychiatric sequelae; also between neuropsychiatric sequelae, defective intelligence and psychological evidence of brain damage. No correlation existed between the electroencephalographic abnormality and neuropsychiatric defect. PMID:13955939

Lung protective mechanical ventilation and two year survival in patients with acute lung injury: prospective cohort study

PubMed Central

Colantuoni, Elizabeth; Mendez-Tellez, Pedro A; Dinglas, Victor D; Sevransky, Jonathan E; Dennison Himmelfarb, Cheryl R; Desai, Sanjay V; Shanholtz, Carl; Brower, Roy G; Pronovost, Peter J

2012-01-01

Objective To evaluate the association of volume limited and pressure limited (lung protective) mechanical ventilation with two year survival in patients with acute lung injury. Design Prospective cohort study. Setting 13 intensive care units at four hospitals in Baltimore, Maryland, USA. Participants 485 consecutive mechanically ventilated patients with acute lung injury. Main outcome measure Two year survival after onset of acute lung injury. Results 485 patients contributed data for 6240 eligible ventilator settings, as measured twice daily (median of eight eligible ventilator settings per patient; 41% of which adhered to lung protective ventilation). Of these patients, 311 (64%) died within two years. After adjusting for the total duration of ventilation and other relevant covariates, each additional ventilator setting adherent to lung protective ventilation was associated with a 3% decrease in the risk of mortality over two years (hazard ratio 0.97, 95% confidence interval 0.95 to 0.99, P=0.002). Compared with no adherence, the estimated absolute risk reduction in two year mortality for a prototypical patient with 50% adherence to lung protective ventilation was 4.0% (0.8% to 7.2%, P=0.012) and with 100% adherence was 7.8% (1.6% to 14.0%, P=0.011). Conclusions Lung protective mechanical ventilation was associated with a substantial long term survival benefit for patients with acute lung injury. Greater use of lung protective ventilation in routine clinical practice could reduce long term mortality in patients with acute lung injury. Trial registration Clinicaltrials.gov NCT00300248. PMID:22491953

Understanding and preventing contrast-induced acute kidney injury.

PubMed

Fähling, Michael; Seeliger, Erdmann; Patzak, Andreas; Persson, Pontus B

2017-03-01

Contrast-induced acute kidney injury (CIAKI) occurs in up to 30% of patients who receive iodinated contrast media and is generally considered to be the third most common cause of hospital-acquired AKI. Accurate assessment of the incidence of CIAKI is obscured, however, by the use of various definitions for diagnosis, the different populations studied and the prophylactic measures put in place. A deeper understanding of the mechanisms that underlie CIAKI is required to enable reliable risk assessment for individual patients, as their medical histories will determine the specific pathways by which contrast media administration might lead to kidney damage. Here, we highlight common triggers that prompt the development of CIAKI and the subsequent mechanisms that ultimately cause kidney damage. We also discuss effective protective measures, such as rapidly acting oral hydration schemes and loop diuretics, in the context of CIAKI pathophysiology. Understanding of how CIAKI arises in different patient groups could enable a marked reduction in incidence and improved outcomes. The ultimate goal is to shape CIAKI prevention strategies for individual patients.

Molecular mechanisms of phoxim-induced silk gland damage and TiO2 nanoparticle-attenuated damage in Bombyx mori.

PubMed

Li, Bing; Yu, Xiaohong; Gui, Suxin; Xie, Yi; Zhao, Xiaoyang; Hong, Jie; Sun, Qingqing; Sang, Xuezi; Sheng, Lei; Cheng, Zhe; Cheng, Jie; Hu, Rengping; Wang, Ling; Shen, Weide; Hong, Fashui

2014-06-01

Phoxim is a useful organophosphate (OP) pesticide used in agriculture in China, however, exposure to this pesticide can result in a significant reduction in cocooning in Bombyx mori (B. mori). Titanium dioxide nanoparticles (TiO2 NPs) have been shown to decrease phoxim-induced toxicity in B. mori; however, very little is known about the molecular mechanisms of silk gland damage due to OP exposure and repair of gland damage by TiO2 NP pretreatment. In the present study, exposure to phoxim resulted in a significant reduction in cocooning rate in addition to silk gland damage, whereas TiO2 NP attenuated phoxim-induced gland damage, increased the antioxidant capacity of the gland, and increased cocooning rate in B. mori. Furthermore, digital gene expression data suggested that phoxim exposure led to significant alterations in the expression of 833 genes. In particular, phoxim exposure caused significant down-regulation of Fib-L, Ser2, Ser3, and P25 genes involved in silk protein synthesis, and up-regulation of SFGH, UCH3, and Salhh genes involved in silk protein hydrolysis. A combination of both phoxim and TiO2 NP treatment resulted in marked changes in the expression of 754 genes, while treatment with TiO2 NPs led to significant alterations in the expression of 308 genes. Importantly, pretreatment with TiO2 NPs increased Fib-L, Ser2, Ser3, and P25 expression, and decreased SFGH, UCH3, and Salhh expression in silk protein in the silk gland under phoxim stress. Therefore, Fib-L, Ser2, Ser3, P25, SFGH, UCH3, and Salhh may be potential biomarkers of silk gland toxicity in B. mori caused by phoxim exposure. Copyright © 2013 Elsevier Ltd. All rights reserved.

In Search of Mechanisms Associated with Mesenchymal Stem Cell-Based Therapies for Acute Kidney Injury

PubMed Central

de Almeida, Danilo C; Donizetti-Oliveira, Cassiano; Barbosa-Costa, Priscilla; Origassa, Clarice ST; Câmara, Niels OS

2013-01-01

Acute kidney injury (AKI) is classically described as a rapid loss of kidney function. AKI affects more than 15% of all hospital admissions and is associated with elevated mortality rates. Although many advances have occurred, intermittent or continuous renal replacement therapies are still considered the best options for reversing mild and severe AKI syndrome. For this reason, it is essential that innovative and effective therapies, without side effects and complications, be developed to treat AKI and the end-stages of renal disease. Mesenchymal stem cell (MSC) based therapies have numerous advantages in helping to repair inflamed and damaged tissues and are being considered as a new alternative for treating kidney injuries. Numerous experimental models have shown that MSCs can act via differentiation-independent mechanisms to help renal recovery. Essentially, MSCs can secrete a pool of cytokines, growth factors and chemokines, express enzymes, interact via cell-to-cell contacts and release bioagents such as microvesicles to orchestrate renal protection. In this review, we propose seven distinct properties of MSCs which explain how renoprotection may be conferred: 1) anti-inflammatory; 2) pro-angiogenic; 3) stimulation of endogenous progenitor cells; 4) anti-apoptotic; 5) anti-fibrotic; 6) anti-oxidant; and 7) promotion of cellular reprogramming. In this context, these mechanisms, either individually or synergically, could induce renal protection and functional recovery. This review summarises the most important effects and benefits associated with MSC-based therapies in experimental renal disease models and attempts to clarify the mechanisms behind the MSC-related renoprotection. MSCs may prove to be an effective, innovative and affordable treatment for moderate and severe AKI. However, more studies need to be performed to provide a more comprehensive global understanding of MSC-related therapies and to ensure their safety for future clinical applications. PMID

Pro-oxidant Induced DNA Damage in Human Lymphoblastoid Cells: Homeostatic Mechanisms of Genotoxic Tolerance

PubMed Central

Seager, Anna L.

2012-01-01

Oxidative stress contributes to many disease etiologies including ageing, neurodegeneration, and cancer, partly through DNA damage induction (genotoxicity). Understanding the i nteractions of free radicals with DNA is fundamental to discern mutation risks. In genetic toxicology, regulatory authorities consider that most genotoxins exhibit a linear relationship between dose and mutagenic response. Yet, homeostatic mechanisms, including DNA repair, that allow cells to tolerate low levels of genotoxic exposure exist. Acceptance of thresholds for genotoxicity has widespread consequences in terms of understanding cancer risk and regulating human exposure to chemicals/drugs. Three pro-oxidant chemicals, hydrogen peroxide (H2O2), potassium bromate (KBrO3), and menadione, were examined for low dose-response curves in human lymphoblastoid cells. DNA repair and antioxidant capacity were assessed as possible threshold mechanisms. H2O2 and KBrO3, but not menadione, exhibited thresholded responses, containing a range of nongenotoxic low doses. Levels of the DNA glycosylase 8-oxoguanine glycosylase were unchanged in response to pro- oxidant stress. DNA repair–focused gene expression arrays reported changes in ATM and BRCA1, involved in double-strand break repair, in response to low-dose pro-oxidant exposure; however, these alterations were not substantiated at the protein level. Determination of oxidatively induced DNA damage in H2O2-treated AHH-1 cells reported accumulation of thymine glycol above the genotoxic threshold. Further, the H2O2 dose-response curve was shifted by modulating the antioxidant glutathione. Hence, observed pro- oxidant thresholds were due to protective capacities of base excision repair enzymes and antioxidants against DNA damage, highlighting the importance of homeostatic mechanisms in “genotoxic tolerance.” PMID:22539617

Phenomenological approach to mechanical damage growth analysis.

PubMed

Pugno, Nicola; Bosia, Federico; Gliozzi, Antonio S; Delsanto, Pier Paolo; Carpinteri, Alberto

2008-10-01

The problem of characterizing damage evolution in a generic material is addressed with the aim of tracing it back to existing growth models in other fields of research. Based on energetic considerations, a system evolution equation is derived for a generic damage indicator describing a material system subjected to an increasing external stress. The latter is found to fit into the framework of a recently developed phenomenological universality (PUN) approach and, more specifically, the so-called U2 class. Analytical results are confirmed by numerical simulations based on a fiber-bundle model and statistically assigned local strengths at the microscale. The fits with numerical data prove, with an excellent degree of reliability, that the typical evolution of the damage indicator belongs to the aforementioned PUN class. Applications of this result are briefly discussed and suggested.

A study of the protective effect and mechanism of ketamine on acute lung injury induced by mechanical ventilation.

PubMed

Wang, W-F; Liu, S; Xu, B

2017-03-01

To investigate the protective effects and mechanism of ketamine on acute lung injury induced by mechanical ventilation. 63 patients with acute lung injury caused by mechanical ventilation in our hospital between June 2014 and May 2015 were chosen and divided into three groups: group A, B, and C. Group A (20 cases) received conventional treatment. Group B (21 cases) was treated with propofol and group C (22 cases) with ketamine. The ventilator application time, the success rate of weaning, the mortality rate, inflammation index (IL-1, Caspase-1, and NF-κB), pulmonary function index and oxygen saturation were compared. The ventilator application time and the mortality rate of group B and group C were significantly (p < 0.05) lower than those of group A. The success rate of weaning of groups B and C was higher (p < 0.05) than that of group A. There was no difference between groups B and C. After intervention, the levels of PaO2 and SpO2 in the three groups increased, while the level of PaCO2decreased with better improvement in group B and group C than in group A (p < 0.05), groups B and C being similar (p > 0.05). After the intervention, the levels of FEV1, FEV1/FVC, FVC and PEER in the three groups increased, but more remarkably in group B and group C (p < 0.05), in which there was no difference. After the intervention, the levels of IL-1β, Caspase-1, and NF-κB in the three groups decreased with the levels of group C obviously lower (p < 0.05) than those of groups B and A, the highest. Both ketamine and propofol can improve the blood gas and pulmonary function index of patients with acute lung injury caused by mechanical ventilation. They shorten the application time of ventilator, improve the success rate of weaning and reduce the mortality rate which is probably related to the reduction of the degree of inflammatory reaction. Ketamine is more effective in reducing inflammatory factors including IL-1β, Caspase-1, and NF-κB than propofol.

Deformation and damage mechanisms of zinc coatings on hot-dip galvanized steel sheets: Part II. Damage modes

NASA Astrophysics Data System (ADS)

Parisot, Rodolphe; Forest, Samuel; Pineau, André; Grillon, François; Demonet, Xavier; Mataigne, Jean-Michel

2004-03-01

Zinc-based coatings are widely used for protection against corrosion of steel-sheet products in the automotive industry. The objective of the present article is to investigate the damage modes at work in three different microstructures of a zinc coating on an interstitial-free steel substrate under tension, planestrain tension, and expansion loading. Plastic-deformation mechanisms are addressed in the companion article. Two main fracture mechanisms, namely, intergranular cracking and transgranular cleavage fracture, were identified in an untempered cold-rolled coating, a tempered cold-rolled coating, and a recrystallized coating. No fracture at the interface between the steel and zinc coating was observed that could lead to spalling, in the studied zinc alloy. A complex network of cleavage cracks and their interaction with deformation twinning is shown to develop in the material. An extensive quantitative analysis based on systematic image analysis provides the number and cumulative length of cleavage cracks at different strain levels for the three investigated microstructures and three loading conditions. Grain refinement by recrystallization is shown to lead to an improved cracking resistance of the coating. A model for crystallographic cleavage combining the stress component normal to the basal plane and the amount of plastic slip on the basal slip systems is proposed and identified from equibiaxial tension tests and electron backscattered diffraction (EBSD) analysis of the cracked grains. This analysis requires the computation of the nonlinear stress-strain response of each grain using a crystal-plasticity constitutive model. The model is then applied successfully to other loading conditions and is shown to account for the preferred orientations of damaged grains observed in the case of plane-strain tension.

Mitochondrial DNA Damage Initiates Acute Lung Injury and Multi-Organ System Failure Evoked in Rats by Intra-Tracheal Pseudomonas Aeruginosa.

PubMed

Lee, Yann-Leei; Obiako, Boniface; Gorodnya, Olena M; Ruchko, Mykhaylo V; Kuck, Jamie L; Pastukh, Viktor M; Wilson, Glenn L; Simmons, Jon D; Gillespie, Mark N

2017-07-01

Although studies in rat cultured pulmonary artery endothelial cells, perfused lungs, and intact mice support the concept that oxidative mitochondrial (mt) DNA damage triggers acute lung injury (ALI), it has not yet been determined whether enhanced mtDNA repair forestalls development of ALI and its progression to multiple organ system failure (MOSF). Accordingly, here we examined the effect of a fusion protein construct targeting the DNA glycosylase, Ogg1, to mitochondria in a rat model intra-tracheal Pseudomonas aeruginosa (strain 103; PA103)-induced ALI and MOSF. Relative to controls, animals given PA103 displayed increases in lung vascular filtration coefficient accompanied by transient lung tissue oxidative mtDNA damage and variable changes in mtDNA copy number without evidence of nuclear DNA damage. The approximate 40% of animals surviving 24 h after bacterial administration exhibited multiple organ dysfunction, manifest as increased serum and tissue-specific indices of kidney and liver failure, along with depressed heart rate and blood pressure. While administration of mt-targeted Ogg1 to control animals was innocuous, the active fusion protein, but not a DNA repair-deficient mutant, prevented bacteria-induced increases in lung tissue oxidative mtDNA damage, failed to alter mtDNA copy number, and attenuated lung endothelial barrier degradation. These changes were associated with suppression of liver, kidney, and cardiovascular dysfunction and with decreased 24 h mortality. Collectively, the present findings indicate that oxidative mtDNA damage to lung tissue initiates PA103-induced ALI and MOSF in rats.

A cumulative shear mechanism for tissue damage initiation in shock-wave lithotripsy.

PubMed

Freund, Jonathan B; Colonius, Tim; Evan, Andrew P

2007-09-01

Evidence suggests that inertial cavitation plays an important role in the renal injury incurred during shock-wave lithotripsy. However, it is unclear how tissue damage is initiated, and significant injury typically occurs only after a sufficient dose of shock waves. Although it has been suggested that shock-induced shearing might initiate injury, estimates indicate that individual shocks do not produce sufficient shear to do so. In this paper, we hypothesize that the cumulative shear of the many shocks is damaging. This mechanism depends on whether there is sufficient time between shocks for tissue to relax to its unstrained state. We investigate the mechanism with a physics-based simulation model, wherein the basement membranes that define the tubules and vessels in the inner medulla are represented as elastic shells surrounded by viscous fluid. Material properties are estimated from in-vitro tests of renal basement membranes and documented mechanical properties of cells and extracellular gels. Estimates for the net shear deformation from a typical lithotripter shock (approximately 0.1%) are found from a separate dynamic shock simulation. The results suggest that the larger interstitial volume (approximately 40%) near the papilla tip gives the tissue there a relaxation time comparable to clinical shock delivery rates (approximately 1 Hz), thus allowing shear to accumulate. Away from the papilla tip, where the interstitial volume is smaller (approximately 20%), the model tissue relaxes completely before the next shock would be delivered. Implications of the model are that slower delivery rates and broader focal zones should both decrease injury, consistent with some recent observations.

Squirrel Damage to Pines

Treesearch

USDA Forest Service

1981-01-01

Flagging (dead branch tips) on jack pine and red pine may be caused by insects, diseases, or mechanical damage. In the Lake States, flagging is often the result of mechanical damage, sometimes girdling, caused when the cones are torn off by red squirrels.

Rho-kinase inhibition acutely augments blood flow in focal cerebral ischemia via endothelial mechanisms.

PubMed

Shin, Hwa Kyoung; Salomone, Salvatore; Potts, E Michelle; Lee, Sae-Won; Millican, Eric; Noma, Kensuke; Huang, Paul L; Boas, David A; Liao, James K; Moskowitz, Michael A; Ayata, Cenk

2007-05-01

Rho-kinase is a serine threonine kinase that increases vasomotor tone via its effects on both endothelium and smooth muscle. Rho-kinase inhibition reduces cerebral infarct size in wild type, but not endothelial nitric oxide synthase deficient (eNOS-/-) mice. The mechanism may be related to Rho-kinase activation under hypoxic/ischemic conditions and impaired vasodilation because of downregulation of eNOS activity. To further implicate Rho-kinase in impaired vascular relaxation during hypoxia/ischemia, we exposed isolated vessels from rat and mouse to 60 mins of hypoxia, and showed that hypoxia reversibly abolished acetylcholine-induced eNOS-dependent relaxation, and that Rho-kinase inhibitor hydroxyfasudil partially preserved this relaxation during hypoxia. We, therefore, hypothesized that if hypoxia-induced Rho-kinase activation acutely impairs vasodilation in ischemic cortex, in vivo, then Rho-kinase inhibitors would acutely augment cerebral blood flow (CBF) as a mechanism by which they reduce infarct size. To test this, we studied the acute cerebral hemodynamic effects of Rho-kinase inhibitors in ischemic core and penumbra during distal middle cerebral artery occlusion (dMCAO) in wild-type and eNOS-/- mice using laser speckle flowmetry. When administered 60 mins before or immediately after dMCAO, Rho-kinase inhibitors hydroxyfasudil and Y-27632 reduced the area of severely ischemic cortex. However, hydroxyfasudil did not reduce the area of CBF deficit in eNOS-/- mice, suggesting that its effect on CBF within the ischemic cortex is primarily endothelium-dependent, and not mediated by its direct vasodilator effect on vascular smooth muscle. Our results suggest that Rho-kinase negatively regulates eNOS activity in acutely ischemic brain, thereby worsening the CBF deficit. Therefore, rapid nontranscriptional upregulation of eNOS activity by small molecule inhibitors of Rho-kinase may be a viable therapeutic approach in acute stroke.

[Sea urchin embryo, DNA-damaged cell cycle checkpoint and the mechanisms initiating cancer development].

PubMed

Bellé, Robert; Le Bouffant, Ronan; Morales, Julia; Cosson, Bertrand; Cormier, Patrick; Mulner-Lorillon, Odile

2007-01-01

Cell division is an essential process for heredity, maintenance and evolution of the whole living kingdom. Sea urchin early development represents an excellent experimental model for the analysis of cell cycle checkpoint mechanisms since embryonic cells contain a functional DNA-damage checkpoint and since the whole sea urchin genome is sequenced. The DNA-damaged checkpoint is responsible for an arrest in the cell cycle when DNA is damaged or incorrectly replicated, for activation of the DNA repair mechanism, and for commitment to cell death by apoptosis in the case of failure to repair. New insights in cancer biology lead to two fundamental concepts about the very first origin of cancerogenesis. Cancers result from dysfunction of DNA-damaged checkpoints and cancers appear as a result of normal stem cell (NCS) transformation into a cancer stem cell (CSC). The second aspect suggests a new definition of "cancer", since CSC can be detected well before any clinical evidence. Since early development starts from the zygote, which is a primary stem cell, sea urchin early development allows analysis of the early steps of the cancerization process. Although sea urchins do not develop cancers, the model is alternative and complementary to stem cells which are not easy to isolate, do not divide in a short time and do not divide synchronously. In the field of toxicology and incidence on human health, the sea urchin experimental model allows assessment of cancer risk from single or combined molecules long before any epidemiologic evidence is available. Sea urchin embryos were used to test the worldwide used pesticide Roundup that contains glyphosate as the active herbicide agent; it was shown to activate the DNA-damage checkpoint of the first cell cycle of development. The model therefore allows considerable increase in risk evaluation of new products in the field of cancer and offers a tool for the discovery of molecular markers for early diagnostic in cancer biology

Assessing the Impact of Mechanical Damage on Full-Thickness Porcine and Human Skin Using an In Vitro Approach

PubMed Central

Builles, Nicolas; Frouin, Éric; Scott, Dan; Ramos, Jeanne; Marti-Mestres, Gilberte

2015-01-01

For most xenobiotics, the rates of percutaneous absorption are limited by diffusion through the horny layer of skin. However, percutaneous absorption of chemicals may seriously increase when the skin is damaged. The aim of this work was to develop an in vitro representative model of mechanically damaged skins. The epidermal barrier was examined following exposure to a razor, a rotating brush, and a microneedle system in comparison to tape-stripping which acted as a reference. Excised full-thickness skins were mounted on a diffusion chamber in order to evaluate the effect of injuries and to mimic physiological conditions. The transepidermal water loss (TEWL) was greatly increased when the barrier function was compromised. Measurements were made for all the damaged biopsies and observed histologically by microscopy. On human and porcine skins, the tape-stripping application (0 to 40 times) showed a proportional increase in TEWL which highlights the destruction of the stratum corneum. Similar results were obtained for all cosmetic instruments. This is reflected in our study by the nonsignificant difference of the mean TEWL scores between 30 strips and mechanical damage. For a specific appreciation, damaged skins were then selected to qualitatively evaluate the absorption of a chlorogenic acid solution using fluorescence microscopy. PMID:26247021

Mechanisms of Acute Kidney Injury Induced by Experimental Lonomia obliqua Envenomation

PubMed Central

Berger, Markus; Santi, Lucélia; Beys-da-Silva, Walter O.; Oliveira, Fabrício Marcus Silva; Caliari, Marcelo Vidigal; Yates, John R.; Ribeiro, Maria Aparecida; Guimarães, Jorge Almeida

2015-01-01

Background Lonomia obliqua caterpillar envenomation causes acute kidney injury (AKI), which can be responsible for its deadly actions. This study evaluates the possible mechanisms involved in the pathogenesis of renal dysfunction. Methods To characterize L. obliqua venom effects we subcutaneously injected rats and examined renal functional, morphological and biochemical parameters at several time points. We also performed discovery based proteomic analysis to measure protein expression to identify molecular pathways of renal disease. Results L. obliqua envenomation causes acute tubular necrosis, which is associated with renal inflammation; formation of hematic casts, resulting from intravascular hemolysis; increase in vascular permeability and fibrosis. The dilation of Bowman’s space and glomerular tuft is related to fluid leakage and intra-glomerular fibrin deposition, respectively, since tissue factor procoagulant activity increases in the kidney. Systemic hypotension also contributes to these alterations and to the sudden loss of basic renal functions, including filtration and excretion capacities, urinary concentration and maintenance of fluid homeostasis. In addition, envenomed kidneys increases expression of proteins involved in cell stress, inflammation, tissue injury, heme-induced oxidative stress, coagulation and complement system activation. Finally, the localization of the venom in renal tissue agrees with morphological and functional alterations, suggesting also a direct nephrotoxic activity. Conclusions Mechanisms of L. obliqua-induced AKI are complex involving mainly glomerular and tubular functional impairment and vascular alterations. These results are important to understand the mechanisms of renal injury and may suggest more efficient ways to prevent or attenuate the pathology of Lonomia’s envenomation. PMID:24798088

Ethyl pyruvate reduces acute lung damage following trauma and hemorrhagic shock via inhibition of NF-κB and HMGB1.

PubMed

Relja, Borna; Wagner, Nils; Franz, Niklas; Dieteren, Scott; Mörs, Katharina; Schmidt, Julia; Marzi, Ingo; Perl, Mario

2018-03-01

After blunt thoracic trauma (TxT) and hemorrhagic shock with resuscitation (H/R) intense local inflammatory response and cell loss frequently impair the pulmonary function. Ethyl pyruvate (EP) has been reported to improve the pathophysiologic derangements in models of acute inflammation. Here, we studied the effects of EP on inflammation and lung damage after TxT+H/R. Twenty four female Lewis rats (180-240g) were randomly divided into 3 groups: two groups underwent TxT followed by hemorrhagic shock (35±3mmHg) for 60min and resuscitation with either Ringers-Lactat (RL) alone or RL supplemented with EP (EP, 50mg/kg). Sham operated animals underwent surgical procedures. Two hours later bronchoalveolar lavage fluid (BAL), lung tissue and blood were collected for analyses. EP significantly improved pO 2 levels compared to RL after TxT+H/R. TxT+H/R induced elevated levels of lactate dehydrogenase, total protein concentration in BAL and lung damage as evidenced by lung histology; these effects were significantly reduced by EP. Local inflammatory markers, lung TNF-alpha protein levels and infiltration with polymorphonuclear leukocytes (PMNL) significantly decreased in EP vs. RL group after TxT+H/R. Indicators of apoptosis as reduced BCL-2 and increased FAS gene expression after TxT+H/R were significantly increased or decreased, respectively, by EP after TxT+H/R. EP reduced TxT+H/R-induced p65 phosphorylation, which was concomitant with reduced HMGB1 levels in lung sections. Taken together, TxT+H/R induced strong inflammatory response and apoptotic changes as well as lung injury which were markedly diminished by EP. Our results suggest that this might be mediated via NF-κB and/or HMGB1 dependent mechanism. Copyright © 2017 Elsevier GmbH. All rights reserved.

Renoprotective effects of asialoerythropoietin in diabetic mice against ischaemia-reperfusion-induced acute kidney injury.

PubMed

Nakazawa, Jun; Isshiki, Keiji; Sugimoto, Toshiro; Araki, Shin-Ichi; Kume, Shinji; Yokomaku, Yukiyo; Chin-Kanasaki, Masami; Sakaguchi, Masayoshi; Koya, Daisuke; Haneda, Masakazu; Kashiwagi, Atsunori; Uzu, Takashi

2010-02-01

Diabetic patients are at higher risk of failure to recover after acute kidney injury, however, the mechanism and therapeutic strategies remain unclear. Erythropoietin is cytoprotective in a variety of non-haematopoietic cells. The aim of the present study was to clarify the mechanism of diabetes-related acceleration of renal damage after ischaemia-reperfusion injury and to examine the therapeutic potential of asialoerythropoietin, a non-haematopoietic erythropoietin derivative, against ischaemia-reperfusion-induced acute kidney injury in diabetic mice. C57BL/6J mice with and without streptozotocin-induced diabetes were subjected to 30 min unilateral renal ischaemia-reperfusion injury at 1 week after induction of diabetes. They were divided into four group: (i) non-diabetic plus ischaemia-reperfusion injury; (ii) non-diabetic plus ischaemia-reperfusion injury plus asialoerythropoietin (3000 IU/kg bodyweight); (iii) diabetic plus ischaemia-reperfusion injury; and (iv) diabetic plus ischemia-reperfusion injury plus asialoerythropoietin. Experiments were conducted at the indicated time periods after ischaemia-reperfusion injury. Ischaemia-reperfusion injury of diabetic kidney resulted in significantly low protein expression levels of bcl-2, an anti-apoptotic molecule, and bone morphogenetic protein-7 (BMP-7), an anti-fibrotic and pro-regenerative factor, compared with non-diabetic kidneys. Diabetic kidney subsequently showed severe damage including increased tubular cell apoptosis, tubulointerstitial fibrosis and decreased tubular proliferation, compared with non-diabetic kidney. Treatment with asialoerythropoietin induced bcl-2 and BMP-7 expression in diabetic kidney and decreased tubular cell apoptosis, tubulointerstitial fibrosis and accelerated tubular proliferation. Reduced induction bcl-2 and BMP-7 may play a role in the acceleration of renal damage after ischaemia-reperfusion injury in diabetic kidney. The renoprotective effects of asialoerythropoietin on acute

Variability in Usual Care Mechanical Ventilation for Pediatric Acute Respiratory Distress Syndrome: Time for a Decision Support Protocol?

PubMed

Newth, Christopher J L; Sward, Katherine A; Khemani, Robinder G; Page, Kent; Meert, Kathleen L; Carcillo, Joseph A; Shanley, Thomas P; Moler, Frank W; Pollack, Murray M; Dalton, Heidi J; Wessel, David L; Berger, John T; Berg, Robert A; Harrison, Rick E; Holubkov, Richard; Doctor, Allan; Dean, J Michael; Jenkins, Tammara L; Nicholson, Carol E

2017-11-01

Although pediatric intensivists philosophically embrace lung protective ventilation for acute lung injury and acute respiratory distress syndrome, we hypothesized that ventilator management varies. We assessed ventilator management by evaluating changes to ventilator settings in response to blood gases, pulse oximetry, or end-tidal CO2. We also assessed the potential impact that a pediatric mechanical ventilation protocol adapted from National Heart Lung and Blood Institute acute respiratory distress syndrome network protocols could have on reducing variability by comparing actual changes in ventilator settings to those recommended by the protocol. Prospective observational study. Eight tertiary care U.S. PICUs, October 2011 to April 2012. One hundred twenty patients (age range 17 d to 18 yr) with acute lung injury/acute respiratory distress syndrome. Two thousand hundred arterial and capillary blood gases, 3,964 oxygen saturation by pulse oximetry, and 2,757 end-tidal CO2 values were associated with 3,983 ventilator settings. Ventilation mode at study onset was pressure control 60%, volume control 19%, pressure-regulated volume control 18%, and high-frequency oscillatory ventilation 3%. Clinicians changed FIO2 by ±5 or ±10% increments every 8 hours. Positive end-expiratory pressure was limited at ~10 cm H2O as oxygenation worsened, lower than would have been recommended by the protocol. In the first 72 hours of mechanical ventilation, maximum tidal volume/kg using predicted versus actual body weight was 10.3 (8.5-12.9) (median [interquartile range]) versus 9.2 mL/kg (7.6-12.0) (p < 0.001). Intensivists made changes similar to protocol recommendations 29% of the time, opposite to the protocol's recommendation 12% of the time and no changes 56% of the time. Ventilator management varies substantially in children with acute respiratory distress syndrome. Opportunities exist to minimize variability and potentially injurious ventilator settings by using a

Self-sealing of thermal fatigue and mechanical damage in fiber-reinforced composite materials

NASA Astrophysics Data System (ADS)

Moll, Jericho L.

Fiber reinforced composite tanks provide a promising method of storage for liquid oxygen and hydrogen for aerospace applications. The inherent thermal fatigue of these vessels leads to the formation of microcracks, which allow gas phase leakage across the tank walls. In this dissertation, self-healing functionality is imparted to a structural composite to effectively seal microcracks induced by both mechanical and thermal loading cycles. Two different microencapsulated healing chemistries are investigated in woven glass fiber/epoxy and uni-weave carbon fiber/epoxy composites. Self-healing of mechanically induced damage was first studied in a room temperature cured plain weave E-glass/epoxy composite with encapsulated dicyclopentadiene (DCPD) monomer and wax protected Grubbs' catalyst healing components. A controlled amount of microcracking was introduced through cyclic indentation of opposing surfaces of the composite. The resulting damage zone was proportional to the indentation load. Healing was assessed through the use of a pressure cell apparatus to detect nitrogen flow through the thickness direction of the damaged composite. Successful healing resulted in a perfect seal, with no measurable gas flow. The effect of DCPD microcapsule size (51 microm and 18 microm) and concentration (0--12.2 wt%) on the self-sealing ability was investigated. Composite specimens with 6.5 wt% 51 microm capsules sealed 67% of the time, compared to 13% for the control panels without healing components. A thermally stable, dual microcapsule healing chemistry comprised of silanol terminated poly(dimethyl siloxane) plus a crosslinking agent and a tin catalyst was employed to allow higher composite processing temperatures. The microcapsules were incorporated into a satin weave E-glass fiber/epoxy composite processed at 120°C to yield a glass transition temperature of 127°C. Self-sealing ability after mechanical damage was assessed for different microcapsule sizees (25 microm and 42

The Basilar Artery on Computed Tomography Angiography Score for Acute Basilar Artery Occlusion Treated with Mechanical Thrombectomy.

PubMed

Yang, Haihua; Ma, Ning; Liu, Lian; Gao, Feng; Mo, Dapeng; Miao, Zhongrong

2018-06-01

Recently, the Basilar Artery on Computed Tomography Angiography (BATMAN) score predicts clinical outcome of acute basilar artery occlusion (BAO), yet there is no extensive external validation. The purpose of this study was to validate the prognostic value of BATMAN scoring system for the prediction of clinical outcome in patients with acute BAO treated with endovascular mechanical thrombectomy by using cerebral digital subtraction angiography (DSA). We analyzed the clinical and angiographic data of consecutive patients with acute BAO from March 2012 to November 2016. The BATMAN scoring system was used to assess the collateral status and thrombus burden. Thrombolysis in Cerebral Infarction (TICI) score 2b-3 was defined as successful recanalization. Receiver operating characteristic (ROC) curve was used to determine the area under the curve (AUC) and the optimum cutoff value. Multivariate regression analysis was used to identify the predictor of clinical outcome. This study included 63 patients with acute BAO who underwent mechanical thrombectomy. Of these patients, 90.5% (57/63) achieved successful recanalization (TICI, 2b-3) and 34.9% (22/63) had a favorable outcome (modified Rankin Scale score 0-2). ROC analysis indicated that the AUC of the BATMAN score was .722 (95% confidence interval [CI], .594-.827), and the optimal cutoff value was 3 (sensitivity = 72.73, specificity = 63.41). In multivariate logistic regression analysis, the BATMAN score higher than 3 was associated with favorable outcome (odds ratio, 5.214; 95% CI, 1.47-18.483; P = .011). The BATMAN score on DSA seems to predict the functional outcome in patients of acute BAO treated with mechanical thrombectomy. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Development of novel force-limiting grasping forceps with a simple mechanism.

PubMed

Sakaguchi, Yasuto; Sato, Toshihiko; Yutaka, Yojiro; Muranishi, Yusuke; Komatsu, Teruya; Yoshizawa, Akihiko; Nakajima, Naoki; Nakamura, Tatsuo; Date, Hiroshi

2018-06-06

In endoscopic surgery, fragile tissues may be damaged by the application of excessive force. Thus, we developed novel endoscopic forceps with a simple force-limiting mechanism. The novel forceps were constructed with a leaf spring, and the spring thickness determines grasping pressure. We established an evaluation system (maximum score is 11 points) for lung tissue damage leading to complications. We tested the conventional forceps (186.8 kPa) and 3 novel spring forceps with the following thicknesses: 1.3 mm (53.0 kPa), 2.2 mm (187.7 kPa) and 2.8 mm (369.2 kPa). After grasping, peripheral canine lung tissues were microscopically examined for acute- and late-phase damages. In the acute phase (20 sites), the novel forceps caused capillary congestion and haemorrhage in the subpleural tissue, whereas the conventional forceps caused deep tissue and pleural damages. In the late phase (30 sites), both forceps caused fibroblast formation and interstitial thickening, which progressed to the deeper tissues as grasping pressure increased. In the acute phase, the median scores were 2.0 and 6.0 for the novel and conventional forceps, respectively (P = 0.003). In the late phase, the median scores were 2.0, 2.5 and 5.0 for 1.3-, 2.2- and 2.8-mm thick forceps, respectively, and 5.0 for the conventional forceps (P < 0.001). In both phases, the novel forceps with grasping pressure set below 187.7 kPa (2.2 mm) caused significantly less lung tissue damage than the conventional forceps. The novel endoscopic forceps are able to regulate the tissue-grasping pressure and induce less damage in lung tissues than conventional forceps.

Recreational stimulants, herbal, and spice cannabis: The core psychobiological processes that underlie their damaging effects.

PubMed

Parrott, Andrew C; Hayley, Amie C; Downey, Luke A

2017-05-01

Recreational drugs are taken for their positive mood effects, yet their regular usage damages well-being. The psychobiological mechanisms underlying these damaging effects will be debated. The empirical literature on recreational cannabinoids and stimulant drugs is reviewed. A theoretical explanation for how they cause similar types of damage is outlined. All psychoactive drugs cause moods and psychological states to fluctuate. The acute mood gains underlie their recreational usage, while the mood deficits on withdrawal explain their addictiveness. Cyclical mood changes are found with every central nervous system stimulant and also occur with cannabis. These mood state changes provide a surface index for more profound psychobiological fluctuations. Homeostatic balance is altered, with repetitive disturbances of the hypothalamic-pituitary-adrenal axis, and disrupted cortisol-neurohormonal secretions. Hence, these drugs cause increased stress, disturbed sleep, neurocognitive impairments, altered brain activity, and psychiatric vulnerability. Equivalent deficits occur with novel psychoactive stimulants such as mephedrone and artificial "spice" cannabinoids. These psychobiological fluctuations underlie drug dependency and make cessation difficult. Psychobiological stability and homeostatic balance are optimally restored by quitting psychoactive drugs. Recreational stimulants such as cocaine or MDMA (3.4-methylenedioxymethamphetamine) and sedative drugs such as cannabis damage human homeostasis and well-being through similar core psychobiological mechanisms. Copyright © 2017 John Wiley & Sons, Ltd.

Kinetic gating mechanism of DNA damage recognition by Rad4/XPC

DOE PAGES

Chen, Xuejing; Velmurugu, Yogambigai; Zheng, Guanqun; ...

2015-01-06

The xeroderma pigmentosum C (XPC) complex initiates nucleotide excision repair by recognizing DNA lesions before recruiting downstream factors. How XPC detects structurally diverse lesions embedded within normal DNA is unknown. Here we present a crystal structure that captures the yeast XPC orthologue (Rad4) on a single register of undamaged DNA. The structure shows that a disulphide-tethered Rad4 flips out normal nucleotides and adopts a conformation similar to that seen with damaged DNA. Contrary to many DNA repair enzymes that can directly reject non-target sites as structural misfits, our results suggest that Rad4/XPC uses a kinetic gating mechanism whereby lesion selectivitymore » arises from the kinetic competition between DNA opening and the residence time of Rad4/XPC per site. This mechanism is further supported by measurements of Rad4-induced lesion-opening times using temperature-jump perturbation spectroscopy. Lastly, kinetic gating may be a general mechanism used by site-specific DNA-binding proteins to minimize time-consuming interrogations of non-target sites.« less

γ-Oryzanol protects against acute cadmium-induced oxidative damage in mice testes.

PubMed

Spiazzi, Cristiano C; Manfredini, Vanusa; Barcellos da Silva, Fabiana E; Flores, Erico M M; Izaguirry, Aryele P; Vargas, Laura M; Soares, Melina B; Santos, Francielli W

2013-05-01

Cadmium is a non-essential heavy metal that is present at low levels mainly in food and water and also in cigar smoke. The present study evaluated the testicular damage caused by acute cadmium exposure and verified the protective role of γ-oryzanol (ORY). Mice were administrated with a single dose of 2.5mg/kg of CdCl2, and then treated with ORY (50mM in canola oil, 5mL/kg). Testes were removed after 24h and tested for lipid peroxidation (TBARS), protein carbonylation, DNA breakage, ascorbic acid, cadmium and non-proteic thiols contents, and for the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST) and δ-aminolevulic acid dehydratase (δ-ALA-D). Cadmium presented a significant alteration in all parameters, except GPx and CAT activities. Therapy reduced in a slight degree cadmium concentration in testes (around 23%). ORY restored SOD and GST activities as well as TBARS production to the control levels. Furthermore, ORY partially recovered δ-ALA-D activity inhibited by cadmium. This study provides the first evidence on the therapeutic properties of ORY in protecting against cadmium-induced testicular toxicity. Copyright © 2013 Elsevier Ltd. All rights reserved.

A Micromechanics-Based Elastoplastic Damage Model for Rocks with a Brittle-Ductile Transition in Mechanical Response

NASA Astrophysics Data System (ADS)

Hu, Kun; Zhu, Qi-zhi; Chen, Liang; Shao, Jian-fu; Liu, Jian

2018-06-01

As confining pressure increases, crystalline rocks of moderate porosity usually undergo a transition in failure mode from localized brittle fracture to diffused damage and ductile failure. This transition has been widely reported experimentally for several decades; however, satisfactory modeling is still lacking. The present paper aims at modeling the brittle-ductile transition process of rocks under conventional triaxial compression. Based on quantitative analyses of experimental results, it is found that there is a quite satisfactory linearity between the axial inelastic strain at failure and the confining pressure prescribed. A micromechanics-based frictional damage model is then formulated using an associated plastic flow rule and a strain energy release rate-based damage criterion. The analytical solution to the strong plasticity-damage coupling problem is provided and applied to simulate the nonlinear mechanical behaviors of Tennessee marble, Indiana limestone and Jinping marble, each presenting a brittle-ductile transition in stress-strain curves.

A new thermo-mechanical coupled DEM model with non-spherical grains for thermally induced damage of rocks

NASA Astrophysics Data System (ADS)

Chen, Zhiqiang; Jin, Xu; Wang, Moran

2018-07-01

Thermally induced damage often occurs in rocks in geophysical systems. Discrete element method (DEM) is a useful tool to model this thermo-mechanical coupled process owing to its explicit representation of fracture initiation and propagation. However, the previous DEM models for this are mostly based on spherical discrete elements, which are not able to capture all consequences (e.g. high ratio of compressive to tensile strength) of real rocks (e.g. granite) composed of complex-geometry grains. In order to overcome this intrinsic limitation, we present a new model allowing to mimick thermally induced damage of brittle rock with non-spherical grains. After validations, the new model is used to study thermal gradient cracking with a special emphasis on the effects from rock heterogeneity. The obtained fracture initiation and propagation are consistent with experimental observations, which demonstrates the ability of current model to reproduce the thermally induced damage of rocks. Meanwhile, the results show that rock heterogeneity influences thermal gradient cracking significantly, and more micro cracks uniformly scattering around the borehole are induced in the heterogeneous sample, which is not good for applications such as nuclear waste disposal. The present model provides a promising approach at micro-scale to explore mechanisms of thermally induced damage of rocks in geological engineering.

Using Continuum Damage Mechanics to Simulate Iceberg Calving from Tidewater Outlet Glaciers

NASA Astrophysics Data System (ADS)

Mercenier, R.; Lüthi, M.; Vieli, A.

2017-12-01

Many ocean terminating glaciers in the Arctic are currently undergoingrapid retreat, thinning and strong accelerations in flow. The processof iceberg calving plays a crucial role for the related dynamical masslosses and occurs when the stresses at the calving front exceed thefracture strength of ice, driving the propagation of cracks andeventually leading to the detachment of ice blocks from the glacierfront. However, the understanding of the processes involved in icebergcalving as well as the capability of flow models to represent thecalving mechanism remain limited.Here, we use a time-dependent two-dimensional finite-element flowmodel coupled to a damage model to simulate the break-off of ice atthe front of idealized tidewater outlet glaciers. The flow modelcomputes flow velocities and the resulting stresses, which are in turnused to calculate the evolution of the glacier geometry anddamage. Damage is defined as a change of rheological properties, e.g.viscosity, due to increasing material degradation. Elements of ice areremoved when the damage variable reaches a critical threshold. Theeffects of material properties and of geometrical parameters such aswater depth, ice thickness and submarine frontal melting on thesimulated calving rates are explored through systematic sensitivityanalyses.The coupled ice flow/damage model allows for successful reproductionof calving front geometries typically observed for different waterdepths. We further use detailed observations from real glaciergeometries to better constrain the model parameters. Theproposed model approach should be applicable to simulate icebergcalving on arbitrary glaciers, and thus be used to analyse theevolution of tidewater glacier variations from the past to the future.

Failure Predictions for VHTR Core Components using a Probabilistic Contiuum Damage Mechanics Model

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

Fok, Alex

2013-10-30

The proposed work addresses the key research need for the development of constitutive models and overall failure models for graphite and high temperature structural materials, with the long-term goal being to maximize the design life of the Next Generation Nuclear Plant (NGNP). To this end, the capability of a Continuum Damage Mechanics (CDM) model, which has been used successfully for modeling fracture of virgin graphite, will be extended as a predictive and design tool for the core components of the very high- temperature reactor (VHTR). Specifically, irradiation and environmental effects pertinent to the VHTR will be incorporated into the modelmore » to allow fracture of graphite and ceramic components under in-reactor conditions to be modeled explicitly using the finite element method. The model uses a combined stress-based and fracture mechanics-based failure criterion, so it can simulate both the initiation and propagation of cracks. Modern imaging techniques, such as x-ray computed tomography and digital image correlation, will be used during material testing to help define the baseline material damage parameters. Monte Carlo analysis will be performed to address inherent variations in material properties, the aim being to reduce the arbitrariness and uncertainties associated with the current statistical approach. The results can potentially contribute to the current development of American Society of Mechanical Engineers (ASME) codes for the design and construction of VHTR core components.« less

Acute Kidney Injury Facilitates Hypocalcemia by Exacerbating the Hyperphosphatemic Effect of Muscle Damage in Rhabdomyolysis.

PubMed

Higaki, Masato; Tanemoto, Masayuki; Shiraishi, Takeshi; Taniguchi, Kei; Fujigaki, Yoshihide; Uchida, Shunya

2015-01-01

Hypocalcemia is an important complication of rhabdomyolysis for which several pathogenic factors, including acute kidney injury (AKI), have been proposed. To gain insight regarding the hypocalcemic roles of AKI in rhabdomyolysis, we retrospectively examined patients with rhabdomyolysis. Of 28,387 patients admitted to the Department of Internal Medicine, 51 patients met the inclusion criteria for the study. Serum calcium was analyzed based on laboratory data including indicators of AKI, serum creatine kinase (CK) and serum inorganic phosphate (iP). Twenty-two patients (43%) had hypocalcemia. Compared with patients without hypocalcemia, they had a higher prevalence of AKI (82 vs. 55%; p = 0.046), higher levels of peak CK (39,100 ± 50,600 vs. 9,800 ± 11,900 IU/l; p = 0.003) and higher levels of peak iP (1.77 ± 1.10 vs. 1.10 ± 0.35 mmol/l; p = 0.007). Indicators of AKI were correlated with peak CK and peak iP and were not significant variables in the regression analysis for hypocalcemia. Peak CK and peak iP were not correlated with each other. Impaired phosphate use by muscle contributed to the increased iP. These findings indicate that muscle damage is the primary hypocalcemic factor in rhabdomyolysis. AKI facilitated hypocalcemia by exacerbating the hyperphosphatemic effects of muscle damage. Aggressive hydration, which could increase oxygen supply and subsequently repair phosphate use in muscle, might reduce the incidence of hypocalcemia in rhabdomyolysis. © 2015 S. Karger AG, Basel.

Endovascular Mechanical Recanalisation of Acute Carotid-T Occlusions: A Single-Center Retrospective Analysis

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

Fesl, Gunther, E-mail: gunther.fesl@med.uni-muenchen.de; Wiesmann, Martin; Patzig, Maximilian

2011-04-15

Purpose: Acute carotid-T occlusion generally responds poorly to thrombolysis. Endovascular mechanical thrombectomy (EMT) seems to be a promising alternative. However, there are few data on EMT in carotid-T occlusions. Materials and Methods: We reviewed data of 14 consecutive patients with acute carotid-T occlusions treated with mechanical recanalisation devices. A clot separation/aspiration system was used in 11 patients; different other mechanical retriever devices were used in seven patients; and stents were used in four patients. Modified Rankin Scale scores at 90 days were recorded to assess functional outcome. Results: Six women and eight men were included in the study. Mean patientmore » age was 59.2 years; median National Institute of Health Stroke Scale score on admission was 19; and mean time to treatment was 4.2 h. Successful recanalisation (Thrombolysis in Myocardial Infarction [TIMI] score II and III) was achieved in 11 patients (78.6%). Seven patients (50.0%) were treated with more than one device, leading to successful recanalisation in six of these patients (85.7%). Subarachnoid haemorrhage and large space-occupying bleedings occurred in one (7.1%) and three (21.4%) patients, respectively. At follow-up, three patients (21.4%) were functionally independent, and six (42.9%) had died. Conclusion: When applying different mechanical devices, we found a high recanalisation rate. However, discrepancy between recanalisation and clinical outcome remained. More data are needed to assess the effect of the different methods on the prognoses of stroke patients.« less

A combination of experimental measurement, constitutive damage model, and diffusion tensor imaging to characterize the mechanical properties of the human brain.

PubMed

Karimi, Alireza; Rahmati, Seyed Mohammadali; Razaghi, Reza

2017-09-01

Understanding the mechanical properties of the human brain is deemed important as it may subject to various types of complex loadings during the Traumatic Brain Injury (TBI). Although many studies so far have been conducted to quantify the mechanical properties of the brain, there is a paucity of knowledge on the mechanical properties of the human brain tissue and the damage of its axon fibers under the various types of complex loadings during the Traumatic Brain Injury (TBI). Although many studies so far have been conducted to quantify the mechanical properties of the brain, there is a paucity of knowledge on the mechanical properties of the human brain tissue and the damage of its axon fibers under the frontal lobe of the human brain. The constrained nonlinear minimization method was employed to identify the brain coefficients according to the axial and transversal compressive data. The pseudo-elastic damage model data was also well compared with that of the experimental data and it not only up to the primary loading but also the discontinuous softening could well address the mechanical behavior of the brain tissue.

Age-related mechanical strength evolution of trabecular bone under fatigue damage for both genders: Fracture risk evaluation.

PubMed

Ben Kahla, Rabeb; Barkaoui, Abdelwahed; Merzouki, Tarek

2018-08-01

Bone tissue is a living composite material, providing mechanical and homeostatic functions, and able to constantly adapt its microstructure to changes in long term loading. This adaptation is conducted by a physiological process, known as "bone remodeling". This latter is manifested by interactions between osteoclasts and osteoblasts, and can be influenced by many local factors, via effects on bone cell differentiation and proliferation. In the current work, age and gender effects on damage rate evolution, throughout life, have been investigated using a mechanobiological finite element modeling. To achieve the aim, a mathematical model has been developed, coupling both cell activities and mechanical behavior of trabecular bone, under cyclic loadings. A series of computational simulations (ABAQUS/UMAT) has been performed on a 3D human proximal femur, allowing to investigate the effects of mechanical and biological parameters on mechanical strength of trabecular bone, in order to evaluate the fracture risk resulting from fatigue damage. The obtained results revealed that mechanical stimulus amplitude affects bone resorption and formation rates, and indicated that age and gender are major factors in bone response to the applied loadings. Copyright © 2018 Elsevier Ltd. All rights reserved.

Early Damage Detection in Composites during Fabrication and Mechanical Testing.

PubMed

Chandarana, Neha; Sanchez, Daniel Martinez; Soutis, Constantinos; Gresil, Matthieu

2017-06-22

Fully integrated monitoring systems have shown promise in improving confidence in composite materials while reducing lifecycle costs. A distributed optical fibre sensor is embedded in a fibre reinforced composite laminate, to give three sensing regions at different levels through-the-thickness of the plate. This study follows the resin infusion process during fabrication of the composite, monitoring the development of strain in-situ and in real time, and to gain better understanding of the resin rheology during curing. Piezoelectric wafer active sensors and electrical strain gauges are bonded to the plate after fabrication. This is followed by progressive loading/unloading cycles of mechanical four point bending. The strain values obtained from the optical fibre are in good agreement with strain data collected by surface mounted strain gauges, while the sensing regions clearly indicate the development of compressive, neutral, and tensile strain. Acoustic emission event detection suggests the formation of matrix (resin) cracks, with measured damage event amplitudes in agreement with values reported in published literature on the subject. The Felicity ratio for each subsequent loading cycle is calculated to track the progression of damage in the material. The methodology developed here can be used to follow the full life cycle of a composite structure, from manufacture to end-of-life.

Early Damage Detection in Composites during Fabrication and Mechanical Testing

PubMed Central

Chandarana, Neha; Sanchez, Daniel Martinez; Soutis, Constantinos; Gresil, Matthieu

2017-01-01

Fully integrated monitoring systems have shown promise in improving confidence in composite materials while reducing lifecycle costs. A distributed optical fibre sensor is embedded in a fibre reinforced composite laminate, to give three sensing regions at different levels through-the-thickness of the plate. This study follows the resin infusion process during fabrication of the composite, monitoring the development of strain in-situ and in real time, and to gain better understanding of the resin rheology during curing. Piezoelectric wafer active sensors and electrical strain gauges are bonded to the plate after fabrication. This is followed by progressive loading/unloading cycles of mechanical four point bending. The strain values obtained from the optical fibre are in good agreement with strain data collected by surface mounted strain gauges, while the sensing regions clearly indicate the development of compressive, neutral, and tensile strain. Acoustic emission event detection suggests the formation of matrix (resin) cracks, with measured damage event amplitudes in agreement with values reported in published literature on the subject. The Felicity ratio for each subsequent loading cycle is calculated to track the progression of damage in the material. The methodology developed here can be used to follow the full life cycle of a composite structure, from manufacture to end-of-life. PMID:28773048

A Hybrid Approach to Composite Damage and Failure Analysis Combining Synergistic Damage Mechanics and Peridynamics

DTIC Science & Technology

2016-03-31

fiber distributions. Task 2.1 is concerned with damage evolution in a peridynamic model of poroelastic materials. Initial results for both tasks are...distributions. Task 2.1 is concerned with damage evolution in a peridynamic model of poroelastic materials. Initial results for both tasks are reported and...Task 2.1: Damage evolution in a peridynamic model of poroelastic materials. Background and Motivation In order to model the presence of pores and

[Progress of researches on mechanism of acupuncture therapy underlying improvement of acute cerebral hemorrhage].

PubMed

Wang, Fan; Wang, Hai-qiao; Dong, Gui-rong

2011-04-01

In the present paper, the authors review the progress of researches on the mechanism of acupuncture therapy underlying improvement of acute cerebral hemorrhage from experimental studies and research methods. The effects of acupuncture intervention mainly involve (1) lessening inflammatory reactions, (2) reducing impairment of free radicals and excitatory amino acids on cerebral neurons, (3) balancing release of vascular bioactive substances to increase regional cerebral blood flow, and (4) promoting repair and regeneration of the neural tissue, etc. In regard to the research methods, many new biological techniques such as biological molecular approaches, neuro-cellular chemical methods, reverse transcription-polymerase chain reaction (RT-PCR) or quantitative real time-PCR, situ hybridization, western blotting, electron microscope, etc., have been extensively applied to researches on the underlying mechanism of acupuncture therapy for cerebral infarction. In addition, the authors also pointed out that in spite of achieving some bigger progresses in experimental studies, most of the results basically reflect static, isolated and regional changes rather than dynamic and whole body changes. For this reason, more vivo research techniques and noninvasive research methods are highly recommended to be used in the future research on the underlying mechanisms of acupuncture therapy for acute cerebral ischemia.

Autonomous Repair Mechanism of Creep Damage in Fe-Au and Fe-Au-B-N Alloys

NASA Astrophysics Data System (ADS)

Zhang, S.; Kwakernaak, C.; Tichelaar, F. D.; Sloof, W. G.; Kuzmina, M.; Herbig, M.; Raabe, D.; Brück, E.; van der Zwaag, S.; van Dijk, N. H.

2015-12-01

The autonomous repair mechanism of creep cavitation during high-temperature deformation has been investigated in Fe-Au and Fe-Au-B-N alloys. Combined electron-microscopy techniques and atom probe tomography reveal how the improved creep properties result from Au precipitation within the creep cavities, preferentially formed on grain boundaries oriented perpendicular to the applied stress. The selective precipitation of Au atoms at the free creep cavity surface results in pore filling, and thereby, autonomous repair of the creep damage. The large difference in atomic size between the Au and Fe strongly hampers the nucleation of precipitates in the matrix. As a result, the matrix acts as a reservoir for the supersaturated solute until damage occurs. Grain boundaries and dislocations are found to act as fast transport routes for solute gold from the matrix to the creep cavities. The mechanism responsible for the self-healing can be characterized by a simple model for cavity growth and cavity filling.

Utilizing the Deep Space Gateway to Characterize DNA Damage Due to Space Radiation and Repair Mechanisms

NASA Astrophysics Data System (ADS)

Zea, L.; Niederwieser, T.; Anthony, J.; Stodieck, L.

2018-02-01

The radiation environment experienced in the Deep Space Gateway enables the interrogation of DNA damage and repair mechanisms, which may serve to determine the likelihood and consequence of the high radiation risk to prolonged human presence beyond LEO.

Preferential Type II Muscle Fiber Damage From Plyometric Exercise

PubMed Central

Macaluso, Filippo; Isaacs, Ashwin W.; Myburgh, Kathryn H.

2012-01-01

Context Plyometric training has been successfully used in different sporting contexts. Studies that investigated the effect of plyometric training on muscle morphology are limited, and results are controversial with regard to which muscle fiber type is mainly affected. Objective To analyze the skeletal muscle structural and ultrastructural change induced by an acute bout of plyometric exercise to determine which type of muscle fibers is predominantly damaged. Design Descriptive laboratory study. Setting Research laboratory. Patients or Other Participants Eight healthy, untrained individuals (age = 22 ± 1 years, height = 179.2 ± 6.4 cm, weight = 78.9 ± 5.9 kg). Intervention(s) Participants completed an acute bout of plyometric exercise (10 sets of 10 squat-jumps with a 1-minute rest between sets). Main Outcome Measure(s) Blood samples were collected 9 days and immediately before and 6 hours and 1, 2, and 3 days after the acute intervention. Muscle samples were collected 9 days before and 3 days after the exercise intervention. Blood samples were analyzed for creatine kinase activity. Muscle biopsies were analyzed for damage using fluorescent and electron transmission microscopy. Results Creatine kinase activity peaked 1 day after the exercise bout (529.0 ± 317.8 U/L). Immunofluorescence revealed sarcolemmal damage in 155 of 1616 fibers analyzed. Mainly fast-twitch fibers were damaged. Within subgroups, 7.6% of type I fibers, 10.3% of type IIa fibers, and 14.3% of type IIx fibers were damaged as assessed by losses in dystrophin staining. Similar damage was prevalent in IIx and IIa fibers. Electron microscopy revealed clearly distinguishable moderate and severe sarcomere damage, with damage quantifiably predominant in type II muscle fibers of both the glycolytic and oxidative subtypes (86% and 84%, respectively, versus only 27% of slow-twitch fibers). Conclusions We provide direct evidence that a single bout of plyometric exercise affected mainly type II muscle

Effects of Acute Lymphoblastic Leukemia on Ceruloplasmin Oxidase, Copper and Several Markers of Oxidative Damage, in Children.

PubMed

Mehdi, Wesen Adel; Yusof, Faridah; Mehde, Atheer Awad; Zainulabdeen, Jwan Abdulmohsin; Raus, Raha Ahmed; Abdulbari, Alaa Shawqi

2015-01-01

Acute leukaemia is characterized by fast growth of abnormal clones of haemopoietic precursor cells inside bone marrow leading to undue accumulation in the bone marrow. Acute lymphoblastic leukemia (ALL) is the most common form of childhood cancer. The study concerned 50 children diagnosed with ALL (mean age, 8.55±2.54) compared to 40 healthy controls (mean age, 8.00±1.85). The Hb, serum copper, ceruloplasmin oxidase, advanced oxidation protein products (AOPPs), total antioxidant activity (TAA) and protein were measured in all groups. One proteinous component was isolated by gel filtration chromatography from the precipitate produced by polyethylene glycol. Significantly higher levels of AOPP, copper and decrease in total antioxidant activity were noted in the cases. Statistical analysis also showed a significant increase (p<0.01) in the activity of serum ceruloplasmin oxidase in patients with ALL compared to normal subjects. The maximum velocity (Vmax) and Michaelis constant had values of 104.2 U/L and 11.7 mM, respectively. The ΔH* values for ceruloplasmin oxidase in ALL patients were positive, confirming the reaction to be endothermic. The results from this study showed a significant increase in AOPP, ceruloplasmine oxidase and decrease in total antioxidant activity .These parameters may play a role in development of DNA damage in childhood patients with acute lymphoblastic leukemia (ALL). The ΔS* and ΔG* values were negative, these refer that the reaction of ES formation is spontaneous, but needs energy in a so-called endergonic reaction. Also the negative ΔS* value of ceruloplasmin oxidase indicates that the complex [ES*] is further modulated through increasing structure arrangement.

Anisotropic mechanical properties of zircon and the effect of radiation damage

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

Beirau, Tobias; Nix, William D.; Bismayer, Ulrich

2016-06-02

Our study provides new insights into the relationship between radiation-dose-dependent structural damage, due to natural U and Th impurities, and the anisotropic mechanical properties (Poisson s ratio, elastic modulus and hardness) of zircon. Natural zircon samples from Sri Lanka (see Muarakami et al. 1991) and synthetic samples, covering a dose range of zero up to 6.8 x 10 18 -decays/g, have been studied by nanoindentation. Measurements along the [100] crystallographic direction and calculations, based on elastic stiffness constants determined by zkan (1976), revealed a general radiation-induced decrease in stiffness (~ 54 %) and hardness (~ 48 %) and an increasemore » of the Poisson s ratio (~ 54 %) with increasing dose. Additional indentations on selected samples along the [001] allowed one to follow the amorphization process to the point that the mechanical properties are isotropic. This work shows that the radiation-dose-dependent changes of the mechanical properties of zircon can be directly correlated with the amorphous fraction as determined by previous investigations with local and global probes (Rios et al. 2000a; Farnan and Salje 2001; Zhang and Salje 2001). This agreement, revealed by the different methods, indicates a huge influence of structural and even local phenomena on the macroscopic mechanical properties.« less

Differential continuum damage mechanics models for creep and fatigue of unidirectional metal matrix composites

NASA Technical Reports Server (NTRS)

Arnold, S. M.; Kruch, S.

1991-01-01

Three multiaxial isothermal continuum damage mechanics models for creep, fatigue, and creep/fatigue interaction of a unidirectional metal matrix composite volume element are presented, only one of which will be discussed in depth. Each model is phenomenological and stress based, with varying degrees of complexity to accurately predict the initiation and propagation of intergranular and transgranular defects over a wide range of loading conditions. The development of these models is founded on the definition of an initially transversely isotropic fatigue limit surface, static fracture surface, normalized stress amplitude function and isochronous creep damage failure surface, from which both fatigue and creep damage evolutionary laws can be obtained. The anisotropy of each model is defined through physically meaningful invariants reflecting the local stress and material orientation. All three transversely isotropic models have been shown, when taken to their isotropic limit, to directly simplify to previously developed and validated creep and fatigue continuum damage theories. Results of a nondimensional parametric study illustrate (1) the flexibility of the present formulation when attempting to characterize a large class of composite materials, and (2) its ability to predict anticipated qualitative trends in the fatigue behavior of unidirectional metal matrix composites. Additionally, the potential for the inclusion of various micromechanical effects (e.g., fiber/matrix bond strength, fiber volume fraction, etc.), into the phenomenological anisotropic parameters is noted, as well as a detailed discussion regarding the necessary exploratory and characterization experiments needed to utilize the featured damage theories.

Protracted Oxidative Alterations in the Mechanism of Hematopoietic Acute Radiation Syndrome

PubMed Central

Gorbunov, Nikolai V.; Sharma, Pushpa

2015-01-01

The biological effects of high-dose total body ionizing irradiation [(thereafter, irradiation (IR)] are attributed to primary oxidative breakage of biomolecule targets, mitotic, apoptotic and necrotic cell death in the dose-limiting tissues, clastogenic and epigenetic effects, and cascades of functional and reactive responses leading to radiation sickness defined as the acute radiation syndrome (ARS). The range of remaining and protracted injuries at any given radiation dose as well as the dynamics of post-IR alterations is tissue-specific. Therefore, functional integrity of the homeostatic tissue barriers may decline gradually within weeks in the post-IR period culminating with sepsis and failure of organs and systems. Multiple organ failure (MOF) leading to moribundity is a common sequela of the hemotapoietic form of ARS (hARS). Onset of MOF in hARS can be presented as “two-hit phenomenon” where the “first hit” is the underlying consequences of the IR-induced radiolysis in cells and biofluids, non-septic inflammation, metabolic up-regulation of pro-oxidative metabolic reactions, suppression of the radiosensitive hematopoietic and lymphoid tissues and the damage to gut mucosa and vascular endothelium. While the “second hit” derives from bacterial translocation and spread of the bacterial pathogens and inflammagens through the vascular system leading to septic inflammatory, metabolic responses and a cascade of redox pro-oxidative and adaptive reactions. This sequence of events can create a ground for development of prolonged metabolic, inflammatory, oxidative, nitrative, and carbonyl, electrophilic stress in crucial tissues and thus exacerbate the hARS outcomes. With this perspective, the redox mechanisms, which can mediate the IR-induced protracted oxidative post-translational modification of proteins, oxidation of lipids and carbohydrates and their countermeasures in hARS are subjects of the current review. Potential role of ubiquitous, radioresistant

Protracted Oxidative Alterations in the Mechanism of Hematopoietic Acute Radiation Syndrome.

PubMed

Gorbunov, Nikolai V; Sharma, Pushpa

2015-02-27

The biological effects of high-dose total body ionizing irradiation [(thereafter, irradiation (IR)] are attributed to primary oxidative breakage of biomolecule targets, mitotic, apoptotic and necrotic cell death in the dose-limiting tissues, clastogenic and epigenetic effects, and cascades of functional and reactive responses leading to radiation sickness defined as the acute radiation syndrome (ARS). The range of remaining and protracted injuries at any given radiation dose as well as the dynamics of post-IR alterations is tissue-specific. Therefore, functional integrity of the homeostatic tissue barriers may decline gradually within weeks in the post-IR period culminating with sepsis and failure of organs and systems. Multiple organ failure (MOF) leading to moribundity is a common sequela of the hemotapoietic form of ARS (hARS). Onset of MOF in hARS can be presented as "two-hit phenomenon" where the "first hit" is the underlying consequences of the IR-induced radiolysis in cells and biofluids, non-septic inflammation, metabolic up-regulation of pro-oxidative metabolic reactions, suppression of the radiosensitive hematopoietic and lymphoid tissues and the damage to gut mucosa and vascular endothelium. While the "second hit" derives from bacterial translocation and spread of the bacterial pathogens and inflammagens through the vascular system leading to septic inflammatory, metabolic responses and a cascade of redox pro-oxidative and adaptive reactions. This sequence of events can create a ground for development of prolonged metabolic, inflammatory, oxidative, nitrative, and carbonyl, electrophilic stress in crucial tissues and thus exacerbate the hARS outcomes. With this perspective, the redox mechanisms, which can mediate the IR-induced protracted oxidative post-translational modification of proteins, oxidation of lipids and carbohydrates and their countermeasures in hARS are subjects of the current review. Potential role of ubiquitous, radioresistant mesenchymal

High-throughput profiling of signaling networks identifies mechanism-based combination therapy to eliminate microenvironmental resistance in acute myeloid leukemia.

PubMed

Zeng, Zhihong; Liu, Wenbin; Tsao, Twee; Qiu, YiHua; Zhao, Yang; Samudio, Ismael; Sarbassov, Dos D; Kornblau, Steven M; Baggerly, Keith A; Kantarjian, Hagop M; Konopleva, Marina; Andreeff, Michael

2017-09-01

The bone marrow microenvironment is known to provide a survival advantage to residual acute myeloid leukemia cells, possibly contributing to disease recurrence. The mechanisms by which stroma in the microenvironment regulates leukemia survival remain largely unknown. Using reverse-phase protein array technology, we profiled 53 key protein molecules in 11 signaling pathways in 20 primary acute myeloid leukemia samples and two cell lines, aiming to understand stroma-mediated signaling modulation in response to the targeted agents temsirolimus (MTOR), ABT737 (BCL2/BCL-XL), and Nutlin-3a (MDM2), and to identify the effective combination therapy targeting acute myeloid leukemia in the context of the leukemia microenvironment. Stroma reprogrammed signaling networks and modified the sensitivity of acute myeloid leukemia samples to all three targeted inhibitors. Stroma activated AKT at Ser473 in the majority of samples treated with single-agent ABT737 or Nutlin-3a. This survival mechanism was partially abrogated by concomitant treatment with temsirolimus plus ABT737 or Nutlin-3a. Mapping the signaling networks revealed that combinations of two inhibitors increased the number of affected proteins in the targeted pathways and in multiple parallel signaling, translating into facilitated cell death. These results demonstrated that a mechanism-based selection of combined inhibitors can be used to guide clinical drug selection and tailor treatment regimens to eliminate microenvironment-mediated resistance in acute myeloid leukemia. Copyright© 2017 Ferrata Storti Foundation.

Pulmonary Mechanics and Mortality in Mechanically Ventilated Patients Without Acute Respiratory Distress Syndrome: A Cohort Study.

PubMed

Fuller, Brian M; Page, David; Stephens, Robert J; Roberts, Brian W; Drewry, Anne M; Ablordeppey, Enyo; Mohr, Nicholas M; Kollef, Marin H

2018-03-01

Driving pressure has been proposed as a major determinant of outcome in patients with acute respiratory distress syndrome (ARDS), but there is little data examining the association between pulmonary mechanics, including driving pressure, and outcomes in mechanically ventilated patients without ARDS. Secondary analysis from 1,705 mechanically ventilated patients enrolled in a clinical study that examined outcomes associated with the use of early lung-protective mechanical ventilation. The primary outcome was mortality and the secondary outcome was the incidence of ARDS. Multivariable models were constructed to: define the association between pulmonary mechanics (driving pressure, plateau pressure, and compliance) and mortality; and evaluate if driving pressure contributed information beyond that provided by other pulmonary mechanics. The mortality rate for the entire cohort was 26.0%. Compared with survivors, non-survivors had significantly higher driving pressure [15.9 (5.4) vs. 14.9 (4.4), P = 0.005] and plateau pressure [21.4 (5.7) vs. 20.4 (4.6), P = 0.001]. Driving pressure was independently associated with mortality [adjusted OR, 1.04 (1.01-1.07)]. Models related to plateau pressure also revealed an independent association with mortality, with similar effect size and interval estimates as driving pressure. There were 152 patients who progressed to ARDS (8.9%). Along with driving pressure and plateau pressure, mechanical power [adjusted OR, 1.03 (1.00-1.06)] was also independently associated with ARDS development. In mechanically ventilated patients, driving pressure and plateau pressure are risk factors for mortality and ARDS, and provide similar information. Mechanical power is also a risk factor for ARDS.

[Hyperhydration and dialysis in acute kidney failure].

PubMed

Saner, Fuat H; Bienholz, Anja; Tyczynski, Bartosz; Kribben, Andreas; Feldkamp, Thorsten

2015-05-01

Despite the advances in critical care medicine, the hospital mortality in patients with acute kidney injury (AKI) requiring dialysis remains high. Depending on the underlying disease the in-house mortality is reported to be up to 80%. Several observational studies demonstrated an association between mortality and fluid overload. A primary mechanism of interest is that fluid overload causes tissue edema and subsequent reduction of perfusion, oxygenation and nutrient delivery. This results in further renal damage. In addition, fluid overload-related dilution within the extracellular space causes artificially low serum creatinine, which masks AKI diagnosis. As a consequence, renal protective management strategies are deferred, which further aggravates kidney injury. This aggravation of renal damage subsequently increases the mortality. This review discusses the role of fluid overload for outcomes in critically ill patients as described in the current literature and assesses criteria for the initiation of renal replacement therapy in this critically ill population. © Georg Thieme Verlag KG Stuttgart · New York.

Tension Strength, Failure Prediction and Damage Mechanisms in 2D Triaxial Braided Composites with Notch

NASA Technical Reports Server (NTRS)

Norman, Timothy L.; Anglin, Colin

1995-01-01

The unnotched and notched (open hole) tensile strength and failure mechanisms of two-dimensional (2D) triaxial braided composites were examined. The effect of notch size and notch position were investigated. Damage initiation and propagation in notched and unnotched coupons were also examined. Theory developed to predict the normal stress distribution near an open hole and failure for tape laminated composites was evaluated for its applicability to 2D triaxial braided textile composite materials. Four different fiber architectures were considered; braid angle, yarn and braider size, percentage of longitudinal yarns and braider angle varied. Tape laminates equivalent to textile composites were also constructed for comparison. Unnotched tape equivalents were stronger than braided textiles but exhibited greater notch sensitivity. Notched textiles and tape equivalents have roughly the same strength at large notch sizes. Two common damage mechanisms were found: braider yarn cracking and near notch longitudinal yarn splitting. Cracking was found to initiate in braider yarns in unnotched and notched coupons, and propagate in the direction of the braider yarns until failure. Damage initiation stress decreased with increasing braid angle. No significant differences in prediction of near notch strain between textile and tape equivalents could be detected for small braid angle, but the correlations were weak for textiles with large braid angle. Notch strength could not be predicted using existing anisotropic theory for braided textiles due to their insensitivity to notch.

Fatigue damage mechanisms in boron-aluminium composite laminates

NASA Technical Reports Server (NTRS)

Dvorak, G. J.; Johnson, W. S.

1980-01-01

The relationship between fatigue and shakedown in metal matrix composites is investigated theoretically and experimentally for unidirectional and laminated 6061 Al-B materials. It is shown that no fatigue damage takes place if the applied stress range is such that the material remains elastic, or shakes down, i.e., resumes elastic cyclic straining after a small number of plastic strain cycles. Fatigue damage occurs only in specimens subjected to stress ranges which cause sustained cyclic plastic straining in the aluminum matrix. If the applied stress range is smaller than that required for fatigue failure, after about 10 to the 6th cycles a saturation damage state is reached which remains essentially unchanged with increasing number of cycles.

Selenium Pretreatment for Mitigation of Ischemia/Reperfusion Injury in Cardiovascular Surgery: Influence on Acute Organ Damage and Inflammatory Response.

PubMed

Steinbrenner, Holger; Bilgic, Esra; Pinto, Antonio; Engels, Melanie; Wollschläger, Lena; Döhrn, Laura; Kellermann, Kristine; Boeken, Udo; Akhyari, Payam; Lichtenberg, Artur

2016-08-01

Ischemia/reperfusion injury (IRI) contributes to morbidity and mortality after cardiovascular surgery requiring cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA). Multi-organ damage is associated with substantial decreases of blood selenium (Se) levels in patients undergoing cardiac surgery with CPB. We compared the influence of a dietary surplus of Se and pretreatment with ebselen, a mimic of the selenoenzyme glutathione peroxidase, on IRI-induced tissue damage and inflammation. Male Wistar rats were fed either a Se-adequate diet containing 0.3 ppm Se or supplemented with 1 ppm Se (as sodium selenite) for 5 weeks. Two other groups of Se-adequate rats received intraperitoneal injection of ebselen (30 mg/kg) or DMSO (solvent control) before surgery. The animals were connected to a heart-lung-machine and underwent 45 min of global ischemia during circulatory arrest at 16 °C, followed by re-warming and reperfusion. Selenite and ebselen suppressed IRI-induced leukocytosis and the increase in plasma levels of tissue damage markers (AST, ALT, LDH, troponin) during surgery but did not prevent the induction of proinflammatory cytokines (IL-6, TNF-α). Both Se compounds affected phosphorylation and expression of proteins related to stress response and inflammation: Ebselen increased phosphorylation of STAT3 transcription factor in the heart and decreased phosphorylation of ERK1/2 MAP kinases in the lungs. Selenite decreased ERK1/2 phosphorylation and HSP-70 expression in the heart. Pretreatment with selenite or ebselen protected against acute IRI-induced tissue damage during CPB and DHCA. Potential implications of their different actions with regard to molecular stress markers on the recovery after surgery represent promising targets for further investigation.

Safety and Efficiency of Low Dose Intra-arterial Tirofiban in Mechanical Thrombectomy During Acute Ischemic Stroke.

PubMed

Yu, Tongya; Lin, Yingying; Jin, Aiping; Zhang, Pei; Zhou, Xiaoyu; Fang, Min; Liu, Xueyuan

2018-06-04

In this study, we aimed to evaluate the safety and efficiency of low dose intra-arterial tirofiban in mechanical thrombectomy of acute ischemic stroke patients to facilitate the reperfusion of distal vessel. We retrospectively analyzed 54 consecutive acute ischemic patients who underwent mechanical thrombectomy for large-vessel occlusion. Patients were divided into two groups based on whether intra-arterial tirofiban was used during mechanical thrombectomy to facilitate the reperfusion of distal vessel. Patients in Non-tirofiban group (n=28) have received mechanical thrombectomy, while Patients in Tirofiban group (n=26) have received mechanical thrombectomy with a low dose intra-arterial tirofiban. We comparatively analyzed two groups of the bleeding complications, recanalization rate, 24-hour National Institutes of Health Stroke Scale score, functional independence of 90 day and mortality rate. Of 54 patients undergoing mechanical thrombectomy, baseline characteristics did not differ between the Tirofiban group and Non-tirofiban cohort. Symptomatic intracranial hemorrhage rates were not different between Tirofiban group and Non-tirofiban group (11.5 % vs. 14.3%). Total 47 (87.0%) patients have realized successful recanalization, no apparent difference between two groups (85.7% vs 88.5%, P>0.05). Mean 24-hour National Institutes of Health Stroke Scale score was 9.24±6.85, 9.11±8.13 in the Non-tirofiban group and 9.39±5.31 in the Tirofiban group respectively, P>0.05. Total 20 (35.7%) patients have achieved functional independence (34.6% vs 39.3%, P>0.05) at 90 days. Patients treated with tirofiban presented lower mortality when compared with those who were not treated with tirofiban without significant difference (10.7% versus 3.8%, P>0.05). Intra-arterial tirofiban may be safe in mechanical thrombectomy of acute ischemic stroke to facilitate the reperfusion of distal vessel, but has no beneficial effect on prognosis. Copyright© Bentham Science Publishers; For

[Mechanism of pain sensation].

PubMed

Gyulaházi, Judit

2009-11-15

Pain, as subjective content of consciousness, is an essential attention-calling sign that helps to survive. Pain relieve is obligatory for every physician, thus, its individual appearance can make the analgesia difficult to carry out. The improving neuroimaging techniques allow understanding the development of pain sensation. Through the 24 articles on the PubMed found with keywords 'pain' and 'neuroimaging', we review here the parts of the pain neuron matrix, their tasks and the assumed mechanism of the acute pain sensation. The mechanism of the individual pain sensation is illustrated by the view of the modular function of the medial part of the pain matrix. Experimental results of empathic pain suggest that pain sensation may occur without real damage of the tissues, as well. The pain network plays main role in chronic pain.

Mechanisms of Endogenous Neuroprotective Effects of Astrocytes in Brain Injury

PubMed Central

2018-01-01

Astrocytes, once believed to serve only as “glue” for the structural support of neurons, have been demonstrated to serve critical functions for the maintenance and protection of neurons, especially under conditions of acute or chronic injury. There are at least seven distinct mechanisms by which astrocytes protect neurons from damage; these are (1) protection against glutamate toxicity, (2) protection against redox stress, (3) mediation of mitochondrial repair mechanisms, (4) protection against glucose-induced metabolic stress, (5) protection against iron toxicity, (6) modulation of the immune response in the brain, and (7) maintenance of tissue homeostasis in the presence of DNA damage. Astrocytes support these critical functions through specialized responses to stress or toxic conditions. The detoxifying activities of astrocytes are essential for maintenance of the microenvironment surrounding neurons and in whole tissue homeostasis. Improved understanding of the mechanisms by which astrocytes protect the brain could lead to the development of novel targets for the development of neuroprotective strategies.

How much can disaster and climate science contribute to loss and damage mechanisms in international climate policy?

NASA Astrophysics Data System (ADS)

Huggel, Christian; Allen, Simon; Eicken, Hajo; Hansen, Gerrit; Stone, Dáithí

2015-04-01

As the 5th Assessment Report of the Intergovernmental Panel on Climate Change (IPCC) recently has shown, there is increasing evidence of observed impacts of climate change on natural and human systems. Some of these impacts are negative and result in damage and loss of lives and assets. In international climate policy negotiations under the UNFCCC the discussions on loss and damage have gained significant traction during the past negotiation rounds. At COP 19 the Warsaw International Mechanism for Loss and Damage (WIM) was created as an institutional arrangement to address this issue. Thereby, loss and damage (L&D) are typically defined as the residual damage and loss that occur beyond mitigation and adaptation efforts. This implies that effective mitigation and adaptation policy can substantially reduce L&D. While there is wide agreement that knowledge and understanding needs to be strengthened on how L&D due to climate change affects countries, in particular highly vulnerable countries and populations, there is still substantial disagreement on several aspects. In fact, after COP20 in Lima a number of options are on the table, including whether L&D should be located under the adaptation framework or form a separate institutional arrangement, or whether a compensation regime should be established to support developing countries. Similarly, the scientific framework for a clear L&D concept, its application in real-world cases, and implications for international climate policy, in particular with respect to questions of responsibility, liability, compensation and financing, is still evolving. Earlier proposals, for instance, have included a threshold concept, with payments released upon crossing of certain thresholds of climate (related) parameters, similar to insurance procedures. The threshold would be defined as a departure of the parameter from baseline conditions, for instance a rainfall event that is more intense than a certain baseline based threshold. Further

Mild MPP+ exposure impairs autophagic degradation through a novel lysosomal acidity-independent mechanism.

PubMed

Miyara, Masatsugu; Kotake, Yaichiro; Tokunaga, Wataru; Sanoh, Seigo; Ohta, Shigeru

2016-10-01

Parkinson's disease (PD) is the second most common neurodegenerative disorder, but its underlying cause remains unknown. Although recent studies using PD-related neurotoxin MPP + suggest autophagy involvement in the pathogenesis of PD, the effect of MPP + on autophagic processes under mild exposure, which mimics the slow progressive nature of PD, remains largely unclear. We examined the effect of mild MPP + exposure (10 and 200 μM for 48 h), which induces a more slowly developing cell death, on autophagic processes and the mechanistic differences with acute MPP + toxicity (2.5 and 5 mM for 24 h). In SH-SY5Y cells, mild MPP + exposure predominantly inhibited autophagosome degradation, whereas acute MPP + exposure inhibited both autophagosome degradation and basal autophagy. Mild MPP + exposure reduced lysosomal hydrolase cathepsin D activity without changing lysosomal acidity, whereas acute exposure decreased lysosomal density. Lysosome biogenesis enhancers trehalose and rapamycin partially alleviated mild MPP + exposure induced impaired autophagosome degradation and cell death, but did not prevent the pathogenic response to acute MPP + exposure, suggesting irreversible lysosomal damage. We demonstrated impaired autophagic degradation by MPP + exposure and mechanistic differences between mild and acute MPP + toxicities. Mild MPP + toxicity impaired autophagosome degradation through novel lysosomal acidity-independent mechanisms. Sustained mild lysosomal damage may contribute to PD. We examined the effects of MPP + on autophagic processes under mild exposure, which mimics the slow progressive nature of Parkinson's disease, in SH-SY5Y cells. This study demonstrated impaired autophagic degradation through a reduction in lysosomal cathepsin D activity without altering lysosomal acidity by mild MPP + exposure. Mechanistic differences between acute and mild MPP + toxicity were also observed. Sustained mild damage of lysosome may be an underlying cause of Parkinson

Intermittent vibration protects aged muscle from mechanical and oxidative damage under prolonged compression.

PubMed

Wong, Sing Wan; Cheung, Brian Chun Ho; Pang, Bruce Tak Keung; Kwong, Ateline; Chung, Anna; Lee, Kenneth Ka Ho; Mak, Arthur Fut Tak

2017-04-11

Deep tissue pressure ulcers, a serious clinical challenge originating in the muscle layer, are hardly detectable at the beginning. The challenge apparently occurs in aged subjects more frequently. As the ulcer propagates to the skin surface, it becomes very difficult to manage and can lead to fatal complications. Preventive measures are thus highly desirable. Although the complex pathological mechanisms have not been fully understood, prolonged and excessive physical challenges and oxidative stress are believed to be involved in the ulcer development. Previous reports have demonstrated that oxidative stress could compromise the mechanical properties of muscle cells, making them easier to be damaged when physical challenges are introduced. In this study, we used senescence accelerated (SAMP8) mice and its control breed (SAMR1) to examine the protective effects of intermittent vibration on aged and control muscle tissues during prolonged epidermal compression under 100mmHg for 6h. Results showed that an application of 35Hz, 0.25g intermittent vibration during compression decreased the compression-induced muscle breakdown in SAMP8 mice, as indicated histologically in terms of number of interstitial nuclei. The fact that no significant difference in muscle damage could be established in the corresponding groups in SAMR1 mice suggests that SAMR1 mice could better accommodate the compression insult than SAMP8 mice. Compression-induced oxidative damage was successfully curbed using intermittent vibration in SAMP8 mice, as indicated by 8-OHdG. A possible explanation is that the anti-oxidative defense could be maintained with intermittent vibration during compression. This was supported by the expression level of PGC-1-alpha, catalase, Gpx-1 and SOD1. Our data suggested intermittent vibration could serve as a preventive measure for deep tissue ulcer, particularly in aged subjects. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mechanical Evaluation of Retinal Damage Associated With Blunt Craniomaxillofacial Trauma: A Simulation Analysis.

PubMed

Geng, Xiaoqi; Liu, Xiaoyu; Wei, Wei; Wang, Yawei; Wang, Lizhen; Chen, Kinon; Huo, Hongqiang; Zhu, Yuanjie; Fan, Yubo

2018-05-01

To evaluate retinal damage as the result of craniomaxillofacial trauma and explain its pathogenic mechanism using finite element (FE) simulation. Computed tomography (CT) images of an adult man were obtained to construct a FE skull model. A FE skin model was built to cover the outer surface of the skull model. A previously validated FE right eye model was symmetrically copied to create a FE left eye model, and both eye models were assembled to the skull model. An orbital fat model was developed to fill the space between the eye models and the skull model. Simulations of a ball-shaped object striking the frontal bone, temporal bone, brow, and cheekbones were performed, and the resulting absorption of the impact energy, intraocular pressure (IOP), and strains on the macula and ora serrata were analyzed to evaluate retinal injuries. Strain was concentrated in the macular regions (0.18 in average) of both eyes when the frontal bone was struck. The peak strain on the macula of the struck-side eye was higher than that of the other eye (>100%) when the temporal bone was struck, whereas there was little difference (<10%) between the two eyes when the brow and cheekbones were struck. Correlation analysis showed that the retinal strain time histories were highly correlated with the IOP time histories ( r > 0.8 and P = 0.000 in all simulation cases). The risk of retinal damage is variable in craniomaxillofacial trauma depending on the struck region, and the damage is highly related to IOP variation caused by indirect blunt eye trauma. This finite element eye model allows us to evaluate and understand the indirect ocular injury mechanisms in craniomaxillofacial trauma for better clinical diagnosis and treatment.

Mechanically induced tube damage in the artificial hydrosalpinx.

PubMed

Kleinstein, J; Neubüser, D; Mussmann, J

1982-01-01

One-sided artificial hydrosalpinx was caused in mature New Zealand rabbits by proximal and distal ligature. After 2 weeks the average secretion accumulation was 2.1 ml, after 8 weeks 6.3 ml. A fold relief could no longer be detected after 8 weeks. The light-microscopical study of the epithelium showed signs of cell degeneration with cell dedifferentiation, pyknosis of the nucleus, and perinuclear aerolae. The ciliation of 66% ciliated cells for the normal oviduct (pars ampullaris) was reduced to 15% after 8 weeks of artificial hydrosalpinx. Based on the hypertrophy of the muscularis the percentage loss of E2 receptors within 4 weeks was smaller in comparison with the percentage reduction of the ciliation during the same time. Finally, after 8 weeks an amount of 15% for the estrogen receptors as well as for the ciliation was achieved--both compared to the untreated oviduct. It is possible that the oviduct damage, caused only by the mechanical influence of the secretion congestion, is the reason for the unfavorable pregnancy rate after salpingoneostomy of a chronic atrophied hydrosalpinx.

Heat transfer in damaged material

NASA Astrophysics Data System (ADS)

Kruis, J.

2013-10-01

Fully coupled thermo-mechanical analysis of civil engineering problems is studied. The mechanical analysis is based on damage mechanics which is useful for modeling of behaviour of quasi-brittle materials, especially in tension. The damage is assumed to be isotropic. The heat transfer is assumed in the form of heat conduction governed by the Fourier law and heat radiation governed by the Stefan-Boltzmann law. Fully coupled thermo-mechanical problem is formulated.

Exogenous skeletal muscle satellite cells promote the repair of levator palpebrae superioris mechanical damage in rat.

PubMed

Ye, Lin; Yao, Yuanyuan; Guo, Hui; Peng, Yun

2018-05-17

Blepharoptosis is a drooping of the upper eyelid, usually due to dysfunction of the levator palpebrae superioris (LPS). Recently, skeletal muscle satellite cells (SSCs) have been reported to promote the repair of damaged skeletal muscle. This study aims to investigate the potential contribution of exogenous SSCs to the regeneration of mechanically damaged LPS. Thirty-two rats were randomly divided into four groups, including control group, SSCs-treated group, SSCs-treated injury group and non-treated injury group. After rats in injury groups were artificially lacerated on both the left and right LPS, HBBS (Hank's Balanced Salt Solution) containing SSCs was injected into upper eyelid tissue. After 7 days, the LPS muscle tissues were excised. In addition, skeletal muscle cells (SMCs) and SSCs were cocultured for use as an in vitro model, and the protective effects of SSCs on cultured SMCs were also investigated. Histological staining revealed that exogenous SSCs repaired the damaged muscle fibers and attenuated the fibrosis of LPS, possibly due to the increased level of IGF-1. In contrast, the level of IL-1β, IL-6, TGF-β1 and Smad2/3 (phospho-T8) were significantly reduced in the SSCs-treated group. The in vitro model using coculture of skeletal muscle cells (SMCs) and SSCs also revealed an increased level of IGF-1 and reduced level of inflammatory factors, resulting in a better cell survival rate. This study found that exogenous SSCs can promote the repair of LPS mechanical damage and provides new insight into the development of novel therapeutic approaches for blepharoptosis.

Protective Role for Antioxidants in Acute Kidney Disease

PubMed Central

Dennis, Joanne M.; Witting, Paul K.

2017-01-01

Acute kidney injury causes significant morbidity and mortality in the community and clinic. Various pathologies, including renal and cardiovascular disease, traumatic injury/rhabdomyolysis, sepsis, and nephrotoxicity, that cause acute kidney injury (AKI), induce general or regional decreases in renal blood flow. The ensuing renal hypoxia and ischemia promotes the formation of reactive oxygen species (ROS) such as superoxide radical anions, peroxides, and hydroxyl radicals, that can oxidatively damage biomolecules and membranes, and affect organelle function and induce renal tubule cell injury, inflammation, and vascular dysfunction. Acute kidney injury is associated with increased oxidative damage, and various endogenous and synthetic antioxidants that mitigate source and derived oxidants are beneficial in cell-based and animal studies. However, the benefit of synthetic antioxidant supplementation in human acute kidney injury and renal disease remains to be realized. The endogenous low-molecular weight, non-proteinaceous antioxidant, ascorbate (vitamin C), is a promising therapeutic in human renal injury in critical illness and nephrotoxicity. Ascorbate may exert significant protection by reducing reactive oxygen species and renal oxidative damage via its antioxidant activity, and/or by its non-antioxidant functions in maintaining hydroxylase and monooxygenase enzymes, and endothelium and vascular function. Ascorbate supplementation may be particularly important in renal injury patients with low vitamin C status. PMID:28686196

Whole body proton irradiation causes acute damage to bone marrow hematopoietic progenitor and stem cells in mice.

PubMed

Chang, Jianhui; Wang, Yingying; Pathak, Rupak; Sridharan, Vijayalakshmi; Jones, Tamako; Mao, Xiao Wen; Nelson, Gregory; Boerma, Marjan; Hauer-Jensen, Martin; Zhou, Daohong; Shao, Lijian

2017-12-01

Exposure to proton irradiation during missions in deep space can lead to bone marrow injury. The acute effects of proton irradiation on hematopoietic stem and progenitor cells remain undefined and thus were investigated. We exposed male C57BL/6 mice to 0.5 and 1.0 Gy proton total body irradiation (proton-TBI, 150 MeV) and examined changes in peripheral blood cells and bone marrow (BM) progenitors and LSK cells 2 weeks after exposure. 1.0 Gy proton-TBI significantly reduced the numbers of peripheral blood cells compared to 0.5 Gy proton-TBI and unirradiated animals, while the numbers of peripheral blood cell counts were comparable between 0.5 Gy proton-TBI and unirradiated mice. The frequencies and numbers of LSK cells and CMPs in BM of 0.5 and 1.0 Gy irradiated mice were decreased in comparison to those of normal controls. LSK cells and CMPs and their progeny exhibited a radiation-induced impairment in clonogenic function. Exposure to 1.0 Gy increased cellular apoptosis but not the production of reactive oxygen species (ROS) in CMPs two weeks after irradiation. LSK cells from irradiated mice exhibited an increase in ROS production and apoptosis. Exposure to proton-TBI can induce acute damage to BM progenitors and LSK cells.

Schisandrin B alleviates acute oxidative stress via modulating Nrf2/Keap1-mediated antioxidant pathway.

PubMed

Ying, Wu; Li, Zheng-Cai; Li-Qing, Yao; Mai, Li; Mei, Tang

2018-05-09

Schisandrin B (Sch B), one of Fructus Schisandrae's main effective components, protects neurons from oxidative stress in the central nervous system. Here we investigated the neuroprotective effect of Sch B in the acute oxidative stress damage and attempted to define the possible mechanisms. From the elevated plus maze (EPM) and open field test (OFT), we found that forcing swimming, an acute stressor, significantly induced anxiety-like behavior which was alleviated by Sch B (p.o.) treatment. In addition, the Sch B treatment suppressed toxicity, malondialdehyde (MDA) and reactive oxygen species (ROS), an important factor for neuron damage. The antioxidant molecules under the control of Nrf2 pathway, such as superoxide dismutase (SOD) and glutathione (GSH), were significantly increased by Sch B treatment. Moreover, a higher percentage of intact cells in the amygdala further verified the neuroprotective effect of Sch B in Nissl staining. Several proteins such as Nrf2 and its endogenous inhibitor Keap1, were abnormal expressed in force swimming mice but were significantly reversed by Sch B treatment. Herein, our results suggested that Sch B may be a potential therapeutic agent against anxiety disease that is associated with oxidative stress. The possible mechanism is attributed to its neuroprotection through enhancing antioxidant effect.

The Different Effects of BMI and WC on Organ Damage in Patients from a Cardiac Rehabilitation Program after Acute Coronary Syndrome

PubMed Central

Xu, Lin; Zhao, Hui; Qiu, Jian; Zhu, Wei; Lei, Hongqiang; Cai, Zekun; Huang, Wenhua; Zhang, Heye; Zhang, Yuan-Ting

2015-01-01

One of the purposes of cardiac rehabilitation (CR) after acute coronary syndrome (ACS) is to monitor and control weight of the patient. Our study is to compare the different obesity indexes, body mass index (BMI), and waist circumference (WC), through one well-designed CR program (CRP) with ACS in Guangzhou city of Guangdong Province, China, in order to identify different effects of BMI and WC on organ damage. In our work, sixty-one patients between October 2013 and January 2014 fulfilled our study. We collected the vital signs by medical records, the clinical variables of body-metabolic status by fasting blood test, and the organ damage variables by submaximal exercise treadmill test (ETT) and ultrasonic cardiogram (UCG) both on our inpatient and four-to-five weeks of outpatient part of CRP after ACS. We mainly used two-tailed Pearson's test and liner regression to evaluate the relationship of BMI/WC and organ damage. Our results confirmed that WC could be more accurate than BMI to evaluate the cardiac function through the changes of left ventricular structure on the CRP after ACS cases. It makes sense of early diagnosis, valid evaluation, and proper adjustment to ACS in CRP of the obesity individuals in the future. PMID:26247035

Protective Role of Nuclear Factor E2-Related Factor 2 against Acute Oxidative Stress-Induced Pancreatic β-Cell Damage

PubMed Central

Fu, Jingqi; Zheng, Hongzhi; Wang, Huihui; Yang, Bei; Zhao, Rui; Lu, Chunwei; Liu, Zhiyuan; Hou, Yongyong; Xu, Yuanyuan; Zhang, Qiang; Qu, Weidong; Pi, Jingbo

2015-01-01

Oxidative stress is implicated in the pathogenesis of pancreatic β-cell dysfunction that occurs in both type 1 and type 2 diabetes. Nuclear factor E2-related factor 2 (NRF2) is a master regulator in the cellular adaptive response to oxidative stress. The present study found that MIN6 β-cells with stable knockdown of Nrf2 (Nrf2-KD) and islets isolated from Nrf2-knockout mice expressed substantially reduced levels of antioxidant enzymes in response to a variety of stressors. In scramble MIN6 cells or wild-type islets, acute exposure to oxidative stressors, including hydrogen peroxide (H2O2) and S-nitroso-N-acetylpenicillamine, resulted in cell damage as determined by decrease in cell viability, reduced ATP content, morphology changes of islets, and/or alterations of apoptotic biomarkers in a concentration- and/or time-dependent manner. In contrast, silencing of Nrf2 sensitized MIN6 cells or islets to the damage. In addition, pretreatment of MIN6 β-cells with NRF2 activators, including CDDO-Im, dimethyl fumarate (DMF), and tert-butylhydroquinone (tBHQ), protected the cells from high levels of H2O2-induced cell damage. Given that reactive oxygen species (ROS) are involved in regulating glucose-stimulated insulin secretion (GSIS) and persistent activation of NRF2 blunts glucose-triggered ROS signaling and GSIS, the present study highlights the distinct roles that NRF2 may play in pancreatic β-cell dysfunction that occurs in different stages of diabetes. PMID:25949772

Mechanisms of DNA Damage Response to Targeted Irradiation in Organotypic 3D Skin Cultures

PubMed Central

Acheva, Anna; Ghita, Mihaela; Patel, Gaurang; Prise, Kevin M.; Schettino, Giuseppe

2014-01-01

DNA damage (caused by direct cellular exposure and bystander signaling) and the complex pathways involved in its repair are critical events underpinning cellular and tissue response following radiation exposures. There are limited data addressing the dynamics of DNA damage induction and repair in the skin particularly in areas not directly exposed. Here we investigate the mechanisms regulating DNA damage, repair, intracellular signalling and their impact on premature differentiation and development of inflammatory-like response in the irradiated and surrounding areas of a 3D organotypic skin model. Following localized low-LET irradiation (225 kVp X-rays), low levels of 53BP1 foci were observed in the 3D model (3.8±0.28 foci/Gy/cell) with foci persisting and increasing in size up to 48 h post irradiation. In contrast, in cell monolayers 14.2±0.6 foci/Gy/cell and biphasic repair kinetics with repair completed before 24 h was observed. These differences are linked to differences in cellular status with variable level of p21 driving apoptotic signalling in 2D and accelerated differentiation in both the directly irradiated and bystander areas of the 3D model. The signalling pathways utilized by irradiated keratinocytes to induce DNA damage in non-exposed areas of the skin involved the NF-κB transcription factor and its downstream target COX-2. PMID:24505255

Extended Kalman filtering for the detection of damage in linear mechanical structures

NASA Astrophysics Data System (ADS)

Liu, X.; Escamilla-Ambrosio, P. J.; Lieven, N. A. J.

2009-09-01

This paper addresses the problem of assessing the location and extent of damage in a vibrating structure by means of vibration measurements. Frequency domain identification methods (e.g. finite element model updating) have been widely used in this area while time domain methods such as the extended Kalman filter (EKF) method, are more sparsely represented. The difficulty of applying EKF in mechanical system damage identification and localisation lies in: the high computational cost, the dependence of estimation results on the initial estimation error covariance matrix P(0), the initial value of parameters to be estimated, and on the statistics of measurement noise R and process noise Q. To resolve these problems in the EKF, a multiple model adaptive estimator consisting of a bank of EKF in modal domain was designed, each filter in the bank is based on different P(0). The algorithm was iterated by using the weighted global iteration method. A fuzzy logic model was incorporated in each filter to estimate the variance of the measurement noise R. The application of the method is illustrated by simulated and real examples.

Propagation prevention: a complementary mechanism for "lung protective" ventilation in acute respiratory distress syndrome.

PubMed

Marini, John J; Gattinoni, Luciano

2008-12-01

To describe the clinical implications of an often neglected mechanism through which localized acute lung injury may be propagated and intensified. Experimental and clinical evidence from the medical literature relevant to the airway propagation hypothesis and its consequences. The diffuse injury that characterizes acute respiratory distress syndrome is often considered a process that begins synchronously throughout the lung, mediated by inhaled or blood-borne noxious agents. Relatively little attention has been paid to possibility that inflammatory lung injury may also begin focally and propagate sequentially via the airway network, proceeding mouth-ward from distal to proximal. Were this true, modifications of ventilatory pattern and position aimed at geographic containment of the injury process could help prevent its generalization and limit disease severity. The purposes of this communication are to call attention to this seldom considered mechanism for extending lung injury that might further justify implementation of low tidal volume/high positive end-expiratory pressure ventilatory strategies for lung protection and to suggest additional therapeutic measures implied by this broadened conceptual paradigm.

Therapeutic Potential of Intravenous Immunoglobulin in Acute Brain Injury

PubMed Central

Thom, Vivien; Arumugam, Thiruma V.; Magnus, Tim; Gelderblom, Mathias

2017-01-01

Acute ischemic and traumatic injury of the central nervous system (CNS) is known to induce a cascade of inflammatory events that lead to secondary tissue damage. In particular, the sterile inflammatory response in stroke has been intensively investigated in the last decade, and numerous experimental studies demonstrated the neuroprotective potential of a targeted modulation of the immune system. Among the investigated immunomodulatory agents, intravenous immunoglobulin (IVIg) stand out due to their beneficial therapeutic potential in experimental stroke as well as several other experimental models of acute brain injuries, which are characterized by a rapidly evolving sterile inflammatory response, e.g., trauma, subarachnoid hemorrhage. IVIg are therapeutic preparations of polyclonal immunoglobulin G, extracted from the plasma of thousands of donors. In clinical practice, IVIg are the treatment of choice for diverse autoimmune diseases and various mechanisms of action have been proposed. Only recently, several experimental studies implicated a therapeutic potential of IVIg even in models of acute CNS injury, and suggested that the immune system as well as neuronal cells can directly be targeted by IVIg. This review gives further insight into the role of secondary inflammation in acute brain injury with an emphasis on stroke and investigates the therapeutic potential of IVIg. PMID:28824617

Micro-mechanical damage of trabecular bone-cement interface under selected loading conditions: a finite element study.

PubMed

Zhang, Qing-Hang; Tozzi, Gianluca; Tong, Jie

2014-01-01

In this study, two micro finite element models of trabecular bone-cement interface developed from high resolution computed tomography (CT) images were loaded under compression and validated using the in situ experimental data. The models were then used under tension and shear to examine the load transfer between the bone and cement and the micro damage development at the bone-cement interface. In addition, one models was further modified to investigate the effect of cement penetration on the bone-cement interfacial behaviour. The simulated results show that the load transfer at the bone-cement interface occurred mainly in the bone cement partially interdigitated region, while the fully interdigitated region seemed to contribute little to the mechanical response. Consequently, cement penetration beyond a certain value would seem to be ineffective in improving the mechanical strength of trabecular bone-cement interface. Under tension and shear loading conditions, more cement failures were found in denser bones, while the cement damage is generally low under compression.

Towards a Universal Calving Law: Modeling Ice Shelves Using Damage Mechanics

NASA Astrophysics Data System (ADS)

Whitcomb, M.; Bassis, J. N.; Price, S. F.; Lipscomb, W. H.

2017-12-01

Modeling iceberg calving from ice shelves and ice tongues is a particularly difficult problem in glaciology because of the wide range of observed calving rates. Ice shelves naturally calve large tabular icebergs at infrequent intervals, but may instead calve smaller bergs regularly or disintegrate due to hydrofracturing in warmer conditions. Any complete theory of iceberg calving in ice shelves must be able to generate realistic calving rate values depending on the magnitudes of the external forcings. Here we show that a simple damage evolution law, which represents crevasse distributions as a continuum field, produces reasonable estimates of ice shelf calving rates when added to the Community Ice Sheet Model (CISM). Our damage formulation is based on a linear stability analysis and depends upon the bulk stress and strain rate in the ice shelf, as well as the surface and basal melt rates. The basal melt parameter in our model enhances crevasse growth near the ice shelf terminus, leading to an increased iceberg production rate. This implies that increasing ocean temperatures underneath ice shelves will drive ice shelf retreat, as has been observed in the Amundsen and Bellingshausen Seas. We show that our model predicts broadly correct calving rates for ice tongues ranging in length from 10 km (Erebus) to over 100 km (Drygalski), by matching the computed steady state lengths to observations. In addition, we apply the model to idealized Antarctic ice shelves and show that we can also predict realistic ice shelf extents. Our damage mechanics model provides a promising, computationally efficient way to compute calving fluxes and links ice shelf stability to climate forcing.

PRAP1 is a novel executor of p53-dependent mechanisms in cell survival after DNA damage

PubMed Central

Huang, B H; Zhuo, J L; Leung, C H W; Lu, G D; Liu, J J; Yap, C T; Hooi, S C

2012-01-01

p53 has a crucial role in governing cellular mechanisms in response to a broad range of genotoxic stresses. During DNA damage, p53 can either promote cell survival by activating senescence or cell-cycle arrest and DNA repair to maintain genomic integrity for cell survival or direct cells to undergo apoptosis to eliminate extensively damaged cells. The ability of p53 to execute these two opposing cell fates depends on distinct signaling pathways downstream of p53. In this study, we showed that under DNA damage conditions induced by chemotherapeutic drugs, gamma irradiation and hydrogen peroxide, p53 upregulates a novel protein, proline-rich acidic protein 1 (PRAP1). We identified functional p53-response elements within intron 1 of PRAP1 gene and showed that these regions interact directly with p53 using ChIP assays, indicating that PRAP1 is a novel p53 target gene. The induction of PRAP1 expression by p53 may promote resistance of cancer cells to chemotherapeutic drugs such as 5-fluorouracil (5-FU), as knockdown of PRAP1 increases apoptosis in cancer cells after 5-FU treatment. PRAP1 appears to protect cells from apoptosis by inducing cell-cycle arrest, suggesting that the induction of PRAP1 expression by p53 in response to DNA-damaging agents contributes to cancer cell survival. Our findings provide a greater insight into the mechanisms underlying the pro-survival role of p53 in response to cytotoxic treatments. PMID:23235459

PRAP1 is a novel executor of p53-dependent mechanisms in cell survival after DNA damage.

PubMed

Huang, B H; Zhuo, J L; Leung, C H W; Lu, G D; Liu, J J; Yap, C T; Hooi, S C

2012-12-13

p53 has a crucial role in governing cellular mechanisms in response to a broad range of genotoxic stresses. During DNA damage, p53 can either promote cell survival by activating senescence or cell-cycle arrest and DNA repair to maintain genomic integrity for cell survival or direct cells to undergo apoptosis to eliminate extensively damaged cells. The ability of p53 to execute these two opposing cell fates depends on distinct signaling pathways downstream of p53. In this study, we showed that under DNA damage conditions induced by chemotherapeutic drugs, gamma irradiation and hydrogen peroxide, p53 upregulates a novel protein, proline-rich acidic protein 1 (PRAP1). We identified functional p53-response elements within intron 1 of PRAP1 gene and showed that these regions interact directly with p53 using ChIP assays, indicating that PRAP1 is a novel p53 target gene. The induction of PRAP1 expression by p53 may promote resistance of cancer cells to chemotherapeutic drugs such as 5-fluorouracil (5-FU), as knockdown of PRAP1 increases apoptosis in cancer cells after 5-FU treatment. PRAP1 appears to protect cells from apoptosis by inducing cell-cycle arrest, suggesting that the induction of PRAP1 expression by p53 in response to DNA-damaging agents contributes to cancer cell survival. Our findings provide a greater insight into the mechanisms underlying the pro-survival role of p53 in response to cytotoxic treatments.

History of mechanical ventilation may affect respiratory mechanics evolution in acute respiratory distress syndrome.

PubMed

Koutsoukou, Antonia; Perraki, Helen; Orfanos, Stylianos E; Koulouris, Nikolaos G; Tromaropoulos, Andreas; Sotiropoulou, Christina; Roussos, Charis

2009-12-01

The aim of this study was to investigate the effect of mechanical ventilation (MV) before acute respiratory distress syndrome (ARDS) on subsequent evolution of respiratory mechanics and blood gases in protectively ventilated patients with ARDS. Nineteen patients with ARDS were stratified into 2 groups according to ARDS onset relative to the onset of MV: In group A (n = 11), MV was applied at the onset of ARDS; in group B (n = 8), MV had been initiated before ARDS. Respiratory mechanics and arterial blood gas were assessed in early (mechanics occurs more commonly in patients who have been ventilated before ARDS onset, suggesting that the history of MV affects the subsequent progress of ARDS even when using protective ventilation.

Fatigue Damage Mechanisms in Advanced Hybrid Titanium Composite Laminates

NASA Technical Reports Server (NTRS)

Johnson, W. Steven; Rhymer, Donald W.; St.Clair, Terry L. (Technical Monitor)

2000-01-01

Hybrid Titanium Composite Laminates (HTCL) are a type of hybrid composite laminate with promise for high-speed aerospace applications, specifically designed for improved damage tolerance and strength at high-temperature (350 F, 177 C). However, in previous testing, HTCL demonstrated a propensity to excessive delamination at the titanium/PMC interface following titanium cracking. An advanced HTCL has been constructed with an emphasis on strengthening this interface, combining a PETI-5/IM7 PMC with Ti-15-3 foils prepared with an alkaline-perborate surface treatment. This paper discusses how the fatigue capabilities of the "advanced" HTCL compare to the first generation HTCL which was not modified for interface optimization, in both tension-tension (R = 0.1) and tension-compression (R=-0.2). The advanced HTCL under did not demonstrate a significant improvement in fatigue life, in either tension-tension or tension-compression loading. However, the advanced HTCL proved much more damage tolerant. The R = 0.1 tests revealed the advanced HTCL to increase the fatigue life following initial titanium ply damage up to 10X that of the initial HTCL at certain stress levels. The damage progression following the initial ply damage demonstrated the effect of the strengthened PMC/titanium interface. Acetate film replication of the advanced HTCL edges showed a propensity for some fibers in the adjacent PMC layers to fail at the point of titanium crack formation, suppressing delamination at the Ti/PMC interface. The inspection of failure surfaces validated these findings, revealing PMC fibers bonded to the majority of the titanium surfaces. Tension compression fatigue (R = -0.2) demonstrated the same trends in cycles between initial damage and failure, damage progression, and failure surfaces. Moreover, in possessing a higher resistance to delamination, the advanced HTCL did not exhibit buckling following initial titanium ply cracking under compression unlike the initial HTCL.

Damage mechanisms avoided or managed for NIF large optics

DOE PAGES

Manes, K. R.; Spaeth, M. L.; Adams, J. J.; ...

2016-02-09

After every other failure mode has been considered, in the end, the high-performance limit of all lasers is set by optical damage. The demands of inertial confinement fusion (ICF) pushed lasers designed as ICF drivers into this limit from their very earliest days. The first ICF lasers were small, and their pulses were short. Their goal was to provide as much power to the target as possible. Typically, they faced damage due to high intensity on their optics. As requests for higher laser energy, longer pulse lengths, and better symmetry appeared, new kinds of damage also emerged, some of themmore » anticipated and others unexpected. This paper will discuss the various types of damage to large optics that had to be considered, avoided to the extent possible, or otherwise managed as the National Ignition Facility (NIF) laser was designed, fabricated, and brought into operation. Furthermore, it has been possible for NIF to meet its requirements because of the experience gained in previous ICF systems and because NIF designers have continued to be able to avoid or manage new damage situations as they have appeared.« less

Types and Consequences of DNA Damage

EPA Science Inventory

This review provides a concise overview of the types of DNA damage and the molecular mechanisms by which a cell senses DNA damage, repairs the damage, converts the damage into a mutation, or dies as a consequence of unrepaired DNA damage. Such information is important in consid...

Effects on Pulmonary Vascular Mechanics of Two Different Lung-Protective Ventilation Strategies in an Experimental Model of Acute Respiratory Distress Syndrome.

PubMed

Santos, Arnoldo; Gomez-Peñalver, Eva; Monge-Garcia, M Ignacio; Retamal, Jaime; Borges, João Batista; Tusman, Gerardo; Hedenstierna, Goran; Larsson, Anders; Suarez-Sipmann, Fernando

2017-11-01

To compare the effects of two lung-protective ventilation strategies on pulmonary vascular mechanics in early acute respiratory distress syndrome. Experimental study. University animal research laboratory. Twelve pigs (30.8 ± 2.5 kg). Acute respiratory distress syndrome was induced by repeated lung lavages and injurious mechanical ventilation. Thereafter, animals were randomized to 4 hours ventilation according to the Acute Respiratory Distress Syndrome Network protocol or to an open lung approach strategy. Pressure and flow sensors placed at the pulmonary artery trunk allowed continuous assessment of pulmonary artery resistance, effective elastance, compliance, and reflected pressure waves. Respiratory mechanics and gas exchange data were collected. Acute respiratory distress syndrome led to pulmonary vascular mechanics deterioration. Four hours after randomization, pulmonary vascular mechanics was similar in Acute Respiratory Distress Syndrome Network and open lung approach: resistance (578 ± 252 vs 626 ± 153 dyn.s/cm; p = 0.714), effective elastance, (0.63 ± 0.22 vs 0.58 ± 0.17 mm Hg/mL; p = 0.710), compliance (1.19 ± 0.8 vs 1.50 ± 0.27 mL/mm Hg; p = 0.437), and reflection index (0.36 ± 0.04 vs 0.34 ± 0.09; p = 0.680). Open lung approach as compared to Acute Respiratory Distress Syndrome Network was associated with improved dynamic respiratory compliance (17.3 ± 2.6 vs 10.5 ± 1.3 mL/cm H2O; p < 0.001), driving pressure (9.6 ± 1.3 vs 19.3 ± 2.7 cm H2O; p < 0.001), and venous admixture (0.05 ± 0.01 vs 0.22 ± 0.03, p < 0.001) and lower mean pulmonary artery pressure (26 ± 3 vs 34 ± 7 mm Hg; p = 0.045) despite of using a higher positive end-expiratory pressure (17.4 ± 0.7 vs 9.5 ± 2.4 cm H2O; p < 0.001). Cardiac index, however, was lower in open lung approach (1.42 ± 0.16 vs 2.27 ± 0.48 L/min; p = 0.005). In this experimental model, Acute

Mechanical ventilation in acute respiratory distress syndrome: The open lung revisited.

PubMed

Amado-Rodríguez, L; Del Busto, C; García-Prieto, E; Albaiceta, G M

2017-12-01

Acute respiratory distress syndrome (ARDS) is still related to high mortality and morbidity rates. Most patients with ARDS will require ventilatory support. This treatment has a direct impact upon patient outcome and is associated to major side effects. In this regard, ventilator-associated lung injury (VALI) is the main concern when this technique is used. The ultimate mechanisms of VALI and its management are under constant evolution. The present review describes the classical mechanisms of VALI and how they have evolved with recent findings from physiopathological and clinical studies, with the aim of analyzing the clinical implications derived from them. Lastly, a series of knowledge-based recommendations are proposed that can be helpful for the ventilator assisted management of ARDS at the patient bedside. Copyright © 2017 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

Damage to the Left Precentral Gyrus Is Associated With Apraxia of Speech in Acute Stroke.

PubMed

Itabashi, Ryo; Nishio, Yoshiyuki; Kataoka, Yuka; Yazawa, Yukako; Furui, Eisuke; Matsuda, Minoru; Mori, Etsuro

2016-01-01

Apraxia of speech (AOS) is a motor speech disorder, which is clinically characterized by the combination of phonemic segmental changes and articulatory distortions. AOS has been believed to arise from impairment in motor speech planning/programming and differentiated from both aphasia and dysarthria. The brain regions associated with AOS are still a matter of debate. The aim of this study was to address this issue in a large number of consecutive acute ischemic stroke patients. We retrospectively studied 136 patients with isolated nonlacunar infarcts in the left middle cerebral artery territory (70.5±12.9 years old, 79 males). In accordance with speech and language assessments, the patients were classified into the following groups: pure form of AOS (pure AOS), AOS with aphasia (AOS-aphasia), and without AOS (non-AOS). Voxel-based lesion-symptom mapping analysis was performed on T2-weighted images or fluid-attenuated inversion recovery images. Using the Liebermeister method, group-wise comparisons were made between the all AOS (pure AOS plus AOS-aphasia) and non-AOS, pure AOS and non-AOS, AOS-aphasia and non-AOS, and pure AOS and AOS-aphasia groups. Of the 136 patients, 22 patients were diagnosed with AOS (7 patients with pure AOS and 15 patients with AOS-aphasia). The voxel-based lesion-symptom mapping analysis demonstrated that the brain regions associated with AOS were centered on the left precentral gyrus. Damage to the left precentral gyrus is associated with AOS in acute to subacute stroke patients, suggesting a role of this brain region in motor speech production. © 2015 American Heart Association, Inc.

Racial and socioeconomic disparities in access to mechanical revascularization procedures for acute ischemic stroke.

PubMed

Attenello, Frank J; Adamczyk, Peter; Wen, Ge; He, Shuhan; Zhang, Katie; Russin, Jonathan J; Sanossian, Nerses; Amar, Arun P; Mack, William J

2014-02-01

Mechanical revascularization procedures performed for treatment of acute ischemic stroke have increased in recent years. Data suggest association between operative volume and mortality rates. Understanding procedural allocation and patient access patterns is critical. Few studies have examined these demographics. Data were collected from the 2008 Nationwide Inpatient Sample database. Patients hospitalized with ischemic stroke and the subset of individuals who underwent mechanical thrombectomy were characterized by race, payer source, population density, and median wealth of the patient's zip code. Demographic data among patients undergoing mechanical thrombectomy procedures were examined. Stroke admission demographics were analyzed according to thrombectomy volume at admitting centers and patient demographics assessed according to the thrombectomy volume at treating centers. Significant allocation differences with respect to frequency of mechanical thrombectomy procedures among stroke patients existed according to race, expected payer, population density, and wealth of the patient's zip code (P < .0001). White, Hispanic, and Asian/Pacific Islander patients received endovascular treatment at higher rates than black and Native American patients. Compared with the white stroke patients, black (P < .001), Hispanic (P < .001), Asian/Pacific Islander (P < .001), and Native American stroke patients (P < .001) all demonstrated decreased frequency of admission to hospitals performing mechanical thrombectomy procedures at high volumes. Among treated patients, blacks (P = .0876), Hispanics (P = .0335), and Asian/Pacific Islanders (P < .001) demonstrated decreased frequency in mechanical thrombectomy procedures performed at high-volume centers when compared with whites. While present, socioeconomic disparities were not as consistent or pronounced as racial differences. We demonstrate variances in endovascular acute stroke treatment allocation according to racial and

Fifty Years of Research in ARDS. Respiratory Mechanics in Acute Respiratory Distress Syndrome.

PubMed

Henderson, William R; Chen, Lu; Amato, Marcelo B P; Brochard, Laurent J

2017-10-01

Acute respiratory distress syndrome is a multifactorial lung injury that continues to be associated with high levels of morbidity and mortality. Mechanical ventilation, although lifesaving, is associated with new iatrogenic injury. Current best practice involves the use of small Vt, low plateau and driving pressures, and high levels of positive end-expiratory pressure. Collectively, these interventions are termed "lung-protective ventilation." Recent investigations suggest that individualized measurements of pulmonary mechanical variables rather than population-based ventilation prescriptions may be used to set the ventilator with the potential to improve outcomes beyond those achieved with standard lung protective ventilation. This review outlines the measurement and application of clinically applicable pulmonary mechanical concepts, such as plateau pressures, driving pressure, transpulmonary pressures, stress index, and measurement of strain. In addition, the concept of the "baby lung" and the utility of dynamic in addition to static measures of pulmonary mechanical variables are discussed.

Evidence for conformational capture mechanism for damage recognition by NER protein XPC/Rad4.

NASA Astrophysics Data System (ADS)

Chakraborty, Sagnik; Steinbach, Peter J.; Paul, Debamita; Min, Jung-Hyun; Ansari, Anjum

Altered flexibility of damaged DNA sites is considered to play an important role in damage recognition by DNA repair proteins. Characterizing lesion-induced DNA dynamics has remained a challenge. We have combined ps-resolved fluorescence lifetime measurements with cytosine analog FRET pair uniquely sensitive to local unwinding/twisting to analyze DNA conformational distributions. This innovative approach maps out with unprecedented sensitivity the alternative conformations accessible to a series of DNA constructs containing 3-base-pair mismatch, suitable model lesions for the DNA repair protein xeroderma pigmentosum C (XPC) complex. XPC initiates eukaryotic nucleotide excision repair by recognizing various DNA lesions primarily through DNA deformability. Structural studies show that Rad4 (yeast ortholog of XPC) unwinds DNA at the lesion site and flips out two nucleotide pairs. Our results elucidate a broad range of conformations accessible to mismatched DNA even in the absence of the protein. Notably, the most severely distorted conformations share remarkable resemblance to the deformed conformation seen in the crystal structure of the Rad4-bound ``recognition'' complex supporting for the first time a possible ``conformational capture'' mechanism for damage recognition by XPC/Rad4. NSF Univ of Illinois-Chicago.

Effects of Zinc Supplementation on DNA Damage in Rats with Experimental Kidney Deficiency.

PubMed

Yegin, Sevim Çiftçi; Dede, Semiha; Mis, Leyla; Yur, Fatmagül

2017-04-01

This study was carried out to determine the effect of zinc on oxidative DNA damage in rats with experimental acute and chronic kidney deficiency. Six groups of five Wistar-Albino rats each were assigned as controls (C), acute kidney deficiency (AKD), zinc-supplemented (+Zn), acute kidney deficiency, zinc-supplemented (AKD + Zn), chronic kidney deficiency (CKD) and zinc-supplemented chronic kidney deficiency (CKD + Zn). The levels of 8-Oxo-2'-deoxyguanosine (8-OHdG) were determined, being the lowest in the CKD group (p < 0.05), higher in the C group than those of rats with CKD but lower than that of all the other groups (p < 0.05). There were no significant differences between the controls and the CKD + Zn group, or between the AKD and the +Zn groups. Among all groups, the highest 8-OHdG level was found in the AKD + Zn group (p < 0.05). DNA damage was greater in acute renal failure than in rats with chronic renal failure. The DNA damage in the zinc group was significantly higher than in the controls.

Copper-mediated DNA damage by the neurotransmitter dopamine and L-DOPA: A pro-oxidant mechanism.

PubMed

Rehmani, Nida; Zafar, Atif; Arif, Hussain; Hadi, Sheikh Mumtaz; Wani, Altaf A

2017-04-01

Oxidative DNA damage has been implicated in the pathogenesis of neurological disorders, cancer and ageing. Owing to the established link between labile copper concentrations and neurological diseases, it is critical to explore the interactions of neurotransmitters and drug supplements with copper. Herein, we investigate the pro-oxidant DNA damage induced by the interaction of L-DOPA and dopamine (DA) with copper. The DNA binding affinity order of the compounds has been determined by in silico molecular docking. Agarose gel electrophoresis reveals that L-DOPA and DA are able to induce strand scission in plasmid pcDNA3.1 (+/-) in a copper dependent reaction. These metabolites also cause cellular DNA breakage in human lymphocytes by mobilizing endogenous copper, as assessed by comet assay. Further, L-DOPA and DA-mediated DNA breaks were detected by the appearance of post-DNA damage sensitive marker γH2AX in cancer cell lines accumulating high copper. Immunofluorescence demonstrated the co-localization of downstream repair factor 53BP1 at the damaged induced γH2AX foci in cancer cells. The present study corroborates and provides a mechanism to the hypothesis that suggests metal-mediated oxidation of catecholamines contributes to the pathogenesis of neurodegenerative diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

Analysis of the Damage Mechanism Related to CO2 Laser Cochleostomy on Guinea Pig Cochlea

PubMed Central

Liu, Xiang; Qian, Xiao-qing; Ma, Rui

2016-01-01

Different types of lasers have been used in inner ear surgery. Therefore, it is of the utmost importance to avoid damage to the inner ear (e.g., hyperthermia and acoustic effects) caused by the use of such lasers. The aim of this study was to use a high powered fibre-enabled CO2 laser (10 W, 606 J/cm2) to perform cochleostomies on guinea pig cochlea and to investigate the possible laser-induced damage mechanisms. The temperature changes in the round window membrane, auditory evoked brainstem response, and morphological of the hair cells were measured and recorded before and after laser application. All of the outcomes differed in comparison with the control group. A rise in temperature and subsequent increased hearing loss were observed in animals that underwent surgery with a 10 W CO2 laser. These findings correlated with increased injury to the cochlear ultrastructure and a higher positive expression of E-cadherin and β-catenin in the damaged organ of Corti. We assume that enhanced cell-cell adhesion and the activated β-catenin-related canonical Wnt-signalling pathway may play a role in the protection of the cochlea to prevent further damage. PMID:28070426

Preventive role of lens antioxidant defense mechanism against riboflavin-mediated sunlight damaging of lens crystallins.

PubMed

Anbaraki, Afrooz; Khoshaman, Kazem; Ghasemi, Younes; Yousefi, Reza

2016-10-01

The main components of sunlight reaching the eye lens are UVA and visible light exerting their photo-damaging effects indirectly by the aid of endogenous photosensitizer molecules such as riboflavin (RF). In this study, lens proteins solutions were incubated with RF and exposed to the sunlight. Then, gel mobility shift analysis and different spectroscopic assessments were applied to examine the structural damaging effects of solar radiation on these proteins. Exposure of lens proteins to direct sunlight, in the presence of RF, leads to marked structural crosslinking, oligomerization and proteolytic instability. These structural damages were also accompanied with reduction in the emission fluorescence of Trp and Tyr and appearance of a new absorption peak between 300 and 400nm which can be related to formation of new chromophores. Also, photo-oxidation of lens crystallins increases their oligomeric size distribution as examined by dynamic light scattering analysis. The above mentioned structural insults, as potential sources of sunlight-induced senile cataract and blindness, were significantly attenuated in the presence of ascorbic acid and glutathione which are two important components of lens antioxidant defense system. Therefore, the powerful antioxidant defense mechanism of eye lens is an important barrier against molecular photo-damaging effects of solar radiations during the life span. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of Ionizing Radiation on Biological Molecules—Mechanisms of Damage and Emerging Methods of Detection

PubMed Central

Reisz, Julie A.; Bansal, Nidhi; Qian, Jiang; Zhao, Weiling

2014-01-01

Abstract Significance: The detrimental effects of ionizing radiation (IR) involve a highly orchestrated series of events that are amplified by endogenous signaling and culminating in oxidative damage to DNA, lipids, proteins, and many metabolites. Despite the global impact of IR, the molecular mechanisms underlying tissue damage reveal that many biomolecules are chemoselectively modified by IR. Recent Advances: The development of high-throughput “omics” technologies for mapping DNA and protein modifications have revolutionized the study of IR effects on biological systems. Studies in cells, tissues, and biological fluids are used to identify molecular features or biomarkers of IR exposure and response and the molecular mechanisms that regulate their expression or synthesis. Critical Issues: In this review, chemical mechanisms are described for IR-induced modifications of biomolecules along with methods for their detection. Included with the detection methods are crucial experimental considerations and caveats for their use. Additional factors critical to the cellular response to radiation, including alterations in protein expression, metabolomics, and epigenetic factors, are also discussed. Future Directions: Throughout the review, the synergy of combined “omics” technologies such as genomics and epigenomics, proteomics, and metabolomics is highlighted. These are anticipated to lead to new hypotheses to understand IR effects on biological systems and improve IR-based therapies. Antioxid. Redox Signal. 21: 260–292. PMID:24382094

Potential Application of Viral Empty Capsids for the Treatment of Acute Lung Injury/Acute Respiratory Distress Syndrome

DTIC Science & Technology

2016-07-01

Particles (VLPs). The rationale is based on the beneficial effect of SV40 VLPs on an Acute Kidney Injury (AKI) model in mice, previously demonstrated...signaling which, as was demonstrated, protect mice kidneys from apoptosis, necrosis and consequent damage induced by a toxic (mercury) insult, increasing...recombinant VP1, without any genetic material. Using a mouse model for toxic Acute Kidney Injury (AKI), we demonstrated that systemic

Sub-surface mechanical damage distributions during grinding of fused silica

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

Suratwala, T I; Wong, L L; Miller, P E

2005-11-28

The distribution and characteristics of surface cracking (i.e. sub-surface damage or SSD) formed during standard grinding processes has been investigated on fused silica glass. The SSD distributions of the ground surfaces were determined by: (1) creating a shallow (18-108 {micro}m) wedge/taper on the surface by magneto-rheological finishing; (2) exposing the SSD by HF acid etching; and (3) performing image analysis of the observed cracks from optical micrographs taken along the surface taper. The observed surface cracks are characterized as near-surface lateral and deeper trailing indent type fractures (i.e., chatter marks). The SSD depth distributions are typically described by a singlemore » exponential distribution followed by an asymptotic cutoff in depth (c{sub max}). The length of the trailing indent is strongly correlated with a given process. Using established fracture indentation relationships, it is shown that only a small fraction of the abrasive particles are being mechanically loaded and causing fracture, and it is likely the larger particles in the abrasive particle size distribution that bear the higher loads. The SSD depth was observed to increase with load and with a small amount of larger contaminant particles. Using a simple brittle fracture model for grinding, the SSD depth distribution has been related to the SSD length distribution to gain insight into ''effective'' size distribution of particles participating in the fracture. Both the average crack length and the surface roughness were found to scale linearly with the maximum SSD depth (c{sub max}). These relationships can serve as useful rules-of-thumb for nondestructively estimating SSD depth and to identify the process that caused the SSD. In certain applications such as high intensity lasers, SSD on the glass optics can serve as a reservoir for minute amounts of impurities that absorb the high intensity laser light and lead to subsequent laser-induced surface damage. Hence a more

[Diagnosis of acute heart failure and relevance of biomarkers in elderly patients].

PubMed

Ruiz Ortega, Raúl Antonio; Manzano, Luis; Montero-Pérez-Barquero, Manuel

2014-03-01

Diagnosis of acute heart failure (HF) is difficult in elderly patients with multiple comorbidities. Risk scales and classification criteria based exclusively on clinical manifestations, such as the Framingham scales, lack sufficient specificity. In addition to clinical manifestations, diagnosis should be based on two key factors: natriuretic peptides and echocardiographic study. When there is clinical suspicion of acute HF, a normal natriuretic peptide level will rule out this process. When a consistent clinical suspicion is present, an echocardiographic study should also be performed. Diagnosis of HF with preserved ejection fraction (HF/pEF) requires detection of an enlarged left atrium or the presence of parameters of diastolic dysfunction. Elevation of cardiac biomarkers seems to be due to myocardial injury and the compensatory mechanisms of the body against this injury (hormone and inflammatory response and repair mechanisms). Elevation of markers of cardiac damage (troponins and natriuretic peptides) have been shown to be useful both in the diagnosis of acute HF and in prediction of outcome. MMP-2 could be useful in the diagnosis of HF/pEF. In addition to biomarkers with diagnostic value, other biomarkers are helpful in prognosis in the acute phase of HF, such as biomarkers of renal failure (eGFR, cystatin and urea), inflammation (cytokines and CRP), and the cell regeneration marker, galectin-3. A promising idea that is under investigation is the use of panels of biomarkers, which could allow more accurate diagnosis and prognosis of acute HF. Copyright © 2014 Elsevier España, S.L. All rights reserved.

Radiation-induced effects on the mechanical properties of natural ZrSiO4: double cascade-overlap damage accumulation

NASA Astrophysics Data System (ADS)

Beirau, Tobias; Nix, William D.; Pöllmann, Herbert; Ewing, Rodney C.

2018-05-01

Several different models are known to describe the structure-dependent radiation-induced damage accumulation process in materials (e.g. Gibbons Proc IEEE 60:1062-1096, 1972; Weber Nuc Instr Met Phys Res B 166-167:98-106, 2000). In the literature, two different models of damage accumulation due to α-decay events in natural ZrSiO4 (zircon) have been described. The direct impact damage accumulation model is based on amorphization occurring directly within the collision cascade. However, the double cascade-overlap damage accumulation model predicts that amorphization will only occur due to the overlap of disordered domains within the cascade. By analyzing the dose-dependent evolution of mechanical properties (i.e., Poisson's ratios, compliance constants, elastic modulus, and hardness) as a measure of the increasing amorphization, we provide support for the double cascade-overlap damage accumulation model. We found no evidence to support the direct impact damage accumulation model. Additionally, the amount of radiation damage could be related to an anisotropic-to-isotropic transition of the Poisson's ratio for stress along and perpendicular to the four-fold c-axis and of the related compliance constants of natural U- and Th-bearing zircon. The isotropification occurs in the dose range between 3.1 × and 6.3 × 1018 α-decays/g.

Radiation-induced effects on the mechanical properties of natural ZrSiO4: double cascade-overlap damage accumulation

NASA Astrophysics Data System (ADS)

Beirau, Tobias; Nix, William D.; Pöllmann, Herbert; Ewing, Rodney C.

2017-11-01

Several different models are known to describe the structure-dependent radiation-induced damage accumulation process in materials (e.g. Gibbons Proc IEEE 60:1062-1096, 1972; Weber Nuc Instr Met Phys Res B 166-167:98-106, 2000). In the literature, two different models of damage accumulation due to α-decay events in natural ZrSiO4 (zircon) have been described. The direct impact damage accumulation model is based on amorphization occurring directly within the collision cascade. However, the double cascade-overlap damage accumulation model predicts that amorphization will only occur due to the overlap of disordered domains within the cascade. By analyzing the dose-dependent evolution of mechanical properties (i.e., Poisson's ratios, compliance constants, elastic modulus, and hardness) as a measure of the increasing amorphization, we provide support for the double cascade-overlap damage accumulation model. We found no evidence to support the direct impact damage accumulation model. Additionally, the amount of radiation damage could be related to an anisotropic-to-isotropic transition of the Poisson's ratio for stress along and perpendicular to the four-fold c-axis and of the related compliance constants of natural U- and Th-bearing zircon. The isotropification occurs in the dose range between 3.1 × and 6.3 × 1018 α-decays/g.