[Rapidly progressive glomerulonephritis: a diagnostic and therapeutic emergency].

PubMed

Halfon, Matthieu; Teta, Daniel; Rotman, Samuel; Pruijm, Menno; Humbert, Antoine

2014-02-26

Rapidly progressive glomerulonephritis (RPG) is a rare clinical syndrome characterized by kidney damage that can lead to irreversible kidney failure. RPG can be caused by primary glomerular disease or can be part of a systemic autoimmune disorder. All RPG have a similar pathophysiology (proliferation of cells in Bowman's capsule and formation of crescents) and clinical evolution (rapidly progressive kidney failure with proteinuria and an active urine sediment). Immunosuppressive therapy and sometimes plasma exchanges are required. Overall- and kidney survival are closely linked to the blood creatinine level at presentation, the percentage of damaged glomeruli, and to the underlying cause. RPG is therefore a diagnostic and therapeutic emergency that needs quick referral to a nephrologist.

Ocular Involvement of Behçet's Syndrome: a Comprehensive Review.

PubMed

Ozyazgan, Yilmaz; Ucar, Didar; Hatemi, Gulen; Yazici, Yusuf

2015-12-01

Behçet's syndrome (BS) is a vasculitis involving several organ systems including the eyes. Ocular involvement is one of the most disabling complications of BS, causing loss of vision that may progress to blindness if left untreated. The typical form of ocular involvement is a relapsing and remitting panuveitis and retinal vasculitis. Initial attacks may spontaneously improve and subsequently disappear in a few weeks but tend to recur if left untreated. Destructive and recurrent attacks, especially with posterior segment and retina involvement, may cause irreversible ocular structural changes and permanent damage in sensory retina, resulting in loss of vision. The risk of irreversible damage to ocular tissue which may result in loss of vision warrants early and intensive treatment especially in patients at high risk such as young men who tend to follow an aggressive disease course. The management strategy involves rapid suppression of inflammation during the attacks and prevention of recurrent attacks. Local and systemic measures including immunosuppressives, corticosteroids, and biologic agents are used for this purpose. Surgery may be required in selected cases. The prognosis of eye involvement has greatly improved over the last decades with the effective use of immunosuppressives.

Study of RF breakdown and multipacting in accelerator components

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

Pande, Manjiri; Singh, P., E-mail: manjiri@barc.gov.in, E-mail: psingh@barc.gov.in

2014-07-01

Radio frequency (RF) structures that are part of accelerators and energy sources, operate with sinusoidally varying electromagnetic fields under high RF energy. Here, RF breakdown and multipacting take place in RF structures and limit their performance. Electron field emission processes in a RF structure are precursors for breakdown processes. RF breakdown is a major phenomena affecting and causing the irreversible damage to RF structures. Breakdown rate and the damage induced by the breakdowns are its important properties. The damage is related to power absorbed during breakdown, while the breakdown rate is determined by the amplitudes of surface electric and magneticmore » fields, geometry, metal surface preparation and conditioning history. It limits working power and produces irreversible surface damage. The breakdown limit depends on the RF circuit, structure geometry, RF frequency, input RF power, pulse width, materials used, surface processing technique and surface electric and magnetic fields. Multipactor (MP) is a low power, electron multiplication based resonance breakdown phenomenon in vacuum and is often observed in RF structures. A multipactor discharge is undesirable, as it can create a reactive component that detunes the resonant cavities and components, generates noise in communication system and induces gas desorption from the conductor surfaces. In RF structures, certain conditions are required to generate multipacting. (author)« less

Irreversible entropy model for damage diagnosis in resistors

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

Cuadras, Angel, E-mail: angel.cuadras@upc.edu; Crisóstomo, Javier; Ovejas, Victoria J.

2015-10-28

We propose a method to characterize electrical resistor damage based on entropy measurements. Irreversible entropy and the rate at which it is generated are more convenient parameters than resistance for describing damage because they are essentially positive in virtue of the second law of thermodynamics, whereas resistance may increase or decrease depending on the degradation mechanism. Commercial resistors were tested in order to characterize the damage induced by power surges. Resistors were biased with constant and pulsed voltage signals, leading to power dissipation in the range of 4–8 W, which is well above the 0.25 W nominal power to initiate failure. Entropymore » was inferred from the added power and temperature evolution. A model is proposed to understand the relationship among resistance, entropy, and damage. The power surge dissipates into heat (Joule effect) and damages the resistor. The results show a correlation between entropy generation rate and resistor failure. We conclude that damage can be conveniently assessed from irreversible entropy generation. Our results for resistors can be easily extrapolated to other systems or machines that can be modeled based on their resistance.« less

Prediction of specific damage or infarction from the measurement of tissue impedance following repetitive brain ischaemia in the rat.

PubMed

Klein, H C; Krop-Van Gastel, W; Go, K G; Korf, J

1993-02-01

The development of irreversible brain damage during repetitive periods of hypoxia and normoxia was studied in anaesthetized rats with unilateral occlusion of the carotid artery (modified Levine model). Rats were exposed to 10 min hypoxia and normoxia until severe damage developed. As indices of damage, whole striatal tissue impedance (reflecting cellular water uptake), sodium/potassium contents (due to exchange with blood). Evans Blue staining (blood-brain barrier [BBB] integrity) and silver staining (increased in irreversibly damaged neurons) were used. A substantial decrease in blood pressure was observed during the hypoxic periods possibly producing severe ischaemia. Irreversibly increased impedance, massive changes in silver staining, accumulation of whole tissue Na and loss of K occurred only after a minimum of two periods of hypoxia, but there was no disruption of the BBB. Microscopic examination of tissue sections revealed that cell death was selective with reversible impedance changes, but became massive and non-specific after irreversible increase of the impedance. The development of brain infarcts could, however, not be predicted from measurements of physiological parameters in the blood. We suggest that the development of cerebral infarction during repetitive periods of hypoxia may serve as a model for the development of brain damage in a variety of clinical conditions. Furthermore, the present model allows the screening of potential therapeutic measuring of the prevention and treatment of both infarction and selective cell death.

NOVELTIES IN MEDICAL TREATMENT OF GLAUCOMA

PubMed Central

Cornel, Ştefan; Mihaela, Timaru Cristina; Adriana, Iliescu Daniela; Mehdi, Batras; Algerino, De Simone

2015-01-01

The purpose of this study is to review the current medical treatment and the new and better alternatives for patients with glaucoma. Glaucoma refers to a group of related eye disorders that have in common an optic neuropathy associated with visual function loss. It is one of the leading causes of irreversible blindness worldwide. Glaucoma can damage vision gradually so it may not be noticed until the disease is at an advanced stage. Early diagnosis and treatment can minimize or prevent optic nerve damage and limit glaucoma-related vision loss. Nowadays, research continues for the improvement of current medical treatment. PMID:26978866

Chilling Stress—The Key Predisposing Factor for Causing Alternaria alternata Infection and Leading to Cotton (Gossypium hirsutum L.) Leaf Senescence

PubMed Central

Zhao, Jingqing; Li, Sha; Jiang, Tengfei; Liu, Zhi; Zhang, Wenwei; Jian, Guiliang; Qi, Fangjun

2012-01-01

Leaf senescence plays a vital role in nutrient recycling and overall capacity to assimilate carbon dioxide. Cotton premature leaf senescence, often accompanied with unexpected short-term low temperature, has been occurring with an increasing frequency in many cotton-growing areas and causes serious reduction in yield and quality of cotton. The key factors for causing and promoting cotton premature leaf senescence are still unclear. In this case, the relationship between the pre-chilling stress and Alternaria alternata infection for causing cotton leaf senescence was investigated under precisely controlled laboratory conditions with four to five leaves stage cotton plants. The results showed short-term chilling stress could cause a certain degree of physiological impairment to cotton leaves, which could be recovered to normal levels in 2–4 days when the chilling stresses were removed. When these chilling stress injured leaves were further inoculated with A. alternata, the pronounced appearance and development of leaf spot disease, and eventually the pronounced symptoms of leaf senescence, occurred on these cotton leaves. The onset of cotton leaf senescence at this condition was also reflected in various physiological indexes such as irreversible increase in malondialdehyde (MDA) content and electrolyte leakage, irreversible decrease in soluble protein content and chlorophyll content, and irreversible damage in leaves' photosynthesis ability. The presented results demonstrated that chilling stress acted as the key predisposing factor for causing A. alternata infection and leading to cotton leaf senescence. It could be expected that the understanding of the key factors causing and promoting cotton leaf senescence would be helpful for taking appropriate management steps to prevent cotton premature leaf senescence. PMID:22558354

Silica crystals and aluminum salts mediate NALP-3 inflammasome activation via phagosomal destabilization

PubMed Central

Hornung, Veit; Bauernfeind, Franz; Halle, Annett; Samstad, Eivind O.; Kono, Hajime; Rock, Kenneth L.; Fitzgerald, Katherine A.; Latz, Eicke

2010-01-01

Inhalation of silica crystals causes inflammation in the alveolar space. Prolonged silica exposure can lead to the development of silicosis, an irreversible, fibrotic pulmonary disease. The mechanisms by which silica and other crystals activate immune cells are not well understood. Here, we demonstrate that silica and aluminum salt crystals activate the NALP3 inflammasome. NALP3 activation requires crystal phagocytosis and crystal uptake leads to lysosomal damage and rupture. Sterile lysosomal damage is also sufficient to induce NALP3 activation and inhibition of phagosomal acidification or cathepsin B impairs NALP3 activation. These results indicate that the NALP3 inflammasome can sense lysosomal damage induced by various means as an endogenous danger signal. PMID:18604214

Characteristics of shear damage for 60Sn-40Pb solder material

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

Fang, H.E.; Chow, C.L.; Wei, Y.

This paper presents an investigation of the development of a continuum damage model capable of accurately analyzing shear damage in 60Sn-40Pb solder material. Based on the theory of damage mechanics, an internal state variable known as the damage variable is introduced to characterize material degradation caused by the change of material microstructures under load. A damage surface in stress space is proposed to quantify damage initiation and its successive expanding surfaces to represent damage hardening. With the aid of irreversible thermodynamics, the damage-coupled constitutive equations and the damage evolution equations are established. A failure criterion is proposed based on themore » accumulation of overall damage in the material. The damage model is implemented in a general purpose finite element program ABAQUS through its user-defined material subroutine UMAT. The program is applied to predict shear deformation in a notched specimen. The predicted failure mode and maximum load agree well with those measured experimentally. The effect of finite element meshing on the numerical results is also examined and discussed.« less

Gain-of-function somatic mutations contribute to inflammation and blood vessel damage that lead to Alzheimer dementia: a hypothesis.

PubMed

Marchesi, Vincent T

2016-02-01

Amyloid deposits are a characteristic feature of advanced Alzheimer dementia (AD), but whether they initiate the disease or are a consequence of it remains an unsettled question. To explore an alternative pathogenic mechanism, I propose that the triggering events that begin the pathogenic cascade are not amyloid deposits but damaged blood vessels caused by inflammatory reactions that lead to ischemia, amyloid accumulation, axonal degeneration, synaptic loss, and eventually irreversible neuronal cell death. Inflammation and blood vessel damage are well recognized complications of AD, but what causes them and why the cerebral microvasculature is affected have never been adequately addressed. Because heritable autosomal dominant mutations of NLRP3, APP, TREX1, NOTCH3, and Col4A1 are known to provoke inflammatory reactions and damage the brain in a wide variety of diseases, I propose that one or more low abundant, gain-of-function somatic mutations of the same 5 gene families damage the microvasculature of the brain that leads to dementia. This implies that the pathogenic triggers that lead to AD are derived not from external invaders or amyloid but from oxidative damage of our own genes. © FASEB.

Nanopore formation in neuroblastoma cells following ultrashort electric pulse exposure

NASA Astrophysics Data System (ADS)

Roth, Caleb C.; Payne, Jason A.; Wilmink, Gerald J.; Ibey, Bennett L.

2011-03-01

Ultrashort or nanosecond electrical pulses (USEP) cause repairable damage to the plasma membranes of cells through formation of nanopores. These nanopores are able to pass small ions such as sodium, calcium, and potassium, but remain impermeable to larger molecules like trypan blue and propidium iodide. What remains uncertain is whether generation of nanopores by ultrashort electrical pulses can inhibit action potentials in excitable cells. In this paper, we explored the sensitivity of excitable cells to USEP using Calcium Green AM 1 ester fluorescence to measure calcium uptake indicative of nanopore formation in the plasma membrane. We determined the threshold for nanopore formation in neuroblastoma cells for three pulse parameters (amplitude, pulse width, and pulse number). Measurement of such thresholds will guide future studies to determine if USEP can inhibit action potentials without causing irreversible membrane damage.

DNA damage during S-phase mediates the proliferation-quiescence decision in the subsequent G1 via p21 expression

PubMed Central

Barr, Alexis R.; Cooper, Samuel; Heldt, Frank S.; Butera, Francesca; Stoy, Henriette; Mansfeld, Jörg; Novák, Béla; Bakal, Chris

2017-01-01

Following DNA damage caused by exogenous sources, such as ionizing radiation, the tumour suppressor p53 mediates cell cycle arrest via expression of the CDK inhibitor, p21. However, the role of p21 in maintaining genomic stability in the absence of exogenous DNA-damaging agents is unclear. Here, using live single-cell measurements of p21 protein in proliferating cultures, we show that naturally occurring DNA damage incurred over S-phase causes p53-dependent accumulation of p21 during mother G2- and daughter G1-phases. High p21 levels mediate G1 arrest via CDK inhibition, yet lower levels have no impact on G1 progression, and the ubiquitin ligases CRL4Cdt2 and SCFSkp2 couple to degrade p21 prior to the G1/S transition. Mathematical modelling reveals that a bistable switch, created by CRL4Cdt2, promotes irreversible S-phase entry by keeping p21 levels low, preventing premature S-phase exit upon DNA damage. Thus, we characterize how p21 regulates the proliferation-quiescence decision to maintain genomic stability. PMID:28317845

Comparison of heat-testing methodology.

PubMed

Bierma, Mark M; McClanahan, Scott; Baisden, Michael K; Bowles, Walter R

2012-08-01

Patients with irreversible pulpitis occasionally present with a chief complaint of sensitivity to heat. To appropriately diagnose the offending tooth, a variety of techniques have been developed to reproduce this chief complaint. Such techniques cause temperature increases that are potentially damaging to the pulp. Newer electronic instruments control the temperature of a heat-testing tip that is placed directly against a tooth. The aim of this study was to determine which method produced the most consistent and safe temperature increase within the pulp. This consistency facilitates the clinician's ability to differentiate between a normal pulp and irreversible pulpitis. Four operators applied the following methods to each of 4 extracted maxillary premolars (for a total of 16 trials per method): heated gutta-percha, heated ball burnisher, hot water, and a System B unit or Elements unit with a heat-testing tip. Each test was performed for 60 seconds, and the temperatures were recorded via a thermocouple in the pulp chamber. Analysis of the data was performed by using the intraclass correlation coefficient. The least consistent warming was found with hot water. The heat-testing tip also demonstrated greater consistency between operators compared with the other methods. Hot water and the heated ball burnisher caused temperature increases high enough to damage pulp tissue. The Elements unit with a heat-testing tip provides the most consistent warming of the dental pulp. Copyright © 2012 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Attribution of irreversible loss to anthropogenic climate change

NASA Astrophysics Data System (ADS)

Huggel, Christian; Bresch, David; Hansen, Gerrit; James, Rachel; Mechler, Reinhard; Stone, Dáithí; Wallimann-Helmer, Ivo

2016-04-01

The Paris Agreement (2015) under the UNFCCC has anchored loss and damage in a separate article which specifies that understanding and support should be enhanced in areas addressing loss and damage such as early warning, preparedness, insurance and resilience. Irreversible loss is a special category under loss and damage but there is still missing clarity over what irreversible loss actually includes. Many negative impacts of climate change may be handled or mitigated by existing risk management, reduction and absorption approaches. Irreversible loss, however, is thought to be insufficiently addressed by risk management. Therefore, countries potentially or actually affected by irreversible loss are calling for other measures such as compensation, which however is highly contested in international climate policy. In Paris (2015) a decision was adopted that loss and damage as defined in the respective article of the agreement does not involve compensation and liability. Nevertheless, it is likely that some sort of mechanism will eventually need to come into play for irreversible loss due to anthropogenic climate change, which might involve compensation, other forms of non-monetary reparation, or transformation. Furthermore, climate litigation has increasingly been attempted to address negative effects of climate change. In this context, attribution is important to understand the drivers of change, what counts as irreversible loss due to climate change, and, possibly, who or what is responsible. Here we approach this issue by applying a detection and attribution perspective on irreversible loss. We first analyze detected climate change impacts as assessed in the IPCC Fifth Assessment Report. We distinguish between irreversible loss in physical, biological and human systems, and accordingly identify the following candidates of irreversible loss in these systems: loss of glaciers and ice sheets, loss of subsurface ice (permafrost) and related loss of lake systems; loss of land area due to coastal and hillslope erosion and sea level change; loss of plant and animal species, loss of ecosystems and biodiversity; loss of human lives, homelands, and cultural identity. Attribution to anthropogenic climate change is analyzed based on recent progress following from the IPCC AR5. Generally, high confidence in attributing irreversible loss to anthropogenic climate change is found in physical systems and more specifically in cryosphere environments, both in mountain and polar regions. Detected loss in terrestrial ecosystems has typically low confidence in attribution whereas loss in some ocean ecosystems (corals) has high confidence. Impacts in human systems that may be classified as irreversible loss are of low confidence in terms of attribution except for the Arctic where higher confidence for a relation with anthropogenic emissions was found. Our analysis suggests that scientific progress in detection and attribution is now at a level that would likely allow policy, or courts, to define mechanisms, or take decisions, as related to irreversible loss in many cryosphere systems. On the other hand, policy may need to consider that at least in the near future it will be difficult to establish clear tracks between irreversible loss in most human systems and anthropogenic climate change, a domain, which however is at the forefront of discussions. We end our discussion with setting out ideas for further clarification of different categories of irreversible loss, including in human systems, and the role of attribution in any policy or legal mechanism in order to help in the development of just and sensible solutions.

Oxidative stress and pathology in muscular dystrophies: focus on protein thiol oxidation and dysferlinopathies.

PubMed

Terrill, Jessica R; Radley-Crabb, Hannah G; Iwasaki, Tomohito; Lemckert, Frances A; Arthur, Peter G; Grounds, Miranda D

2013-09-01

The muscular dystrophies comprise more than 30 clinical disorders that are characterized by progressive skeletal muscle wasting and degeneration. Although the genetic basis for many of these disorders has been identified, the exact mechanism for pathogenesis generally remains unknown. It is considered that disturbed levels of reactive oxygen species (ROS) contribute to the pathology of many muscular dystrophies. Reactive oxygen species and oxidative stress may cause cellular damage by directly and irreversibly damaging macromolecules such as proteins, membrane lipids and DNA; another major cellular consequence of reactive oxygen species is the reversible modification of protein thiol side chains that may affect many aspects of molecular function. Irreversible oxidative damage of protein and lipids has been widely studied in Duchenne muscular dystrophy, and we have recently identified increased protein thiol oxidation in dystrophic muscles of the mdx mouse model for Duchenne muscular dystrophy. This review evaluates the role of elevated oxidative stress in Duchenne muscular dystrophy and other forms of muscular dystrophies, and presents new data that show significantly increased protein thiol oxidation and high levels of lipofuscin (a measure of cumulative oxidative damage) in dysferlin-deficient muscles of A/J mice at various ages. The significance of this elevated oxidative stress and high levels of reversible thiol oxidation, but minimal myofibre necrosis, is discussed in the context of the disease mechanism for dysferlinopathies, and compared with the situation for dystrophin-deficient mdx mice. © 2013 The Authors Journal compilation © 2013 FEBS.

Drug-induced corneal damage.

PubMed

2014-04-01

Corneal damage can have a variety of causes, including infections, chemical splashes, environmental factors (radiation, trauma, contact lenses, etc.), and systemic diseases (genetic, autoimmune, inflammatory, metabolic, etc.). A wide range of drugs can also damage the cornea. The severity of drug-induced corneal changes can range from simple asymptomatic deposits to irreversible, sight-threatening damage. Several factors can influence the onset of corneal lesions. Some factors, such as the dose, are treatment-related, while others such as contact lenses, are patient-related. A variety of mechanisms may be involved, including corneal dryness, changes in the corneal epithelium, impaired wound healing and deposits. Many drugs can damage the cornea through direct contact, after intraocular injection or instillation, including VEGF inhibitors, anti-inflammatory drugs, local anaesthetics, glaucoma drugs, fluoroquinolones, and preservatives. Some systemically administered drugs can also damage the cornea, notably cancer drugs, amiodarone and isotretinoin. Vulnerable patients should be informed of this risk if they are prescribed a drug with the potential to damage the cornea so that they can identify problems in a timely manner. It may be necessary to discontinue the suspect drug when signs and symptoms of corneal damage occur.

Effects of A NBC (Nuclear, Biological, and Chemical) Nutrient Solution on Physiological and Psychological Status during Sustained Activity in the Heat

DTIC Science & Technology

1987-07-17

of sugar (3). Kety (14) reported that a significant decrease in the blood glucose level is consistently associated with manifestations of impaired...Brozek J, Keys A. Relationship of speed of motor reaction to blood sugar level during acute starvation in man, abstracted. Fed Proc 1945;4:28. 9. Blom...profound low blood sugar can cause irreversible brain damage (21,30). Since hypoglycemia did not develop, it was not possible to assess the effects of

Fabry disease: Review and experience during newborn screening.

PubMed

Hsu, Ting-Rong; Niu, Dau-Ming

2018-05-01

Fabry disease (FD) is an X-linked lysosomal storage disease and is the result of mutation in the α-Galactosidase A gene; such mutations cause a deficiency in α-Galactosidase A enzyme and an accumulation of glycosphingolipid in tissue. Affected males with classic FD have little or no enzyme activity and have an early onset of symptoms and signs, including acroparesthesias, hypohidrosis, angiokeratomas, gastrointestinal dysfunction and/or a characteristic corneal dystrophy during childhood/adolescence. Males with late-onset FD who have residual enzyme activity develop progressive multi-systemic involvement that leads to renal failure and hypertrophic cardiomyopathy, as well as cerebrovascular disease; these events mostly occur during the fourth to seventh decades of life. Heterozygous females can develop vital organ damage that in turn causes severe morbidity and mortality; these symptoms may be as severe as those in affected males. For the treatable disease, this review aims to raise awareness of early recognition and further management of FD based on newborn screening. As newborn screening for FD has been implemented worldwide, it allows the early detection of individuals with Fabry mutations. Based on screening studies, the prevalence of the later-onset type FD is much higher than that of classical type FD. Newborn screening studies have also revealed that patients with FD may develop insidious but ongoing irreversible organ damage. The timing of enzyme replacement therapy, which is able to stabilize the progression of disease, is important in order to prevent irreversible organ damage. Therapies that may become available in the future include pharmacological chaperones and substrate reduction therapy, both of which are still under investigation as ways of improving the health of individuals with FD. Copyright © 2017 Elsevier Inc. All rights reserved.

The Effect of Cannabis on the Brain: Can it cause brain anomalies that lead to increased risk for Schizophrenia?

PubMed Central

DeLisi, Lynn E.

2015-01-01

Purpose of This Review This review explores what is known about cannabis’s association with schizophrenia, cannabis’s effects on the brain, and whether the brain changes known to be present in schizophrenia could be caused by cannabis and thus lead to a psychosis. Recent Findings The heavy use of cannabis is known to be associated with some adverse consequences, such as the occurrence of acute psychotic episodes and the development of chronic schizophrenia in some people even after its use has terminated. Recent studies have produced controversy about whether cannabis in heavy use can cause irreversible brain damage, particularly to adolescents and thus, whether a chronic psychosis could be a result of brain changes caused by cannabis. Summary From the evidence that exists, it appears that the above view is unlikely and that cannabis may even have benign effects on brain structure, not producing deleterious damage. However, its neurochemical interactions with the dopaminergic pathway may, particularly in genetically vulnerable individuals, have adverse consequences. PMID:18332661

History-independent cyclic response of nanotwinned metals

NASA Astrophysics Data System (ADS)

Pan, Qingsong; Zhou, Haofei; Lu, Qiuhong; Gao, Huajian; Lu, Lei

2017-11-01

Nearly 90 per cent of service failures of metallic components and structures are caused by fatigue at cyclic stress amplitudes much lower than the tensile strength of the materials involved. Metals typically suffer from large amounts of cumulative, irreversible damage to microstructure during cyclic deformation, leading to cyclic responses that are unstable (hardening or softening) and history-dependent. Existing rules for fatigue life prediction, such as the linear cumulative damage rule, cannot account for the effect of loading history, and engineering components are often loaded by complex cyclic stresses with variable amplitudes, mean values and frequencies, such as aircraft wings in turbulent air. It is therefore usually extremely challenging to predict cyclic behaviour and fatigue life under a realistic load spectrum. Here, through both atomistic simulations and variable-strain-amplitude cyclic loading experiments at stress amplitudes lower than the tensile strength of the metal, we report a history-independent and stable cyclic response in bulk copper samples that contain highly oriented nanoscale twins. We demonstrate that this unusual cyclic behaviour is governed by a type of correlated ‘necklace’ dislocation consisting of multiple short component dislocations in adjacent twins, connected like the links of a necklace. Such dislocations are formed in the highly oriented nanotwinned structure under cyclic loading and help to maintain the stability of twin boundaries and the reversible damage, provided that the nanotwins are tilted within about 15 degrees of the loading axis. This cyclic deformation mechanism is distinct from the conventional strain localizing mechanisms associated with irreversible microstructural damage in single-crystal, coarse-grained, ultrafine-grained and nanograined metals.

Two-dimensional strain gradient damage modeling: a variational approach

NASA Astrophysics Data System (ADS)

Placidi, Luca; Misra, Anil; Barchiesi, Emilio

2018-06-01

In this paper, we formulate a linear elastic second gradient isotropic two-dimensional continuum model accounting for irreversible damage. The failure is defined as the condition in which the damage parameter reaches 1, at least in one point of the domain. The quasi-static approximation is done, i.e., the kinetic energy is assumed to be negligible. In order to deal with dissipation, a damage dissipation term is considered in the deformation energy functional. The key goal of this paper is to apply a non-standard variational procedure to exploit the damage irreversibility argument. As a result, we derive not only the equilibrium equations but, notably, also the Karush-Kuhn-Tucker conditions. Finally, numerical simulations for exemplary problems are discussed as some constitutive parameters are varying, with the inclusion of a mesh-independence evidence. Element-free Galerkin method and moving least square shape functions have been employed.

Importance of iodine in pregnancy.

PubMed

Carreto-Molina, Nicolás; García-Solís, Pablo; Solís-S, Juan Carlos; Robles-Osorio, Ludivina; Hernández-Montiel, Hebert Luis; Vega-Malagón, Genaro

2012-09-01

Iodine is an essential constituent of thyroid hormones (TH). TH actively take part in critical periods of brain development during embryonic, fetal and postnatal stages. Therefore the absence of TH or iodine in these critical periods produces an irreversible brain damage. In fact, it is known that iodine deficiency is the leading cause of preventable brain damage worldwide. Because of the physiological adjustments during pregnancy iodine requirements increase significantly from 150 microg per day in non-pregnant adult women to 250 microg per day. Moreover, recent epidemiological studies around the world show that iodine intake during pregnancy is insufficient in many countries, even in developed countries like Australia, Spain and Italy. In the present work an overview of the importance of iodine nutrition during pregnancy is given.

Research on Splicing Method of Digital Relic Fragment Model

NASA Astrophysics Data System (ADS)

Yan, X.; Hu, Y.; Hou, M.

2018-04-01

In the course of archaeological excavation, a large number of pieces of cultural relics were unearthed, and the restoration of these fragments was done manually by traditional arts and crafts experts. In this process, cultural relics experts often try to splice the existing cultural relics, and then use adhesive to stick together the fragments of correct location, which will cause irreversible secondary damage to cultural relics. In order to minimize such damage, the surveyors combine 3D laser scanning with computer technology, and use the method of establishing digital cultural relics fragments model to make virtual splicing of cultural relics. The 3D software on the common market can basically achieve the model translation and rotation, using this two functions can be achieved manually splicing between models, mosaic records after the completion of the specific location of each piece of fragments, so as to effectively reduce the damage to the relics had tried splicing process.

An overview of the management of patients with chronic pancreatitis.

PubMed

Johnstone, Carolyn C

2016-11-23

Chronic pancreatitis is a complex inflammatory condition characterised by irreversible damage to the pancreas. This article explores the pathophysiology of this condition and its effects on pancreatic function. It outlines the causes and presenting features of chronic pancreatitis, as well as its effect on patients' quality of life and the changes to their lifestyle that are likely to be required. Chronic pancreatitis cannot be cured; therefore, treatment aims to control pain, manage problems associated with malabsorption, and assess and manage long-term complications that may develop, such as insulin dependence.

[Temperature-dependent changes in the microcirculation of the dental pulp].

PubMed

Raab, W H; Müller, H

1989-07-01

Laser Doppler flowmetry was used to study the changes in the blood flow within the dental pulp as a reaction to thermal stimuli between 17 degrees C and 57 degree C. Temperatures below 31 degrees C resulted in a reduction, temperatures above 43 degrees C in an increase in blood flow. Temperatures higher than 49 degrees C caused irreversible damage to the pulp's microcirculation. Experimental nerve blocks showed that the reactive increase is linked to the afferent rather than the sympathetic innervation of the tooth pulp.

Motes v. Hall County.

PubMed

1983-09-07

In a challenge to Georgia's involuntary sterilization statute, the state Supreme Court ruled that the standard of evidence required by the statute before granting a state-initiated sterilization petition did not meet constitutional requirements. Recognizing procreation as a fundamental right, the court held that authorization of involuntary sterilization of mental incompetents must be based on the elevated standard of "clear and convincing evidence" that the person is irreversibly and incurably mentally incompetent, whether by mental retardation or brain damage, and is unable to care for a child without causing serious mental of physical harm to the child.

[Severe vitamin B12 deficiency in infants breastfed by vegans].

PubMed

Roed, Casper; Skovby, Flemming; Lund, Allan Meldgaard

2009-10-19

Weight loss and reduction of motor skills resulted in paediatric evaluation of a 10-month-old girl and a 12-month-old boy. Both children suffered form anaemia and delayed development due to vitamin B12 deficiency caused by strict maternal vegan diet during pregnancy and nursing. Therapy with cyanocobalamin was instituted with remission of symptoms. Since infants risk irreversible neurologic damage following severe vitamin B12 deficiency, early diagnosis and treatment are mandatory. Vegan and vegetarian women should take vitamin B12 supplementation during the pregnancy and nursing period.

Acute Liver Failure including Acetaminophen Overdose

PubMed Central

Fontana, Robert J.

2008-01-01

Synopsis Acute liver failure (ALF) is a dramatic and highly unpredictable clinical syndrome defined by the sudden onset of coagulopathy and encephalopathy. Although many disease processes can cause ALF, acetaminophen overdose is the leading cause in the United States, and has a 66% chance of recovery with early N-acetylcysteine treatment and supportive care. Cerebral edema and infectious complications are notoriously difficult to detect and treat in ALF patients and may lead to irreversible brain damage and multi-organ failure. Emergency liver transplantation is associated with a 70% 1-year patient survival but 20% of listed patients die, highlighting the importance of early referral of ALF patients with a poor prognosis to a liver transplant center. PMID:18570942

Freezing does not alter multiscale tendon mechanics and damage mechanisms in tension.

PubMed

Lee, Andrea H; Elliott, Dawn M

2017-12-01

It is common in biomechanics to use previously frozen tissues, where it is assumed that the freeze-thaw process does not cause consequential mechanical or structural changes. We have recently quantified multiscale tendon mechanics and damage mechanisms using previously frozen tissue, where damage was defined as an irreversible change in the microstructure that alters the macroscopic mechanical parameters. Because freezing has been shown to alter tendon microstructures, the objective of this study was to determine if freezing alters tendon multiscale mechanics and damage mechanisms. Multiscale testing using a protocol that was designed to evaluate tendon damage (tensile stress-relaxation followed by unloaded recovery) was performed on fresh and previously frozen rat tail tendon fascicles. At both the fascicle and fibril levels, there was no difference between the fresh and frozen groups for any of the parameters, suggesting that there is no effect of freezing on tendon mechanics. After unloading, the microscale fibril strain fully recovered, and interfibrillar sliding only partially recovered, suggesting that the tendon damage is localized to the interfibrillar structures and that mechanisms of damage are the same in both fresh and previously frozen tendons. © 2017 New York Academy of Sciences.

Expansive Soil Crack Depth under Cumulative Damage

PubMed Central

Shi, Bei-xiao; Chen, Sheng-shui; Han, Hua-qiang; Zheng, Cheng-feng

2014-01-01

The crack developing depth is a key problem to slope stability of the expansive soil and its project governance and the crack appears under the roles of dry-wet cycle and gradually develops. It is believed from the analysis that, because of its own cohesion, the expansive soil will have a certain amount of deformation under pulling stress but without cracks. The soil body will crack only when the deformation exceeds the ultimate tensile strain that causes cracks. And it is also believed that, due to the combined effect of various environmental factors, particularly changes of the internal water content, the inherent basic physical properties of expansive soil are weakened, and irreversible cumulative damages are eventually formed, resulting in the development of expansive soil cracks in depth. Starting from the perspective of volumetric strain that is caused by water loss, considering the influences of water loss rate and dry-wet cycle on crack developing depth, the crack developing depth calculation model which considers the water loss rate and the cumulative damages is established. Both the proposal of water loss rate and the application of cumulative damage theory to the expansive soil crack development problems try to avoid difficulties in matrix suction measurement, which will surely play a good role in promoting and improving the research of unsaturated expansive soil. PMID:24737974

Subsidence problems related to the development of siliciclastic karst on the Citronelle Formation of southwestern Alabama

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

Isphording, W.C.; Flowers, G.C.

1985-01-01

The irreversible transformation of kaolinite to gibbsite and the concomitant negative volume change associated with the reaction has resulted in residential structural damage in Mobile, Alabama. Failure of the insurance company to honor damage resulting from a sinkhole collapse clause resulted in litigation. The main points of contention in the trial were: (1) were the small depressions in the owner's yard caused by dissolution of material, resulting in the formation of subteranean voids., (2) does the language used in the policy, i.e., We cover for damages caused by sinkhole collapse due to the dissolution of limestone or similar rock formations,more » mean that because the Citronelle Sand is a rock formation that the resident should recover for damage to his house. Evidence introduced for the plaintiff included x-ray diffractograms, SEM photographs and grain size analyses. A summary of literature on the development of karst in non-carbonate terranes was also produced x-ray diffractograms indicated that gibbsite was being formed in the vadose zone; SEM photographs clearly revealed the presence of euhedral gibbsite crystals on both quartz grains and kaolinite. Size analyses were offered to disprove the allegation that the subsidence was a piping effect caused solely by removal of the silt component. Mass-balance equations and chemical analyses of groundwater were used to demonstrate that not only was kaolinite altering to gibbsite, causing loss of volume, but that some quartz was also being taken into solution. After consideration of the evidence, the jury found in favor of the plaintiff and the resident was compensated for damage.« less

An unusual etiology in cold injury: Liquefied petroleum gas.

PubMed

Kapı, Emin; Bozkurt, Mehmet; Taylan Filinte, Gaye; Kuvat, Samet Vasfi; Alioğlu, Celal

2017-05-01

Cold injury is a condition that causes reversible and irreversible damage when tissues are exposed to cold. This injury occurs due to various etiologies, and the most commonly observed ones include contact with liquefied petroleum gas (LPG) used in households, vehicles, and industry. LPG is a type of gas stored in liquid state under high pressure within cylinders. LPG contains a mixture of propane and butane gases. Direct contact of these gases with the tissues has the potential to cause metabolic, toxic, and respiratory damage. In this study, we present the cases of four patients with cold injury in the face and upper extremity caused by a pressurized jet stream of liquid gas that escaped out of the valves of the LPG cylinders. The patients had bullous lesions in the upper extremities and the face and second- and third-degree cold injuries with fibrotic and necrotic areas. The superficial defects secondarily healed with minimal scarring, while the necrotic finger had to be amputated. Cold injury on the skin caused by high-pressure jet streams of liquid gas as in our study is a rare occurrence. Our patients are important cases due to the rare etiology of cold injury.

Laser-Induced Thermal Damage of Skin

DTIC Science & Technology

1977-12-01

identify by block number) Skin Burns Skin Model Laser Effects \\Thermal Predictions 20 ABSTRACT (Continue on reverse side it necessary and identify by...block number) A computerized model was developed for predicting thermal damage of skin by laser exposures. Thermal, optical, and physiological data are...presented for the model. Model predictions of extent of irreversible damage were compared with histologic determinations of the extent of damage

Characterization of damaged skin by impedance spectroscopy: chemical damage by dimethyl sulfoxide.

PubMed

White, Erick A; Orazem, Mark E; Bunge, Annette L

2013-10-01

To relate changes in the electrochemical impedance spectra to the progression and mechanism of skin damage arising from exposure to dimethyl sulfoxide (DMSO). Electrochemical impedance spectra measured before and after human cadaver skin was treated with neat DMSO or phosphate buffered saline (control) for 1 h or less were compared with electrical circuit models representing two contrasting theories describing the progression of DMSO damage. Flux of a model lipophilic compound (p-chloronitrobenzene) was also measured. The impedance spectra collected before and after 1 h treatment with DMSO were consistent with a single circuit model; whereas, the spectra collected after DMSO exposure for 0.25 h were consistent with the model circuits observed before and after DMSO treatment for 1 h combined in series. DMSO treatments did not significantly change the flux of p-chloronitrobenzene compared to control. Impedance measurements of human skin exposed to DMSO for less than about 0.5 h were consistent with the presence of two layers: one damaged irreversibly and one unchanged. The thickness of the damaged layer increased proportional to the square-root of treatment time until about 0.5 h, when DMSO affected the entire stratum corneum. Irreversible DMSO damage altered the lipophilic permeation pathway minimally.

Non-thermal damage to lead tungstate induced by intense short-wavelength laser radiation (Conference Presentation)

NASA Astrophysics Data System (ADS)

Vozda, Vojtech; Boháček, Pavel; Burian, Tomáš; Chalupský, Jaromir; Hájková, Vera; Juha, Libor; Vyšín, Ludek; Gaudin, Jérôme; Heimann, Philip A.; Hau-Riege, Stefan P.; Jurek, Marek; Klinger, Dorota; Krzywinski, Jacek; Messerschmidt, Marc; Moeller, Stefan P.; Nagler, Robert; Pelka, Jerzy B.; Rowen, Michael; Schlotter, William F.; Swiggers, Michele L.; Sinn, Harald; Sobierajski, Ryszard; Tiedtke, Kai; Toleikis, Sven; Tschentscher, Thomas; Turner, Joshua J.; Wabnitz, Hubertus; Nelson, Art J.; Kozlova, Maria V.; Vinko, Sam M.; Whitcher, Thomas; Dzelzainis, Thomas; Renner, Oldrich; Saksl, Karel; Fäustlin, Roland R.; Khorsand, Ali R.; Fajardo, Marta; Iwan, Bianca S.; Andreasson, Jakob; Hajdu, Janos; Timneanu, Nicusor; Wark, Justin S.; Riley, David; Lee, Richard W.; Nagasono, Mitsuru; Yabashi, Makina

2017-05-01

Interaction of short-wavelength free-electron laser (FEL) beams with matter is undoubtedly a subject to extensive investigation in last decade. During the interaction various exotic states of matter, such as warm dense matter, may exist for a split second. Prior to irreversible damage or ablative removal of the target material, complicated electronic processes at the atomic level occur. As energetic photons impact the target, electrons from inner atomic shells are almost instantly photo-ionized, which may, in some special cases, cause bond weakening, even breaking of the covalent bonds, subsequently result to so-called non-thermal melting. The subject of our research is ablative damage to lead tungstate (PbWO4) induced by focused short-wavelength FEL pulses at different photon energies. Post-mortem analysis of complex damage patterns using the Raman spectroscopy, atomic-force (AFM) and Nomarski (DIC) microscopy confirms an existence of non-thermal melting induced by high-energy photons in the ionic monocrystalline target. Results obtained at Linac Coherent Light Source (LCLS), Free-electron in Hamburg (FLASH), and SPring-8 Compact SASE Source (SCSS) are presented in this Paper.

Development of ocular viscosity characterization method.

PubMed

Shu-Hao Lu; Guo-Zhen Chen; Leung, Stanley Y Y; Lam, David C C

2016-08-01

Glaucoma is the second leading cause for blindness. Irreversible and progressive optic nerve damage results when the intraocular pressure (IOP) exceeds 21 mmHg. The elevated IOP is attributed to blocked fluid drainage from the eye. Methods to measure the IOP are widely available, but methods to measure the viscous response to blocked drainage has yet been developed. An indentation method to characterize the ocular flow is developed in this study. Analysis of the load-relaxation data from indentation tests on drainage-controlled porcine eyes showed that the blocked drainage is correlated with increases in ocular viscosity. Successful correlation of the ocular viscosity with drainage suggests that ocular viscosity maybe further developed as a new diagnostic parameter for assessment of normal tension glaucoma where nerve damage occurs without noticeable IOP elevation; and as a diagnostic parameter complimentary to conventional IOP in conventional diagnosis.

Heat effect of pulsed Er:YAG laser radiation

NASA Astrophysics Data System (ADS)

Hibst, Raimund; Keller, Ulrich

1990-06-01

Pulsed Er:YAG laser radiation has been found to be effective for dental enamel and dentin removal. Damage to the surrounding hard tissue is little, but before testing the Er:YAG laser clinically for the preparation of cavities, possible effects on the soft tissue of the pulp must be known. In order to estimate pulp damage , temperature rise in dentin caused by the laser radiation was measured by a thermocouple. Additionally, temperature distributions were observed by means of a thermal imaging system. The heat effect of a single Er:YAG laser pulse is little and limited to the vicinity of the impact side. Because heat energy is added with each additional pulse , the temperature distribution depends not only on the radiant energy, but also on the number of pulses and the repetition rate. Both irradiation conditions can be found , making irreversible pulp damage either likely or unlikely. The experimental observations can be explained qualitatively by a simple model of the ablation process.

Nano-enhanced aerospace composites for increased damage tolerance and service life damage monitoring

NASA Astrophysics Data System (ADS)

Paipetis, A.; Matikas, T. E.; Barkoula, N. M.; Karapappas, P.; Vavouliotis, A.; Kostopoulos, V.

2009-03-01

This study deals with new generation composite systems which apart from the primary reinforcement at the typical fiber scale (~10 μm) are also reinforced at the nanoscale. This is performed via incorporation of nano-scale additives in typical aerospace matrix systems, such as epoxies. Carbon Nanotubes (CNTs) are ideal candidates as their extremely high aspect ratio and mechanical properties render them advantageous to other nanoscale materials. The result is the significant increase in the damage tolerance of the novel composite systems even at very low CNT loadings. By monitoring the resistance change of the CNT network, information both on the real time deformation state of the composite is obtained as a reversible change in the bulk resistance of the material, and the damage state of the material as an irreversible change in the bulk resistance of the material. The irreversible monotonic increase of the electrical resistance can be related to internal damage in the hybrid composite system and may be used as an index of the remaining lifetime of a structural component.

Silent Damage of Noise on Cochlear Afferent Innervation in Guinea Pigs and the Impact on Temporal Processing

PubMed Central

He, Tingting; Aiken, Steve; Bance, Manohar; Yin, Shankai; Wang, Jian

2012-01-01

Noise-exposure at levels low enough to avoid a permanent threshold shift has been found to cause a massive, delayed degeneration of spiral ganglion neurons (SGNs) in mouse cochleae. Damage to the afferent innervation was initiated by a loss of synaptic ribbons, which is largely irreversible in mice. A similar delayed loss of SGNs has been found in guinea pig cochleae, but at a reduced level, suggesting a cross-species difference in SGN sensitivity to noise. Ribbon synapse damage occurs “silently” in that it does not affect hearing thresholds as conventionally measured, and the functional consequence of this damage is not clear. In the present study, we further explored the effect of noise on cochlear afferent innervation in guinea pigs by focusing on the dynamic changes in ribbon counts over time, and resultant changes in temporal processing. It was found that (1) contrary to reports in mice, the initial loss of ribbons largely recovered within a month after the noise exposure, although a significant amount of residual damage existed; (2) while the response threshold fully recovered in a month, the temporal processing continued to be deteriorated during this period. PMID:23185359

Blood glutamate scavenging as a novel neuroprotective treatment for paraoxon intoxication.

PubMed

Ruban, Angela; Mohar, Boaz; Jona, Ghil; Teichberg, Vivian I

2014-02-01

Organophosphate-induced brain damage is an irreversible neuronal injury, likely because there is no pharmacological treatment to prevent or block secondary damage processes. The presence of free glutamate (Glu) in the brain has a substantial role in the propagation and maintenance of organophosphate-induced seizures, thus contributing to the secondary brain damage. This report describes for the first time the ability of blood glutamate scavengers (BGS) oxaloacetic acid in combination with glutamate oxaloacetate transaminase to reduce the neuronal damage in an animal model of paraoxon (PO) intoxication. Our method causes a rapid decrease of blood Glu levels and creates a gradient that leads to the efflux of the excess brain Glu into the blood, thus reducing neurotoxicity. We demonstrated that BGS treatment significantly prevented the peripheral benzodiazepine receptor (PBR) density elevation, after PO exposure. Furthermore, we showed that BGS was able to rescue neurons in the piriform cortex of the treated rats. In conclusion, these results suggest that treatment with BGS has a neuroprotective effect in the PO intoxication. This is the first time that this approach is used in PO intoxication and it may be of high clinical significance for the future treatment of the secondary neurologic damage post organophosphates exposure.

Blood glutamate scavenging as a novel neuroprotective treatment for paraoxon intoxication

PubMed Central

Ruban, Angela; Mohar, Boaz; Jona, Ghil; Teichberg, Vivian I

2014-01-01

Organophosphate-induced brain damage is an irreversible neuronal injury, likely because there is no pharmacological treatment to prevent or block secondary damage processes. The presence of free glutamate (Glu) in the brain has a substantial role in the propagation and maintenance of organophosphate-induced seizures, thus contributing to the secondary brain damage. This report describes for the first time the ability of blood glutamate scavengers (BGS) oxaloacetic acid in combination with glutamate oxaloacetate transaminase to reduce the neuronal damage in an animal model of paraoxon (PO) intoxication. Our method causes a rapid decrease of blood Glu levels and creates a gradient that leads to the efflux of the excess brain Glu into the blood, thus reducing neurotoxicity. We demonstrated that BGS treatment significantly prevented the peripheral benzodiazepine receptor (PBR) density elevation, after PO exposure. Furthermore, we showed that BGS was able to rescue neurons in the piriform cortex of the treated rats. In conclusion, these results suggest that treatment with BGS has a neuroprotective effect in the PO intoxication. This is the first time that this approach is used in PO intoxication and it may be of high clinical significance for the future treatment of the secondary neurologic damage post organophosphates exposure. PMID:24149933

Efficacy of Blunt Force Trauma, a Novel Mechanical Cervical Dislocation Device, and a Non-Penetrating Captive Bolt Device for On-Farm Euthanasia of Pre-Weaned Kits, Growers, and Adult Commercial Meat Rabbits.

PubMed

Walsh, Jessica L; Percival, Aaron; Turner, Patricia V

2017-12-15

The commercial meat rabbit industry is without validated on-farm euthanasia methods, potentially resulting in inadequate euthanasia protocols. We evaluated blunt force trauma (BFT), a mechanical cervical dislocation device (MCD), and a non-penetrating captive bolt device (NPCB) for euthanasia of pre-weaned kits, growers, and adult rabbits. Trials were conducted on three commercial meat rabbit farms using 170 cull rabbits. Insensibility was assessed by evaluating absence of brainstem and spinal reflexes, rhythmic breathing, and vocalizations. Survey radiographs on a subsample of rabbits ( n = 12) confirmed tissue damage prior to gross dissection and microscopic evaluation. All 63 rabbits euthanized by the NPCB device were rendered immediately and irreversibly insensible. The MCD device was effective in 46 of 49 (94%) rabbits. Method failure was highest for BFT with euthanasia failures in 13 of 58 (22%) rabbits. Microscopically, brain sections from rabbits killed with the NPCB device had significantly more damage than those from rabbits killed with BFT ( p = 0.001). We conclude that BFT is neither consistently humane nor effective as a euthanasia method. MCD is an accurate and reliable euthanasia method generally causing clean dislocation and immediate and irreversible insensibility, and the NPCB device was 100% effective and reliable in rabbits >150 g.

Nondestructive evaluation of composite materials by electrical resistance measurement

NASA Astrophysics Data System (ADS)

Mei, Zhen

This dissertation investigates electrical resistance measurement for nondestructive evaluation of carbon fiber (CF) reinforced polymer matrix composites. The method involves measuring the DC electrical resistance in either the longitudinal or through thickness direction. The thermal history and thermal properties of thermoplastic/CF composites were studied by longitudinal and through-thickness resistance measurements. The resistance results were consistent with differential scanning calorimetry (DSC) and thermomechanical analysis (TMA) results. The resistance measurements gave more information on the melting of the polymer matrix than TMA. They were more sensitive to the glass transition of the polymer matrix than DSC. The through-thickness resistance decreased as autohesion progressed. The activation energy of autohesion was 21.2 kJ/mol for both nylon-6 and polyphenylene sulfide (PPS)/CF composites. Adhesive bonding and debonding were monitored in real-time by measurement of the through-thickness resistance between the adherends in an adhesive joint during heating and subsequent cooling. Debonding occurred during cooling when the pressure or temperature during prior bonding was not sufficiently high. A long heating time below the melting temperature (T m) was found to be detrimental to subsequent PPS adhesive joint development above Tm, due to curing reactions below Tm and consequent reduced mass flow response above Tm. A high heating rate (small heating time) enhanced the bonding more than a high pressure. The longitudinal resistance measurement was used to investigate the effects of temperature and stress on the interface between a concrete substrate and its epoxy/CF composite retrofit. The resistance of the retrofit was increased by bond degradation, whether the degradation was due to heat or stress. The degradation was reversible. Irreversible disturbance in the fiber arrangement occurred slightly as thermal or load cycling occurred, as indicated by the resistance decreasing cycle by cycle. This dissertation also addresses the use of the electrical resistance method to observe thermal and mechanical damage in real time. A temperature increase caused the interlaminar contact resistance to decrease reversibly within each thermal cycle, while thermal damage caused the resistance to decrease abruptly and irreversibly, due to matrix molecular movement and the consequent increase in the chance of fibers of one lamina touching those of an adjacent lamina. The through-thickness volume resistivity irreversibly and gradually decreased upon mechanical damage, which was probably fiber-matrix debonding. Moreover, it reversibly and abruptly increased upon matrix micro-structural change, which occurred reversibly near the peak stress of a stress cycle.

E-cigarettes and flavorings induce inflammatory and pro-senescence responses in oral epithelial cells and periodontal fibroblasts.

PubMed

Sundar, Isaac K; Javed, Fawad; Romanos, Georgios E; Rahman, Irfan

2016-11-22

Electronic-cigarettes (e-cigs) represent a significant and increasing proportion of tobacco product consumption, which may pose an oral health concern. Oxidative/carbonyl stress via protein carbonylation is an important factor in causing inflammation and DNA damage. This results in stress-induced premature senescence (a state of irreversible growth arrest which re-enforces chronic inflammation) in gingival epithelium, which may contribute to the pathogenesis of oral diseases. We show that e-cigs with flavorings cause increased oxidative/carbonyl stress and inflammatory cytokine release in human periodontal ligament fibroblasts, Human Gingival Epithelium Progenitors pooled (HGEPp), and epigingival 3D epithelium. We further show increased levels of prostaglandin-E2 and cycloxygenase-2 are associated with upregulation of the receptor for advanced glycation end products (RAGE) by e-cig exposure-mediated carbonyl stress in gingival epithelium/tissue. Further, e-cigs cause increased oxidative/carbonyl and inflammatory responses, and DNA damage along with histone deacetylase 2 (HDAC2) reduction via RAGE-dependent mechanisms in gingival epithelium. A greater response is elicited by flavored e-cigs. Increased oxidative stress, pro-inflammatory and pro-senescence responses (DNA damage and HDAC2 reduction) can result in dysregulated repair due to proinflammatory and pro-senescence responses in periodontal cells. These data highlight the pathologic role of e-cig aerosol and its flavoring to cells and tissues of the oral cavity in compromised oral health.

Basic radiological assessment of synovial diseases: a pictorial essay

PubMed Central

Turan, Aynur; Çeltikçi, Pınar; Tufan, Abdurrahman; Öztürk, Mehmet Akif

2017-01-01

The synovium is a specialized tissue lining the synovial joints, bursae, and tendon sheaths of the body. It is affected by various localized or systemic disorders. Synovial diseases can be classified as inflammatory, infectious, degenerative, traumatic, hemorrhagic, and neoplastic. Damage in other intraarticular structures, particularly cartilages, generally occurs as a part of pathologic processes involving the synovium, leading to irreversible joint destruction. Imaging has an essential role in the early detection of synovial diseases prior to irreversible joint damage. Obtaining and understanding characteristic imaging findings of synovial diseases enables a proper diagnosis for early treatment. This article focuses on the recent literature that is related with the role of imaging in synovial disease. PMID:28638696

Safety concerns over the use of intestinal permeation enhancers: A mini-review.

PubMed

McCartney, Fiona; Gleeson, John P; Brayden, David J

2016-01-01

Intestinal permeation enhancers (PEs) are key components in ∼12 oral peptide formulations in clinical trials for a range of molecules, primarily insulin and glucagon-like-peptide 1 (GLP-1) analogs. The main PEs comprise medium chain fatty acid-based systems (sodium caprate, sodium caprylate, and N-[8-(2-hydroxybenzoyl) amino] caprylate (SNAC)), bile salts, acyl carnitines, and EDTA. Their mechanism of action is complex with subtle differences between the different molecules. With the exception of SNAC and EDTA, most PEs fluidize the plasma membrane causing plasma membrane perturbation, as well as enzymatic and intracellular mediator changes that lead to alteration of intestinal epithelial tight junction protein expression. The question arises as to whether PEs can cause irreversible epithelial damage and tight junction openings sufficient to permit co-absorption of payloads with bystander pathogens, lipopolysaccharides and its fragment, or exo- and endotoxins that may be associated with sepsis, inflammation and autoimmune conditions. Most PEs seem to cause membrane perturbation to varying extents that is rapidly reversible, and overall evidence of pathogen co-absorption is generally lacking. It is unknown however, whether the intestinal epithelial damage-repair cycle is sustained during repeat-dosing regimens for chronic therapy.

Plasma Membrane ATPase Activity following Reversible and Irreversible Freezing Injury 1

PubMed Central

Iswari, S.; Palta, Jiwan P.

1989-01-01

Plasma membrane ATPase has been proposed as a site of functional alteration during early stages of freezing injury. To test this, plasma membrane was purified from Solanum leaflets by a single step partitioning of microsomes in a dextran-polyethylene glycol two phase system. Addition of lysolecithin in the ATPase assay produced up to 10-fold increase in ATPase activity. ATPase activity was specific for ATP with a Km around 0.4 millimolar. Presence of the ATPase enzyme was identified by immunoblotting with oat ATPase antibodies. Using the phase partitioning method, plasma membrane was isolated from Solanum commersonii leaflets which had four different degrees of freezing damage, namely, slight (reversible), partial (partially reversible), substantial and total (irreversible). With slight (reversible) damage the plasma membrane ATPase specific activity increased 1.5- to 2-fold and its Km was decreased by about 3-fold, whereas the specific activity of cytochrome c reductase and cytochrome c oxidase in the microsomes were not different from the control. However, with substantial (lethal, irreversible) damage, there was a loss of membrane protein, decrease in plasma membrane ATPase specific activity and decrease in Km, while cytochrome c oxidase and cytochrome c reductase were unaffected. These results support the hypothesis that plasma membrane ATPase is altered by slight freeze-thaw stress. Images Figure 1 Figure 2 PMID:16666856

Avoiding neuromuscular stimulation in liver irreversible electroporation using radiofrequency electric fields

NASA Astrophysics Data System (ADS)

Castellví, Quim; Mercadal, Borja; Moll, Xavier; Fondevila, Dolors; Andaluz, Anna; Ivorra, Antoni

2018-02-01

Electroporation-based treatments typically consist of the application of high-voltage dc pulses. As an undesired side effect, these dc pulses cause electrical stimulation of excitable tissues such as motor nerves. The present in vivo study explores the use of bursts of sinusoidal voltage in a frequency range from 50 kHz to 2 MHz, to induce irreversible electroporation (IRE) whilst avoiding neuromuscular stimulation. A series of 100 dc pulses or sinusoidal bursts, both with an individual duration of 100 µs, were delivered to rabbit liver through thin needles in a monopolar electrode configuration, and thoracic movements were recorded with an accelerometer. Tissue samples were harvested three hours after treatment and later post-processed to determine the dimensions of the IRE lesions. Thermal damage due to Joule heating was ruled out via computer simulations. Sinusoidal bursts with a frequency equal to or above 100 kHz did not cause thoracic movements and induced lesions equivalent to those obtained with conventional dc pulses when the applied voltage amplitude was sufficiently high. IRE efficacy dropped with increasing frequency. For 100 kHz bursts, it was estimated that the electric field threshold for IRE is about 1.4 kV cm-1 whereas that of dc pulses is about 0.5 kV cm-1.

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

An Irreversible Constitutive Law for Modeling the Delamination Process using Interface Elements

NASA Technical Reports Server (NTRS)

Goyal, Vinay K.; Johnson, Eric R.; Davila, Carlos G.; Jaunky, Navin; Ambur, Damodar (Technical Monitor)

2002-01-01

An irreversible constitutive law is postulated for the formulation of interface elements to predict initiation and progression of delamination in composite structures. An exponential function is used for the constitutive law such that it satisfies a multi-axial stress criterion for the onset of delamination, and satisfies a mixed mode fracture criterion for the progression of delamination. A damage parameter is included to prevent the restoration of the previous cohesive state between the interfacial surfaces. To demonstrate the irreversibility capability of the constitutive law, steady-state crack growth is simulated for quasi-static loading-unloading cycle of various fracture test specimens.

An Irreversible Constitutive Law for Modeling the Delamination Process Using Interface Elements

NASA Technical Reports Server (NTRS)

Goyal, Vinay K.; Johnson, Eric R.; Davila, Carlos G.; Jaunky, Navin; Bushnell, Dennis M. (Technical Monitor)

2002-01-01

An irreversible constitutive law is postulated for the formulation of interface elements to predict initiation and progression of delamination in composite structures. An exponential function is used for the constitutive law such that it satisfies a multi-axial stress criterion for the onset of delamination, and satisfies a mixed mode fracture criterion for the progression of delamination. A damage parameter is included to prevent the restoration of the previous cohesive state between the interfacial surfaces. To demonstrate the irreversibility capability of the constitutive law, steady-state crack growth is simulated for quasi-static loading-unloading cycle of various fracture test specimens.

Emerging Therapeutics to Overcome Chemoresistance in Epithelial Ovarian Cancer: A Mini-Review.

PubMed

Cornelison, Robert; Llaneza, Danielle C; Landen, Charles N

2017-10-18

Ovarian cancer is the fifth leading cause of cancer death among women and the most lethal gynecologic malignancy. One of the leading causes of death in high-grade serous ovarian cancer (HGSOC) is chemoresistant disease, which may present as intrinsic or acquired resistance to therapies. Here we discuss some of the known molecular mechanisms of chemoresistance that have been exhaustively investigated in chemoresistant ovarian cancer, including drug efflux pump multidrug resistance protein 1 (MDR1), the epithelial-mesenchymal transition, DNA damage and repair capacity. We also discuss novel therapeutics that may address some of the challenges in bringing approaches that target chemoresistant processes from bench to bedside. Some of these new therapies include novel drug delivery systems, targets that may halt adaptive changes in the tumor, exploitation of tumor mutations that leave cancer cells vulnerable to irreversible damage, and novel drugs that target ribosomal biogenesis, a process that may be uniquely different in cancer versus non-cancerous cells. Each of these approaches, or a combination of them, may provide a greater number of positive outcomes for a broader population of HGSOC patients.

Clinical manifestations and management of Gaucher disease.

PubMed

Linari, Silvia; Castaman, Giancarlo

2015-01-01

Gaucher disease is a rare multi-systemic metabolic disorder caused by the inherited deficiency of the lysosomal enzyme β-glucocerebrosidase, which leads to the accumulation of its normal substrate, glucocerebroside, in tissue macrophages with damage to haematological, visceral and bone systems. Anaemia, thrombocytopenia, enlargement of liver and/or spleen, skeletal abnormalities (osteopenia, lytic lesions, pathological fractures, chronic bone pain, bone crisis, bone infarcts, osteonecrosis and skeletal deformities) are typical manifestations of the most prevalent form of the disease, the so-called non-neuronopathic type 1. However, severity and coexistence of different symptoms are highly variable. The determination of deficient β-glucocerebrosidase activity in leukocytes or fibroblasts by enzymatic assay is the gold standard for the diagnosis of Gaucher disease. Comprehensive and reproducible evaluation and monitoring of all clinically relevant aspects are fundamental for the effective management of Gaucher disease patients. Enzyme replacement therapy has been shown to be effective in reducing glucocerebroside storage burden and diminishing the deleterious effects caused by its accumulation. Tailored treatment plan for each patient should be directed to symptom relief, general improvement of quality of life, and prevention of irreversible damage.

Biological Activities of Reactive Oxygen and Nitrogen Species: Oxidative Stress versus Signal Transduction

PubMed Central

Weidinger, Adelheid; Kozlov, Andrey V.

2015-01-01

In the past, reactive oxygen and nitrogen species (RONS) were shown to cause oxidative damage to biomolecules, contributing to the development of a variety of diseases. However, recent evidence has suggested that intracellular RONS are an important component of intracellular signaling cascades. The aim of this review was to consolidate old and new ideas on the chemical, physiological and pathological role of RONS for a better understanding of their properties and specific activities. Critical consideration of the literature reveals that deleterious effects do not appear if only one primary species (superoxide radical, nitric oxide) is present in a biological system, even at high concentrations. The prerequisite of deleterious effects is the formation of highly reactive secondary species (hydroxyl radical, peroxynitrite), emerging exclusively upon reaction with another primary species or a transition metal. The secondary species are toxic, not well controlled, causing irreversible damage to all classes of biomolecules. In contrast, primary RONS are well controlled (superoxide dismutase, catalase), and their reactions with biomolecules are reversible, making them ideal for physiological/pathophysiological intracellular signaling. We assume that whether RONS have a signal transducing or damaging effect is primarily defined by their quality, being primary or secondary RONS, and only secondly by their quantity. PMID:25884116

Diabetes-Induced Reactive Oxygen Species: Mechanism of Their Generation and Role in Renal Injury

PubMed Central

Fakhruddin, Selim; Alanazi, Wael

2017-01-01

Diabetes induces the onset and progression of renal injury through causing hemodynamic dysregulation along with abnormal morphological and functional nephron changes. The most important event that precedes renal injury is an increase in permeability of plasma proteins such as albumin through a damaged glomerular filtration barrier resulting in excessive urinary albumin excretion (UAE). Moreover, once enhanced UAE begins, it may advance renal injury from progression of abnormal renal hemodynamics, increased glomerular basement membrane (GBM) thickness, mesangial expansion, extracellular matrix accumulation, and glomerulosclerosis to eventual end-stage renal damage. Interestingly, all these pathological changes are predominantly driven by diabetes-induced reactive oxygen species (ROS) and abnormal downstream signaling molecules. In diabetic kidney, NADPH oxidase (enzymatic) and mitochondrial electron transport chain (nonenzymatic) are the prominent sources of ROS, which are believed to cause the onset of albuminuria followed by progression to renal damage through podocyte depletion. Chronic hyperglycemia and consequent ROS production can trigger abnormal signaling pathways involving diverse signaling mediators such as transcription factors, inflammatory cytokines, chemokines, and vasoactive substances. Persistently, increased expression and activation of these signaling molecules contribute to the irreversible functional and structural changes in the kidney resulting in critically decreased glomerular filtration rate leading to eventual renal failure. PMID:28164134

Hand-arm vibration syndrome: A rarely seen diagnosis.

PubMed

Campbell, Rebecca A; Janko, Matthew R; Hacker, Robert I

2017-06-01

Hand-arm vibration syndrome (HAVS) is a collection of sensory, vascular, and musculoskeletal symptoms caused by repetitive trauma from vibration. This case report demonstrates how to diagnose HAVS on the basis of history, physical examination, and vascular imaging and its treatment options. A 41-year-old man who regularly used vibrating tools presented with nonhealing wounds on his right thumb and third digit. Arteriography revealed occlusions of multiple arteries in his hand with formation of collaterals. We diagnosed HAVS, and his wounds healed after several weeks with appropriate treatment. HAVS is a debilitating condition with often irreversible vascular damage, requiring early diagnosis and treatment.

Bronchiectasis: Current Concepts in Pathogenesis, Immunology, and Microbiology.

PubMed

Boyton, Rosemary J; Altmann, Daniel M

2016-05-23

Bronchiectasis is a disorder of persistent lung inflammation and recurrent infection, defined by a common pathological end point: irreversible bronchial dilatation arrived at through diverse etiologies. This suggests an interplay between immunogenetic susceptibility, immune dysregulation, bacterial infection, and lung damage. The damaged epithelium impairs mucus removal and facilitates bacterial infection with increased cough, sputum production, and airflow obstruction. Lung infection is caused by respiratory bacterial and fungal pathogens, including Pseudomonas aeruginosa, Haemophilus, Aspergillus fumigatus, and nontuberculous mycobacteria. Recent studies have highlighted the relationship between the lung microbiota and microbial-pathogen niches. Disease may result from environments favoring interleukin-17-driven neutrophilia. Bronchiectasis may present in autoimmune disease, as well as conditions of immune dysregulation, such as combined variable immune deficiency, transporter associated with antigen processing-deficiency syndrome, and hyperimmunoglobulin E syndrome. Differences in prevalence across geography and ethnicity implicate an etiological mix of genetics and environment underpinning susceptibility.

Notch Inhibition Induces Cochlear Hair Cell Regeneration and Recovery of Hearing after Acoustic Trauma

PubMed Central

Mizutari, Kunio; Fujioka, Masato; Hosoya, Makoto; Bramhall, Naomi; Okano, Hirotaka James; Okano, Hideyuki; Edge, Albert S.B.

2013-01-01

SUMMARY Hearing loss due to damage to auditory hair cells is normally irreversible because mammalian hair cells do not regenerate. Here, we show that new hair cells can be induced and can cause partial recovery of hearing in ears damaged by noise trauma, when Notch signaling is inhibited by a γ-secretase inhibitor selected for potency in stimulating hair cell differentiation from inner ear stem cells in vitro. Hair cell generation resulted from an increase in the level of bHLH transcription factor, Atoh1, in response to inhibition of Notch signaling. In vivo prospective labeling of Sox2-expressing cells with a Cre/lox system unambiguously demonstrated that hair cell generation resulted from transdifferentiation of supporting cells. Manipulating cell fate of cochlear sensory cells in vivo by pharmacological inhibition of Notch signaling is thus a potential therapeutic approach to the treatment of deafness. PMID:23312516

Management of complications of cosmetic iris implants in a phakic eye: a case report and literature review.

PubMed

Bore, Millicent; Choudhari, Nikhil; Chaurasia, Sunita

2018-03-21

To report the intricacies of managing complications that arose out of cosmetic iris implants (BrightOcular) placement. Interventional case report. A thirty-year-old gentleman presented with complaint of progressive loss of vision after having cosmetic iris implant surgery to change his eye colour. He then developed raised intraocular pressures and had a right eye trabeculectomy conducted with the implants in situ. Subsequently, he had implant removal surgery because of persistent implant-associated complications. The vision was impaired due to progressive corneal oedema and glaucoma. Various considerations were taken while planning for surgical intervention because of the extensive structural damage to the anterior segment of the eye. This case report highlights that cosmetic iris implants are dangerous intraocular devices and management of the associated complications is also challenging. As these devices cause irreversible structural and functional damage, their use should be discouraged in normal eyes.

In situ transmission electron microscopy of transistor operation and failure.

PubMed

Wang, Baoming; Islam, Zahabul; Haque, Aman; Chabak, Kelson; Snure, Michael; Heller, Eric; Glavin, Nicholas

2018-08-03

Microscopy is typically used as a post-mortem analytical tool in performance and reliability studies on nanoscale materials and devices. In this study, we demonstrate real time microscopy of the operation and failure of AlGaN/GaN high electron mobility transistors inside the transmission electron microscope. Loading until failure was performed on the electron transparent transistors to visualize the failure mechanisms caused by self-heating. At lower drain voltages, thermo-mechanical stresses induce irreversible microstructural deformation, mostly along the AlGaN/GaN interface, to initiate the damage process. At higher biasing, the self-heating deteriorates the gate and catastrophic failure takes place through metal/semiconductor inter-diffusion and/or buffer layer breakdown. This study indicates that the current trend of recreating the events, from damage nucleation to catastrophic failure, can be replaced by in situ microscopy for a quick and accurate account of the failure mechanisms.

Time-Dependent Impact of Irreversible Electroporation on Pancreas, Liver, Blood Vessels and Nerves: A Systematic Review of Experimental Studies.

PubMed

Vogel, J A; van Veldhuisen, E; Agnass, P; Crezee, J; Dijk, F; Verheij, J; van Gulik, T M; Meijerink, M R; Vroomen, L G; van Lienden, K P; Besselink, M G

2016-01-01

Irreversible electroporation (IRE) is a novel ablation technique in the treatment of unresectable cancer. The non-thermal mechanism is thought to cause mostly apoptosis compared to necrosis in thermal techniques. Both in experimental and clinical studies, a waiting time between ablation and tissue or imaging analysis to allow for cell death through apoptosis, is often reported. However, the dynamics of the IRE effect over time remain unknown. Therefore, this study aims to summarize these effects in relation to the time between treatment and evaluation. A systematic search was performed in Pubmed, Embase and the Cochrane Library for original articles using IRE on pancreas, liver or surrounding structures in animal or human studies. Data on pathology and time between IRE and evaluation were extracted. Of 2602 screened studies, 36 could be included, regarding IRE in liver (n = 24), pancreas (n = 4), blood vessels (n = 4) and nerves (n = 4) in over 440 animals (pig, rat, goat and rabbit). No eligible human studies were found. In liver and pancreas, the first signs of apoptosis and haemorrhage were observed 1-2 hours after treatment, and remained visible until 24 hours in liver and 7 days in pancreas after which the damaged tissue was replaced by fibrosis. In solitary blood vessels, the tunica media, intima and lumen remained unchanged for 24 hours. After 7 days, inflammation, fibrosis and loss of smooth muscle cells were demonstrated, which persisted until 35 days. In nerves, the median time until demonstrable histological changes was 7 days. Tissue damage after IRE is a dynamic process with remarkable time differences between tissues in animals. Whereas pancreas and liver showed the first damages after 1-2 hours, this took 24 hours in blood vessels and 7 days in nerves.

Evaluation of damage induced by Kwkt and Pikt zymocins against Brettanomyces/Dekkera spoilage yeast, as compared to sulphur dioxide.

PubMed

Oro, L; Ciani, M; Bizzaro, D; Comitini, F

2016-07-01

Over the last few decades, the use of zymocins as biological tools to counteract contamination by spoilage yeast in beverages and food has been widely studied. This study examined the damage induced by the Kwkt and Pikt, two zymocins produced by Kluyeromyces wickerhamii and Wickerhanomyces anomalus, respectively, with antimicrobial activity against Brettanomyces/Dekkera wine-spoilage yeast. The physiological and biochemical characterization of both of these proteins revealed that only Pikt showed a strict relationship between β-glucosidase activity and killer activity. The minimum inhibitory concentrations and minimum fungicidal concentrations of Kwkt and Pikt showed inhibitory activities against Brettanomyces/Dekkera yeast. Cytofluorimetric evaluation of cell death was based on both cell membrane permeability and cell metabolism, using fluorescence techniques under increasing zymocin levels over different incubation times. The antimicrobial actions of Kwkt and Pikt were also compared with the mode of action of sulphur dioxide. In this last case, the induction of the viable but noncultivable (VBNC) state was confirmed, with the consequent recovery of Brettanomyces yeast after medium replacement. In contrast, Kwkt and Pikt caused irreversible death of these yeast, without recovery of sensitive cells. Kwkt and Pikt could be proposed as fungistatic or fungicide biocontrol agents in winemaking to control the colonization and development of Brettanomyces/Dekkera yeasts. These data support the potential use of zymocins to reduce wine contamination as an alternative to sulphur dioxide that act on sensitive cells. Differently from sulphur dioxide, that could induce a reversible VBNC state, Kwkt and Pikt determine the irreversible damage on sensitive yeasts, ensuring the complete control of spoilage Brettanomyces yeast. © 2016 The Society for Applied Microbiology.

Testing a generalized domain model of photodegradation and self-healing using novel optical characterization techniques and the effects of an applied electric field

NASA Astrophysics Data System (ADS)

Anderson, Benjamin R.

Reversible photodegradation is a relatively new phenomenon which is not well understood. Previous research into the phenomenon has focused primarily on non-linear measurements such as amplified spontaneous emission(ASE) and two-photon fluorescence(TPF). We expand on this research by considering linear optical mea- surements, such as transmittance imaging and absorption spectroscopy, of disperse orange 11(DO11) dye-doped (poly)methyl-methacralate(PMMA) thin films and find photodegradation to contain both a reversible component and irreversible component, with the irreversible component having a small nonlinear susceptibility. From absorption measurements, and the small nonlinear susceptibility of the irreversible component, we hypothesize that the reversible component corresponds to damage to the dye, and the irreversible component is due to damage to the polymer host. Also, we develop models of depth dependent photodegradation taking pump beam absorption and propagation into account. We find that pump absorption must be taken into account, and that ignoring the effect leads to an underestimation of the true decay rate and degree of damage. In addition, we find pump propagation effects occur on large length scales, such that they are negligible when compared to absorption and typical sample thicknesses. Finally, we perform electric field dependent reversible photodegradation measurements and find that the underlying mechanism of reversible photodegradation is sensitive to the dye-doped polymer's electrical properties. We develop an extension to the correlated chromophore domain model to include the effect of an applied field, and find the model to fit experimental data for varying intensity, temperature, and applied electric field with only one set of model parameters.

Partially-irreversible sorption of formaldehyde in five polymers

NASA Astrophysics Data System (ADS)

Ye, Wei; Cox, Steven S.; Zhao, Xiaomin; Frazier, Charles E.; Little, John C.

2014-12-01

Due to its environmental ubiquity and concern over its potential toxicity, the mass-transfer characteristics of formaldehyde are of critical importance to indoor air quality research. Previous studies have suggested that formaldehyde mass transfer in polymer is partially irreversible. In this study, mechanisms that could cause the observed irreversibility were investigated. Polycarbonate and four other polymeric matrices were selected and subjected to formaldehyde sorption/desorption cycles. Mass transfer of formaldehyde was partially irreversible in all cases, and three potential mechanisms were evaluated. First, attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) analysis was used to investigate possible formaldehyde polymerization on polymer surfaces. ATR-FTIR showed no detectable paraformaldehyde or formaldehyde on the film surfaces that had been exposed to formaldehyde and air. ATR-FTIR did detect aliphatic acids suggesting oxidation had occurred on film surfaces as a result of exposure to formaldehyde. However, additional study suggested that air is not the primary cause for irreversibility. Second, statistical physics theory was tested as a possible explanation. According to this theory, reversible and irreversible sorption could be taking place simultaneously. The irreversible fraction should be constant during sorption and the fraction could be determined by performing a complete sorption/desorption test. The sorption/desorption data was consistent with this theory. Third, chemisorption was considered as another possible cause for irreversibility. Extraction/fluorimetry testing of post-sorption and post-desorption polymer films showed measurable quantities of formaldehyde suggesting that some of the chemisorbed formaldehyde was reversible at the higher extraction temperature. Further quantitative study on chemical reaction products is needed.

Oxygen removal during pathogen inactivation with riboflavin and UV light preserves protein function in plasma for transfusion.

PubMed

Feys, H B; Van Aelst, B; Devreese, K; Devloo, R; Coene, J; Vandekerckhove, P; Compernolle, V

2014-05-01

Photochemical pathogen inactivation technologies (PCT) for individual transfusion products act by inhibition of replication through irreversibly damaging nucleic acids. Concern on the collateral impact of PCT on the blood component's integrity has caused reluctance to introduce this technology in routine practice. This work aims to uncover the mechanism of damage to plasma constituents by riboflavin pathogen reduction technology (RF-PRT). Activity and antigen of plasma components were determined following RF-PRT in the presence or absence of dissolved molecular oxygen. Employing ADAMTS13 as a sentinel molecule in plasma, our data show that its activity and antigen are reduced by 23 ± 8% and 29 ± 9% (n = 24), respectively, which corroborates with a mean decrease of 25% observed for other coagulation factors. Western blotting of ADAMTS13 shows decreased molecular integrity, with no obvious indication of additional proteolysis nor is riboflavin able to directly inhibit the enzyme. However, physical removal of dissolved oxygen prior to RF-PRT protects ADAMTS13 as well as FVIII and fibrinogen from damage, indicating a direct role for reactive oxygen species. Redox dye measurements indicate that superoxide anions are specifically generated during RF-PRT. Protein carbonyl content as a marker of disseminated irreversible biomolecular damage was significantly increased (3·1 ± 0·8 vs. 1·6 ± 0·5 nmol/mg protein) following RF-PRT, but not in the absence of dissolved molecular oxygen (1·8 ± 0·4 nmol/mg). RF-PRT of single plasma units generates reactive oxygen species that adversely affect biomolecular integrity of relevant plasma constituents, a side-effect, which can be bypassed by applying hypoxic conditions during the pathogen inactivation process. © 2013 International Society of Blood Transfusion.

Free radical development in phacoemulsification cataract surgery.

PubMed

Takahashi, Hiroshi

2005-02-01

Phacoemulsification and aspiration (PEA) has become the most popular cataract surgery, due to the establishment of safe surgical techniques and development of associated instruments. However, corneal endothelial damage still represents a serious complication, as excessive damage can lead to irreversible bullous keratopathy. In addition to causes such as mechanical or heat injuries, free radical formation due to ultrasound has been posited as another cause of corneal endothelium damage in PEA. Ultrasound in aqueous solution induces cavitation, directly causing water molecule disintegration and resulting in the formation of hydroxylradicals, the most potent of the reactive oxygen species. Considering the oxidative insult to endothelial cells caused by free radicals, their presence in the anterior chamber may represent one of the most harmful factors during these procedures. Indeed, some researchers have recently started to evaluate PEA from the perspective of oxidative stress. Conversely, the major ingredient in ophthalmic viscosurgical devices (OVDs), which are indispensable for maintaining the anterior chamber in PEA surgery, is sodium hyaluronate, a known free radical scavenger. OVDs can thus be expected to provide some anti-free radical effect during PEA procedures. In addition, since commercially available OVDs display different properties regarding retention in the anterior chamber during PEA, the anti-free radical effect of OVDs is likely to depend on behavior during irrigation and aspiration. The present study followed standard PEA procedures in an eye model and measured hydroxylradicals in the anterior chamber using electron spin resonance. The kinetics of free radical intensity and effects of several OVDs during clinical PEA were also demonstrated. These studies may be of significance in re-evaluating OVDs as a chemical protectant for corneal endothelium, since the OVD has thus far only been regarded as a physical barrier. In addition, many reports about corneal endothelium damage during PEA have been published, but objective evaluation of various damaging factors has been difficult. The present assay of free radicals in a simulation of clinical PEA offers the first method to quantitatively assess stress on the corneal endothelium.

Cholinesterase reactivators and bioscavengers for pre- and post-exposure treatments of organophosphorus poisoning.

PubMed

Masson, Patrick; Nachon, Florian

2017-08-01

Organophosphorus agents (OPs) irreversibly inhibit acetylcholinesterase (AChE) causing a major cholinergic syndrome. The medical counter-measures of OP poisoning have not evolved for the last 30 years with carbamates for pretreatment, pyridinium oximes-based AChE reactivators, antimuscarinic drugs and neuroprotective benzodiazepines for post-exposure treatment. These drugs ensure protection of peripheral nervous system and mitigate acute effects of OP lethal doses. However, they have significant limitations. Pyridostigmine and oximes do not protect/reactivate central AChE. Oximes poorly reactivate AChE inhibited by phosphoramidates. In addition, current neuroprotectants do not protect the central nervous system shortly after the onset of seizures when brain damage becomes irreversible. New therapeutic approaches for pre- and post-exposure treatments involve detoxification of OP molecules before they reach their molecular targets by administrating catalytic bioscavengers, among them phosphotriesterases are the most promising. Novel generation of broad spectrum reactivators are designed for crossing the blood-brain barrier and reactivate central AChE. This is an article for the special issue XVth International Symposium on Cholinergic Mechanisms. © 2017 International Society for Neurochemistry.

Potential pharmacological strategies for the improved treatment of organophosphate-induced neurotoxicity.

PubMed

Kaur, Shamsherjit; Singh, Satinderpal; Chahal, Karan Singh; Prakash, Atish

2014-11-01

Organophosphates (OP) are highly toxic compounds that cause cholinergic neuronal excitotoxicity and dysfunction by irreversible inhibition of acetylcholinesterase, resulting in delayed brain damage. This delayed secondary neuronal destruction, which arises primarily in the cholinergic areas of the brain that contain dense accumulations of cholinergic neurons and the majority of cholinergic projection, could be largely responsible for persistent profound neuropsychiatric and neurological impairments such as memory, cognitive, mental, emotional, motor, and sensory deficits in the victims of OP poisoning. The therapeutic strategies for reducing neuronal brain damage must adopt a multifunctional approach to the various steps of brain deterioration: (i) standard treatment with atropine and related anticholinergic compounds; (ii) anti-excitotoxic therapies to prevent cerebral edema, blockage of calcium influx, inhibition of apoptosis, and allow for the control of seizure; (iii) neuroprotection by aid of antioxidants and N-methyl-d-aspartate (NMDA) antagonists (multifunctional drug therapy), to inhibit/limit the secondary neuronal damage; and (iv) therapies targeting chronic neuropsychiatric and neurological symptoms. These neuroprotective strategies may prevent secondary neuronal damage in both early and late stages of OP poisoning, and thus may be a beneficial approach to treating the neuropsychological and neuronal impairments resulting from OP toxicity.

Hypertonic stress induces rapid and widespread protein damage in C. elegans

PubMed Central

Burkewitz, Kris; Choe, Keith

2011-01-01

Proteostasis is defined as the homeostatic mechanisms that maintain the function of all cytoplasmic proteins. We recently demonstrated that the capacity of the proteostasis network is a critical factor that defines the limits of cellular and organismal survival in hypertonic environments. The current studies were performed to determine the extent of protein damage induced by cellular water loss. Using worm strains expressing fluorescently tagged foreign and endogenous proteins and proteins with temperature-sensitive point mutations, we demonstrate that hypertonic stress causes aggregation and misfolding of diverse proteins in multiple cell types. Protein damage is rapid. Aggregation of a polyglutamine yellow fluorescent protein reporter is observable with <1 h of hypertonic stress, and aggregate volume doubles approximately every 10 min. Aggregate formation is irreversible and occurs after as little as 10 min of exposure to hypertonic conditions. To determine whether endogenous proteins are aggregated by hypertonic stress, we quantified the relative amount of total cellular protein present in detergent-insoluble extracts. Exposure for 4 h to 400 mM or 500 mM NaCl induced a 55–120% increase in endogenous protein aggregation. Inhibition of insulin signaling or acclimation to mild hypertonic stress increased survival under extreme hypertonic conditions and prevented aggregation of endogenous proteins. Our results demonstrate that hypertonic stress causes widespread and dramatic protein damage and that cells have a significant capacity to remodel the network of proteins that function to maintain proteostasis. These findings have important implications for understanding how cells cope with hypertonic stress and other protein-damaging stressors. PMID:21613604

Deep tissue penetration of nanoparticles using pulsed-high intensity focused ultrasound

NASA Astrophysics Data System (ADS)

You, Dong Gil; Yoon, Hong Yeol; Jeon, Sangmin; Um, Wooram; Son, Sejin; Park, Jae Hyung; Kwon, Ick Chan; Kim, Kwangmeyung

2017-11-01

Recently, ultrasound (US)-based drug delivery strategies have received attention to improve enhanced permeation and retention (EPR) effect-based passive targeting efficiency of nanoparticles in vitro and in vivo conditions. Among the US treatment techniques, pulsed-high intensity focused ultrasound (pHIFU) have specialized for improving tissue penetration of various macromolecules and nanoparticles without irreversible tissue damages. In this study, we have demonstrated that pHIFU could be utilized to improve tissue penetration of fluorescent dye-labeled glycol chitosan nanoparticles (FCNPs) in femoral tissue of mice. pHIFU could improve blood flow of the targeted-blood vessel in femoral tissue. In addition, tissue penetration of FCNPs was specifically increased 5.7-, 8- and 9.3-folds than that of non-treated (0 W pHIFU) femoral tissue, when the femoral tissue was treated with 10, 20 and 50 W of pHIFU, respectively. However, tissue penetration of FCNPs was significantly reduced after 3 h post-pHIFU treatment (50 W). Because overdose (50 W) of pHIFU led to irreversible tissue damages, including the edema and chapped red blood cells. These overall results support that pHIFU treatment can enhance the extravasation and tissue penetration of FCNPs as well as induce irreversible tissue damages. We expect that our results can provide advantages to optimize pHIFU-mediated delivery strategy of nanoparticles for further clinical applications.

Evaluation of Ultrasound-Induced Damage to Escherichia coli and Staphylococcus aureus by Flow Cytometry and Transmission Electron Microscopy

PubMed Central

Li, Jiao; Ahn, Juhee; Liu, Donghong; Chen, Shiguo; Ye, Xingqian

2016-01-01

As a nonthermal sterilization technique, ultrasound has attracted great interest in the field of food preservation. In this study, flow cytometry and transmission electron microscopy were employed to investigate ultrasound-induced damage to Escherichia coli and Staphylococcus aureus. For flow cytometry studies, single staining with propidium iodide (PI) or carboxyfluorescein diacetate (cFDA) revealed that ultrasound treatment caused cell death by compromising membrane integrity, inactivating intracellular esterases, and inhibiting metabolic performance. The results showed that ultrasound damage was independent of initial bacterial concentrations, while the mechanism of cellular damage differed according to the bacterial species. For the Gram-negative bacterium E. coli, ultrasound worked first on the outer membrane rather than the cytoplasmic membrane. Based on the double-staining results, we inferred that ultrasound treatment might be an all-or-nothing process: cells ruptured and disintegrated by ultrasound cannot be revived, which can be considered an advantage of ultrasound over other nonthermal techniques. Transmission electron microscopy studies revealed that the mechanism of ultrasound-induced damage was multitarget inactivation, involving the cell wall, cytoplasmic membrane, and inner structure. Understanding of the irreversible antibacterial action of ultrasound has great significance for its further utilization in the food industry. PMID:26746712

Ecological carrying capacity assessment of diving site: A case study of Mabul Island, Malaysia.

PubMed

Zhang, Li-Ye; Chung, Shan-Shan; Qiu, Jian-Wen

2016-12-01

Despite considered a non-consumptive use of the marine environment, diving-related activities can cause damages to coral reefs. It is imminent to assess the maximum numbers of divers that can be accommodated by a diving site before it is subject to irreversible deterioration. This study aimed to assess the ecological carrying capacity of a diving site in Mabul Island, Malaysia. Photo-quadrat line transect method was used in the benthic survey. The ecological carrying capacity was assessed based on the relationship between the number of divers and the proportion of diver damaged hard corals in Mabul Island. The results indicated that the proportion of diver damaged hard corals occurred exponentially with increasing use. The ecological carrying capacity of Mabul Island is 15,600-16,800 divers per diving site per year at current levels of diver education and training with a quarterly threshold of 3900-4200 per site. Our calculation shows that management intervention (e.g. limiting diving) is justified at 8-14% of hard coral damage. In addition, the use of coral reef dominated diving sites should be managed according to their sensitivity to diver damage and the depth of the reefs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Environmental degradation of Opalinus Clay with cyclic variations in relative humidity

NASA Astrophysics Data System (ADS)

Wild, Katrin; Walter, Patric; Madonna, Claudio; Amann, Florian

2016-04-01

Clay shales are considered as favorable host rocks for nuclear waste repositories due to their low permeability, high sorption capacity and the potential for self-sealing. However, the favorable characteristics of the rock mass may change during tunnel excavation. Excavation is accompanied by stress redistribution and the development of an excavation damage zone. Furthermore, unloading and exposure to atmospheric conditions with a lower relative humidity (RH) causes desaturation of the rock mass close to the tunnel. This leads to shrinkage and the formation of desiccation cracks. During the open drift stage, seasonal atmospheric changes, especially RH variations, may alter the rock mass and influence the long-term crack evolution. This contribution discusses the influence of RH variation on the mechanical behavior of OPA. A series of specimens were exposed to short-term and long-term, stepwise cyclic RH variations between about 60 and 95% at constant temperature. Strains were measured using strain gauges to monitor the volumetric response during RH cycles. After each applied RH cycle, Brazilian tensile strength (BTS) tests were performed to identify whether there is a change in tensile strength due to environmental damage caused by the change in RH. Swelling and shrinkage of the specimens accompanied by irreversible volumetric expansion was observed as a consequence of the exposure to RH cycles. However, the irreversible strain was limited to the direction normal to bedding suggesting that internal damage is restricted along the bedding planes. No significant effect of cyclic RH variations on the BTS of the specimens was observed. The strength parallel to bedding remained constant over several cycles while the strength normal to bedding shows a slightly decreasing trend after 2 cycles. Furthermore, the water retention characteristics of the specimens were not altered significantly during stepwise RH cycling as the evolution of the water content was reversible throughout the cycles. For the RH variation used, the results suggest that the long-term crack evolution around excavations in OPA is not expected to be significantly influenced by environmental degradation but dominated by other processes such as consolidation and creep.

Efficacy of Blunt Force Trauma, a Novel Mechanical Cervical Dislocation Device, and a Non-Penetrating Captive Bolt Device for On-Farm Euthanasia of Pre-Weaned Kits, Growers, and Adult Commercial Meat Rabbits

PubMed Central

Walsh, Jessica L.; Percival, Aaron

2017-01-01

Simple Summary Developing effective and humane on-farm euthanasia methods is essential for all livestock industries to ensure that animals do not suffer and are killed humanely. Approved methods are lacking for commercial meat rabbits, potentially leading to poor welfare. We assessed several methods of on-farm killing of cull rabbits of different ages to determine which methods were most effective and humane. These included blunt force trauma (the most commonly used method on rabbit farms), a novel mechanical cervical dislocation device, and a non-penetrating captive bolt device. We evaluated method effectiveness by examining animal reflexes and behaviours after applying the method as well as by examining radiographs of rabbit heads for signs of skull damage, and by assessing the degree of trauma to the brain through dissection and microscopy, because more trauma is generally correlated with enhanced method effectiveness and irreversibility. We found that blunt force trauma resulted in an unacceptably high failure rate, particularly in mature rabbits, whereas the mechanical cervical dislocation and non-penetrating captive bolt devices were both highly effective for killing rabbits humanely and irreversibly. The non-penetrating captive bolt device was the most effective with a 100% success rate and could be used on all rabbits weighing more than 150 g. Abstract The commercial meat rabbit industry is without validated on-farm euthanasia methods, potentially resulting in inadequate euthanasia protocols. We evaluated blunt force trauma (BFT), a mechanical cervical dislocation device (MCD), and a non-penetrating captive bolt device (NPCB) for euthanasia of pre-weaned kits, growers, and adult rabbits. Trials were conducted on three commercial meat rabbit farms using 170 cull rabbits. Insensibility was assessed by evaluating absence of brainstem and spinal reflexes, rhythmic breathing, and vocalizations. Survey radiographs on a subsample of rabbits (n = 12) confirmed tissue damage prior to gross dissection and microscopic evaluation. All 63 rabbits euthanized by the NPCB device were rendered immediately and irreversibly insensible. The MCD device was effective in 46 of 49 (94%) rabbits. Method failure was highest for BFT with euthanasia failures in 13 of 58 (22%) rabbits. Microscopically, brain sections from rabbits killed with the NPCB device had significantly more damage than those from rabbits killed with BFT (p = 0.001). We conclude that BFT is neither consistently humane nor effective as a euthanasia method. MCD is an accurate and reliable euthanasia method generally causing clean dislocation and immediate and irreversible insensibility, and the NPCB device was 100% effective and reliable in rabbits >150 g. PMID:29244782

Photosynthetic, antioxidative, molecular and ultrastructural responses of young cacao plants to Cd toxicity in the soil.

PubMed

Pereira de Araújo, Romária; Furtado de Almeida, Alex-Alan; Silva Pereira, Lidiane; Mangabeira, Pedro A O; Olimpio Souza, José; Pirovani, Carlos P; Ahnert, Dário; Baligar, Virupax C

2017-10-01

Cadmium (Cd) is a highly toxic metal for plants, even at low concentrations in the soil. The annual production of world cocoa beans is approximately 4 million tons. Most of these fermented and dried beans are used in the manufacture of chocolate. Recent work has shown that the concentration of Cd in these beans has exceeded the critical level (0.6mgkg -1 DM). The objective of this study was to evaluate the toxicity of Cd in young plants of CCN 51 cacao genotype grown in soil with different concentrations of Cd (0, 0.05 and 0.1gkg -1 soil) through photosynthetic, antioxidative, molecular and ultrastructural changes. The increase of Cd concentration in the soil altered mineral nutrient absorption by competition or synergism, changed photosynthetic activity caused by reduction in chloroplastidic pigment content and damage to the photosynthetic machinery evidenced by the Fv/Fm ratio and expression of the psbA gene and increased GPX activity in the root and SOD in leaves. Additionally, ultrastructural alterations in roots and leaves were also evidenced with the increase of the concentration of Cd in the soil, whose toxicity caused rupture of biomembranes in root and leaf cells, reduction of the number of starch grains in foliar cells, increase of plastoglobules in chloroplasts and presence of multivesiculated bodies in root cells. It was concluded, therefore, that soil Cd toxicity caused damage to the photosynthetic machinery, antioxidative metabolism, gene expression and irreversible damage to root cells ultrastructure of CCN 51 cocoa plants, whose damage intensity depended on the exposure time to the metal. Copyright © 2017. Published by Elsevier Inc.

Cerebral blood flow in humans following resuscitation from cardiac arrest

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

Cohan, S.L.; Mun, S.K.; Petite, J.

1989-06-01

Cerebral blood flow was measured by xenon-133 washout in 13 patients 6-46 hours after being resuscitated from cardiac arrest. Patients regaining consciousness had relatively normal cerebral blood flow before regaining consciousness, but all patients who died without regaining consciousness had increased cerebral blood flow that appeared within 24 hours after resuscitation (except in one patient in whom the first measurement was delayed until 28 hours after resuscitation, by which time cerebral blood flow was increased). The cause of the delayed-onset increase in cerebral blood flow is not known, but the increase may have adverse effects on brain function and maymore » indicate the onset of irreversible brain damage.« less

Solving a layout design problem by analytic hierarchy process (AHP) and data envelopment analysis (DEA) approach

NASA Astrophysics Data System (ADS)

Tuzkaya, Umut R.; Eser, Arzum; Argon, Goner

2004-02-01

Today, growing amounts of waste due to fast consumption rate of products started an irreversible environmental pollution and damage. A considerable part of this waste is caused by packaging material. With the realization of this fact, various waste policies have taken important steps. Here we considered a firm, where waste Aluminum constitutes majority of raw materials for this fir0m. In order to achieve a profitable recycling process, plant layout should be well designed. In this study, we propose a two-step approach involving Analytic Hierarchy Process (AHP) and Data Envelopment Analysis (DEA) to solve facility layout design problems. A case example is considered to demonstrate the results achieved.

The specific interaction of the photosensitizer methylene blue with acetylcholinesterase provides a model system for studying the molecular consequences of photodynamic therapy.

PubMed

Silman, Israel; Roth, Esther; Paz, Aviv; Triquigneaux, Mathilde M; Ehrenshaft, Marilyn; Xu, Yechun; Shnyrov, Valery L; Sussman, Joel L; Deterding, Leesa J; Ashani, Yacov; Mason, Ronald P; Weiner, Lev

2013-03-25

The photosensitizer, methylene blue (MB), generates singlet oxygen ((1)O2) that irreversibly inhibits Torpedo californica acetylcholinesterase (TcAChE). In the dark MB inhibits reversibly, binding being accompanied by a bathochromic shift that can be used to show its displacement by other reversible inhibitors binding to the catalytic 'anionic' subsite (CAS), the peripheral 'anionic' subsite (PAS), or bridging them. Data concerning both reversible and irreversible inhibition are here reviewed. MB protects TcAChE from thermal denaturation, and differential scanning calorimetry reveals a ~8 °C increase in the denaturation temperature. The crystal structure of the MB/TcAChE complex reveals a single MB stacked against W279 in the PAS, pointing down the gorge towards the CAS. The intrinsic fluorescence of the irreversibly inhibited enzyme displays new emission bands that can be ascribed to N'-formylkynurenine (NFK); this was indeed confirmed using anti-NFK antibodies. Mass spectroscopy revealed that two Trp residues, Trp84 in the CAS, and Trp279 in the PAS, were the only Trp residues, out of a total of 14, significantly modified by photo-oxidation, both being converted to NFK. In the presence of competitive inhibitors that displace MB from the gorge, their modification is completely prevented. Thus, photo-oxidative damage caused by MB involves targeted release of (1)O2 by the bound photosensitizer within the aqueous milieu of the active-site gorge. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Enhancement of lutetium texaphyrin phototherapy with Mitomycin C

NASA Astrophysics Data System (ADS)

Thiemann, Patricia A.; Woodburn, Kathryn W.

1998-05-01

Lutetium texaphyrin (Lu-Tex) photodynamic therapy (PDT) relies on the presence of the water-soluble Lu-Tex, oxygen, and light (activation around 730 nm). Cytotoxic oxygen species are produced that cause irreversible damage to biological substrates. Damage may be inflicted via direct cell kill mechanisms or through vasculature effects that cause hypoxia. The addition of hypoxia enhanced drugs, such as Mitomycin C (MMC), can potentially increase the anti-tumor response. RIF-1 bearing C3H mice received 10 micrometers ol Lu-Tex/kg and were illuminated with 100 J/cm2 3 hours postinjection. Mice received MMC (2.5 or 5 mg/kg, before and after light) in conjunction with PDT and were compared to subsets of drug alone controls. A significant improvement in PDT response was observed when MMC was added to the dosing regimen; the effect was more pronounced at the highest MMC dose of 5 mg/kg: MMC prior to PDT gave a median tumor regrowth time (10X original volume) of 28 days compared to MMC and PDT alone, 16.3 and 14.9 days, respectively. The anti-tumor activity of lutetium texaphyrin induced PDT was improved by the addition of the bioreductive alkylating agent mitomycin C.

The irreversible ERBB1/2/4 inhibitor neratinib interacts with the PARP1 inhibitor niraparib to kill ovarian cancer cells.

PubMed

Booth, Laurence; Roberts, Jane L; Samuel, Peter; Avogadri-Connors, Francesca; Cutler, Richard E; Lalani, Alshad S; Poklepovic, Andrew; Dent, Paul

2018-06-03

The irreversible ERBB1/2/4 inhibitor neratinib has been shown to rapidly down-regulate the expression of ERBB1/2/4 as well as the levels of c-MET, PDGFRα and mutant RAS proteins via autophagic degradation. Neratinib interacted in an additive to synergistic fashion with the approved PARP1 inhibitor niraparib to kill ovarian cancer cells. Neratinib and niraparib caused the ATM-dependent activation of AMPK which in turn was required to cause mTOR inactivation, ULK-1 activation and ATG13 phosphorylation. The drug combination initially increased autophagosome levels followed later by autolysosome levels. Preventing autophagosome formation by expressing activated mTOR or knocking down of Beclin1, or knock down of the autolysosome protein cathepsin B, reduced drug combination lethality. The drug combination caused an endoplasmic reticulum stress response as judged by enhanced eIF2α phosphorylation that was responsible for reducing MCL-1 and BCL-XL levels and increasing ATG5 and Beclin1 expression. Knock down of BIM, but not of BAX or BAK, reduced cell killing. Expression of activated MEK1 prevented the drug combination increasing BIM expression and reduced cell killing. Downstream of the mitochondrion, drug lethality was partially reduced by knock down of AIF, but expression of dominant negative caspase 9 was not protective. Our data demonstrate that neratinib and niraparib interact to kill ovarian cancer cells through convergent DNA damage and endoplasmic reticulum stress signaling. Cell killing required the induction of autophagy and was cathepsin B and AIF -dependent, and effector caspase independent.

Oxidative stress in dry age-related macular degeneration and exfoliation syndrome.

PubMed

Chiras, Dimitrios; Kitsos, George; Petersen, Michael B; Skalidakis, Iosif; Kroupis, Christos

2015-02-01

Oxidative stress refers to cellular or molecular damage caused by reactive oxygen species, which especially occurs in age-related conditions as a result of an imbalance between the production of reactive oxygen species and the antioxidant defense response. Dry age-related macular degeneration (AMD) and exfoliation syndrome (XFS) are two common and complex age-related conditions that can cause irreversible vision loss. Two subtypes of AMD, which is the leading cause of blindness in the Western world, exist: the most prevalent dry type and the most severe wet type. Early dry AMD is characterized by formation of drusen, which are sub-retinal deposits, in the macular area and may progress to geographic atrophy with more dramatic manifestation. XFS is a systemic disorder of the extracellular matrix characterized by the accumulation of elastic fibrils that leads, in most cases, to glaucoma development with progressive and irreversible vision loss. Due to the aging population, the prevalence of these already-widespread conditions is increasing and is resulting in significant economic and psychological costs for individuals and for society. The exact composition of the abnormal drusen and XFS material as well as the mechanisms responsible for their production and accumulation still remain elusive, and consequently treatment for both diseases is lacking. However, recent epidemiologic, genetic and molecular studies support a major role for oxidative stress in both dry AMD and XFS development. Understanding the early molecular events in their pathogenesis and the exact role of oxidative stress may provide novel opportunities for therapeutic intervention for the prevention of progression to advanced disease.

Environmental impact assessment of cottage industries of Kashmir, India.

PubMed

Wani, Khursheed Ahmad; Jaiswal, Y K

2011-07-01

Our objective was to carry out environmental impact assessment of small scale industries in Kashmir (India). A prepared questionnaire was circulated among the workers, owners and residents to assess the pros and cons of the small scale industries in Kashmir. The study revealed that most of the small scale industries in Kashmir valley have an impact on the quality of the environment and may cause discomfort to the people living very close to these industries. It has been observed that small scale industries lack efficient waste management system. However, the generated wastes from these units may be used effectively, as a raw material in various ways when managed properly and may minimize the impact on the quality of the environment and may also contribute in improving the economy of the State. The proliferation of small scale industries has caused an irreversible damage to the agricultural land of the area studied.

Orthodontic elastic separator-induced periodontal abscess: a case report.

PubMed

Becker, Talia; Neronov, Alex

2012-01-01

Aim. Orthodontic elastic bands were proposed as being the source of gingival abscesses that can rapidly lead to bone loss and teeth exfoliation. We report an adolescent, otherwise, healthy patient whose periodontal status was sound. Shortly after undergoing preparations for orthodontic treatment consisting of orthodontic separators, he presented with a periodontal abscess for which there was no apparent etiology. A non-orthoradial X-ray was inconclusive, but an appropriate one revealed a subgingival orthodontic separator as the cause of the abscess. Removal of the separator and thorough scaling led to complete resolution of the abscess, but there was already residual mild damage to the alveolar bone. Summary. Failure to use appropriate imaging to reveal the cause of gingival abscesses can result in the delay of implementing treatment and halting irreversible alveolar bone loss. An inflammatory process restricted to the gingiva and refractive to conventional therapy should raise the possibility of a foreign body etiology.

Orthodontic Elastic Separator-Induced Periodontal Abscess: A Case Report

PubMed Central

Becker, Talia; Neronov, Alex

2012-01-01

Aim. Orthodontic elastic bands were proposed as being the source of gingival abscesses that can rapidly lead to bone loss and teeth exfoliation. We report an adolescent, otherwise, healthy patient whose periodontal status was sound. Shortly after undergoing preparations for orthodontic treatment consisting of orthodontic separators, he presented with a periodontal abscess for which there was no apparent etiology. A non-orthoradial X-ray was inconclusive, but an appropriate one revealed a subgingival orthodontic separator as the cause of the abscess. Removal of the separator and thorough scaling led to complete resolution of the abscess, but there was already residual mild damage to the alveolar bone. Summary. Failure to use appropriate imaging to reveal the cause of gingival abscesses can result in the delay of implementing treatment and halting irreversible alveolar bone loss. An inflammatory process restricted to the gingiva and refractive to conventional therapy should raise the possibility of a foreign body etiology. PMID:22567456

Oxygen Toxicity and Special Operations Forces Diving: Hidden and Dangerous

PubMed Central

Wingelaar, Thijs T.; van Ooij, Pieter-Jan A. M.; van Hulst, Rob A.

2017-01-01

In Special Operations Forces (SOF) closed-circuit rebreathers with 100% oxygen are commonly utilized for covert diving operations. Exposure to high partial pressures of oxygen (PO2) could cause damage to the central nervous system (CNS) and pulmonary system. Longer exposure time and higher PO2 leads to faster development of more serious pathology. Exposure to a PO2 above 1.4 ATA can cause CNS toxicity, leading to a wide range of neurologic complaints including convulsions. Pulmonary oxygen toxicity develops over time when exposed to a PO2 above 0.5 ATA and can lead to inflammation and fibrosis of lung tissue. Oxygen can also be toxic for the ocular system and may have systemic effects on the inflammatory system. Moreover, some of the effects of oxygen toxicity are irreversible. This paper describes the pathophysiology, epidemiology, signs and symptoms, risk factors and prediction models of oxygen toxicity, and their limitations on SOF diving. PMID:28790955

Genetic linkage of autosomal dominant juvenile glaucoma to 1q21-q31 in three affected pedigrees

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

Wiggs, J.L.; Paglinauan, C.; Fine, A.

1994-05-15

Glaucoma is a common disorder that results in irreversible damage to the optic nerve, causing absolute blindness. In most cases, the optic nerve is damaged by an elevation of the intraocular pressure that is the result of an abnormality in the normal drainage function of the trabecular meshwork. A family history of glaucoma is an important risk factor for the disease, suggesting that genetic defects predisposing to this condition are likely. Three pedigrees segregating an autosomal dominant juvenile glaucoma demonstrated significant linkage to a group of closely spaced markers on chromosome 1. These results confirm the initial mapping of thismore » disease and suggest that this region on chromosome 1 contains an important locus for juvenile glaucoma. The authors describe recombination events that improve the localization of the responsible gene, reducing the size of the candidate region from 30 to 12 cM. 27 refs., 2 figs., 1 tab.« less

Early detection of aging cartilage and osteoarthritis in mice and patient samples using atomic force microscopy

NASA Astrophysics Data System (ADS)

Stolz, Martin; Gottardi, Riccardo; Raiteri, Roberto; Miot, Sylvie; Martin, Ivan; Imer, Raphaël; Staufer, Urs; Raducanu, Aurelia; Düggelin, Marcel; Baschong, Werner; Daniels, A. U.; Friederich, Niklaus F.; Aszodi, Attila; Aebi, Ueli

2009-03-01

The pathological changes in osteoarthritis-a degenerative joint disease prevalent among older people-start at the molecular scale and spread to the higher levels of the architecture of articular cartilage to cause progressive and irreversible structural and functional damage. At present, there are no treatments to cure or attenuate the degradation of cartilage. Early detection and the ability to monitor the progression of osteoarthritis are therefore important for developing effective therapies. Here, we show that indentation-type atomic force microscopy can monitor age-related morphological and biomechanical changes in the hips of normal and osteoarthritic mice. Early damage in the cartilage of osteoarthritic patients undergoing hip or knee replacements could similarly be detected using this method. Changes due to aging and osteoarthritis are clearly depicted at the nanometre scale well before morphological changes can be observed using current diagnostic methods. Indentation-type atomic force microscopy may potentially be developed into a minimally invasive arthroscopic tool to diagnose the early onset of osteoarthritis in situ.

Characterization of photoactivated singlet oxygen damage in single-molecule optical trap experiments.

PubMed

Landry, Markita P; McCall, Patrick M; Qi, Zhi; Chemla, Yann R

2009-10-21

Optical traps or "tweezers" use high-power, near-infrared laser beams to manipulate and apply forces to biological systems, ranging from individual molecules to cells. Although previous studies have established that optical tweezers induce photodamage in live cells, the effects of trap irradiation have yet to be examined in vitro, at the single-molecule level. In this study, we investigate trap-induced damage in a simple system consisting of DNA molecules tethered between optically trapped polystyrene microspheres. We show that exposure to the trapping light affects the lifetime of the tethers, the efficiency with which they can be formed, and their structure. Moreover, we establish that these irreversible effects are caused by oxidative damage from singlet oxygen. This reactive state of molecular oxygen is generated locally by the optical traps in the presence of a sensitizer, which we identify as the trapped polystyrene microspheres. Trap-induced oxidative damage can be reduced greatly by working under anaerobic conditions, using additives that quench singlet oxygen, or trapping microspheres lacking the sensitizers necessary for singlet state photoexcitation. Our findings are relevant to a broad range of trap-based single-molecule experiments-the most common biological application of optical tweezers-and may guide the development of more robust experimental protocols.

Characterization of Photoactivated Singlet Oxygen Damage in Single-Molecule Optical Trap Experiments

PubMed Central

Landry, Markita P.; McCall, Patrick M.; Qi, Zhi; Chemla, Yann R.

2009-01-01

Abstract Optical traps or “tweezers” use high-power, near-infrared laser beams to manipulate and apply forces to biological systems, ranging from individual molecules to cells. Although previous studies have established that optical tweezers induce photodamage in live cells, the effects of trap irradiation have yet to be examined in vitro, at the single-molecule level. In this study, we investigate trap-induced damage in a simple system consisting of DNA molecules tethered between optically trapped polystyrene microspheres. We show that exposure to the trapping light affects the lifetime of the tethers, the efficiency with which they can be formed, and their structure. Moreover, we establish that these irreversible effects are caused by oxidative damage from singlet oxygen. This reactive state of molecular oxygen is generated locally by the optical traps in the presence of a sensitizer, which we identify as the trapped polystyrene microspheres. Trap-induced oxidative damage can be reduced greatly by working under anaerobic conditions, using additives that quench singlet oxygen, or trapping microspheres lacking the sensitizers necessary for singlet state photoexcitation. Our findings are relevant to a broad range of trap-based single-molecule experiments—the most common biological application of optical tweezers—and may guide the development of more robust experimental protocols. PMID:19843445

Glaucoma and its association with obstructive sleep apnea: A narrative review

PubMed Central

Chaitanya, Aditya; Pai, Vijaya H.; Mohapatra, Aswini Kumar; Ve, Ramesh S.

2016-01-01

Obstructive sleep apnea (OSA) is one of the systemic risk factors for glaucoma which causes irreversible visual field (VF) damage. We reviewed the published data of all types of studies on the association between these two conditions and papers regarding functional and structural changes related to glaucomatous damage using Scopus, web of science, and PubMed databases. There is evidence that the prevalence of glaucoma is higher in OSA patients, which independent of intraocular pressure (IOP). Studies have reported thinning of retinal nerve fiber layer (RNFL), alteration of optic nerve head, choroidal and macular thickness, and reduced VF sensitivity in patients of OSA with no history glaucoma. A negative correlation of apnea-hypopnea index with RNFL and VF indices has been described in some studies. Raised IOP was noted which is possibly related to obesity, supine position during sleep, and raised intracranial pressure. Diurnal fluctuations of IOP show more variations in OSA patients before and after continuous positive airway pressure (CPAP) therapy when compared with the normal cases. The vascular factors behind the pathogenesis include recurrent hypoxia with increased vascular resistance, oxidative stress damage to the optic nerve. In conclusion, comprehensive glaucoma evaluation should be recommended in patients with OSA and should also periodically monitor IOP during CPAP treatment which may trigger the progression of glaucomatous damage. PMID:27843225

Estimating retinal vascular permeability using the adiabatic approximation to the tissue homogeneity model with fluorescein videoangiography

NASA Astrophysics Data System (ADS)

Tichauer, Kenneth M.; Osswald, Christian R.; Dosmar, Emily; Guthrie, Micah J.; Hones, Logan; Sinha, Lagnojita; Xu, Xiaochun; Mieler, William F.; St. Lawrence, Keith; Kang-Mieler, Jennifer J.

2015-06-01

Clinical symptoms of diabetic retinopathy are not detectable until damage to the retina reaches an irreversible stage, at least by today's treatment standards. As a result, there is a push to develop new, "sub-clinical" methods of predicting the onset of diabetic retinopathy before the onset of irreversible damage. With diabetic retinopathy being associated with the accumulation of long-term mild damage to the retinal vasculature, retinal blood vessel permeability has been proposed as a key parameter for detecting preclinical stages of retinopathy. In this study, a kinetic modeling approach used to quantify vascular permeability in dynamic contrast-enhanced medical imaging was evaluated in noise simulations and then applied to retinal videoangiography data in a diabetic rat for the first time to determine the potential for this approach to be employed clinically as an early indicator of diabetic retinopathy. Experimental levels of noise were found to introduce errors of less than 15% in estimates of blood flow and extraction fraction (a marker of vascular permeability), and fitting of rat retinal fluorescein angiography data provided stable maps of both parameters.

Irreversible impacts of heat on the emissions of monoterpenes, sesquiterpenes, phenolic BVOC and green leaf volatiles from several tree species

NASA Astrophysics Data System (ADS)

Kleist, E.; Mentel, T. F.; Andres, S.; Bohne, A.; Folkers, A.; Kiendler-Scharr, A.; Rudich, Y.; Springer, M.; Tillmann, R.; Wildt, J.

2012-12-01

Climate change will induce extended heat waves to parts of the vegetation more frequently. High temperatures may act as stress (thermal stress) on plants changing emissions of biogenic volatile organic compounds (BVOCs). As BVOCs impact the atmospheric oxidation cycle and aerosol formation, it is important to explore possible alterations of BVOC emissions under high temperature conditions. Applying heat to European beech, Palestine oak, Scots pine, and Norway spruce in a laboratory setup either caused the well-known exponential increases of BVOC emissions or induced irreversible changes of BVOC emissions. Considering only irreversible changes of BVOC emissions as stress impacts, we found that high temperatures decreased the de novo emissions of monoterpenes, sesquiterpenes and phenolic BVOC. This behaviour was independent of the tree species and whether the de novo emissions were constitutive or induced by biotic stress. In contrast, application of thermal stress to conifers amplified the release of monoterpenes stored in resin ducts of conifers and induced emissions of green leaf volatiles. In particular during insect attack on conifers, the plants showed de novo emissions of sesquiterpenes and phenolic BVOCs, which exceeded constitutive monoterpene emissions from pools. The heat-induced decrease of de novo emissions was larger than the increased monoterpene release caused by damage of resin ducts. For insect-infested conifers the net effect of thermal stress on BVOC emissions could be an overall decrease. Global change-induced heat waves may put hard thermal stress on plants. If so, we project that BVOC emissions increase is more than predicted by models only in areas predominantly covered with conifers that do not emit high amounts of sesquiterpenes and phenolic BVOCs. Otherwise overall effects of high temperature stress will be lower increases of BVOC emissions than predicted by algorithms that do not consider stress impacts.

Unreal perpetual motion machine, Rydberg constant and Carnot non-unitary efficiency as a consequence of the atomic irreversibility

NASA Astrophysics Data System (ADS)

Lucia, Umberto

2018-02-01

A perpetual motion machine is a completely ideal engine which cannot be realized. Carnot introduced the concept of the ideal engine which operates on a completely reversible cycle, without any dissipation, but with an upper limit in it. So, even in ideal condition without any dissipation, there is something that prevents the conversion of all the energy absorbed by an ideal reservoir into work. But what is the cause of irreversibility? Here we highlight the atomic nature of this irreversibility, proving that it is no more than the continuous interaction of the atoms with the surrounding field. The macroscopic irreversibility is the consequence of the microscopic irreversibility.

Parametric study of irreversible electroporation with different needle electrodes: electrical and thermal analysis.

PubMed

Nickfarjam, Abolfazl; Firoozabadi, S Mohammad P

2014-08-01

Irreversible electroporation (IRE) is a new tumour ablation method used in cancer treatment procedures. In a successful IRE treatment it is crucial to impose minimum thermal damage to the tumour and its surrounding healthy tissue, while subjecting the entire tumour to a strong electric field. Here we present a 3D model of a subcutaneous tumour in a four-layer skin using a geometry-based finite element approach. Four common needle electrode configurations were studied in this paper. The study evaluated six essential factors which are important in the electrical and thermal distributions in tumour and normal tissue. The results revealed that a hexagonal 3 × 3 geometry provides the maximum electrical coverage of the tumour, compared to other electrode configurations. However, in some cases the hexagonal 2 × 2 geometry can ablate the entire tumour with less damage to normal tissue. We found that the deeper insertion of 2- and 4-electrode geometries can lead to more damage to healthy tissue. The results also indicate that the insertion of the electrodes into tumour tissue can increase thermal damage dramatically due to existing large electrical conductivity. These findings suggest that needle electrodes should not be placed within the tumour tissue if the goal is to prevent thermal damage. This method can be used as a trade-off between electric field coverage in tumour tissue and thermal damage to both tumour and normal tissue.

Rhabdomyolysis after sleeve gastrectomy: increase in muscle enzymes does not predict fatal outcome.

PubMed

Foresteri, Pietro; Pietro, Forestieri; Formato, Antonio; Antonio, Formato; Pilone, Vincenzo; Vincenzo, Pilone; Romano, Antonietta; Antonietta, Romano; Monda, Antonietta; Angela, Monda; Tramontano, Salvatore; Salvatore, Tramontano

2008-03-01

Rhabdomyolysis (RML) is a clinical and biochemical syndrome caused by destruction of skeletal muscles and constitutes a complication of bariatric surgery, with an incidence near to 22%. It is accompanied by increase in serum of intracellular enzymes. Laboratory data as predictive of prognosis have been evaluated by some authors. We report a case of RML after a sleeve gastrectomy, with good prognosis despite a very extensive muscle damage and very high seric and urinary peaks of intracellular enzymes. We describe a 34-years-old super-obese male (body mass index, 54.3 kg/m2) who underwent to laparoscopic sleeve gastrectomy. After 24 h, patient complained of pain in gluteal region, oliguria, and high levels of creatine phosphokinase that reached to 58,395 IU/l. Acute renal failure related to RML was diagnosed. Dialysis was not necessary. Ambulatorial control of renal function after dimission did not reveal a permanent damage. RML is a biochemical syndrome recently associated with bariatric surgery. Early diagnosis is ever necessary. Laboratory data represent markers for diagnosis and prognostic indicator of renal failure. There is no clear relation between seric levels of intracellular enzymes and irreversible renal damage and RML-related mortality.

Establishment of dsDNA/GNs/chit/GCE biosensor and electrochemical study on interaction between 6-mercaptopurine and DNA.

PubMed

Tang, Wenwei; Zhang, Min; Zeng, Xinping

2014-01-01

In this paper, the anti-cancer drug 6-mercaptopurine (6-MP) was taken as the detection object. The biosensor of dsDNA/GNs/chit/GCE was established using the grapheme (GNs) and chitosan (chit) as the compound modified material. The electrochemical behavior of 6-MP on the sensor was discussed, and the damage and its mechanism of 6-MP on DNA were studied. The experimental result showed that, after the modification of GNs-chit, the electrode activation area of GNs/chit/GCE increased remarkably, which was improved from 1.76cm2 to 8.64 cm2, and the responsive oxidation peak current of GNs/chit/GCE to K3[Fe(CN)6] also increased remarkably. At the meantime, it was demonstrated that DNA was effectively fixed on the GNs/chit/GCE electrode;6-MP caused obvious damage to dsDNA, and the damage degree on the adenine was bigger than that on the guanine; the interaction between 6-MP and dsDNA was preliminarily deduced as the intercalation, and its electrochemical oxidation process was an irreversible process controlled by the adsorption.

Impact of acid mine drainage on haematological, histopathological and genotoxic effects in golden mahaseer, Tor putitora.

PubMed

Shahi, Neetu; Sarma, Debaji; Pandey, Jyoti; Das, Partha; Sarma, Dandadhar; Mallik, Sumanta Kumar

2016-07-01

The present study was carried out to evaluate sub-lethal mechanism of acid mine drainage toxicity in fingerlings (9.5 ± 2.4 cm) of golden mahseer, Tor putitora. Exposed fingerlings showed significant reduction (P < 0.01) in blood erythrocytes, neutrophils, thrombocytes, lymphocytes and leukocytes in contrast to increase in number of immature circulating cells. Hyperplasia, degeneration of glomeruli, presence of inflammatory cells and increased number of melanomacrophage aggregates, vacuolization of cell cytoplasm, hepatocyte swelling were marked in kidney and liver of fish. Ladder in, an increment of 180-200 bp of hepatic and kidney DNA, by electrophoresis were consistent with DNA damage. 10 day exposure to acid mine drainage resulted in reduction of double stranded DNA to 46.0 and 48.0 in hepatocytes and kidney cells respectively. Significant increase (P < 0.01) in tail length and percent tail DNA was evident by comet assay. The results suggest that exposure to acid mine drainage might cause irreversible damage to immune cells, tissue and DNA of fish, and this model of DNA damage may contribute in identifying novel molecular mechanism of interest for bioremediation application.

Time-Dependent Impact of Irreversible Electroporation on Pancreas, Liver, Blood Vessels and Nerves: A Systematic Review of Experimental Studies

PubMed Central

Agnass, P.; Crezee, J.; Dijk, F.; Verheij, J.; van Gulik, T. M.; Meijerink, M. R.; Vroomen, L. G.; van Lienden, K. P.; Besselink, M. G.

2016-01-01

Introduction Irreversible electroporation (IRE) is a novel ablation technique in the treatment of unresectable cancer. The non-thermal mechanism is thought to cause mostly apoptosis compared to necrosis in thermal techniques. Both in experimental and clinical studies, a waiting time between ablation and tissue or imaging analysis to allow for cell death through apoptosis, is often reported. However, the dynamics of the IRE effect over time remain unknown. Therefore, this study aims to summarize these effects in relation to the time between treatment and evaluation. Methods A systematic search was performed in Pubmed, Embase and the Cochrane Library for original articles using IRE on pancreas, liver or surrounding structures in animal or human studies. Data on pathology and time between IRE and evaluation were extracted. Results Of 2602 screened studies, 36 could be included, regarding IRE in liver (n = 24), pancreas (n = 4), blood vessels (n = 4) and nerves (n = 4) in over 440 animals (pig, rat, goat and rabbit). No eligible human studies were found. In liver and pancreas, the first signs of apoptosis and haemorrhage were observed 1–2 hours after treatment, and remained visible until 24 hours in liver and 7 days in pancreas after which the damaged tissue was replaced by fibrosis. In solitary blood vessels, the tunica media, intima and lumen remained unchanged for 24 hours. After 7 days, inflammation, fibrosis and loss of smooth muscle cells were demonstrated, which persisted until 35 days. In nerves, the median time until demonstrable histological changes was 7 days. Conclusions Tissue damage after IRE is a dynamic process with remarkable time differences between tissues in animals. Whereas pancreas and liver showed the first damages after 1–2 hours, this took 24 hours in blood vessels and 7 days in nerves. PMID:27870918

Lysosome and Phagosome Stability in Lethal Cell Injury

PubMed Central

Hawkins, Hal K.; Ericsson, Jan L. E.; Biberfeld, Peter; Trump, Benjamin F.

1972-01-01

In two types of cell injury in a tissue culture system, the possibility was tested that lysosome rupture may be a lethal cellular reaction to injury, and thus an important general cause of irreversibility of damage in injured tissue. Prior labeling of secondary lysosomes with the fluorochrome acridine orange, or with ferritin, was used to trace changes in lysosomes after applying an injury. The metabolic inhibitors iodoacetate and cyanide were used together to block the cell's energy supply, or attachment of antiserum and subsequent complement attack were used to damage the surface membrane, producing rapid loss of cell volume control. Living cells were studied by time-lapse phase-contrast cinemicrography and fluorescence microscopy, and samples were fixed at intervals for electron microscopy. The cytolytic action of complement was lethal to sensitized cells within 2 hours, but results showed that lysosomes did not rupture for approximately 4 hours and in fact did not release the fluorescent dye until after reaching the postmortem necrotic phase of injury. Cells treated with metabolic inhibitors also showed irreversible alterations, while lysosomes remained intact and retained the ferritin marker. The fluorochrome marker, acridine orange, escaped from lysosomes early after metabolic injury, but the significance of this observation is not clear. The results are interpreted as evidence against the concept that lysosome rupture threatens the survival of injured cells. The original suicide bag mechanism of cell damage thus is apparently not operative in the systems studied. Lysosomes appear to be relatively stable organelles which, following injury of the types studied, burst only after cell death, acting then as scavengers which help to clear cellular debris. ImagesFigs 5-7Fig 18Fig 19Fig 20Figs 21-23Fig 8Fig 9Fig 10Fig 11Figs 24-27Fig 12Figs 13 and 14Fig 1Fig 2Fig 3Fig 4Fig 15Fig 16Fig 17 PMID:4340333

High transduction efficiency of circulating first trimester fetal mesenchymal stem cells: potential targets for in utero ex vivo gene therapy.

PubMed

Campagnoli, Cesare; Bellantuono, Ilaria; Kumar, Sailesh; Fairbairn, Leslie J; Roberts, Irene; Fisk, Nicholas M

2002-08-01

We recently reported the existence of fetal mesenchymal stem cells in first trimester fetal blood. Here we demonstrate that fetal mesenchymal stem cells from as early as eight weeks of gestation can be retrovirally transduced with 99% efficiency without selection. Circulating fetal mesenchymal stem cells are known to readily expand and differentiate into multiple tissue types both in vitro and in vivo, and might be suitable vehicles for prenatal gene delivery. With advances in early fetal blood sampling techniques, we suggest that genetic disorders causing irreversible damage before birth could be treated in utero in the late first/early second trimester by genetically manipulated autologous fetal stem cells.

Protective effects of D-Trp6-luteinising hormone-releasing hormone microcapsules against cyclophosphamide-induced gonadotoxicity in female rats.

PubMed

Bokser, L; Szende, B; Schally, A V

1990-06-01

The possible protective effect of an agonist of luteinising hormone-releasing hormone (LH-RH) against the ovarian damage caused by cyclophosphamide was investigated in rats. D-Trp6-LH-RH microcapsules were injected once a month for 3 months, in a dose calculated to release 25 micrograms day-1. Control animals received the injection vehicle. Sixty days after the first injection of microcapsules, cyclophosphamide was given at a loading dose of 50 mg kg-1 followed by 5 mg kg-1 day-1 for 30 days, while the treatment with D-Trp6-LH-RH was continued. When the ovaries were examined 3 months and 5 months after discontinuation of treatment, a significant reduction in the total number of follicles (P less than 0.01) was found in non-pretreated animals given cyclophosphamide. This reduction affected mainly follicles larger than 100 microns. An irreversible disintegration and destruction of granulosa cells was also observed in this group. In animals pretreated with D-Trp6-LH-RH, administration of cyclophosphamide caused no reduction in the number and diameter of follicles. Thus, the treatment with D-Trp6-LH-RH microcapsules before and during chemotherapy prevented the ovarian injury inflicted by cyclophosphamide. The suppression of gonadal function by LH-RH analogues could be possibly utilised for the protection of the ovaries against damage caused by cytotoxic drugs.

Protective effects of D-Trp6-luteinising hormone-releasing hormone microcapsules against cyclophosphamide-induced gonadotoxicity in female rats.

PubMed Central

Bokser, L.; Szende, B.; Schally, A. V.

1990-01-01

The possible protective effect of an agonist of luteinising hormone-releasing hormone (LH-RH) against the ovarian damage caused by cyclophosphamide was investigated in rats. D-Trp6-LH-RH microcapsules were injected once a month for 3 months, in a dose calculated to release 25 micrograms day-1. Control animals received the injection vehicle. Sixty days after the first injection of microcapsules, cyclophosphamide was given at a loading dose of 50 mg kg-1 followed by 5 mg kg-1 day-1 for 30 days, while the treatment with D-Trp6-LH-RH was continued. When the ovaries were examined 3 months and 5 months after discontinuation of treatment, a significant reduction in the total number of follicles (P less than 0.01) was found in non-pretreated animals given cyclophosphamide. This reduction affected mainly follicles larger than 100 microns. An irreversible disintegration and destruction of granulosa cells was also observed in this group. In animals pretreated with D-Trp6-LH-RH, administration of cyclophosphamide caused no reduction in the number and diameter of follicles. Thus, the treatment with D-Trp6-LH-RH microcapsules before and during chemotherapy prevented the ovarian injury inflicted by cyclophosphamide. The suppression of gonadal function by LH-RH analogues could be possibly utilised for the protection of the ovaries against damage caused by cytotoxic drugs. Images Figure 2 PMID:2142603

Cochlear Homocysteine Metabolism at the Crossroad of Nutrition and Sensorineural Hearing Loss.

PubMed

Partearroyo, Teresa; Vallecillo, Néstor; Pajares, María A; Varela-Moreiras, Gregorio; Varela-Nieto, Isabel

2017-01-01

Hearing loss (HL) is one of the most common causes of disability, affecting 360 million people according to the World Health Organization (WHO). HL is most frequently of sensorineural origin, being caused by the irreversible loss of hair cells and/or spiral ganglion neurons. The etiology of sensorineural HL (SNHL) is multifactorial, with genetic and environmental factors such as noise, ototoxic substances and aging playing a role. The nutritional status is central in aging disability, but the interplay between nutrition and SNHL has only recently gained attention. Dietary supplementation could therefore constitute the first step for the prevention and potential repair of hearing damage before it reaches irreversibility. In this context, different epidemiological studies have shown correlations among the nutritional condition, increased total plasma homocysteine (tHcy) and SNHL. Several human genetic rare diseases are also associated with homocysteine (Hcy) metabolism and SNHL confirming this potential link. Accordingly, rodent experimental models have provided the molecular basis to understand the observed effects. Thus, increased tHcy levels and vitamin deficiencies, such as folic acid (FA), have been linked with SNHL, whereas long-term dietary supplementation with omega-3 fatty acids improved Hcy metabolism, cell survival and hearing acuity. Furthermore, pharmacological supplementations with the anti-oxidant fumaric acid that targets Hcy metabolism also improved SNHL. Overall these results strongly suggest that cochlear Hcy metabolism is a key player in the onset and progression of SNHL, opening the way for the design of prospective nutritional therapies.

Cochlear Homocysteine Metabolism at the Crossroad of Nutrition and Sensorineural Hearing Loss

PubMed Central

Partearroyo, Teresa; Vallecillo, Néstor; Pajares, María A.; Varela-Moreiras, Gregorio; Varela-Nieto, Isabel

2017-01-01

Hearing loss (HL) is one of the most common causes of disability, affecting 360 million people according to the World Health Organization (WHO). HL is most frequently of sensorineural origin, being caused by the irreversible loss of hair cells and/or spiral ganglion neurons. The etiology of sensorineural HL (SNHL) is multifactorial, with genetic and environmental factors such as noise, ototoxic substances and aging playing a role. The nutritional status is central in aging disability, but the interplay between nutrition and SNHL has only recently gained attention. Dietary supplementation could therefore constitute the first step for the prevention and potential repair of hearing damage before it reaches irreversibility. In this context, different epidemiological studies have shown correlations among the nutritional condition, increased total plasma homocysteine (tHcy) and SNHL. Several human genetic rare diseases are also associated with homocysteine (Hcy) metabolism and SNHL confirming this potential link. Accordingly, rodent experimental models have provided the molecular basis to understand the observed effects. Thus, increased tHcy levels and vitamin deficiencies, such as folic acid (FA), have been linked with SNHL, whereas long-term dietary supplementation with omega-3 fatty acids improved Hcy metabolism, cell survival and hearing acuity. Furthermore, pharmacological supplementations with the anti-oxidant fumaric acid that targets Hcy metabolism also improved SNHL. Overall these results strongly suggest that cochlear Hcy metabolism is a key player in the onset and progression of SNHL, opening the way for the design of prospective nutritional therapies. PMID:28487633

Electric Ablation with Irreversible Electroporation (IRE) in Vital Hepatic Structures and Follow-up Investigation

PubMed Central

Chen, Xinhua; Ren, Zhigang; Zhu, Tongyin; Zhang, Xiongxin; Peng, Zhiyi; Xie, Haiyang; Zhou, Lin; Yin, Shengyong; Sun, Junhui; Zheng, Shusen

2015-01-01

Irreversible electroporation (IRE) with microsecond-pulsed electric fields (μsPEFs) can effectively ablate hepatocellular carcinomas in animal models. This preclinical study evaluates the feasibility and safety of IRE on porcine livers. Altogether, 10 pigs were included. Computed tomography (CT) was used to guide two-needle electrodes that were inserted near the hilus hepatis and gall bladder. Animals were followed-up at 2 hours and at 2, 7 and 14 days post-treatment. During and after μsPEF ablation, electrocardiographs found no cardiovascular events, and contrast CT found no portal vein thrombosis. There was necrosis in the ablation zone. Mild cystic oedema around the gall bladder was found 2 hours post-treatment. Pathological studies showed extensive cell death. There was no large vessel damage, but there was mild endothelial damage in some small vessels. Follow-up liver function tests and routine blood tests showed immediate liver function damage and recovery from the damage, which correlated to the pathological changes. These results indicate that μsPEF ablation affects liver tissue and is less effective in vessels, which enable μsPEFs to ablate central tumour lesions close to the hilus hepatis and near large vessels and bile ducts, removing some of the limitations and contraindications of conventional thermal ablation. PMID:26549662

Electric Ablation with Irreversible Electroporation (IRE) in Vital Hepatic Structures and Follow-up Investigation.

PubMed

Chen, Xinhua; Ren, Zhigang; Zhu, Tongyin; Zhang, Xiongxin; Peng, Zhiyi; Xie, Haiyang; Zhou, Lin; Yin, Shengyong; Sun, Junhui; Zheng, Shusen

2015-11-09

Irreversible electroporation (IRE) with microsecond-pulsed electric fields (μsPEFs) can effectively ablate hepatocellular carcinomas in animal models. This preclinical study evaluates the feasibility and safety of IRE on porcine livers. Altogether, 10 pigs were included. Computed tomography (CT) was used to guide two-needle electrodes that were inserted near the hilus hepatis and gall bladder. Animals were followed-up at 2 hours and at 2, 7 and 14 days post-treatment. During and after μsPEF ablation, electrocardiographs found no cardiovascular events, and contrast CT found no portal vein thrombosis. There was necrosis in the ablation zone. Mild cystic oedema around the gall bladder was found 2 hours post-treatment. Pathological studies showed extensive cell death. There was no large vessel damage, but there was mild endothelial damage in some small vessels. Follow-up liver function tests and routine blood tests showed immediate liver function damage and recovery from the damage, which correlated to the pathological changes. These results indicate that μsPEF ablation affects liver tissue and is less effective in vessels, which enable μsPEFs to ablate central tumour lesions close to the hilus hepatis and near large vessels and bile ducts, removing some of the limitations and contraindications of conventional thermal ablation.

Irreversible climate change due to carbon dioxide emissions.

PubMed

Solomon, Susan; Plattner, Gian-Kasper; Knutti, Reto; Friedlingstein, Pierre

2009-02-10

The severity of damaging human-induced climate change depends not only on the magnitude of the change but also on the potential for irreversibility. This paper shows that the climate change that takes place due to increases in carbon dioxide concentration is largely irreversible for 1,000 years after emissions stop. Following cessation of emissions, removal of atmospheric carbon dioxide decreases radiative forcing, but is largely compensated by slower loss of heat to the ocean, so that atmospheric temperatures do not drop significantly for at least 1,000 years. Among illustrative irreversible impacts that should be expected if atmospheric carbon dioxide concentrations increase from current levels near 385 parts per million by volume (ppmv) to a peak of 450-600 ppmv over the coming century are irreversible dry-season rainfall reductions in several regions comparable to those of the "dust bowl" era and inexorable sea level rise. Thermal expansion of the warming ocean provides a conservative lower limit to irreversible global average sea level rise of at least 0.4-1.0 m if 21st century CO(2) concentrations exceed 600 ppmv and 0.6-1.9 m for peak CO(2) concentrations exceeding approximately 1,000 ppmv. Additional contributions from glaciers and ice sheet contributions to future sea level rise are uncertain but may equal or exceed several meters over the next millennium or longer.

Irreversible climate change due to carbon dioxide emissions

PubMed Central

Solomon, Susan; Plattner, Gian-Kasper; Knutti, Reto; Friedlingstein, Pierre

2009-01-01

The severity of damaging human-induced climate change depends not only on the magnitude of the change but also on the potential for irreversibility. This paper shows that the climate change that takes place due to increases in carbon dioxide concentration is largely irreversible for 1,000 years after emissions stop. Following cessation of emissions, removal of atmospheric carbon dioxide decreases radiative forcing, but is largely compensated by slower loss of heat to the ocean, so that atmospheric temperatures do not drop significantly for at least 1,000 years. Among illustrative irreversible impacts that should be expected if atmospheric carbon dioxide concentrations increase from current levels near 385 parts per million by volume (ppmv) to a peak of 450–600 ppmv over the coming century are irreversible dry-season rainfall reductions in several regions comparable to those of the “dust bowl” era and inexorable sea level rise. Thermal expansion of the warming ocean provides a conservative lower limit to irreversible global average sea level rise of at least 0.4–1.0 m if 21st century CO2 concentrations exceed 600 ppmv and 0.6–1.9 m for peak CO2 concentrations exceeding ≈1,000 ppmv. Additional contributions from glaciers and ice sheet contributions to future sea level rise are uncertain but may equal or exceed several meters over the next millennium or longer. PMID:19179281

NEUROPHYSIOLOGICAL CONSEQUENCES IN HIPPOCAMPUS AS A FUNCTION OF DEVELOPMENTAL HYPOTHYROIDISM.

EPA Science Inventory

Thyroid hormones are essential for maturation and function of the mammalian central nervous system. Severe congenital hypothyroidism results in irreversible structural damage and mental retardation in children. Although a variety of environmental contaminants have been demonstrat...

Immediate, irreversible, posttraumatic coma: a review indicating that bilateral brainstem injury rather than widespread hemispheric damage is essential for its production.

PubMed

Rosenblum, William I

2015-03-01

Traumatic brain injury may result in immediate long-lasting coma. Much attention has been given to predicting this outcome from the initial examination because these predictions can guide future treatment and interactions with the patient's family. Reports of diffuse axonal injury in these cases have ascribed the coma to widespread damage in the deep white matter that disconnects the hemispheres from the ascending arousal system (AAS). However, brainstem lesions are also present in such cases, and the AAS may be interrupted at the brainstem level. This review examines autopsy and imaging literature that assesses the presence, extent, and predictive value of lesions in both sites. The evidence suggests that diffuse injury to the deep white matter is not the usual cause of immediate long-lasting posttraumatic coma. Instead, brainstem lesions in the rostral pons or midbrain are almost always the cause but only if the lesions are bilateral. Moreover, recovery is possible if critical brainstem inputs to the AAS are spared. The precise localization of the latter is subject to ongoing investigation with advanced imaging techniques using magnets of very high magnetic gradients. Limited availability of this equipment plus the need to verify the findings continue to require meticulous autopsy examination.

Suppression of E. multilocularis Hydatid Cysts after Ionizing Radiation Exposure

PubMed Central

Zhou, Rong; Zhang, Hong

2013-01-01

Background Heavy-ion therapy has an advantage over conventional radiotherapy due to its superb biological effectiveness and dose conformity in cancer therapy. It could be a potential alternate approach for hydatid cyst treatment. However, there is no information currently available on the cellular and molecular basis for heavy-ion irradiation induced cell death in cystic echinococcosis. Methododology/Principal Findings LD50 was scored by protoscolex death. Cellular and ultrastructural changes within the parasite were studied by light and electron microscopy, mitochondrial DNA (mtDNA) damage and copy number were measured by QPCR, and apoptosis was determined by caspase 3 expression and caspase 3 activity. Ionizing radiation induced sparse cytoplasm, disorganized and clumped organelles, large vacuoles and devoid of villi. The initial mtDNA damage caused by ionizing radiation increased in a dose-dependent manner. The kinetic of DNA repair was slower after carbon-ion radiation than that after X-rays radiation. High dose carbon-ion radiation caused irreversible mtDNA degradation. Cysts apoptosis was pronounced after radiation. Carbon-ion radiation was more effective to suppress hydatid cysts than X-rays. Conclusions These studies provide a framework to the evaluation of attenuation effect of heavy-ion radiation on cystic echinococcosis in vitro. Carbon-ion radiation is more effective to suppress E. multilocularis than X-rays. PMID:24205427

Red cell metabolism studies on Skylab

NASA Technical Reports Server (NTRS)

Mengel, C. E.

1977-01-01

Blood samples from Spacelab crewmembers were studied for possible environment effects on red cell components. Analysis involved peroxidation of red cell lipids, enzymes of red cell metabolism, and levels of 2,3-diphosphoglyceric acid and adenosine triphosphate. Results show that there is no evidence of lipid peroxidation, that biochemical effect known to be associated with irreversible red cell damage. Changes observed in glycolytic intermediates and enzymes cannot be directly implicated as indicating evidence of red cell damage.

[Identification of early irreversible damage area in a rat model of cerebral ischemia and reperfusion].

PubMed

Liu, S; Guo, Y

2000-02-01

To observe the early neuron ischemic damage in focal cerebral ischemia/reperfusion with histostaining methods of argyrophil III (AG III), Toludine blue(TB), and H&E, and to make out the 'separating line' between the areas of reversible and irreversible early ischemic damage. Forty-two male Wistar rats were randomly divided into the following groups: pseudo-surgical, blank-control, O2R0(occluded for 2 hours and reperfused for 0 hour), O2R0.5, O2R2, O2R4, O2R24. There were 6 rats in each group. Rats in experimental groups were suffered focal cerebral ischemia/reperfusion through a nylon suture method. After a special processor for tissue manage, the brain were coronal sectioned and stained with H&E, TB, and AG III. The area where dark neurons dwell in (ischemic core) were calculated with image analysis system. The success rate of ischemic model for this experiment is 90%. After being stained with argyrophil III method, normal neurons appear yellow or pale brown, which is hardly distinguished from the pale brown background. The ischemic neuron stained black, and has collapsed body and "corkscrew-like" axon or dentries, which were broken to some extent. The neuropil in the dark neurons dwelt area appears gray or pale black, which is apparently different from the pale brown neighborhood area. The distribution of dark neurons in cortex varies according to different layers, and has a character of columnar form. The dark neurons present as early as 2 hours ischemia without reperfusion with AG III method. AG III stain could selectively display early ischemic neurons, the area dwelt by dark neurons represent early ischemic core. Dark neuron is possibly the irreversibly damaged neuron. Identification of dark neurons could be helpful in the discrimination between early ischemic center and penumbra.

Kainate and metabolic perturbation mimicking spinal injury differentially contribute to early damage of locomotor networks in the in vitro neonatal rat spinal cord.

PubMed

Taccola, G; Margaryan, G; Mladinic, M; Nistri, A

2008-08-13

Acute spinal cord injury evolves rapidly to produce secondary damage even to initially spared areas. The result is loss of locomotion, rarely reversible in man. It is, therefore, important to understand the early pathophysiological processes which affect spinal locomotor networks. Regardless of their etiology, spinal lesions are believed to include combinatorial effects of excitotoxicity and severe stroke-like metabolic perturbations. To clarify the relative contribution by excitotoxicity and toxic metabolites to dysfunction of locomotor networks, spinal reflexes and intrinsic network rhythmicity, we used, as a model, the in vitro thoraco-lumbar spinal cord of the neonatal rat treated (1 h) with either kainate or a pathological medium (containing free radicals and hypoxic/aglycemic conditions), or their combination. After washout, electrophysiological responses were monitored for 24 h and cell damage analyzed histologically. Kainate suppressed fictive locomotion irreversibly, while it reversibly blocked neuronal excitability and intrinsic bursting induced by synaptic inhibition block. This result was associated with significant neuronal loss around the central canal. Combining kainate with the pathological medium evoked extensive, irreversible damage to the spinal cord. The pathological medium alone slowed down fictive locomotion and intrinsic bursting: these oscillatory patterns remained throughout without regaining their control properties. This phenomenon was associated with polysynaptic reflex depression and preferential damage to glial cells, while neurons were comparatively spared. Our model suggests distinct roles of excitotoxicity and metabolic dysfunction in the acute damage of locomotor networks, indicating that different strategies might be necessary to treat the various early components of acute spinal cord lesion.

Analysis of thermal damage in vocal cords for the prevention of collateral laser treatment effects

NASA Astrophysics Data System (ADS)

Fanjul Vélez, Félix; Luis Arce-Diego, José; del Barrio Fernández, Ángela; Borragán Torre, Alfonso

2007-05-01

The importance of vocal cords for the interaction with the world around is obviously known. Vocal cords disorders can be divided mainly into three categories: difficulty of movement of one or both vocal folds, lesion formation on them, and difficulty or lack of mucosal wave movement. In this last case, a laser heating treatment can be useful in order to improve tissue vibration. However, thermal damage should be considered to adjust laser parameters and so to prevent irreversible harmful effects to the patient. in this work, an analysis of thermal damage in vocal folds is proposed. Firstly thermo-optical laser-tissue interaction is studied, by means of a RTT (Radiation Transfer Theory) model solved with a Monte Carlo approach for the optical propagation of radiation, and a bio-heat equation, with a finite difference numerical method based solution, taking into account blood perfusion and boundary effects, for the thermal distribution. The spatial-temporal temperature distributions are obtained for two widely used lasers, Nd:YAG (1064 nm) and KTP (532 nm). From these data, an Arrhenius thermal damage analysis allows a prediction of possible laser treatment harmful effects on vocal cords that could cause scar formation or tissue burn. Different source powers and exposition times are considered, in such a way that an approximation of adequate wavelength, power and duration is achieved, in order to implement an efficient and safe laser treatment.

Abandoning the dead donor rule? A national survey of public views on death and organ donation

PubMed Central

Nair-Collins, Michael; Green, Sydney R; Sutin, Angelina R

2015-01-01

Brain dead organ donors are the principal source of transplantable organs. However, it is controversial whether brain death is the same as biological death. Therefore, it is unclear whether organ removal in brain death is consistent with the ‘dead donor rule’, which states that organ removal must not cause death. Our aim was to evaluate the public's opinion about organ removal if explicitly described as causing the death of a donor in irreversible apneic coma. We conducted a cross-sectional internet survey of the American public (n=1096). Questionnaire domains included opinions about a hypothetical scenario of organ removal described as causing the death of a patient in irreversible coma, and items measuring willingness to donate organs after death. Some 71% of the sample agreed that it should be legal for patients to donate organs in the scenario described and 67% agreed that they would want to donate organs in a similar situation. Of the 85% of the sample who agreed that they were willing to donate organs after death, 76% agreed that they would donate in the scenario of irreversible coma with organ removal causing death. There appears to be public support for organ donation in a scenario explicitly described as violating the dead donor rule. Further, most but not all people who would agree to donate when organ removal is described as occurring after death would also agree to donate when organ removal is described as causing death in irreversible coma. PMID:25260779

Involvement of HLA class I molecules in the immune escape of urologic tumors.

PubMed

Carretero, R; Gil-Julio, H; Vázquez-Alonso, F; Garrido, F; Castiñeiras, J; Cózar, J M

2014-04-01

To analyze the influence of different alterations in human leukocyte antigen class I molecules (HLA I) in renal cell carcinoma, as well as in bladder and prostate cancer. We also study the correlation between HLA I expression and the progression of the disease and the response after immunotherapy protocols. It has been shown, experimentally, that the immune system can recognize and kill neoplastic cells. By analyzing the expression of HLA I molecules on the surface of cancer cells, we were able to study the tumor escape mechanisms against the immune system. Alteration or irreversible damage in HLA I molecules is used by the neoplastic cells to escape the immune system. The function of these molecules is to recognize endogenous peptides and present them to T cells of the immune system. There is a clear relationship between HLA I reversible alterations and success of therapy. Irreversible lesions also imply a lack of response to treatment. The immune system activation can reverse HLA I molecules expression in tumors with reversible lesions, whereas tumors with irreversible ones do not respond to such activation. Determine the type of altered HLA I molecules in tumors is of paramount importance when choosing the type of treatment to keep looking for therapeutic success. Those tumors with reversible lesions can be treated with traditional immunotherapy; however, tumour with irreversible alterations should follow alternative protocols, such as the use of viral vectors carrying the HLA genes to achieve damaged re-expression of the protein. From studies in urologic tumors, we can conclude that the HLA I molecules play a key role in these tumors escape to the immune system. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

Strand Plasticity Governs Fatigue in Colloidal Gels

NASA Astrophysics Data System (ADS)

van Doorn, Jan Maarten; Verweij, Joanne E.; Sprakel, Joris; van der Gucht, Jasper

2018-05-01

The repeated loading of a solid leads to microstructural damage that ultimately results in catastrophic material failure. While posing a major threat to the stability of virtually all materials, the microscopic origins of fatigue, especially for soft solids, remain elusive. Here we explore fatigue in colloidal gels as prototypical inhomogeneous soft solids by combining experiments and computer simulations. Our results reveal how mechanical loading leads to irreversible strand stretching, which builds slack into the network that softens the solid at small strains and causes strain hardening at larger deformations. We thus find that microscopic plasticity governs fatigue at much larger scales. This gives rise to a new picture of fatigue in soft thermal solids and calls for new theoretical descriptions of soft gel mechanics in which local plasticity is taken into account.

Effects of radiotherapy on parotid salivary sialochemistry in head and neck cancer patients.

PubMed

Gupta, S C; Singla, Alok; Singh, Mangal; Thaliath, B Paul; Geeta, Jaiswal

2009-12-01

To determine the effects of high dose irradiation on parotid salivary sodium and pH concentration at subsequent duration of 1.5, 3 and 6 months following radiotherapy. Eighty parotid glands of head and neck cancer patients were irradiated with mean dose of 66 Gy. The stimulated parotid flow (PF) was collected by a cannulation of Stenson's duct followed by analysis of sodium (PF sodium) by Easylyte Sodium/Potassium auto analyzer and pH by litmus narrow band pH paper. A steep elevation of PF sodium was found in post-RT period after 1.5 months of starting RT followed by gradual increase up to 6 months and pH changed towards acidity. A high dose of 66 Gy causes irreversible damage to parotid salivary duct system.

Modern high powered led curing lights and their effect on pulp chamber temperature of bulk and incrementally cured composite resin.

PubMed

Oberholzer, T G; Makofane, M E; du Preez, I C; George, R

2012-06-01

Pulpal temperature changes induced by modern high powered light emitting diodes (LEDs) are of concern when used to cure composite resins. This study showed an increase in pulp chamber temperature with an increase in power density for all light cure units (LCU) when used to bulk cure composite resin. Amongst the three LEDs tested, the Elipar Freelight-2 recorded the highest temperature changes. Bulk curing recorded a significantly larger rise in pulp chamber temperature change than incrementally cured resin for all light types except for the Smartligh PS. Both the high powered LED and the conventional curing units can generate heat. Though this temperature rise may not be sufficient to cause irreversible pulpal damage, it would be safer to incrementally cure resins.

PPARγ in emphysema: blunts the damage and triggers repair?

PubMed Central

Kelly, Neil J.; Shapiro, Steven D.

2014-01-01

Cigarette smoke is the most common cause of pulmonary emphysema, which results in an irreversible loss of lung structure and function. Th1 and Th17 immune responses have been implicated in emphysema pathogenesis; however, the drivers of emphysema-associated immune dysfunction are not fully understood. In this issue of the JCI, Shan and colleagues found that peroxisome proliferator–activated receptor γ (PPARγ) is downregulated in APCs isolated from the lungs of emphysematous chronic smokers and mice exposed to cigarette smoke. Furthermore, treatment with a PPARγ agonist prevented emphysema development and appeared to reduce emphysema-associated lung volume expansion in mice exposed to cigarette smoke. Further work will need to be done to evaluate the potential of PPARγ agonists to restore lung capacity in emphysematous patients. PMID:24569365

Engineering craniofacial structures: facing the challenge.

PubMed

Zaky, S H; Cancedda, R

2009-12-01

The human innate regenerative ability is known to be limited by the intensity of the insult together with the availability of progenitor cells, which may cause certain irreparable damage. It is only recently that the paradigm of tissue engineering found its way to the treatment of irreversibly affected body structures with the challenge of reconstructing the lost part. In the current review, we underline recent trials that target engineering of human craniofacial structures, mainly bone, cartilage, and teeth. We analyze the applied engineering strategies relative to the selection of cell types to lay down a specific targeted tissue, together with their association with an escorting scaffold for a particular engineered site, and discuss their necessity to be sustained by growth factors. Challenges and expectations for facial skeletal engineering are discussed in the context of future treatment.

Homozygous G320V mutation in the HJV gene causing juvenile hereditary haemochromatosis type A. A case report.

PubMed

Militaru, Mariela S; Popp, Radu A; Trifa, Adrian P

2010-06-01

While classical hereditary haemochromatosis, usually associated with mutations in the HFE gene, has an adult age onset and a long, progressive evolution, juvenile haemochromatosis, most often associated with mutations in the HJV gene, is a more severe, rapidly progressive condition and has an onset before the age of 30. We report a 26-year old woman with a severe iron overload, affected by hypogonadotropic hypogonadism and moderate dilative cardiomyopathy, in whom the molecular analysis revealed a homozygous genotype for G320V mutation in the HJV gene. As juvenile haemochromatosis is a severe disease, death usually occurring from cardiac involvement, an efficient iron removal from the body strategy should be started as soon as possible, in order to prevent irreversible damage.

[Intra-osseous ganglion cyst of the carpal bones. A review of the literature underlining the importance of systematic computed tomography].

PubMed

Dumas, P; Georgiou, C; Chignon-Sicard, B; Balaguer, T; Lebreton, E; Dumontier, C

2013-02-01

The intraosseous ganglion cyst (IOGC) is a benign and lytic bone tumor affecting mostly the metaphyseal and epiphyseal regions of long bones. Its location on the short bones, including the carpal bones has been little reported in the literature. Our review of the literature shows consensus about the surgical techniques to use, but there is currently no real consensus about its pathophysiology, and its diagnostic work-up. Complications related to this lesion (mainly the risk of pathologic fracture) are potentially serious, and can cause irreversible damage. They therefore require accurate assessment to guide the choice of medical or surgical treatment, including a CT scan, which - we believe - is essential. Copyright © 2012. Published by Elsevier SAS.

The influence of innate and adaptative immune responses on the differential clinical outcomes of leprosy.

PubMed

Fonseca, Adriana Barbosa de Lima; Simon, Marise do Vale; Cazzaniga, Rodrigo Anselmo; de Moura, Tatiana Rodrigues; de Almeida, Roque Pacheco; Duthie, Malcolm S; Reed, Steven G; de Jesus, Amelia Ribeiro

2017-02-06

Leprosy is a chronic infectious disease caused by Mycobacterium leprae. According to official reports from 121 countries across five WHO regions, there were 213 899 newly diagnosed cases in 2014. Although leprosy affects the skin and peripheral nerves, it can present across a spectrum of clinical and histopathological forms that are strongly influenced by the immune response of the infected individuals. These forms comprise the extremes of tuberculoid leprosy (TT), with a M. leprae-specific Th1, but also a Th17, response that limits M. leprae multiplication, through to lepromatous leprosy (LL), with M. leprae-specific Th2 and T regulatory responses that do not control M. leprae replication but rather allow bacterial dissemination. The interpolar borderline clinical forms present with similar, but less extreme, immune biases. Acute inflammatory episodes, known as leprosy reactions, are complications that may occur before, during or after treatment, and cause further neurological damages that can cause irreversible chronic disabilities. This review discusses the innate and adaptive immune responses, and their interactions, that are known to affect pathogenesis and influence the clinical outcome of leprosy.

Upcoming Methods and Specifications of Continuous Intraocular Pressure Monitoring Systems for Glaucoma

PubMed Central

Molaei, Amir; Karamzadeh, Vahid; Safi, Sare; Esfandiari, Hamed; Dargahi, Javad; Khosravi, Mohammad Azam

2018-01-01

Glaucoma is the leading cause of irreversible blindness and vision loss in the world. Although intraocular pressure (IOP) is no longer considered the only risk factor for glaucoma, it is still the most important one. In most cases, high IOP is secondary to trabecular meshwork dysfunction. High IOP leads to compaction of the lamina cribrosa and subsequent damage to retinal ganglion cell axons. Damage to the optic nerve head is evident on funduscopy as posterior bowing of the lamina cribrosa and increased cupping. Currently, the only documented method to slow or halt the progression of this disease is to decrease the IOP; hence, accurate IOP measurement is crucial not only for diagnosis, but also for the management. Due to the dynamic nature and fluctuation of the IOP, a single clinical measurement is not a reliable indicator of diurnal IOP; it requires 24-hour monitoring methods. Technological advances in microelectromechanical systems and microfluidics provide a promising solution for the effective measurement of IOP. This paper provides a broad overview of the upcoming technologies to be used for continuous IOP monitoring. PMID:29403593

Application of environmental scanning electron microscopy to determine biological surface structure.

PubMed

Kirk, S E; Skepper, J N; Donald, A M

2009-02-01

The use of environmental scanning electron microscopy in biology is growing as more becomes understood about the advantages and limitations of the technique. These are discussed and we include new evidence about the effect of environmental scanning electron microscopy imaging on the viability of mammalian cells. We show that although specimen preparation for high-vacuum scanning electron microscopy introduces some artefacts, there are also challenges in the use of environmental scanning electron microscopy, particularly at higher resolutions. This suggests the two technologies are best used in combination. We have used human monocyte-derived macrophages as a test sample, imaging their complicated and delicate membrane ruffles and protrusions. We have also explored the possibility of using environmental scanning electron microscopy for dynamic experiments, finding that mammalian cells cannot be imaged and kept alive in the environmental scanning electron microscopy. The dehydration step in which the cell surface is exposed causes irreversible damage, probably via loss of membrane integrity during liquid removal in the specimen chamber. Therefore, mammalian cells should be imaged after fixation where possible to protect against damage as a result of chamber conditions.

A new cause of ischaemic priapism: Synthetic cannabinoids.

PubMed

Ortac, M; Pazır, Y; Kadıoğlu, A

2018-04-01

Priapism is a urological emergency that needs early intervention and may lead to irreversible cavernosal damage. Ischaemic priapism is the most common type, which is frequently idiopathic and commonly associated with haematological diseases, medications or recreational drugs. Synthetic cannabinoids (SCs) have been increasingly used all over the world, particularly among young-adult population. SCs can cause severe adverse effects on several organ systems. However, there are no studies in the literature which have stated the possible relationship between using of SCs and priapism. We present a case of 28-year-old man who was diagnosed with a 58-hr lasting priapism after regular administrations of SCs. The priapism did not resolve neither after applying aspiration with irrigation nor shunt surgery. Finally, penile prosthesis implantation was performed as last treatment option. The SCs have been increasingly used among young population in recent years; therefore, new SC-related ischaemic priapism cases might be encountered in the emergency departments. © 2018 Blackwell Verlag GmbH.

[Sportsmen's groin. Definition, differential diagnostics and therapy].

PubMed

Muschaweck, U; Gollwitzer, H; Conze, J

2015-02-01

Groin pain in athletes is a common problem and can have extensive consequences for professional athletes. The anatomical and functional complexity of the groin as well as radiating pain from remote anatomical regions can make the differential diagnostic a challenge and requires special attention. As there are a wide variety of possible causes for groin pain, a multidisciplinary approach is required. The treating orthopedic surgeon needs to pay special attention to prearthritic hip deformities to avoid irreversible damage of the hip joint. By a meticulous patient history and identification of the pain character, followed by clinical, sonographic and radiographic investigations, a differential diagnosis can usually be achieved. Besides typical orthopedic causes pathological findings particularly in the area of the groin need to be considered, clarified and adequately treated; therefore, a clear terminology of the different diseases is necessary. Sportsmen's groin is not a hernia but should be perceived as a separate entity due to its typical pain character and detection of a measurable protrusion of the posterior wall of the inguinal canal by ultrasound.

Image processing techniques applied to the detection of optic disk: a comparison

NASA Astrophysics Data System (ADS)

Kumari, Vijaya V.; Narayanan, Suriya N.

2010-02-01

In retinal image analysis, the detection of optic disk is of paramount importance. It facilitates the tracking of various anatomical features and also in the extraction of exudates, drusens etc., present in the retina of human eye. The health of retina crumbles with age in some people during the presence of exudates causing Diabetic Retinopathy. The existence of exudates increases the risk for age related macular Degeneration (AMRD) and it is the leading cause for blindness in people above the age of 50.A prompt diagnosis when the disease is at the early stage can help to prevent irreversible damages to the diabetic eye. Screening to detect diabetic retinopathy helps to prevent the visual loss. The optic disk detection is the rudimentary requirement for the screening. In this paper few methods for optic disk detection were compared which uses both the properties of optic disk and model based approaches. They are uniquely used to give accurate results in the retinal images.

43 CFR 11.21 - Emergency restorations.

Code of Federal Regulations, 2011 CFR

2011-10-01

....21 Public Lands: Interior Office of the Secretary of the Interior NATURAL RESOURCE DAMAGE ASSESSMENTS... of a natural resource emergency, the natural resource trustee shall contact the National Response... requiring immediate action to avoid an irreversible loss of natural resources or to prevent or reduce any...

43 CFR 11.21 - Emergency restorations.

Code of Federal Regulations, 2010 CFR

2010-10-01

....21 Public Lands: Interior Office of the Secretary of the Interior NATURAL RESOURCE DAMAGE ASSESSMENTS... of a natural resource emergency, the natural resource trustee shall contact the National Response... requiring immediate action to avoid an irreversible loss of natural resources or to prevent or reduce any...

On the relationship between indentation hardness and modulus, and the damage resistance of biological materials.

PubMed

Labonte, David; Lenz, Anne-Kristin; Oyen, Michelle L

2017-07-15

The remarkable mechanical performance of biological materials is based on intricate structure-function relationships. Nanoindentation has become the primary tool for characterising biological materials, as it allows to relate structural changes to variations in mechanical properties on small scales. However, the respective theoretical background and associated interpretation of the parameters measured via indentation derives largely from research on 'traditional' engineering materials such as metals or ceramics. Here, we discuss the functional relevance of indentation hardness in biological materials by presenting a meta-analysis of its relationship with indentation modulus. Across seven orders of magnitude, indentation hardness was directly proportional to indentation modulus. Using a lumped parameter model to deconvolute indentation hardness into components arising from reversible and irreversible deformation, we establish criteria which allow to interpret differences in indentation hardness across or within biological materials. The ratio between hardness and modulus arises as a key parameter, which is related to the ratio between irreversible and reversible deformation during indentation, the material's yield strength, and the resistance to irreversible deformation, a material property which represents the energy required to create a unit volume of purely irreversible deformation. Indentation hardness generally increases upon material dehydration, however to a larger extent than expected from accompanying changes in indentation modulus, indicating that water acts as a 'plasticiser'. A detailed discussion of the role of indentation hardness, modulus and toughness in damage control during sharp or blunt indentation yields comprehensive guidelines for a performance-based ranking of biological materials, and suggests that quasi-plastic deformation is a frequent yet poorly understood damage mode, highlighting an important area of future research. Instrumented indentation is a widespread tool for characterising the mechanical properties of biological materials. Here, we show that the ratio between indentation hardness and modulus is approximately constant in biological materials. A simple elastic-plastic series deformation model is employed to rationalise part of this correlation, and criteria for a meaningful comparison of indentation hardness across biological materials are proposed. The ratio between indentation hardness and modulus emerges as the key parameter characterising the relative amount of irreversible deformation during indentation. Despite their comparatively high hardness to modulus ratio, biological materials are susceptible to quasiplastic deformation, due to their high toughness: quasi-plastic deformation is hence hypothesised to be a frequent yet poorly understood phenomenon, highlighting an important area of future research. Copyright © 2017 Acta Materialia Inc. All rights reserved.

Angiography in the Isolated Perfused Kidney: Radiological Evaluation of Vascular Protection in Tissue Ablation by Nonthermal Irreversible Electroporation

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

Wendler, Johann Jakob, E-mail: johann.wendler@med.ovgu.de; Pech, Maciej; Blaschke, Simon

2012-04-15

Purpose: The nonthermal irreversible electroporation (NTIRE) is a novel nonthermal tissue ablation technique by local application of high-voltage current within microseconds leading to a delayed apoptosis. The purpose of this experimental study was the first angiographic evaluation of the acute damage of renal vascular structure in NTIRE. Methods: Results of conventional dynamic digital substraction angiography (DSA) and visualization of the terminal vascular bed of renal parenchyma by high-resolution X-ray in mammography technique were evaluated before, during, and after NTIRE of three isolated perfused porcine ex vivo kidneys. Results: In the dedicated investigation, no acute vascular destruction of the renal parenchymamore » and no dysfunction of the kidney perfusion model were observed during or after NTIRE. Conspicuous were concentric wave-like fluctuations of the DSA contrast agent simultaneous to the NTIRE pulses resulting from NTIRE pulse shock wave. Conclusion: The NTIRE offers an ablation method with no acute collateral vascular damage in angiographic evaluation.« less

Molecular determination of glutaric aciduria type I in individuals from southwest Iran.

PubMed

Baradaran, Masumeh; Galehdari, Hamid; Aminzadeh, Majid; Azizi Malmiri, Reza; Tangestani, Raheleh; Karimi, Zahra

2014-09-01

Glutaric Aciduria type 1 (GA1) is a metabolic inborn error and is characterized by increasing excursion of glutaric acid and its derivates, presented in microcephaly and dystonia. The disease is resulted from mutational inactivation in the GCDH gene encoding the glutaryl-CoA dehydrogenase. The defective enzyme causes the accumulation of an excessive level of intermediate breakdown products that leads to the brain damage. In spite of the clinical features, diagnosis of GAI has been often confusing, because of variability in the clinical manifestations of patients. Early diagnosis and treatment can though prevent irreversible disease progression and consequent brain damage; otherwise the affected individuals will die in their first decade of lives. The GCDH gene was also analyzed to (detect or identify) disease causing mutations using gene amplification and direct sequencing in 18 patients. Among 18 patients, 10 patients (55.5%) were homozygous or compounded heterozygous for the recurrent mutation E181Q, three patients (16.7%) were homozygous for the known mutation R402Q and one patient (5.6%) was compound heterozygous for S255L. All three detected missense mutations are pathogenic, which cause structural changes in the binding site and tetramerization or functional deficiency. Four other individuals (22.2%) with a preliminary diagnosis of GAI were negative for any pathogenic mutations. Most GA1 affected persons in southwest Iran are with Persian ethnicity and the most common mutation in Khuzestan Province is prominent in comparison to  previous reports from Iran.

The prion-like domain of FUS is multiphosphorylated following DNA damage without altering nuclear localization.

PubMed

Rhoads, Shannon N; Monahan, Zachary T; Yee, Debra S; Leung, Andrew Y; Newcombe, Cameron G; O'Meally, Robert N; Cole, Robert N; Shewmaker, Frank P

2018-06-13

FUS is an abundant, predominantly nuclear protein involved in RNA processing. Under various conditions, FUS functionally associates with RNA and other macromolecules to form distinct, reversible phase-separated liquid structures. Persistence of the phase-separated state and increased cytoplasmic localization are both hypothesized to predispose FUS to irreversible aggregation, which is a pathological hallmark of subtypes of amyotrophic lateral sclerosis and frontotemporal dementia. We previously showed that phosphorylation of FUS's prion-like domain suppressed phase separation and toxic aggregation, proportionally to the number of added phosphates. However, phosphorylation of FUS's prion-like domain was previously reported to promote its cytoplasmic localization, potentially favoring pathological behavior. Here, we used mass spectrometry and human cell models to further identify phosphorylation sites within FUS's prion-like domain, specifically following DNA-damaging stress. In total, 28 putative sites have been identified, about half of which are DNA-dependent protein kinase (DNA-PK) consensus sites. Custom antibodies were developed to confirm the phosphorylation of two of these sites (Ser26 and Ser30). Both sites were usually phosphorylated in a sub-population of cellular FUS following a variety of DNA-damaging stresses, but not necessarily equally or simultaneously. Importantly, we found DNA-PK-dependent multi-phosphorylation of FUS's prion-like domain does not cause cytoplasmic localization.

Qualitative and quantitative changes in phospholipids and proteins investigated by spectroscopic techniques in animal depression model.

PubMed

Depciuch, J; Sowa-Kucma, M; Nowak, G; Papp, M; Gruca, P; Misztak, P; Parlinska-Wojtan, M

2017-04-05

Depression becomes nowadays a high mortality civilization disease with one of the major causes being chronic stress. Raman, Fourier Transform Infra Red (FTIR) and Ultraviolet-Visible (UV-vis) spectroscopies were used to determine the changes in the quantity and structure of phospholipids and proteins in the blood serum of rats subjected to chronic mild stress, which is a common animal depression model. Moreover, the efficiency of the imipramine treatment was evaluated. It was found that chronic mild stress not only damages the structure of the phospholipids and proteins, but also decreases their level in the blood serum. A 5weeks imipramine treatment did increase slightly the quantity of proteins, leaving the damaged phospholipids unchanged. Structural information from phospholipids and proteins was obtained by UV-vis spectroscopy combined with the second derivative of the FTIR spectra. Indeed, the structure of proteins in blood serum of stressed rats was normalized after imipramine therapy, while the impaired structure of phospholipids remained unaffected. These findings strongly suggest that the depression factor, which is chronic mild stress, may induce permanent (irreversible) damages into the phospholipid structure identified as shortened carbon chains. This study shows a possible new application of spectroscopic techniques in the diagnosis and therapy monitoring of depression. Copyright © 2016 Elsevier B.V. All rights reserved.

Qualitative and quantitative changes in phospholipids and proteins investigated by spectroscopic techniques in animal depression model

NASA Astrophysics Data System (ADS)

Depciuch, J.; Sowa-Kucma, M.; Nowak, G.; Papp, M.; Gruca, P.; Misztak, P.; Parlinska-Wojtan, M.

2017-04-01

Depression becomes nowadays a high mortality civilization disease with one of the major causes being chronic stress. Raman, Fourier Transform Infra Red (FTIR) and Ultraviolet-Visible (UV-vis) spectroscopies were used to determine the changes in the quantity and structure of phospholipids and proteins in the blood serum of rats subjected to chronic mild stress, which is a common animal depression model. Moreover, the efficiency of the imipramine treatment was evaluated. It was found that chronic mild stress not only damages the structure of the phospholipids and proteins, but also decreases their level in the blood serum. A 5 weeks imipramine treatment did increase slightly the quantity of proteins, leaving the damaged phospholipids unchanged. Structural information from phospholipids and proteins was obtained by UV-vis spectroscopy combined with the second derivative of the FTIR spectra. Indeed, the structure of proteins in blood serum of stressed rats was normalized after imipramine therapy, while the impaired structure of phospholipids remained unaffected. These findings strongly suggest that the depression factor, which is chronic mild stress, may induce permanent (irreversible) damages into the phospholipid structure identified as shortened carbon chains. This study shows a possible new application of spectroscopic techniques in the diagnosis and therapy monitoring of depression.

Evaluation and Control of Soil Degradation in Russia on the Basis of the Assessment of Soil Ecological Functions

NASA Astrophysics Data System (ADS)

Yakovlev, Aleksandr

2016-04-01

Sustainable development of the territory is possible only under certain environmental requirements. These requirements are based on the implementation of the concept, conventionally called "zero land degradation", which cannot be reached in the process of real land use. "Zero degradation" is the establishment of acceptable ecological state of the environment and permissible anthropogenic impact on it, wherein self-healing of nature quality is possible and there is no accumulation of irreversible environmental damage. The values of parameters that characterize the relationship between the ecological state of the environment, in particular, land degradation, and the socio-economic development of the Russian Federation are represented in the materials of recent issues of the Russian State environmental report (2012 - 2014). Environmental problems in Russia are actively discussed in relation to issues of environmental and socio-economic development of the neighboring countries of the Eurasian region. So the Law "On Soil Protection", which was developed and adopted by the Union: Russia, Belarus, Kazakhstan, is dedicated to the protection of soil and soil degradation control. Ecological Doctrine of Russia (2012) and the State Environmental Program (2012-2020) identify the main strategic steps to combat land degradation in our country. In the first place, it has been tasked to identify and eliminate past environmental damage followed by the organization of nature "from scratch", in accordance with environmental regulations. Currently the Ministry of natural resources of Russia started implementation of the Federal program on environmental-economic assessment and the elimination of past environmental damage. The main steps of this program are: the works related to the inventory of degraded and contaminated lands and their subsequent reclamation and return to the appropriate land use system. The territory must comply with officially approved environmental requirements. The list of requirements can be divided into two areas: - the standards and norms of environmental assessment for all components of environment, - requirements to the level of environmental stress on the land when designing the system of nature management. Environmental requirements for components of the environment are based primarily on stringent environmental and health standards (maximum permissible concentration, permissible residual oil content in the soil, etc.), compliance of which involves the maintenance of the ecological state of nature in close to background rates. The assessment of environmental stress in planning and land management is not provided with official regulations and is based primarily on expert opinions. However, projects and land use programs must pass the corresponding procedure of environmental expertise. Rating, ranking and regulation of soil and land quality allow to establish the level of its disturbance and the ability to heal itself, according to the methodological approach developed and adopted by several Russian Agencies (Environmental, Agricultural and Land use Agencies). The basis for assessing the ecological status of soils was based on the five-level evaluation scale according to which a fairly conventional boundary of reversibility is considered to be the third (threshold) level, and irreversible accumulation of environmental damage occurs when reaching . fourth and fifth level of loss of environmental quality of soils. According to a separate study in the field of environmental regulation irreversible changes occur in the loss of more than a quarter of Bioorganic capacity of soils. The main condition for sustainable development is the development, which does not cause irreversible damage to nature and society, based on compliance with environmental quality requirements for components of the environment, particularly soils and lands and secure planning and safe placement of the productive forces. Acknowledgments: This study was supported by the Russian Science Foundation, project no. 143800023.

[Effect of long-wave ultraviolet light (UV-A) and medium-wave ultraviolet rays (UV-B) on human skin. Critical comparison].

PubMed

Raab, W

1980-04-15

When discussing the effects of ultraviolet radiation on human skin, one should carefully distinguish between the long wave ultraviolet light (UV-A) and the short wave radiations (UV-B and UV-C). Ultraviolet A induces immediate pigmentation but, if high energies are applied, a permanent pigmentation is elicited. This type of ultraviolet A-induced pigmentation has been called "spontaneous" pigmentation as no erythematous reaction is necessary to induce or accelerate melanine formation. Ultraviolet B provokes erythema and consecutive pigmentation. Upon chronic exposure, ultraviolet B causes the wellknown actinic damage of the skin and even provokes carcinoma. With exposures to the sunlight (global radiation), one should be most careful. The public must be informed extensively about the dangers of excessive sunbaths. The use of artificial "suns" with spectra between 260 and 400 nm is limited as it may cause the same type of damage as the global radiation. An exact schedule for use of artificial lamps is strongly recommended. After one cycle of exposures, an interruption is necessary until the next cycle of irradiations may start. Upon continual use for tanning of the skin, artificial lamps may provoke irreversible damage of the skin. Radiation sources with emission spectra of wavelengths between 315 and 400 nm exclusively are well suited for the induction of skin pigmentation (cosmetic use). Potent radiation such as UVASUN systems provoke a "pleasant" permanent pigmentation after exposures for less than one hour. The use of ultraviolet A (UV-A) does not carry any risk for the human skin.

Chitosan effects on physiochemical indicators of drought-induced leaf stress

USDA-ARS?s Scientific Manuscript database

Water deficit stress in crops is associated with leaf senescence, a damaging oxidative process that is irreversible once it is initiated. This study was conducted to assess the effect of chitosan, a marine polysaccharide with unique bioactive properties that scavenges for reactive oxygen species; h...

Inhalants. Specialized Information Service.

ERIC Educational Resources Information Center

Do It Now Foundation, Phoenix, AZ.

The document presents a collection of articles about inhalant abuse. Article 1 presents findings on the psychophysiological effects related to the use of amyl or butyl nitrate as a "recreational drug." Article 2 suggests a strong association between chronic sniffing of the solvent toulene and irreversible brain damage. Article 3 warns…

Structural changes and damage of single-crystal turbine blades during life tests of an aviation gas turbine engine

NASA Astrophysics Data System (ADS)

Ospennikova, O. G.; Orlov, M. R.; Kolodochkina, V. G.; Nazarkin, R. M.

2015-04-01

The irreversible structural changes of the single-crystal ZhS32-VI nickel superalloy blades of a high-pressure turbine that occur during life tests of a gas turbine engine are studied. The main operation damages in the hottest section of the blade airfoil are found to be the fracture of the heat-resistant coating in the leading edge and the formation of thermomechanical fatigue cracks. The possibility of reconditioning repair of the blades is considered.

Post-veraison irreversible stem shrinkage in grapevine (Vitis vinifera) is caused by periderm formation.

PubMed

Van de Wal, Bart A E; Leroux, Olivier; Steppe, Kathy

2018-05-01

Grapevines are characterized by a period of irreversible stem shrinkage around the onset of ripening of the grape berries. Since this shrinkage is unrelated to meteorological conditions or drought, it is often suggested that it is caused by the increased sink strength of the grape berries during this period. However, no studies so far have experimentally investigated the mechanisms underlying this irreversible stem shrinkage. We therefore combined continuous measurements of stem diameter variations and histology of potted 2-year-old grapevines (Vitis vinifera L. 'Boskoop Glory'). Sink strength was altered by pruning all grape clusters (treatment P), while non-pruned grapevines served as control (treatment C). Unexpectedly, our results showed irreversible post-veraison stem shrinkage in both treatments, suggesting that the shrinkage is not linked to grape berry sink strength. Anatomical analysis indicated that the shrinkage is the result of the formation of successive concentric periderm layers, and the subsequent dehydration and compression of the older bark tissues, an anatomical feature that is characteristic of Vitis stems. Stem shrinkage is hence unrelated to grape berry development, in contrast to what has been previously suggested.

HYPOTHYRODISM INDUCED BY EARLY POSTNATAL EXPOSURE TO PROPYLTHIOURACIL IMPAIRS SYNAPTIC TRANSMISSION IN VIVO IN THE HIPPOCAMPUS OF THE ADULT RAT.

EPA Science Inventory

Thyroid hormones are essential for maturation and function of the mammalian central nervous system. Severe congenital hypothyroidism results in irreversible structural damage and mental retardation in children. Although a variety of environmental contaminants have been demonstrat...

Beneficial and paradoxical roles of selenium at nutritional levels of intake in healthspan and longevity

USDA-ARS?s Scientific Manuscript database

Accumulation of damage to the genome and macromolecules is a hallmark of aging, age-associated degeneration, and genome instability syndromes. Although the processes of aging are irreversible, they can be modulated by genome maintenance pathways and environmental factors such as diet. Selenium (Se) ...

40 CFR 717.3 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... adverse reaction to health or the environment. (b) Firm or company means any person, that is subject to... activities, or long-lasting or irreversible damage to health or the environment. (j) Site means a contiguous... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Definitions. 717.3 Section 717.3...

Magnetic Resonance Measurement of Turbulent Kinetic Energy for the Estimation of Irreversible Pressure Loss in Aortic Stenosis

PubMed Central

Dyverfeldt, Petter; Hope, Michael D.; Tseng, Elaine E.; Saloner, David

2013-01-01

OBJECTIVES The authors sought to measure the turbulent kinetic energy (TKE) in the ascending aorta of patients with aortic stenosis and to assess its relationship to irreversible pressure loss. BACKGROUND Irreversible pressure loss caused by energy dissipation in post-stenotic flow is an important determinant of the hemodynamic significance of aortic stenosis. The simplified Bernoulli equation used to estimate pressure gradients often misclassifies the ventricular overload caused by aortic stenosis. The current gold standard for estimation of irreversible pressure loss is catheterization, but this method is rarely used due to its invasiveness. Post-stenotic pressure loss is largely caused by dissipation of turbulent kinetic energy into heat. Recent developments in magnetic resonance flow imaging permit noninvasive estimation of TKE. METHODS The study was approved by the local ethics review board and all subjects gave written informed consent. Three-dimensional cine magnetic resonance flow imaging was used to measure TKE in 18 subjects (4 normal volunteers, 14 patients with aortic stenosis with and without dilation). For each subject, the peak total TKE in the ascending aorta was compared with a pressure loss index. The pressure loss index was based on a previously validated theory relating pressure loss to measures obtainable by echocardiography. RESULTS The total TKE did not appear to be related to global flow patterns visualized based on magnetic resonance–measured velocity fields. The TKE was significantly higher in patients with aortic stenosis than in normal volunteers (p < 0.001). The peak total TKE in the ascending aorta was strongly correlated to index pressure loss (R2 = 0.91). CONCLUSIONS Peak total TKE in the ascending aorta correlated strongly with irreversible pressure loss estimated by a well-established method. Direct measurement of TKE by magnetic resonance flow imaging may, with further validation, be used to estimate irreversible pressure loss in aortic stenosis. PMID:23328563

Magnetic resonance measurement of turbulent kinetic energy for the estimation of irreversible pressure loss in aortic stenosis.

PubMed

Dyverfeldt, Petter; Hope, Michael D; Tseng, Elaine E; Saloner, David

2013-01-01

The authors sought to measure the turbulent kinetic energy (TKE) in the ascending aorta of patients with aortic stenosis and to assess its relationship to irreversible pressure loss. Irreversible pressure loss caused by energy dissipation in post-stenotic flow is an important determinant of the hemodynamic significance of aortic stenosis. The simplified Bernoulli equation used to estimate pressure gradients often misclassifies the ventricular overload caused by aortic stenosis. The current gold standard for estimation of irreversible pressure loss is catheterization, but this method is rarely used due to its invasiveness. Post-stenotic pressure loss is largely caused by dissipation of turbulent kinetic energy into heat. Recent developments in magnetic resonance flow imaging permit noninvasive estimation of TKE. The study was approved by the local ethics review board and all subjects gave written informed consent. Three-dimensional cine magnetic resonance flow imaging was used to measure TKE in 18 subjects (4 normal volunteers, 14 patients with aortic stenosis with and without dilation). For each subject, the peak total TKE in the ascending aorta was compared with a pressure loss index. The pressure loss index was based on a previously validated theory relating pressure loss to measures obtainable by echocardiography. The total TKE did not appear to be related to global flow patterns visualized based on magnetic resonance-measured velocity fields. The TKE was significantly higher in patients with aortic stenosis than in normal volunteers (p < 0.001). The peak total TKE in the ascending aorta was strongly correlated to index pressure loss (R(2) = 0.91). Peak total TKE in the ascending aorta correlated strongly with irreversible pressure loss estimated by a well-established method. Direct measurement of TKE by magnetic resonance flow imaging may, with further validation, be used to estimate irreversible pressure loss in aortic stenosis. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

The vapor activity of oregano, perilla, tea tree, lavender, clove, and geranium oils against a Trichophyton mentagrophytes in a closed box.

PubMed

Inouye, Shigeharu; Nishiyama, Yayoi; Uchida, Katsuhisa; Hasumi, Yayoi; Yamaguchi, Hideyo; Abe, Shigeru

2006-12-01

The vapor activity of six essential oils against a Trichophyton mentagrophytes was examined using a closed box. The antifungal activity was determined from colony size, which was correlated with the inoculum size. As judged from the minimum inhibitory dose and the minimum fungicidal dose determined after vapor exposure for 24 h, the vapor activity of the six essential oils was ranked in the following order: oregano > clove, perilla > geranium, lavender, tea tree. The vapors of oregano, perilla, tea tree, and lavender oils killed the mycelia by short exposure, for 3 h, but the vapors of clove and geranium oils were only active after overnight exposure. The vapor of oregano and other oils induced lysis of the mycelia. Morphological examination by scanning electron microscope (SEM) revealed that the cell membrane and cell wall were damaged in a dose- and time-dependent manner by the action of oregano vapor, causing rupture and peeling of the cell wall, with small bulges coming from the cell membrane. The vapor activity increased after 24 h, but mycelial accumulation of the active oil constituents was maximized around 15 h, and then decreased in parallel with the decrease of vapor concentration. This suggested that the active constituent accumulated on the fungal cells around 15 h caused irreversible damage, which eventually led to cellular death.

A comparison of temperature increases produced by "premium" and "standard" diamond burs: An in-vitro study.

PubMed

Segal, Pnina; Sap, Danny; Ben-Amar, Ariel; Levartovsky, Shifra; Matalon, Shlomo

2016-02-01

Vital tooth preparations may cause irreversible thermal damage to the pulp. The manufacturing techniques of dental burs may decrease heat production and minimize the risk of overheating and trauma to the dental pulp. Strauss (Raanana, Israel) has introduced "premium" diamond burs, claiming superior efficiency and longevity. We sought to determine the safest preparation methods by performing a comparison of intrapulpal temperature increases caused with "standard" and "premium" burs. Three types of diamond burs (F1R, F21R, and K2) were tested on extracted human teeth (n = 8 teeth per bur type). Premium and standard manufacturing techniques were compared for each bur type (n = 24 teeth per group; total 48 teeth). An intrapulpal thermocouple was used to measure the temperature during the procedure. Comparisons were analyzed with the t test and one-way ANOVA. P ≤ .05 was considered significant. All premium burs demonstrated lower temperature increases compared to the standard burs (P ≤ .001 for F21R and K2, P = .086 for F1R). The temperature increases with premium burs were similar for different bur shapes, but the temperature increases with standard burs depended on the bur shape (P < .001). Using premium diamond burs for tooth preparation may reduce the risk of pulp tissue damage, and thus reduce postoperative pulp-associated complications.

Trace elements in ALS patients and their relationships with clinical severity.

PubMed

Oggiano, Riccardo; Solinas, Giuliana; Forte, Giovanni; Bocca, Beatrice; Farace, Cristiano; Pisano, Andrea; Sotgiu, Maria Alessandra; Clemente, Simonetta; Malaguarnera, Michele; Fois, Alessandro Giuseppe; Pirina, Pietro; Montella, Andrea; Madeddu, Roberto

2018-04-01

An exploratory study of trace elements in ALS and their relationships with clinical severity was detected. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that causes irreversible damage in humans, with the consequent loss of function of motoneurons (MNs), with a prognosis up to 5 years after diagnosis. Except to genetic rare cases it is not known the etiology of the disorder. Aim of our research is to investigate the possible role of heavy metals in the severity of the disease. In this study, by the use of plasma mass (ICP-MS), we have analyzed the content of essential and heavy metals such: Pb, Cd, Al, Hg, Mn, Fe, Cu, Zn, Se, Mg, and Ca, in blood, urine and hair of ALS patients and controls; moreover we divided the patients in two groups for disease severity and analyzed the difference among the groups, in order to study a possible involvement of metals in the severity of the damage. Our results suggest a protective role of Selenium, involved in protective antioxidant mechanisms, and a risk factor in the case of presence of Lead in blood. The levels of the other metals are not easy to interpret, because these may be due to life style and for essential metals a consequence of the disease condition, not a cause. Copyright © 2018 Elsevier Ltd. All rights reserved.

Qualitative and quantitative changes in phospholipids and proteins investigated by spectroscopic techniques in olfactory bulbectomy animal depression model.

PubMed

Depciuch, J; Parlinska-Wojtan, M

2018-01-30

Depression becomes nowadays a high mortality civilization disease with one of the potential causes being impaired smell. In this study Raman, Fourier Transform Infra Red (FTIR) and Ultraviolet-Visible (UV-vis) spectroscopies were used to determine the changes in the quantity and structure of phospholipids and proteins in the blood serum of bulbectomized rats (OB_NaCl), which is a common animal depression model. The efficiency of amitriptyline (AMI) treatment was also evaluated. The obtained results show a significant decrease in the phospholipid and protein fractions (as well as changes in their secondary structures) in blood serum of bulbectomized rats. AMI treatment in bulbectomized rats increased protein level and did not affect the level of phospholipids. Structural information from phospholipids and proteins was obtained from UV-vis spectroscopy combined with the second derivative of the FTIR spectra. Indeed, the structure of proteins in blood serum of bulbectomized rats was normalized after amitriptyline therapy, while the damaged structure of phospholipids remained unaffected. These findings strongly suggest that impaired smell could be one of the causes of depression and may induce permanent (irreversible) damages into the phospholipid structure identified as shortened carbon chains. This study shows a possible new application of spectroscopic techniques in the diagnosis and therapy monitoring of depression. Copyright © 2017 Elsevier B.V. All rights reserved.

Experimental investigations and finite element simulation of cutting heat in vibrational and conventional drilling of cortical bone.

PubMed

Wang, Yu; Cao, Meng; Zhao, Xiangrui; Zhu, Gang; McClean, Colin; Zhao, Yuanyuan; Fan, Yubo

2014-11-01

Heat generated during bone drilling could cause irreversible thermal damage, which can lead to bone necrosis or even osteomyelitis. In this study, vibrational drilling was applied to fresh bovine bones to investigate the cutting heat in comparison with conventional drilling through experimental investigation and finite element analysis (FEA). The influence of vibrational frequency and amplitude on cutting heat generation and conduction were studied. The experimental results showed that, compared with the conventional drilling, vibrational drilling could significantly reduce the cutting temperature in drilling of cortical bone (P<0.05): the cutting temperature tended to decrease with increasing vibrational frequency and amplitude. The FEA results also showed that the vibrational amplitude holds a significant effect on the cutting heat conduction. Copyright © 2014 IPEM. Published by Elsevier Ltd. All rights reserved.

[Postoperative cortical blindness after right upper lung lobectomy].

PubMed

Bausili, M; Abreu, S; Unzueta, M C; García Álvarez, M; Crespí, J; Moral, M V

2012-03-01

Changes in vision after non-ophthalmic surgery are a serious complication that can have devastating consequences due to its potential irreversibility. This not only leads to medical problems, but also legal ones. Many causes that affect sight during the peri-operative period have been identified, whether due to optic nerve damage or of extra-ocular origin (in the neuro-optic pathways and/or cerebral cortex). AU these may have a multifactorial origin, and there is still controversy as regards it pathogenesis and treatment. We present the case of a thoracic surgery patient who had a bilateral amaurosis in the post-operative period, which had a favourable outcome. Copyright © 2010 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España.. All rights reserved.

[Application value of corneal hysteresis in diagnosis and treatment of glaucoma].

PubMed

He, L Y; Liang, L; Zhu, M N

2017-02-11

Glaucoma is the first leading cause of irreversible blindness world widely, but the pathogenesis was still unclear. The collagen fibers from cornea and sclera connect to each other and both of them have similar extracellular matrix components. The biomechanical characteristics of optic nerve lamina cribrosa may associated with the biomechanical properties of the cornea. Therefore, the study of corneal physiological can indirectly reflex the compression and damage in optic nerve lamina cribrosa. The technical developments in corneal hysteresis examination had been updated these years constantly. Many researches implicated that low corneal hysteresis involved in pathogenesis and progression of glaucoma which refresh our recognition of the relationship between cornea and glaucoma. This review summarized the characteristics of corneal hysteresis, the examination and the connection with glaucoma to provide the reference for clinical work. (Chin J Ophthalmol, 2017, 53: 140-143) .

Impaired proteostasis: role in the pathogenesis of diabetes mellitus.

PubMed

Jaisson, Stéphane; Gillery, Philippe

2014-08-01

In living organisms, proteins are regularly exposed to 'molecular ageing', which corresponds to a set of non-enzymatic modifications that progressively cause irreversible damage to proteins. This phenomenon is greatly amplified under pathological conditions, such as diabetes mellitus. For their survival and optimal functioning, cells have to maintain protein homeostasis, also called 'proteostasis'. This process acts to maintain a high proportion of functional and undamaged proteins. Different mechanisms are involved in proteostasis, among them degradation systems (the main intracellular proteolytic systems being proteasome and lysosomes), folding systems (including molecular chaperones), and enzymatic mechanisms of protein repair. There is growing evidence that the disruption of proteostasis may constitute a determining event in pathophysiology. The aim of this review is to demonstrate how such a dysregulation may be involved in the pathogenesis of diabetes mellitus and in the onset of its long-term complications.

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.

Effect of high-intensity irradiation from dental photopolymerization on the isolated and superfused vertebrate retina.

PubMed

Rassaei, Mohammad; Thelen, Martin; Abumuaileq, Ramzi; Hescheler, Jürgen; Lüke, Matthias; Schneider, Toni

2013-03-01

Light or electromagnetic radiation may damage the neurosensory retina during irradiation of photopolymerizing resinous materials. Direct and indirect effects of irradiation emitted from polymerisation curing light may represent a severe risk factor for the eyes and the skin of the lamp operators, as well as for the patient's oral mucosa. Bovine superfused retinas were used to record their light-evoked electroretinogram (ERG) as ex vivo ERGs. Both the a- and the b-waves were used as indicators for retinal damage on the functional level. The isolated retinas were routinely superfused with a standard nutrient solution under normoglycemic conditions (5 mM D-glucose). The change in the a- and b-wave amplitude and implicit time, caused by low and high intensity irradiation, was calculated and followed over time. From the results, it can be deduced that the irradiation from LED high-power lamps affects severely the normal physiological function of the bovine retina. Irradiations of 1,200 lx irreversibly damaged the physiological response. In part, this may be reversible at lower intensities, but curing without using the appropriate filter will bleach the retinal rhodopsin to a large extent within 20 to 40 s of standard application times. Constant exposure to intense ambient irradiation affects phototransduction (a-wave) as well as transretinal signalling. The proper use of the UV- and blue-light filtering device is highly recommended, and may prevent acute and long lasting damage of the neurosensory retina.

Propofol and sodium thiopental protect against MK-801-induced neuronal necrosis in the posterior cingulate/retrosplenial cortex.

PubMed

Jevtovic-Todorovic, V; Wozniak, D F; Powell, S; Olney, J W

2001-09-21

N-Methyl-D-aspartate (NMDA) antagonists act by an anti-excitotoxic action to provide neuroprotection against acute brain injury, but these agents can also cause toxic effects. In low doses they induce reversible neuronal injury, but in higher doses they cause irreversible degeneration of cerebrocortical neurons. GABAmimetic drugs protect against the reversible neurotoxic changes in rat brain. Here we show that two GABAmimetic anesthetic agents--propofol and sodium thiopental--protect against the irreversible neurodegenerative reaction induced by the powerful NMDA antagonist, MK-801.

[On the problem of irreversible brain damage due to neuroleptic long-term therapy. Experimental studies on rats (author's transl)].

PubMed

Hackenberg, P; Lange, E

1975-01-01

Reports in clinical literature about persistent terminal extrapyramidal hyperkinesis in neuroleptic long-term treated patients and speculation about demential brain decomposition in such cases give rise to support irreversible psychopharmacotoxical brain damage. Histopathological and animal experimental results in this question given up to this day are not in agreement with each other. Therefore an own chlorpromazine long-term experiment in rats is reported with special regard to biometric-statistical results. Experiments were performed in 36 adult albino rats of either sex, weighing 300-400 g, fed by a standard diet, receiving food and water ad libitum. The animals were divided into 3 groups of 12 animals accidentally. Group I received 15 mg/kg/die chlorpromazine per os by means of a throat probe, group II 10 mg/kg/die, group III was left untreated (controls). The experiment was carried out for 6 months, the animals were killed by perfusion of Bouin's solution 6-8 weeks after interruption of chlorpromazine application. 8 mum paraffin sections were stained by kresylviolet. After histological examination the material was investigated statistically. In the ncl. N. XII, ncl. N. VII, ncl, orig et term. N.V., ncl. cochlearis ant., ncl. vestibularis princeps, Oliva sup., and ncl. dentatus the glia/neurons ratio was stated by counting 200 cells, and in the formation reticularis 400 cells in each animal. The calculated differences in the glia/neurons ratio between the groups were evaluated for statistical significance by the chi2-test. In the ncl. dentatus, oliva sup., ncl, cochlearis ventr., and ncl, vestibularis glia cells and neurons were counted in a plane of 1.2 mm2, in the formatio reticularis and in homologuous parts of cerebellar stratum moleculare in a plane of 2.4 mm2. The differences between the mean values of the groups were verified for statistical significance by means of the t-test. In histological examination only 50% of the animals of group I showed a slight loss of neurons and increase of glia cells. Statistically however, significant increase of glia cells was found in the glia/neurons ratio all over the investigated area (rhombencephalic brain stem and cerebellum) and for the ncl. dentatus, the oliva sup., and the ncl. cochlearis ventr. especially (table 1, fig.3). This change in the glia/neurons ratio is caused by a tendency for decreasing of neurons and increasing of glia cells, too (table 2). In the nucleus dentatus the loss of neurons was found to be of high significance. These changes are supposed to be due to chlorpromazine action, and in this manner the experimental results speak for an irreversible psychopharmacotoxical brain damage.

Spectroscopic studies of the mechanism of reversible photodegradation of 1-substituted aminoanthraquinone-doped polymers

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

Hung, Sheng-Ting, E-mail: Sheng-Ting.Hung@jila.colorado.edu; Clays, Koen; Department of Chemistry, University of Leuven, Leuven B-3001

2016-03-21

The mechanism of reversible photodegradation of 1-substituted aminoanthraquinones doped into poly(methyl methacrylate) and polystyrene is investigated. Time-dependent density functional theory is employed to predict the transition energies and corresponding oscillator strengths of the proposed reversibly and irreversibly damaged dye species. Ultraviolet–visible and Fourier transform infrared (FTIR) spectroscopy are used to characterize which species are present. FTIR spectroscopy indicates that both dye and polymer undergo reversible photodegradation when irradiated with a visible laser. These findings suggest that photodegradation of 1-substituted aminoanthraquinones doped in polymers originates from interactions between dyes and photoinduced thermally degraded polymers, and the metastable product may recover ormore » further degrade irreversibly.« less

Abandoning the dead donor rule? A national survey of public views on death and organ donation.

PubMed

Nair-Collins, Michael; Green, Sydney R; Sutin, Angelina R

2015-04-01

Brain dead organ donors are the principal source of transplantable organs. However, it is controversial whether brain death is the same as biological death. Therefore, it is unclear whether organ removal in brain death is consistent with the 'dead donor rule', which states that organ removal must not cause death. Our aim was to evaluate the public's opinion about organ removal if explicitly described as causing the death of a donor in irreversible apneic coma. We conducted a cross-sectional internet survey of the American public (n=1096). Questionnaire domains included opinions about a hypothetical scenario of organ removal described as causing the death of a patient in irreversible coma, and items measuring willingness to donate organs after death. Some 71% of the sample agreed that it should be legal for patients to donate organs in the scenario described and 67% agreed that they would want to donate organs in a similar situation. Of the 85% of the sample who agreed that they were willing to donate organs after death, 76% agreed that they would donate in the scenario of irreversible coma with organ removal causing death. There appears to be public support for organ donation in a scenario explicitly described as violating the dead donor rule. Further, most but not all people who would agree to donate when organ removal is described as occurring after death would also agree to donate when organ removal is described as causing death in irreversible coma. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Evaluation of the safety of irreversible electroporation on the stomach wall using a pig model

PubMed Central

Li, Jiannan; Zeng, Jianying; Chen, Jibing; Shi, Jian; Luo, Xiaomei; Fang, Gang; Chai, Wei; Zhang, Wenlong; Liu, Tongjun; Niu, Lizhi

2017-01-01

The aim of the present study was to evaluate the effects of irreversible electroporation (IRE) on the stomach wall following the direct application of IRE onto the organ surface. IRE ablation was performed in 8 Tibetan mini-pigs, which were randomly assigned into two groups based on their ablated areas: Group A, gastric cardia, fundus of stomach, gastric body and group B, lesser gastric curvature, greater gastric curvature, stomach pylorus. Two IRE needles were placed in the space between the stomach wall and the liver (not inserted into the stomach tissue), and three lesions were created in each pig. Serum aminotransferase and white blood cell (WBC) levels were measured. Gastroscopy and endoscopic ultrasonography were performed. From each group, 2 pigs were sacrificed on day 7 post-IRE; the remaining pigs were sacrificed on day 28 post-IRE. There were no signs of perforation on the stomach wall. Serum aminotransferase and WBC levels increased in both groups on day 1 post-IRE and decreased gradually thereafter. The gastroscopy procedure revealed oval ulcers on day 7 post-IRE and smaller ulcers on day 28 post-IRE. Transmural necrosis, inflammation and fibrosis were observed at 7 days post-IRE. Healing ulcers were observed at 28 days post-IRE. In conclusion, IRE ablation caused damage to the stomach wall; however, IRE did not induce any perforation. PMID:28672987

Is thermodynamic irreversibility a consequence of the expansion of the Universe?

NASA Astrophysics Data System (ADS)

Osváth, Szabolcs

2018-02-01

This paper explains thermodynamic irreversibility by applying the expansion of the Universe to thermodynamic systems. The effect of metric expansion is immeasurably small on shorter scales than intergalactic distances. Multi-particle systems, however, are chaotic, and amplify any small disturbance exponentially. Metric expansion gives rise to time-asymmetric behaviour in thermodynamic systems in a short time (few nanoseconds in air, few ten picoseconds in water). In contrast to existing publications, this paper explains without any additional assumptions the rise of thermodynamic irreversibility from the underlying reversible mechanics of particles. Calculations for the special case which assumes FLRW metric, slow motions (v ≪ c) and approximates space locally by Euclidean space show that metric expansion causes entropy increase in isolated systems. The rise of time-asymmetry, however, is not affected by these assumptions. Any influence of the expansion of the Universe on the local metric causes a coupling between local mechanics and evolution of the Universe.

Tolerance of chufa (Cyperus esculentus L.) plants, representing the higher plant compartment in bioregenerative life support systems, to super-optimal air temperatures

NASA Astrophysics Data System (ADS)

Shklavtsova, E. S.; Ushakova, S. A.; Shikhov, V. N.; Anishchenko, O. V.

2013-01-01

Plants intended to be included in the photosynthesizing compartment of the bioregenerative life support system (BLSS) need to be studied in terms of both their production parameters under optimal conditions and their tolerance to stress factors that might be caused by emergency situations. The purpose of this study was to investigate tolerance of chufa (Cyperus esculentus L.) plants to the super-optimal air temperature of 45 ± 1 °C as dependent upon PAR (photosynthetically active radiation) intensity and the duration of the exposure to the stress factor. Chufa plants were grown hydroponically, on expanded clay, under artificial light. The nutrient solution was Knop's mineral medium. Until the plants were 30 days old, they had been grown at 690 μmol m-2 s-1 PAR and air temperature 25 °C. Thirty-day-old plants were exposed to the temperature 45 °C for 6 h, 20 h, and 44 h at PAR intensities 690 μmol m-2 s-1 and 1150 μmol m-2 s-1. The exposure to the damaging air temperature for 44 h at 690 μmol m-2 s-1 PAR caused irreversible damage to PSA, resulting in leaf mortality. In chufa plants exposed to heat shock treatment at 690 μmol m-2 s-1 PAR for 6 h and 20 h, respiration exceeded photosynthesis, and CO2 release in the light was recorded. Functional activity of photosynthetic apparatus, estimated from parameters of pulse-modulated chlorophyll fluorescence in Photosystem 2 (PS 2), decreased 40% to 50%. After the exposure to the stress factor was finished, functional activity of PSA recovered its initial values, and apparent photosynthesis (Papparent) rate after a 20-h exposure to the stress factor was 2.6 times lower than before the elevation of the temperature. During the first hours of plant exposure to the temperature 45 °C at 1150 μmol m-2 s-1 PAR, respiration rate was higher than photosynthesis rate, but after 3-4 h of the exposure, photosynthetic processes exceeded oxidative ones and CO2 absorption in the light was recorded. At the end of the 6-h exposure, Papparent rate was close to that recorded prior to the exposure, and no significant changes were observed in the functional activity of PSA. At the end of the 20-h exposure, Papparent rate was close to its initial value, but certain parameters of the functional activity of PSA decreased 25% vs. their initial values. During the repair period, the parameters of external gas exchange recovered their initial values, and parameters of pulse-modulated chlorophyll fluorescence were 20-30% higher than their initial values. Thus, exposure of chufa plants to the damaging temperature of the air for 20 h did not cause any irreversible damage to the photosynthetic apparatus of plants at either 690 μmol m-2 s-1 or 1150 μmol m-2 s-1 PAR, and higher PAR intensity during the heat shock treatment enhanced heat tolerance of the plants.

An "Off-the-Shelf" System for Intraprocedural Electrical Current Evaluation and Monitoring of Irreversible Electroporation Therapy.

PubMed

Neal, Robert E; Kavnoudias, Helen; Thomson, Kenneth R

2015-06-01

Irreversible electroporation (IRE) ablation uses a series of brief electric pulses to create nanoscale defects in cell membranes, killing the cells. It has shown promise in numerous soft-tissue tumor applications. Larger voltages between electrodes will increase ablation volume, but exceeding electrical limits may risk damage to the patient, cause ineffective therapy delivery, or require generator restart. Monitoring electrical current for these conditions in real-time enables managing these risks. This capacity is not presently available in clinical IRE generators. We describe a system using a Tektronix TCP305 AC/DC Current Probe connected to a TCPA300 AC/DC Current Probe Amplifier, which is read on a computer using a Protek DSO-2090 USB computer-interfacing oscilloscope. Accuracy of the system was tested with a resistor circuit and by comparing measured currents with final outputs from the NanoKnife clinical electroporation pulse generator. Accuracy of measured currents was 1.64 ± 2.4 % relative to calculations for the resistor circuit and averaged 0.371 ± 0.977 % deviation from the NanoKnife. During clinical pulse delivery, the system offers real-time evaluation of IRE procedure progress and enables a number of methods for identifying approaching issues from electrical behavior of therapy delivery, facilitating protocol changes before encountering therapy delivery issues. This system can monitor electrical currents in real-time without altering the electric pulses or modifying the pulse generator. This facilitates delivering electric pulse protocols that remain within the optimal range of electrical currents-sufficient strength for clinically relevant ablation volumes, without the risk of exceeding safe electric currents or causing inadequate ablation.

[The morphofunctional state of the bone marrow in lead and zinc intoxication].

PubMed

Vladimtseva, T M; Pashkevich, I A; Salmina, A B

2006-01-01

The nucleolus is a compulsory nuclear structure of all cells of eukaryotes. The quantitative and qualitative characteristics of nuclei show the functional activity of a cell, the rate of its synthesis of RNA and portents, and its metabolic state. Heavy metals (zinc chloride and lead acetate) were comparatively investigated for their effects on the nucleolar apparatus of bone marrow cells in in vivo experiments. Zinc chloride and lead acetate were ascertained to damage the nucleolar apparatus of cells, thus decreasing their transcriptional activity or irreversibly damaging them.

The Intracellular Redox Stress Caused by Hexavalent Chromium is Selective for Proteins that Have Key Roles in Cell Survival and Thiol Redox Control

PubMed Central

Myers, Judith M.; Antholine, William E.; Myers, Charles R.

2011-01-01

Hexavalent chromium [Cr(VI)] compounds (e.g. chromates) are strong oxidants that readily enter cells where they are reduced to reactive Cr intermediates that can directly oxidize some cell components and can promote the generation of reactive oxygen and nitrogen species. Inhalation is a major route of exposure which directly exposes the bronchial epithelium. Previous studies with non-cancerous human bronchial epithelial cells (BEAS-2B) demonstrated that Cr(VI) treatment results in the irreversible inhibition of thioredoxin reductase (TrxR) and the oxidation of thioredoxins (Trx) and peroxiredoxins (Prx). The mitochondrial Trx/Prx system is somewhat more sensitive to Cr(VI) than the cytosolic Trx/Prx system, and other redox-sensitive mitochondrial functions are subsequently affected including electron transport complexes I and II. Studies reported here show that Cr(VI) does not cause indiscriminant thiol oxidation, and that the Trx/Prx system is among the most sensitive of cellular protein thiols. Trx/Prx oxidation is not unique to BEAS-2B cells, as it was also observed in primary human bronchial epithelial cells. Increasing the intracellular levels of ascorbate, an endogenous Cr(VI) reductant, did not alter the effects on TrxR, Trx, or Prx. The peroxynitrite scavenger MnTBAP did not protect TrxR, Trx, Prx, or the electron transport chain from the effects of Cr(VI), implying that peroxynitrite is not required for these effects. Nitration of tyrosine residues of TrxR was not observed following Cr(VI) treatment, further ruling out peroxynitrite as a significant contributor to the irreversible inhibition of TrxR. Cr(VI) treatments that disrupt the TrxR/Trx/Prx system did not cause detectable mitochondrial DNA damage. Overall, the redox stress that results from Cr(VI) exposure shows selectivity for key proteins which are known to be important for redox signaling, antioxidant defense, and cell survival. PMID:21237240

Single cell wound generates electric current circuit and cell membrane potential variations that requires calcium influx.

PubMed

Luxardi, Guillaume; Reid, Brian; Maillard, Pauline; Zhao, Min

2014-07-24

Breaching of the cell membrane is one of the earliest and most common causes of cell injury, tissue damage, and disease. If the compromise in cell membrane is not repaired quickly, irreversible cell damage, cell death and defective organ functions will result. It is therefore fundamentally important to efficiently repair damage to the cell membrane. While the molecular aspects of single cell wound healing are starting to be deciphered, its bio-physical counterpart has been poorly investigated. Using Xenopus laevis oocytes as a model for single cell wound healing, we describe the temporal and spatial dynamics of the wound electric current circuitry and the temporal dynamics of cell membrane potential variation. In addition, we show the role of calcium influx in controlling electric current circuitry and cell membrane potential variations. (i) Upon wounding a single cell: an inward electric current appears at the wound center while an outward electric current is observed at its sides, illustrating the wound electric current circuitry; the cell membrane is depolarized; calcium flows into the cell. (ii) During cell membrane re-sealing: the wound center current density is maintained for a few minutes before decreasing; the cell membrane gradually re-polarizes; calcium flow into the cell drops. (iii) In conclusion, calcium influx is required for the formation and maintenance of the wound electric current circuitry, for cell membrane re-polarization and for wound healing.

Synthesis and antibacterial activity of new peptides from Alfalfa RuBisCO protein hydrolysates and mode of action via a membrane damage mechanism against Listeria innocua.

PubMed

Kobbi, Sabrine; Nedjar, Naima; Chihib, Nourdine; Balti, Rafik; Chevalier, Mickael; Silvain, Amandine; Chaabouni, Semia; Dhulster, Pascal; Bougatef, Ali

2018-02-01

In this work we evaluated the mode of action of six new synthesized peptides (Met-Asp-Asn; Glu-leu-Ala-Ala-Ala-Cys; Leu-Arg-Asp-Asp-Phe; Gly-Asn-Ala-Pro-Gly-Ala-Val-Ala; Ala-Leu-Arg-Met-Ser-Gly and Arg-Asp-Arg-Phe-Leu), previously identified, from the most active peptide fractions of RuBisCO peptic hydrolysate against Listeria innocua via a membrane damage mechanism. Antibacterial effect and the minimum inhibitory concentrations (MIC) of these peptides were evaluated against six strains and their hemolytic activities towards bovine erythrocytes were determined. Prediction of the secondary structure of peptides indicated that these new antibacterial peptides are characterized by a short peptide chains (3-8 amino acid) and a random coli structure. Moreover, it was observed that one key characteristic of antibacterial peptides is the presence of specific amino acids such as cysteine, glycine, arginine and aspartic acid. In addition the determination of the extracellular potassium concentration revealed that treatment with pure RuBisCO peptides could cause morphological changes of L. innocua and destruction of the cell integrity via irreversible membrane damage. The results could provide information for investigating the antibacterial model of antibacterial peptides derived from RuBisCO protein hydrolysates. Copyright © 2017 Elsevier Ltd. All rights reserved.

Ultrastructural aspects of mouse nerve-muscle preparation exposed to Bothrops jararacussu and Bothrops bilineatus venoms and their toxins BthTX-I and Bbil-TX: Unknown myotoxic effects.

PubMed

Melaré, Rodolfo; Floriano, Rafael Stuani; Gracia, Marta; Rodrigues-Simioni, Léa; Cruz-Höfling, Maria Alice da; Rocha, Thalita

2016-11-01

Bites by Bothrops snakes normally induce local pain, haemorrhage, oedema and myonecrosis. Mammalian isolated nerve-muscle preparations exposed to Bothrops venoms and their phospholipase A 2 toxins (PLA 2 ) can exhibit a neurotoxic pattern as increase in frequency of miniature end-plate potentials (MEPPs) as well as in amplitude of end-plate potentials (EPPs); neuromuscular facilitation followed by complete and irreversible blockade without morphological evidence for muscle damage. In this work, we analysed the ultrastructural damage induced by Bothrops jararacussu and Bothrops bilineatus venoms and their PLA 2 toxins (BthTX-I and Bbil-TX) in mouse isolated nerve-phrenic diaphragm preparations (PND). Under transmission electron microscopy (TEM), PND preparations previously exposed to B. jararacussu and B. bilineatus venoms and BthTX-I and Bbil-TX toxins showed hypercontracted and loosed myofilaments; unorganized sarcomeres; clusters of edematous sarcoplasmic reticulum and mitochondria; abnormal chromatin distribution or apoptotic-like nuclei. The principal affected organelles, mitochondria and sarcoplasmic reticulum, were those related to calcium buffering and, resulting in sarcomeres and myofilaments hypercontraction. Schwann cells were also damaged showing edematous axons and mitochondria as well as myelin sheath alteration. These ultrastructural changes caused by both of Bothrops venoms and toxins indicate that the neuromuscular blockade induced by them in vitro can also be associated with nerve and muscle degeneration. © 2016 Wiley Periodicals, Inc.

On the geoethical implications of wind erosion

NASA Astrophysics Data System (ADS)

Károly, Tatárvári

2016-04-01

Human activities exerts an ever growing impact on our environment, and this is undeniably the responsibility of mankind. In spite of this fact there is almost no process in our environment that can be described exactly with complete exactness, and the working of which is known in full extent. Wind erosion is such a process. Although water erosion is mentioned ever more often in scientific circles as a from of erosion, its effect is restrained to a certain region, although it may cause perceptibly damage of a greater extent in short time. Wind erosion, apart from the fact that it may have global impact, may play an important role in the warming of our climate according to recent studies. First of all, wind erosion may cause damage far from its origin in human health, nutrition, or in the environment in general. Today several surveys have proved, that erosion caused by wind significantly contributes to the air pollution of cities, the fine dust carried as drift by the wind may cause severe environmental damage in accumulation zones. Microbes, toxic material may attach themselves to the dust carried this way and carried on and by the wings of the wind they may cause health issues in humans animals and plants as well. In spite of these facts there are almost no measures against wind erosion employed in arable land, although our ever doughtier climate and changes would make these necessary. Reduction of organic matter content presents a great problem in a large part of cultivated land, so the risk of the production of high quality food raises questions of more and more ethical nature. Who is responsible? The fact, that the chemicals used in a growing extent by agriculture may reach many people causing considerable damage to the environment also raises serious ethical questions. More and more periods with extreme weather conditions are experienced in Hungary and Europe as the effect of climate change. Drought periods are longer and more frequent as the intensity of precipitation changes, this also increases the occurrence of bush-fires, and the growing extent of uncovered soil surface shall intensify wind erosion as well accelerating the negative effects described above. Who will be held responsible for this? Who should bear the larger cost of production in agriculture that is caused by the cost of research necessary to uncover the methods of prevention of irreversible damages caused in nature and environment? Because the field of research requires an interdisciplinary approach, research and innovation requires huge funds, the different approaches to the problem in every single field, and different reasoning methods represent a hurdle as well. In search for possible solutions it is necessary that political decision-makers adopt regulations which have solid scientific fundamentals, and also the cooperation of mankind active in science and economy is crucial. This is the only way of finding sustainable and long term solutions to the problem.

Indoor air quality of a museum in a subtropical climate: the Oscar Niemeyer museum in Curitiba, Brazil.

PubMed

Godoi, Ricardo H M; Carneiro, Barbara H B; Paralovo, Sarah L; Campos, Vania P; Tavares, Tania M; Evangelista, Heitor; Van Grieken, Rene; Godoi, Ana F L

2013-05-01

The assessment of damage to indoor cultural heritage, in particular by pollutants, is nowadays a major and growing concern for curators and conservators. Nevertheless, although many museums have been widely investigated in Europe, the effects of particulate matter and gaseous pollutants in museums under tropical and subtropical climates and with different economic realities are still unclear. An important portion of the world's cultural heritage is currently in tropical countries where both human and financial resources for preserving museum collections are limited. Hence, our aim is to assess the damage that can be caused to the artwork by pollution in hot and humid environments, where air quality and microclimatic condition differences can cause deterioration. As a case study, particulate matter as well as gases were collected at the Oscar Niemeyer Museum (MON) in Curitiba, Brazil, where large modern and contemporary works of art are displayed. NO2, SO2, O3, Acetic Acid, Formic Acids and BTEX, in the ambient air, were sampled by means of passive diffusive sampling and their concentrations were determined by IC or GC-MS. The particulate matter was collected in bulk form and analyzed with the use of energy dispersive X-ray fluorescence and aethalometer. The chemical compositions of individual particles were quantitatively elucidated, including low-Z components like C, N and O, as well as higher-Z elements, using automated electron probe microanalysis. The gaseous and particulate matter levels were then compared with the concentrations obtained for the same pollutants in other museums, located in places with different climates, and with some reference values provided by international cultural heritage conservation centers. Results are interpreted separately and as a whole with the specific aim of identifying compounds that could contribute to the chemical reactions taking place on the surfaces of artifacts and which could potentially cause irreversible damage to the artworks. Copyright © 2013 Elsevier B.V. All rights reserved.

Experimental and Modelling Investigations of the Coupled Elastoplastic Damage of a Quasi-brittle Rock

NASA Astrophysics Data System (ADS)

Zhang, Jiu-Chang

2018-02-01

Triaxial compression tests are conducted on a quasi-brittle rock, limestone. The analyses show that elastoplastic deformation is coupled with damage. Based on the experimental investigation, a coupled elastoplastic damage model is developed within the framework of irreversible thermodynamics. The coupling effects between the plastic and damage dissipations are described by introducing an isotropic damage variable into the elastic stiffness and yield criterion. The novelty of the model is in the description of the thermodynamic force associated with damage, which is formulated as a state function of both elastic and plastic strain energies. The latter gives a full consideration on the comprehensive effects of plastic strain and stress changing processes in rock material on the development of damage. The damage criterion and potential are constructed to determine the onset and evolution of damage variable. The return mapping algorithms of the coupled model are deduced for three different inelastic corrections. Comparisons between test data and numerical simulations show that the coupled elastoplastic damage model is capable of describing the main mechanical behaviours of the quasi-brittle rock.

Biomarkers in Immunoglobulin Light Chain Amyloidosis.

PubMed

Kufová, Z; Sevcikova, T; Growkova, K; Vojta, P; Filipová, J; Adam, Z; Pour, L; Penka, M; Rysava, R; Němec, P; Brozova, L; Vychytilova, P; Jurczyszyn, A; Grosicki, S; Barchnicka, A; Hajdúch, M; Simicek, M; Hájek, R

2017-01-01

Immunoglobulin light chain amyloidosis (AL amyloidosis - ALA) is a monoclonal gammopathy characterized by presence of aberrant plasma cells producing amyloidogenic immunoglobulin light chains. This leads to formation of amyloid fibrils in various organs and tissues, mainly in heart and kidney, and causes their dysfunction. As amyloid depositing in target organs is irreversible, there is a big effort to identify biomarker that could help to distinguish ALA from other monoclonal gammopathies in the early stages of disease, when amyloid deposits are not fatal yet. High throughput technologies bring new opportunities to modern cancer research as they enable to study disease within its complexity. Sophisticated methods such as next generation sequencing, gene expression profiling and circulating microRNA profiling are new approaches to study aberrant plasma cells from patients with light chain amyloidosis and related diseases. While generally known mutation in multiple myeloma patients (KRAS, NRAS, MYC, TP53) were not found in ALA, number of mutated genes is comparable. Transcriptome of ALA patients proves to be more similar to monoclonal gammopathy of undetermined significance patients, moreover level of circulating microRNA, that are known to correlate with heart damage, is increased in ALA patients, where heart damage in ALA typical symptom.Key words: amyloidosis - plasma cell - genome - transcriptome - microRNA.

Molecular mechanisms of liver preconditioning

PubMed Central

Alchera, Elisa; Dal Ponte, Caterina; Imarisio, Chiara; Albano, Emanuele; Carini, Rita

2010-01-01

Ischemia/reperfusion (I/R) injury still represents an important cause of morbidity following hepatic surgery and limits the use of marginal livers in hepatic transplantation. Transient blood flow interruption followed by reperfusion protects tissues against damage induced by subsequent I/R. This process known as ischemic preconditioning (IP) depends upon intrinsic cytoprotective systems whose activation can inhibit the progression of irreversible tissue damage. Compared to other organs, liver IP has additional features as it reduces inflammation and promotes hepatic regeneration. Our present understanding of the molecular mechanisms involved in liver IP is still largely incomplete. Experimental studies have shown that the protective effects of liver IP are triggered by the release of adenosine and nitric oxide and the subsequent activation of signal networks involving protein kinases such as phosphatidylinositol 3-kinase, protein kinase C δ/ε and p38 MAP kinase, and transcription factors such as signal transducer and activator of transcription 3, nuclear factor-κB and hypoxia-inducible factor 1. This article offers an overview of the molecular events underlying the preconditioning effects in the liver and points to the possibility of developing pharmacological approaches aimed at activating the intrinsic protective systems in patients undergoing liver surgery. PMID:21182220

Optimizing phytoremediation of heavy metal-contaminated soil by exploiting plants' stress adaptation.

PubMed

Barocsi, Attila; Csintalan, Zsolt; Kocsanyi, Laszlo; Dushenkov, Slavik; Kuperberg, J Michael; Kucharski, Rafal; Richter, Peter I

2003-01-01

Soil phytoextraction is based on the ability of plants to extract contaminants from the soil. For less bioavailable metals, such as Pb, a chelator is added to the soil to mobilize the metal. The effect can be significant and in certain species, heavy metal accumulation can rapidly increase 10-fold. Accumulation of high levels of toxic metals may result in irreversible damage to the plant. Monitoring and controlling the phytotoxicity caused by EDTA-induced metal accumulation is crucial to optimize the remedial process, i.e. to achieve maximum uptake. We describe an EDTA-application procedure that minimizes phytotoxicity by increasing plant tolerance and allows phytoextraction of elevated levels of Pb and Cd. Brassica juncea is tested in soil with typical Pb and Cd concentrations of 500 mg kg-1 and 15 mg kg-1, respectively. Instead of a single dose treatment, the chelator is applied in multiple doses, that is, in several small increments, thus providing time for plants to initiate their adaptation mechanisms and raise their damage threshold. In situ monitoring of plant stress conditions by chlorophyll fluorescence recording allows for the identification of the saturating heavy metal accumulation process and of simultaneous plant deterioration.

The Nature of Cold-induced Dormancy in Urediospores of Puccinia graminis tritici

PubMed Central

Maheshwari, Ramesh; Sussman, Alfred S.

1971-01-01

When air-dry urediospores of the wheat stem rust, Puccinia graminis f. sp. tritici, are exposed to temperatures below freezing, their germinability is markedly reduced, even after prolonged thawing at room temperature. Germinability is fully restored by a brief heat-shock or by vapor phase hydration. We have found that this “cold dormancy” cannot be reversed once the spores contact liquid water. Enhanced loss of metabolites occurs immediately upon suspension of cold-dormant urediospores in liquid without a prior heat-shock. Such leakage is two to three times greater than from untreated or heatshocked cold-dormant spores and accounts for up to 70% of the soluble pool of metabolites normally present in germinating urediospores. Respiratory activity of cold-dormant urediospores declines rapidly during incubation in liquid. Incorporation of isotopic carbon into cold-dormant urediospores is only a fraction of that of untreated or heat-activated spores. Thus, cold shock transforms the spores into a state of supersensitivity to liquid water, which is reversed by heat-shock or slow hydration by vapor phase equilibration. The primary cause of damage to cold-dormant cells exposed to liquid water appears to be irreversible permeability damage, followed by metabolic injury. PMID:16657610

Non-Thermal Electromagnetic Radiation Damage to Lens Epithelium

PubMed Central

Bormusov, Elvira; P.Andley, Usha; Sharon, Naomi; Schächter, Levi; Lahav, Assaf; Dovrat, Ahuva

2008-01-01

High frequency microwave electromagnetic radiation from mobile phones and other modern devices has the potential to damage eye tissues, but its effect on the lens epithelium is unknown at present. The objective of this study was to investigate the non-thermal effects of high frequency microwave electromagnetic radiation (1.1GHz, 2.22 mW) on the eye lens epithelium in situ. Bovine lenses were incubated in organ culture at 35°C for 10-15 days. A novel computer-controlled microwave source was used to investigate the effects of microwave radiation on the lenses. 58 lenses were used in this study. The lenses were divided into four groups: (1) Control lenses incubated in organ culture for 10 to15 days. (2) Electromagnetic radiation exposure group treated with 1.1 GHz, 2.22 mW microwave radiation for 90 cycles of 50 minutes irradiation followed by 10 minutes pause and cultured up to 10 days. (3) Electromagnetic radiation exposure group treated as group 2 with 192 cycles of radiation and cultured for 15 days. (4) Lenses exposed to 39.5ºC for 2 hours 3 times with 24 hours interval after each treatment beginning on the second day of the culture and cultured for 11 days. During the culture period, lens optical quality was followed daily by a computer-operated scanning laser beam. At the end of the culture period, control and treated lenses were analyzed morphologically and by assessment of the lens epithelial ATPase activity. Exposure to 1.1 GHz, 2.22 mW microwaves caused a reversible decrease in lens optical quality accompanied by irreversible morphological and biochemical damage to the lens epithelial cell layer. The effect of the electromagnetic radiation on the lens epithelium was remarkably different from those of conductive heat. The results of this investigation showed that electromagnetic fields from microwave radiation have a negative impact on the eye lens. The lens damage by electromagnetic fields was distinctly different from that caused by conductive heat. PMID:19517034

The application of antimicrobial photodynamic therapy (aPDT) in dentistry: a critical review

PubMed Central

Carrera, E T; Dias, H B; Corbi, S C T; Marcantonio, R A C; Bernardi, A C A; Bagnato, V S; Hamblin, M R; Rastelli, A N S

2017-01-01

In recent years there have been an increasing number of in vitro and in vivo studies that show positive results regarding antimicrobial photodynamic therapy (aPDT) used in dentistry. These include applications in periodontics, endodontics, and mucosal infections caused by bacteria present as biofilms. Antimicrobial photodynamic therapy is a therapy based on the combination of a non-toxic photosensitizer (PS) and appropriate wavelength visible light, which in the presence of oxygen is activated to produce reactive oxygen species (ROS). ROS induce a series of photochemical and biological events that cause irreversible damage leading to the death of microorganisms. Many light-absorbing dyes have been mentioned as potential PS for aPDT and different wavelengths have been tested. However, there is no consensus on a standard protocol yet. Thus, the goal of this review was to summarize the results of research on aPDT in dentistry using the PubMed database focusing on recent studies of the effectiveness aPDT in decreasing microorganisms and microbial biofilms, and also to describe aPDT effects, mechanisms of action and applications. PMID:29151775

The application of antimicrobial photodynamic therapy (aPDT) in dentistry: a critical review

NASA Astrophysics Data System (ADS)

Carrera, E. T.; Dias, H. B.; Corbi, S. C. T.; Marcantonio, R. A. C.; Bernardi, A. C. A.; Bagnato, V. S.; Hamblin, M. R.; Rastelli, A. N. S.

2016-12-01

In recent years there have been an increasing number of in vitro and in vivo studies that show positive results regarding antimicrobial photodynamic therapy (aPDT) used in dentistry. These include applications in periodontics, endodontics, and mucosal infections caused by bacteria present as biofilms. Antimicrobial photodynamic therapy is a therapy based on the combination of a non-toxic photosensitizer (PS) and appropriate wavelength visible light, which in the presence of oxygen is activated to produce reactive oxygen species (ROS). ROS induce a series of photochemical and biological events that cause irreversible damage leading to the death of microorganisms. Many light-absorbing dyes have been mentioned as potential PS for aPDT and different wavelengths have been tested. However, there is no consensus on a standard protocol yet. Thus, the goal of this review was to summarize the results of research on aPDT in dentistry using the PubMed database focusing on recent studies of the effectiveness aPDT in decreasing microorganisms and microbial biofilms, and also to describe aPDT effects, mechanisms of action and applications.

Lymphogranuloma venereum: diagnostic and treatment challenges.

PubMed

Ceovic, Romana; Gulin, Sandra Jerkovic

2015-01-01

Lymphogranuloma venereum is a sexually transmitted disease caused by L1, L2, and L3 serovars of Chlamydia trachomatis. In the last 10 years outbreaks have appeared in North America, Europe, and Australia in the form of proctitis among men who have sex with men. Three stages of disease have been described. The disease in primary stage may go undetected when only a painless papule, pustule, or ulceration appears. The diagnosis is difficult to establish on clinical grounds alone and frequently relies upon either serologic testing, culture, or more recently, nucleic acid amplification testing of direct specimens. A proper treatment regimen cures the infection and prevents further damage to tissues. Lymphogranuloma venereum causes potentially severe infections with possibly irreversible sequels if adequate treatment is not begun promptly. Early and accurate diagnosis is essential. Doxycycline is the drug of choice. Pregnant and lactating women should be treated with erythromycin or azithromycin. Patient must be followed up during the treatment, until disease signs and symptoms have resolved. Repeated testing for syphilis, hepatitis B and C, and HIV to detect early infection should be performed.

Lymphogranuloma venereum: diagnostic and treatment challenges

PubMed Central

Ceovic, Romana; Gulin, Sandra Jerkovic

2015-01-01

Lymphogranuloma venereum is a sexually transmitted disease caused by L1, L2, and L3 serovars of Chlamydia trachomatis. In the last 10 years outbreaks have appeared in North America, Europe, and Australia in the form of proctitis among men who have sex with men. Three stages of disease have been described. The disease in primary stage may go undetected when only a painless papule, pustule, or ulceration appears. The diagnosis is difficult to establish on clinical grounds alone and frequently relies upon either serologic testing, culture, or more recently, nucleic acid amplification testing of direct specimens. A proper treatment regimen cures the infection and prevents further damage to tissues. Lymphogranuloma venereum causes potentially severe infections with possibly irreversible sequels if adequate treatment is not begun promptly. Early and accurate diagnosis is essential. Doxycycline is the drug of choice. Pregnant and lactating women should be treated with erythromycin or azithromycin. Patient must be followed up during the treatment, until disease signs and symptoms have resolved. Repeated testing for syphilis, hepatitis B and C, and HIV to detect early infection should be performed. PMID:25870512

New laser sources for clinical treatment and diagnostics of neonatal jaundice

NASA Astrophysics Data System (ADS)

Hamza, Mostafa; El-Ahl, Mohammad H. S.; Hamza, Ahmad M.

2001-06-01

An elevated serum bilirubin concentration in the newborn infant presents a therapeutic as well as a diagnostic problem to the physician. It has long been recognized that high levels of bilirubin cause irreversible brain damage and even death. The authors introduce the use of semiconductor diode lasers and diode-pumped solid-state lasers that can be used for solving such diagnostic and therapeutic problems. These new laser sources can improve the ergonomics of using laser, enhance performance capabilities and reduce the cost of employing laser energy to pump bilirubin out of an infant's body. The choice of laser wavelengths follows the principles of bilirubinometry and phototherapy of neonatal jaundice. The wide spread use of these new laser sources for clinical monitoring and treatment of neonatal hyperbilirubinemia will be made possible as each incremental or quantum jump cost reduction is achieved. Our leading clinical experience as well as the selection rules of laser wavelengths will be presented.

Eco-analytical Methodology in Environmental Problems Monitoring

NASA Astrophysics Data System (ADS)

Agienko, M. I.; Bondareva, E. P.; Chistyakova, G. V.; Zhironkina, O. V.; Kalinina, O. I.

2017-01-01

Among the problems common to all mankind, which solutions influence the prospects of civilization, the problem of ecological situation monitoring takes very important place. Solution of this problem requires specific methodology based on eco-analytical comprehension of global issues. Eco-analytical methodology should help searching for the optimum balance between environmental problems and accelerating scientific and technical progress. The fact that Governments, corporations, scientists and nations focus on the production and consumption of material goods cause great damage to environment. As a result, the activity of environmentalists is developing quite spontaneously, as a complement to productive activities. Therefore, the challenge posed by the environmental problems for the science is the formation of geo-analytical reasoning and the monitoring of global problems common for the whole humanity. So it is expected to find the optimal trajectory of industrial development to prevent irreversible problems in the biosphere that could stop progress of civilization.

Role of vinpocetine in cerebrovascular diseases.

PubMed

Patyar, Sazal; Prakash, Ajay; Modi, Manish; Medhi, Bikash

2011-01-01

A cerebrovascular accident, or stroke, is defined as the abrupt onset of a neurological deficit, which can be due to ischemia. Cerebral ischemia is caused by a reduction in blood flow that thereby decreases cerebral metabolism. Chronic cerebral hypoperfusion leads to irreversible brain damage and plays an important role in the development of certain types of dementia. Vinpocetine, chemically known as ethyl apovincaminate, is a vinca alkaloid that exhibits cerebral blood-flow enhancing and neuroprotective effects. Non-clinical and clinical studies have suggested multiple mechanisms responsible for the beneficial neuroprotective effects of vinpocetine. As no significant side effects related to vinpocetine treatment have been reported, it is considered to be safe for long-term use. This vasoactive alkaloid is widely marketed as a supplement for vasodilation and as a nootropic for the improvement of memory. The present review focuses on studies investigating the role of vinpocetine in cerebrovascular diseases.

Modelling of thermal shock experiments of carbon based materials in JUDITH

NASA Astrophysics Data System (ADS)

Ogorodnikova, O. V.; Pestchanyi, S.; Koza, Y.; Linke, J.

2005-03-01

The interaction of hot plasma with material in fusion devices can result in material erosion and irreversible damage. Carbon based materials are proposed for ITER divertor armour. To simulate carbon erosion under high heat fluxes, electron beam heating in the JUDITH facility has been used. In this paper, carbon erosion under energetic electron impact is modeled by the 3D thermomechanics code 'PEGASUS-3D'. The code is based on a crack generation induced by thermal stress. The particle emission observed in thermal shock experiments is a result of breaking bonds between grains caused by thermal stress. The comparison of calculations with experimental data from JUDITH shows good agreement for various incident power densities and pulse durations. A realistic mean failure stress has been found. Pre-heating of test specimens results in earlier onset of brittle destruction and enhanced particle loss in agreement with experiments.

Effect of blood pressure lowering on markers of kidney disease progression.

PubMed

Udani, Suneel M; Koyner, Jay L

2009-10-01

Hypertension remains a common comorbidity and cause of chronic kidney disease (CKD). As the number of patients with CKD grows, so does the need to identify modifiable risk factors for CKD progression. Data on slowing progression of CKD or preventing end-stage renal disease with aggressive blood pressure control have not yielded definitive conclusions regarding ideal blood pressure targets. Shifting the focus of antihypertensive therapy to alternative markers of end-organ damage, specifically proteinuria, has yielded some promise in preventing the progression of CKD. Nevertheless, proteinuria and decline in estimated GFR may represent an irreversible degree of injury to the kidney that limits the impact of any therapy. The identification and use of novel markers of kidney injury to assess the impact of antihyper-tensive therapy may yield clearer direction with regard to optimal management of hypertension in the setting of CKD.

Electrical neurostimulation with imbalanced waveform mitigates dissolution of platinum electrodes

PubMed Central

Kumsa, Doe; Hudak, Eric M; Montague, Fred W; Kelley, Shawn C; Untereker, Darrel F; Hahn, Benjamin P; Condit, Chris; Cholette, Martin; Lee, Hyowon; Bardot, Dawn; Takmakov, Pavel

2017-01-01

Objective Electrical neurostimulation has traditionally been limited to the use of charge-balanced waveforms. Charge-imbalanced and monophasic waveforms are not used to deliver clinical therapy, because it is believed that these stimulation paradigms may generate noxious electrochemical species that cause tissue damage. Approach In this study, we investigated the dissolution of platinum as one of such irreversible reactions over a range of charge densities up to 160 µC cm−2 with current-controlled first phase, capacitive discharge second phase waveforms of both cathodic-first and anodic-first polarity. We monitored the concentration of platinum in solution under different stimulation delivery conditions including charge-balanced, charge-imbalanced, and monophasic pulses. Main results We observed that platinum dissolution decreased during charge-imbalanced and monophasic stimulation when compared to charge-balanced waveforms. Significance This observation provides an opportunity to re-evaluate the charge-balanced waveform as the primary option for sustainable neural stimulation. PMID:27650936

Assessment and management of dental erosion.

PubMed

Wang, Xiaojie; Lussi, Adrian

2010-07-01

Studies have shown a growing trend toward increasing prevalence of dental erosion, associated with the declining prevalence of caries disease in industrialized countries. Erosion is an irreversible chemical process that results in tooth substance loss and leaves teeth susceptible to damage as a result of wear over the course of an individual's lifetime. Therefore, early diagnosis and adequate prevention are essential to minimize the risk of tooth erosion. Clinical appearance is the most important sign to be used to diagnose erosion. The Basic Erosive Wear Examination (BEWE) is a simple method to fulfill this task. The determination of a variety of risk and protective factors (patient-dependent and nutrition-dependent factors) as well as their interplay are necessary to initiate preventive measures tailored to the individual. When tooth loss caused by erosive wear reaches a certain level, oral rehabilitation becomes necessary. Copyright 2010 Elsevier Inc. All rights reserved.

Nanotechnology, a new paradigm in atherosclerosis treatment.

PubMed

Martín Giménez, Virna M; Ruiz-Roso, María Belén; Camargo, Alejandra Beatriz; Kassuha, Diego; Manucha, Walter

Atherosclerosis, a known and prevalent disease, causes progressive deterioration of affected vessels, inducing a blood flow reduction with different complications, and its symptoms usually manifest in advanced stages of the disease. Therefore, the classic therapeutic alternatives are insufficient because the damages are many times irreversible. For this reason, there is a need to implement intelligent forms of drug administration and develop new therapeutic targets that reduce the progression of atherosclerotic lesion. The implementation of new tools for prevention, diagnosis and treatment of this cardiovascular disease is of special interest, focusing our attention on achieving a more effective control of the immune system. Finally, this review highlights the latest knowledge about nanotechnology as a powerful, modern, and promising therapeutic alternative applied to atherosclerotic disease, as well as warning of the potential complications with their use. Copyright © 2016 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

Management of asymptomatic gene carriers of transthyretin familial amyloid polyneuropathy

PubMed Central

Barroso, Fabio; González‐Duarte, Alejandra; Conceição, Isabel; Obici, Laura; Keohane, Denis; Amass, Leslie

2016-01-01

ABSTRACT Transthyretin familial amyloid polyneuropathy (TTR‐FAP) is a rare, severe, and irreversible, adult‐onset, hereditary disorder caused by autosomal‐dominant mutations in the TTR gene that increase the intrinsic propensity of transthyretin protein to misfold and deposit systemically as insoluble amyloid fibrils in nerve tissues, the heart, and other organs. TTR‐FAP is characterized by relentless, progressively debilitating polyneuropathy, and leads to death, on average, within 10 years of symptom onset without treatment. With increased availability of disease‐modifying treatment options for a wider spectrum of patients with TTR‐FAP, timely detection of the disease may offer substantial clinical benefits. This review discusses mutation‐specific predictive genetic testing in first‐degree relatives of index patients diagnosed with TTR‐FAP and the structured clinical follow‐up of asymptomatic gene carriers for prompt diagnosis and early therapeutic intervention before accumulation of substantial damage. Muscle Nerve 54: 353–360, 2016 PMID:27273296

Pathophysiology and preventive strategies of anthracycline-induced cardiotoxicity

PubMed Central

Chung, Woo-Baek; Youn, Ho-Joong

2016-01-01

Cardiotoxicity is a well-known complication following treatment with anthracyclines. However, they are still widely used in chemotherapy for breast cancer, lymphoma, leukemia, and sarcoma, among others. Patient clinical characteristics, such as age, sex, comorbidities, anthracycline dose and infusion schedule, and the combined anti-cancer agents used, are diverse among cancer types. It is difficult to recommend guidelines for the prevention or management of anthracycline-induced cardiotoxicity applicable to all cancer types. Therefore, anthracycline-induced cardiotoxicity remains a major limitation in the proper management of cancer patients treated with an anthracycline-combined regimen. Efforts have been extensive to determine the mechanism and treatment of anthracycline-induced cardiotoxicity. Because cardiotoxicity causes irreversible damage to the myocardium, prevention is a more effective approach than treatment of cardiotoxicity after symptomatic or asymptomatic cardiac dysfunction develops. This article will review the pathophysiological mechanisms of anthracycline-induced cardiotoxicity and strategies for protecting the myocardium from anthracycline. PMID:27378126

A case against Dutch euthanasia.

PubMed

Fenigsen, Richard

1989-01-01

The growing acceptance of voluntary active euthanasia by the Dutch is examined in relation to the plastic cards requesting active euthanasia carried by many people in The Netherlands, public opinion polls, and support by leading medical figures of the movement to legalize euthanasia. The author draws upon his experience as a hospital doctor to condemn the practice of active euthanasia, arguing that its voluntariness is often counterfeit and always questionable, that it is inseparable from overtly involuntary forms of euthanasia, and that its promise of sparing the sick person agony is false. "Voluntary" euthanasia also brings an ominous change in society because of the message it sends to the elderly and sick, the weak and the dependent; because the fallibility of medical judgments are inconsistent with the irreversibility of the act; and because the fallacious reasoning of the philosophy threatens to cause irreparable damage to the medical profession.

Immunogenic cancer cell death selectively induced by near infrared photoimmunotherapy initiates host tumor immunity.

PubMed

Ogawa, Mikako; Tomita, Yusuke; Nakamura, Yuko; Lee, Min-Jung; Lee, Sunmin; Tomita, Saori; Nagaya, Tadanobu; Sato, Kazuhide; Yamauchi, Toyohiko; Iwai, Hidenao; Kumar, Abhishek; Haystead, Timothy; Shroff, Hari; Choyke, Peter L; Trepel, Jane B; Kobayashi, Hisataka

2017-02-07

Immunogenic cell death (ICD) is a form of cell death that activates an adaptive immune response against dead-cell-associated antigens. Cancer cells killed via ICD can elicit antitumor immunity. ICD is efficiently induced by near-infrared photo-immunotherapy (NIR-PIT) that selectively kills target-cells on which antibody-photoabsorber conjugates bind and are activated by NIR light exposure. Advanced live cell microscopies showed that NIR-PIT caused rapid and irreversible damage to the cell membrane function leading to swelling and bursting, releasing intracellular components due to the influx of water into the cell. The process also induces relocation of ICD bio markers including calreticulin, Hsp70 and Hsp90 to the cell surface and the rapid release of immunogenic signals including ATP and HMGB1 followed by maturation of immature dendritic cells. Thus, NIR-PIT is a therapy that kills tumor cells by ICD, eliciting a host immune response against tumor.

Orphan diseases of the nose and paranasal sinuses: Pathogenesis – clinic – therapy

PubMed Central

Laudien, Martin

2015-01-01

Rare rhinological diseases are a diagnostic challenge. Sometimes it takes months or even years from the primary manifestation of the disease until the definitive diagnosis is establibshed. During these times the disease proceeds in an uncontrolled or insufficiently treated way. (Irreversible) damage results and sometimes life-threatening situations occur. The unexpected course of a (misdiagnosed) disease should lead to further diagnostic reflections and steps in order to detect also rare diseases as early as possible. The present paper discusses granulomatous diseases of the nose and paranasal sinuses caused by mycobacteria, treponema, Klebsiella, fungi, and protozoa as well as vasculitis, sarcoidosis, rosacea, cocaine-induced midline destruction, nasal extranodal NK/T cell lymphoma, and cholesterol granuloma. Furthermore, diseases with disorders of the mucociliary clearance such as primary ciliary dyskinesia and cystic fibrosis are presented, taking into consideration the current literature. PMID:26770278

Causes and management of infertility in systemic lupus erythematosus.

PubMed

Hickman, Richard A; Gordon, Caroline

2011-09-01

SLE is a multi-system, autoimmune condition that can influence both male and female fertility. Inability to conceive may be attributed to several factors that may act singly or in combination: (i) older age in patients with SLE compared with healthy controls; (ii) disease-related infertility; and (iii) infertility through gonadotoxic treatments. In addition, psychosocial factors related to the disease may lower fecundity and may be associated with apparent infertility. Many therapeutic avenues are open to counteract reproductive damage in the management of SLE and to assist conception once infertility is diagnosed. These treatments can include the administration of gonadotrophin-receptor hormone analogues while receiving CYC treatment, the use of assisted reproductive technologies, such as in vitro fertilization and psychosocial intervention to promote a healthier relationship with their partner. Knowledge of how these reproductive problems occur and its prevention/treatment in SLE patients should avert irreversible infertility as well as give hope to SLE patients with infertility.

Does non-acetylated salicylate inhibit thromboxane biosynthesis in human platelets?

PubMed

Danesh, B J; McLaren, M; Russell, R I; Lowe, G D; Forbes, C D

1988-08-01

Ingestion of aspirin (acetyl salicylic acid: ASA) may promote bleeding complications due to inhibition of thromboxane biosynthesis, which results in the prolongation of bleeding time. The effect is believed to be achieved by the irreversible acetylation of the enzyme cyclooxygenase by aspirin. This alteration in platelet function by aspirin prohibits its use in patients with bleeding disorders such as haemophiliacs. Choline magnesium trisalicylate (CMT; Napp Laboratories Ltd) is a non-acetylated salicylate with analgesic and anti-inflammatory effects similar to that of aspirin. However, despite a comparable salicylate absorption from the two drugs, CMT is found to have no inhibitory action in platelet aggregation and to cause less gastric mucosal damage and gastrointestinal blood loss than aspirin. To investigate the role of the acetyl moiety in the inhibition of platelet thromboxane biosynthesis, we studied the effect of CMT and ASA on bleeding time, serum thromboxane B2 (TxB2) and thromboxane (Tx) generation in healthy volunteers.

Inefficient differentiation response to cell cycle stress leads to genomic instability and malignant progression of squamous carcinoma cells

PubMed Central

Alonso-Lecue, Pilar; de Pedro, Isabel; Coulon, Vincent; Molinuevo, Rut; Lorz, Corina; Segrelles, Carmen; Ceballos, Laura; López-Aventín, Daniel; García-Valtuille, Ana; Bernal, José M; Mazorra, Francisco; Pujol, Ramón M; Paramio, Jesús; Ramón Sanz, J; Freije, Ana; Toll, Agustí; Gandarillas, Alberto

2017-01-01

Squamous cell carcinoma (SCC) or epidermoid cancer is a frequent and aggressive malignancy. However in apparent paradox it retains the squamous differentiation phenotype except for very dysplastic lesions. We have shown that cell cycle stress in normal epidermal keratinocytes triggers a squamous differentiation response involving irreversible mitosis block and polyploidisation. Here we show that cutaneous SCC cells conserve a partial squamous DNA damage-induced differentiation response that allows them to overcome the cell division block. The capacity to divide in spite of drug-induced mitotic stress and DNA damage made well-differentiated SCC cells more genomically instable and more malignant in vivo. Consistently, in a series of human biopsies, non-metastatic SCCs displayed a higher degree of chromosomal alterations and higher expression of the S phase regulator Cyclin E and the DNA damage signal γH2AX than the less aggressive, non-squamous, basal cell carcinomas. However, metastatic SCCs lost the γH2AX signal and Cyclin E, or accumulated cytoplasmic Cyclin E. Conversely, inhibition of endogenous Cyclin E in well-differentiated SCC cells interfered with the squamous phenotype. The results suggest a dual role of cell cycle stress-induced differentiation in squamous cancer: the resulting mitotic blocks would impose, when irreversible, a proliferative barrier, when reversible, a source of genomic instability, thus contributing to malignancy. PMID:28661481

Viscoelastoplastic Deformation and Damage Response of Titanium Alloy, Ti-6Al-4V, at Elevated Temperatures

NASA Technical Reports Server (NTRS)

Arnold, Steven M.; Lerch, Bradley A.; Saleeb, Atef F.; Kasemer, Matthew P.

2013-01-01

Time-dependent deformation and damage behavior can significantly affect the life of aerospace propulsion components. Consequently, one needs an accurate constitutive model that can represent both reversible and irreversible behavior under multiaxial loading conditions. This paper details the characterization and utilization of a multi-mechanism constitutive model of the GVIPS class (Generalized Viscoplastic with Potential Structure) that has been extended to describe the viscoelastoplastic deformation and damage of the titanium alloy Ti-6Al-4V. Associated material constants were characterized at five elevated temperatures where viscoelastoplastic behavior was observed, and at three elevated temperatures where damage (of both the stiffness reduction and strength reduction type) was incurred. Experimental data from a wide variety of uniaxial load cases were used to correlate and validate the proposed GVIPS model. Presented are the optimized material parameters, and the viscoelastoplastic deformation and damage responses at the various temperatures.

Confronting challenges to economic analysis of biological invasions in forests

Treesearch

Thomas P Holmes

2010-01-01

Biological invasions of forests by non-indigenous organisms present a complex, persistent, and largely irreversible threat to forest ecosystems around the globe. Rigorous assessments of the economic impacts of introduced species, at a national scale, are needed to provide credible information to policy makers. It is proposed here that microeconomic models of damage due...

A Hands-On Approach to Teaching Environmental Awareness and Pollutant Remediation to Undergraduate Chemistry Students

ERIC Educational Resources Information Center

Salman Ashraf, S.; Rauf, M. A.; Abdullah, Fatema H.

2012-01-01

Background: One of the unfortunate side effects of the industrial revolution has been the constant assault of the environment with various forms of pollution. Lately, this issue has taken a more critical dimension as prospects of global climate change and irreversible ecosystem damage are becoming a reality. Purpose: College graduates (especially…

UV-damaged DNA binding protein-1 and de-etiolated-1 regulate golden 2-like transcription factor by assembling a cullin 4-based ubiquitin ligase in tomato

USDA-ARS?s Scientific Manuscript database

Fleshy fruit undergo a novel developmental program that ends in the irreversible process of ripening and eventual tissue senescence. During these maturation processes, fruit undergo numerous physiological, biochemical and structural alterations, making them more attractive to seed dispersal organism...

Sox2 and Jagged1 Expression in Normal and Drug-Damaged Adult Mouse Inner Ear

PubMed Central

Campbell, Sean; Taylor, Ruth R.; Forge, Andrew; Hume, Clifford R.

2007-01-01

Inner ear hair cells detect environmental signals associated with hearing, balance, and body orientation. In humans and other mammals, significant hair cell loss leads to irreversible hearing and balance deficits, whereas hair cell loss in nonmammalian vertebrates is repaired by the spontaneous generation of replacement hair cells. Research in mammalian hair cell regeneration is hampered by the lack of in vivo damage models for the adult mouse inner ear and the paucity of cell-type-specific markers for non-sensory cells within the sensory receptor epithelia. The present study delineates a protocol to drug damage the adult mouse auditory epithelium (organ of Corti) in situ and uses this protocol to investigate Sox2 and Jagged1 expression in damaged inner ear sensory epithelia. In other tissues, the transcription factor Sox2 and a ligand member of the Notch signaling pathway, Jagged1, are involved in regenerative processes. Both are involved in early inner ear development and are expressed in developing support cells, but little is known about their expressions in the adult. We describe a nonsurgical technique for inducing hair cell damage in adult mouse organ of Corti by a single high-dose injection of the aminoglycoside kanamycin followed by a single injection of the loop diuretic furosemide. This drug combination causes the rapid death of outer hair cells throughout the cochlea. Using immunocytochemical techniques, Sox2 is shown to be expressed specifically in support cells in normal adult mouse inner ear and is not affected by drug damage. Sox2 is absent from auditory hair cells, but is expressed in a subset of vestibular hair cells. Double-labeling experiments with Sox2 and calbindin suggest Sox2-positive hair cells are Type II. Jagged1 is also expressed in support cells in the adult ear and is not affected by drug damage. Sox2 and Jagged1 may be involved in the maintenance of support cells in adult mouse inner ear. PMID:18157569

Micromechanical modelling of polyethylene

NASA Astrophysics Data System (ADS)

Alvarado Contreras, Jose Andres

2008-10-01

The increasing use of polyethylene in diverse applications motivates the need for understanding how its molecular properties relate to the overall behaviour of the material. Although microstructure and mechanical properties of polymers have been the subject of several studies, the irreversible microstructural rearrangements occurring at large deformations are not completely understood. The purpose of this thesis is to describe how the concepts of Continuum Damage Mechanics can be applied to modelling of polyethylene materials under different loading conditions. The first part of the thesis consists of the theoretical formulation and numerical implementation of a three-dimensional micromechanical model for crystalline polyethylene. Based on the theory of shear slip on crystallographic planes, the proposed model is expressed in the framework of viscoplasticity coupled with degradation at large deformations. Earlier models aid in the interpretation of the mechanical behaviour of crystalline polyethylene under different loading conditions; however, they cannot predict the microstructural damage caused by deformation. The model, originally due to Parks and Ahzi (199o), was further developed in the light of the concept of Continuum Damage Mechanics to consider the original microstructure, the particular irreversible rearrangements, and the deformation mechanisms. Damage mechanics has been a matter of intensive research by many authors, yet it has not been introduced to the micromodelling of semicrystalline polymeric materials such as polyethylene. Regarding the material representation, the microstructure is simplified as an aggregate of randomly oriented and perfectly bonded crystals. To simulate large deformations, the new constitutive model attempts to take into account existence of intracrystalline microcracks. The second part of the work presents the theoretical formulation and numerical implementation of a three-dimensional constitutive model for the mechanical behaviour of semicrystalline polyethylene. The model proposed herein attempts to describe the deformation and degradation process in semicrystalline polyethylene following the approach of damage mechanics. Structural degradation, an important phenomenon at large deformations, has not received sufficient attention in the literature. The modifications to the constitutive equations consist essentially of introducing the concept of Continuum Damage Mechanics to describe the rupture of the intermolecular (van der Waals) bonds that hold crystals as coherent structures. In order to model the mechanical behaviour, the material morphology is simplified as a collection of inclusions comprising the crystalline and amorphous phases with their characteristic average volume fractions. In the spatial arrangement, each inclusion consists of crystalline material lying in a thin lamella attached to an amorphous layer. To consider microstructural damage, two different approaches are analyzed. The first approach assumes damage occurs only in the crystalline phase, i.e., degradation of the amorphous phase is ignored. The second approach considers the effect of damage on the mechanical behaviour of both the amorphous and crystalline phases. To illustrate the proposed constitutive formulations, the models were used to predict the responses of crystalline and semicrystalline polyethylene under uniaxial tension and simple shear. The numerical simulations were compared with experimental data previously obtained by Bartczak et al. (1994), G'Sell and Jonas (1981), G'Sell et al. (1983), Hillmansen et al. (2000), and Li et al. (2001). Our model's predictions show a consistently good agreement with the experimental results and a significant improvement with respect to the ones obtained by Parks and Ahzi (1990), Schoenfeld et al. (1995), Yang and Chen (2001), Lee et al. (i993b), Lee et al. (1993a), and Nikolov et al. (2006). The newly proposed formulations demonstrate that these types of constitutive models based on Continuum Damage Mechanics are appropriate for predicting large deformations and failure in polyethylene materials.

Effect of surfactants and temperature on the hyperfiltration performance of poly(ether/urea) membranes

NASA Technical Reports Server (NTRS)

Leban, M. I.; Wydeven, T. J.

1984-01-01

The individual and combined effects of pasteurization temperature (347 K) and surfactants (anionic, cationic, and neutral) on a poly(ether/urea) thin-film hyperfiltration membrane were studied. Performance of this positively charged membrane was measured in terms of sodium chloride rejection and water flux. The observed effect was mostly on water flux and minimal on salt rejection. Pasteurization temperature caused an irreversible flux decline (flux decline slope of 0.09). The gradual flux reduction caused by neutral and cationic surfactants was reversible, whereas the flux reduction caused by anionic surfactant was irreversible and of similar magnitude to flux reduction caused by pasteurization temperature. The effects of anionic surfactant and pasteurization temperature were additive. Because of flux decline at elevated temperatures the poly(ether/urea) membrane is not very attractive for long-term spaceflight use.

Delayed injection of polypyrrole doped with iodine particle suspension after spinal cord injury in rats improves functional recovery and decreased tissue damage evaluated by 3.0 Tesla in vivo magnetic resonance imaging.

PubMed

Mondragon-Lozano, Rodrigo; Ríos, Camilo; Roldan-Valadez, Ernesto; Cruz, Guillermo J; Olayo, Maria G; Olayo, Roberto; Salgado-Ceballos, Hermelinda; Morales, Juan; Mendez-Armenta, Marisela; Alvarez-Mejia, Laura; Fabela, Omar; Morales-Guadarrama, Axayacatl; Sánchez-Torres, Stephanie; Diaz-Ruiz, Araceli

2017-04-01

Traumatic spinal cord injury (SCI) causes irreversible damage with loss of motor, sensory, and autonomic functions. Currently, there is not an effective treatment to restore the lost neurologic functions. Injection of polypyrrole-iodine(PPy-I) particle suspension is proposed as a therapeutic strategy. This is an in vivo animal study. This study evaluates the use of such particles in rats after SCI by examining spared nervous tissue and the Basso, Beattie, and Bresnahan (BBB) scale to evaluate the functional outcome. Diffusive magnetic resonance imaging (MRI) was employed to measure the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) as non-invasive biomarkers of damage after SCI. Fractional anisotropy decreased, whereas ADC increased in all groups after the lesion. There were significant differences in FA when compared with the SCI-PPy-I group versus the SCI group (p<.05). Significant positive correlations between BBB and FA (r 2 =0.449, p<.05) and between FA and preserved tissue (r 2 =0.395, p<.05) were observed, whereas significant negative associations between BBB and ADC (r 2 =0.367, p<.05) and between ADC and preserved tissue (r 2 =0.421, p<.05) were observed. The results suggested that PPy-I is neuroprotective as it decreased the amount of damaged tissue while improving the motor function. Non-invasive MRI proved to be useful in the characterization of SCI and recovery. Copyright © 2016 Elsevier Inc. All rights reserved.

Loss of trabeculae by mechano-biological means may explain rapid bone loss in osteoporosis.

PubMed

Mulvihill, Brianne M; McNamara, Laoise M; Prendergast, Patrick J

2008-10-06

Osteoporosis is characterized by rapid and irreversible loss of trabecular bone tissue leading to increased bone fragility. In this study, we hypothesize two causes for rapid loss of bone trabeculae; firstly, the perforation of trabeculae is caused by osteoclasts resorbing a cavity so deep that it cannot be refilled and, secondly, the increases in bone tissue elastic modulus lead to increased propensity for trabecular perforation. These hypotheses were tested using an algorithm that was based on two premises: (i) bone remodelling is a turnover process that repairs damaged bone tissue by resorbing and returning it to a homeostatic strain level and (ii) osteoblast attachment is under biochemical control. It was found that a mechano-biological algorithm based on these premises can simulate the remodelling cycle in a trabecular strut where damaged bone is resorbed to form a pit that is subsequently refilled with new bone. Furthermore, the simulation predicts that there is a depth of resorption cavity deeper than which refilling of the resorption pits is impossible and perforation inevitably occurs. However, perforation does not occur by a single fracture event but by continual removal of microdamage after it forms beneath the resorption pit. The simulation also predicts that perforations would occur more easily in trabeculae that are more highly mineralized (stiffer). Since both increased osteoclast activation rates and increased mineralization have been measured in osteoporotic bone, either or both may contribute to the rapid loss of trabecular bone mass observed in osteoporotic patients.

Novel therapeutic strategies for lung disorders associated with airway remodelling and fibrosis.

PubMed

Royce, Simon G; Moodley, Yuben; Samuel, Chrishan S

2014-03-01

Inflammatory cell infiltration, cytokine release, epithelial damage, airway/lung remodelling and fibrosis are central features of inflammatory lung disorders, which include asthma, chronic obstructive pulmonary disease, acute respiratory distress syndrome and idiopathic pulmonary fibrosis. Although the lung has some ability to repair itself from acute injury, in the presence of ongoing pathological stimuli and/or insults that lead to chronic disease, it no longer retains the capacity to heal, resulting in fibrosis, the final common pathway that causes an irreversible loss of lung function. Despite inflammation, genetic predisposition/factors, epithelial-mesenchymal transition and mechanotransduction being able to independently contribute to airway remodelling and fibrosis, current therapies for inflammatory lung diseases are limited by their ability to only target the inflammatory component of the disease without having any marked effects on remodelling (epithelial damage and fibrosis) that can cause lung dysfunction independently of inflammation. Furthermore, as subsets of patients suffering from these diseases are resistant to currently available therapies (such as corticosteroids), novel therapeutic approaches are required to combat all aspects of disease pathology. This review discusses emerging therapeutic approaches, such as trefoil factors, relaxin, histone deacetylase inhibitors and stem cells, amongst others that have been able to target airway inflammation and airway remodelling while improving related lung dysfunction. A better understanding of the mode of action of these therapies and their possible combined effects may lead to the identification of their clinical potential in the setting of lung disease, either as adjunct or alternative therapies to currently available treatments. © 2013.

Beta-lactam antibiotic-induced platelet dysfunction: Evidence for irreversible inhibition of platelet activation in vitro and in vivo after prolonged exposure to penicillin

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

Burroughs, S.F.; Johnson, G.J.

beta-Lactam antibiotics cause platelet dysfunction with bleeding complications. Previous in vitro studies documented reversible inhibition of agonist-receptor interaction. This mechanism is inadequate to explain the effect of beta-lactam antibiotics in vivo. Platelet function does not return to normal immediately after drug treatment, implying irreversible inhibition of platelet function. We report here evidence of irreversible platelet functional and biochemical abnormalities after in vitro and in vivo exposure to beta-lactam antibiotics. Irreversible binding of (14C)-penicillin (Pen) occurred in vitro. After 24 hours' in vitro incubation with 10 to 20 mmol/L Pen, or ex vivo after antibiotic treatment, irreversible functional impairment occurred; butmore » no irreversible inhibition of alpha 2 adrenergic receptors, measured with (3H)-yohimbine, or high-affinity thromboxane A2/prostaglandin H2 (TXA2/PGH2) receptors, measured with agonist (3H)-U46619 and antagonist (3H)-SQ29548, occurred. However, low-affinity platelet TXA2/PGH2 receptors were decreased 40% after Pen exposure in vitro or in vivo, indicating irreversible membrane alteration. Two postreceptor biochemical events were irreversibly inhibited in platelets incubated with Pen for 24 hours in vitro or ex vivo after antibiotic treatment. Thromboxane synthesis was inhibited 28.3% to 81.7%. Agonist-induced rises in cytosolic calcium ((Ca2+)i) were inhibited 40.1% to 67.5% in vitro and 26.6% to 52.2% ex vivo. Therefore, Pen binds to platelets after prolonged exposure, resulting in irreversible dysfunction attributable to inhibition of TXA2 synthesis and impairment of the rise in (Ca2+)i. The loss of low-affinity TXA2/PGH2 receptors suggests that the primary site of action of these drugs is on the platelet membrane.« less

Reversible and irreversible vascular bioeffects induced by ultrasound and microbubbles in chorioallantoic membrane model

NASA Astrophysics Data System (ADS)

Tarapacki, Christine; Kuebler, Wolfgang M.; Tabuchi, Arata; Karshafian, Raffi

2017-03-01

Background: The application of ultrasound and microbubbles at therapeutic conditions has been shown to improve delivery of molecules, cause vasoconstriction, modulate blood flow and induce a vascular shut down in in vivo cancerous tissues. The underlying mechanism has been associated with the interaction of ultrasonically-induced microbubble oscillation and cavitation with the blood vessel wall. In this study, the effect of ultrasound and microbubbles on blood flow and vascular architecture was studied using a fertilized chicken egg CAM (chorioallantoic membrane) model. Methods: CAM at day 12 of incubation (Hamburger-Hamilton stage 38-40) were exposed to ultrasound at varying acoustic pressures (160, 240 and 320 kPa peak negative pressure) in the presence of Definity microbubbles and 70 kDa FITC dextran fluorescent molecules. A volume of 50 µL Definity microbubbles were injected into a large anterior vein of the CAM prior to ultrasound exposure. The ultrasound treatment sequence consisted of 5 s exposure at 500 kHz frequency, 8 cycles and 1 kHz pulse repetition frequency with 5 s off for a total exposure of 2 minutes. Fluorescent videos and images of the CAM vasculature were acquired using intravital microscopy prior, during and following the ultrasound exposure. Perfusion was quantified by measuring the length of capillaries in a region of interest using Adobe Illustrator. Results and Discussion: The vascular bioeffects induced by USMB increased with acoustic peak negative pressure. At 160 kPa, no visible differences were observed compared to the control. At 240 kPa, a transient decrease in perfusion with subsequent recovery within 15 minutes was observed, whereas at 320 kPa, the fluorescent images showed an irreversible vascular damage. The study indicates that a potential mechanism for the transient decrease in perfusion may be related to blood coagulation. The results suggest that ultrasound and microbubbles can induce reversible and irreversible vascular changes depending on the ultrasound exposure pressure.

Parkinson's disease: carbidopa, nausea, and dyskinesia.

PubMed

Hinz, Marty; Stein, Alvin; Cole, Ted

2014-01-01

When l-dopa use began in the early 1960s for the treatment of Parkinson's disease, nausea and reversible dyskinesias were experienced as continuing side effects. Carbidopa or benserazide was added to l-dopa in 1975 solely to control nausea. Subsequent to the increasing use of carbidopa has been the recognition of irreversible dyskinesias, which have automatically been attributed to l-dopa. The research into the etiology of these phenomena has identified the causative agent of the irreversible dyskinesias as carbidopa, not l-dopa. The mechanism of action of the carbidopa and benserazide causes irreversible binding and inactivation of vitamin B6 throughout the body. The consequences of this action are enormous, interfering with over 300 enzyme and protein functions. This has the ability to induce previously undocumented profound antihistamine dyskinesias, which have been wrongly attributed to l-dopa and may be perceived as irreversible if proper corrective action is not taken.

Parkinson’s disease: carbidopa, nausea, and dyskinesia

PubMed Central

Hinz, Marty; Stein, Alvin; Cole, Ted

2014-01-01

When l-dopa use began in the early 1960s for the treatment of Parkinson’s disease, nausea and reversible dyskinesias were experienced as continuing side effects. Carbidopa or benserazide was added to l-dopa in 1975 solely to control nausea. Subsequent to the increasing use of carbidopa has been the recognition of irreversible dyskinesias, which have automatically been attributed to l-dopa. The research into the etiology of these phenomena has identified the causative agent of the irreversible dyskinesias as carbidopa, not l-dopa. The mechanism of action of the carbidopa and benserazide causes irreversible binding and inactivation of vitamin B6 throughout the body. The consequences of this action are enormous, interfering with over 300 enzyme and protein functions. This has the ability to induce previously undocumented profound antihistamine dyskinesias, which have been wrongly attributed to l-dopa and may be perceived as irreversible if proper corrective action is not taken. PMID:25484598

Salvaging an angled implant abutment with damaged internal threads: a clinical report.

PubMed

Imam, Ahmad Y; Yilmaz, Burak; Özçelik, Tuncer Burak; McGlumphy, Edwin

2013-05-01

This clinical report describes a technique to fit an existing fixed detachable implant-supported prosthesis to a zygomatic implant abutment with stripped internal threads. The threads of the abutment were retapped and a wide diameter/wide head retaining screw was used to secure the existing prosthesis on the abutment. Care is needed in the retrieval of broken screws so as not to damage the internal threads of the implants, which might lead to irreversible complications. Copyright © 2013 The Editorial Council of the Journal of Prosthetic Dentistry. Published by Mosby, Inc. All rights reserved.

Fluctuation theorems in feedback-controlled open quantum systems: Quantum coherence and absolute irreversibility

NASA Astrophysics Data System (ADS)

Murashita, Yûto; Gong, Zongping; Ashida, Yuto; Ueda, Masahito

2017-10-01

The thermodynamics of quantum coherence has attracted growing attention recently, where the thermodynamic advantage of quantum superposition is characterized in terms of quantum thermodynamics. We investigate the thermodynamic effects of quantum coherent driving in the context of the fluctuation theorem. We adopt a quantum-trajectory approach to investigate open quantum systems under feedback control. In these systems, the measurement backaction in the forward process plays a key role, and therefore the corresponding time-reversed quantum measurement and postselection must be considered in the backward process, in sharp contrast to the classical case. The state reduction associated with quantum measurement, in general, creates a zero-probability region in the space of quantum trajectories of the forward process, which causes singularly strong irreversibility with divergent entropy production (i.e., absolute irreversibility) and hence makes the ordinary fluctuation theorem break down. In the classical case, the error-free measurement ordinarily leads to absolute irreversibility, because the measurement restricts classical paths to the region compatible with the measurement outcome. In contrast, in open quantum systems, absolute irreversibility is suppressed even in the presence of the projective measurement due to those quantum rare events that go through the classically forbidden region with the aid of quantum coherent driving. This suppression of absolute irreversibility exemplifies the thermodynamic advantage of quantum coherent driving. Absolute irreversibility is shown to emerge in the absence of coherent driving after the measurement, especially in systems under time-delayed feedback control. We show that absolute irreversibility is mitigated by increasing the duration of quantum coherent driving or decreasing the delay time of feedback control.

Peptidylarginine deiminases: novel drug targets for prevention of neuronal damage following hypoxic ischemic insult (HI) in neonates.

PubMed

Lange, Sigrun; Rocha-Ferreira, Eridan; Thei, Laura; Mawjee, Priyanka; Bennett, Kate; Thompson, Paul R; Subramanian, Venkataraman; Nicholas, Anthony P; Peebles, Donald; Hristova, Mariya; Raivich, Gennadij

2014-08-01

Neonatal hypoxic ischaemic (HI) injury frequently causes neural impairment in surviving infants. Our knowledge of the underlying molecular mechanisms is still limited. Protein deimination is a post-translational modification caused by Ca(+2) -regulated peptidylarginine deiminases (PADs), a group of five isozymes that display tissue-specific expression and different preference for target proteins. Protein deimination results in altered protein conformation and function of target proteins, and is associated with neurodegenerative diseases, gene regulation and autoimmunity. In this study, we used the neonatal HI and HI/infection [lipopolysaccharide (LPS) stimulation] murine models to investigate changes in protein deimination. Brains showed increases in deiminated proteins, cell death, activated microglia and neuronal loss in affected brain areas at 48 h after hypoxic ischaemic insult. Upon treatment with the pan-PAD inhibitor Cl-amidine, a significant reduction was seen in microglial activation, cell death and infarct size compared with control saline or LPS-treated animals. Deimination of histone 3, a target protein of the PAD4 isozyme, was increased in hippocampus and cortex specifically upon LPS stimulation and markedly reduced following Cl-amidine treatment. Here, we demonstrate a novel role for PAD enzymes in neural impairment in neonatal HI Encephalopathy, highlighting their role as promising new candidates for drug-directed intervention in neurotrauma. Hypoxic Ischaemic Insult (HI) results in activation of peptidylarginine deiminases (PADs) because of calcium dysregulation. Target proteins undergo irreversible changes of protein bound arginine to citrulline, resulting in protein misfolding. Infection in synergy with HI causes up-regulation of TNFα, nuclear translocation of PAD4 and change in gene regulation as a result of histone deimination. Pharmacological PAD inhibition significantly reduced HI brain damage. © 2014 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.

PET imaging in ischemic cerebrovascular disease: current status and future directions.

PubMed

Heiss, Wolf-Dieter

2014-10-01

Cerebrovascular diseases are caused by interruption or significant impairment of the blood supply to the brain, which leads to a cascade of metabolic and molecular alterations resulting in functional disturbance and morphological damage. These pathophysiological changes can be assessed by positron emission tomography (PET), which permits the regional measurement of physiological parameters and imaging of the distribution of molecular markers. PET has broadened our understanding of the flow and metabolic thresholds critical for the maintenance of brain function and morphology: in this application, PET has been essential in the transfer of the concept of the penumbra (tissue with perfusion below the functional threshold but above the threshold for the preservation of morphology) to clinical stroke and thereby has had great impact on developing treatment strategies. Radioligands for receptors can be used as early markers of irreversible neuronal damage and thereby can predict the size of the final infarcts; this is also important for decisions concerning invasive therapy in large ("malignant") infarctions. With PET investigations, the reserve capacity of blood supply to the brain can be tested in obstructive arteriosclerosis of the supplying arteries, and this again is essential for planning interventions. The effect of a stroke on the surrounding and contralateral primarily unaffected tissue can be investigated, and these results help to understand the symptoms caused by disturbances in functional networks. Chronic cerebrovascular disease causes vascular cognitive disorders, including vascular dementia. PET permits the detection of the metabolic disturbances responsible for cognitive impairment and dementia, and can differentiate vascular dementia from degenerative diseases. It may also help to understand the importance of neuroinflammation after stroke and its interaction with amyloid deposition in the development of dementia. Although the clinical application of PET investigations is limited, this technology had and still has a great impact on research into cerebrovascular diseases.

[Possibilities of dialysis therapy in irreversible renal failure in rheumatoid arthritis with secondary amyloidosis].

PubMed

Vachtenheim, J; Tocík, J; Novák, Z; Zeman, P

1990-11-01

The authors discuss their initial experience with the treatment of secondary amyloidosis in rheumatoid arthritis with irreversible renal failure in patients included in a regular dialyzation programme. The hitherto assembled 15-month experience justifies the inclusion of patients with this cause of irreversible renal failure in a dialyzation programme. The reverse is not only wrong from the medical aspect but is inhuman and interferes with the life of families of these patients. Although the procedure during a regular dialyzation programme of these patients with rheumatoid arthritis with secondary amyloidosis is more complicated, more pretentious and more responsible, it is our medical duty to carry this burden together with the patient.

Quantifying irreversible movement in steep, fractured bedrock permafrost on Matterhorn (CH)

NASA Astrophysics Data System (ADS)

Weber, Samuel; Beutel, Jan; Faillettaz, Jérome; Hasler, Andreas; Krautblatter, Michael; Vieli, Andreas

2017-02-01

Understanding rock slope kinematics in steep, fractured bedrock permafrost is a challenging task. Recent laboratory studies have provided enhanced understanding of rock fatigue and fracturing in cold environments but were not successfully confirmed by field studies. This study presents a unique time series of fracture kinematics, rock temperatures and environmental conditions at 3500 m a. s. l. on the steep, strongly fractured Hörnligrat of the Matterhorn (Swiss Alps). Thanks to 8 years of continuous data, the longer-term evolution of fracture kinematics in permafrost can be analyzed with an unprecedented level of detail. Evidence for common trends in spatiotemporal pattern of fracture kinematics could be found: a partly reversible seasonal movement can be observed at all locations, with variable amplitudes. In the wider context of rock slope stability assessment, we propose separating reversible (elastic) components of fracture kinematics, caused by thermoelastic strains, from the irreversible (plastic) component due to other processes. A regression analysis between temperature and fracture displacement shows that all instrumented fractures exhibit reversible displacements that dominate fracture kinematics in winter. Furthermore, removing this reversible component from the observed displacement enables us to quantify the irreversible component. From this, a new metric - termed index of irreversibility - is proposed to quantify relative irreversibility of fracture kinematics. This new index can identify periods when fracture displacements are dominated by irreversible processes. For many sensors, irreversible enhanced fracture displacement is observed in summer and its initiation coincides with the onset of positive rock temperatures. This likely indicates thawing-related processes, such as meltwater percolation into fractures, as a forcing mechanism for irreversible displacements. For a few instrumented fractures, irreversible displacements were found at the onset of the freezing period, suggesting that cryogenic processes act as a driving factor through increasing ice pressure. The proposed analysis provides a tool for investigating and better understanding processes related to irreversible kinematics.

[Floppy baby with macrocytic anemia and vegan mother].

PubMed

Schlapbach, L J; Schütz, B; Nuoffer, J M; Brekenfeld, C; Müller, G; Fluri, S

2007-08-29

We report the case of a 7 month-old girl that presented with acute anemia, generalized muscular hypotonia and failure to thrive. Laboratory evaluation revealed cobalamin deficiency, due to a vegan diet of the mother. The clinical triad of an acquired floppy baby syndrome with megaloblastic anemia and failure to thrive is pathognomic for infantile cobalamin deficiency. Neurological abnormalities are often irreversible and may be associated with delayed myelinization in the MRI. A normal cobalamin level in maternal serum and absence of anemia do not exclude subclinical deficiency. If cobalamin deficiency is suspected, e.g. in pregnant women on vegan diet, urinary methylmalonic acid excretion and plasma homocysteine levels should be determined and cobalamin substitution should be started at an early stage to avoid potentially irreversible damage of the fetus.

Reserve stem cells: Reprogramming of differentiated cells fuels repair, metaplasia, and neoplasia in the adult gastrointestinal tract

PubMed Central

Mills, Jason C.; Sansom, Owen J.

2016-01-01

It has long been known that differentiated cells can switch fates, especially in vitro, but only recently has there been a critical mass of publications describing the mechanisms adult, post-mitotic cells use in vivo to reverse their differentiation state. We propose that this sort of cellular reprogramming is a fundamental cellular process akin to apoptosis or mitosis. Because reprogramming can invoke regenerative cells from mature cells, it is critical to the longterm maintenance of tissues like the pancreas, which encounter large insults during adulthood but lack constitutively active adult stem cells to repair the damage. However, even in tissues with adult stem cells, like stomach and intestine, reprogramming may allow mature cells to serve as reserve (“quiescent”) stem cells when normal stem cells are compromised. We propose that the potential downside to reprogramming is that it increases risk for cancers that occur late in adulthood. Mature, long-lived cells may have years of exposure to mutagens. Mutations that affect the physiological function of differentiated, post-mitotic cells may lead to apoptosis, but mutations in genes that govern proliferation might not be selected against. Hence, reprogramming with reentry into the cell cycle might unmask those mutations, causing an irreversible progenitor-like, proliferative state. We review recent evidence showing that reprogramming fuels irreversible metaplastic and precancerous proliferations in stomach and pancreas. Finally, we illustrate how we think reprogrammed differentiated cells are likely candidates as cells of origin for cancers of the intestine. PMID:26175494

Percutaneous irreversible electroporation for breast tissue and breast cancer: safety, feasibility, skin effects and radiologic-pathologic correlation in an animal study.

PubMed

Li, Sheng; Chen, Fei; Shen, Lujun; Zeng, Qi; Wu, Peihong

2016-08-05

To study the safety, feasibility and skin effects of irreversible electroporation (IRE) for breast tissue and breast cancer in animal models. Eight pigs were used in this study. IRE was performed on the left breasts of the pigs with different skin-electrode distances, and the right breasts were used as controls. The electrodes were placed 1-8 mm away from the skin, with an electrode spacing of 1.5-2 cm. Imaging and pathological examinations were performed at specific time points for follow-up evaluation. Vital signs, skin damage, breast tissue changes and ablation efficacy were also closely observed. Eight rabbit models with or without VX2 breast tumor implantations were used to further assess the damage caused by and the repair of thin skin after IRE treatment for breast cancer. Contrast-enhanced ultrasound and elastosonography were used to investigate ablation efficacy and safety. During IRE, the color of the pig breast skin reversibly changed. When the skin-electrode distance was 3 mm, the breast skin clearly changed, becoming white in the center and purple in the surrounding region during IRE. One small purulent skin lesion was detected several days after IRE. When the skin-electrode distance was 5-8 mm, the breast skin became red during IRE. However, the skin architecture was normal when evaluated using gross pathology and hematoxylin-eosin staining. When the skin-electrode distance was 1 mm, skin atrophy and yellow glabrescence occurred in the rabbit breasts after IRE. When the skin-electrode distance was ≥5 mm, there was no skin damage in the rabbit model regardless of breast cancer implantation. After IRE, complete ablation of the targeted breast tissue or cancer was confirmed, and apoptosis was detected in the target tissue and outermost epidermal layer. In the ablated breasts of the surviving animals, complete mammary regeneration with normal skin and hair was observed. Furthermore, no massive fibrosis or mass formation were detected on ultrasound or through hematoxylin-eosin staining. After IRE, the skin architecture was well preserved when the skin-electrode distance was ≥5 mm. Moreover, breast regeneration occurred without mass formation or obvious fibrosis.

The warning-sign hierarchy between quantitative subcortical motor mapping and continuous motor evoked potential monitoring during resection of supratentorial brain tumors.

PubMed

Seidel, Kathleen; Beck, Jürgen; Stieglitz, Lennart; Schucht, Philippe; Raabe, Andreas

2013-02-01

Mapping and monitoring are believed to provide an early warning sign to determine when to stop tumor removal to avoid mechanical damage to the corticospinal tract (CST). The objective of this study was to systematically compare subcortical monopolar stimulation thresholds (1-20 mA) with direct cortical stimulation (DCS)-motor evoked potential (MEP) monitoring signal abnormalities and to correlate both with new postoperative motor deficits. The authors sought to define a mapping threshold and DCS-MEP monitoring signal changes indicating a minimal safe distance from the CST. A consecutive cohort of 100 patients underwent tumor surgery adjacent to the CST while simultaneous subcortical motor mapping and DCS-MEP monitoring was used. Evaluation was done regarding the lowest subcortical mapping threshold (monopolar stimulation, train of 5 stimuli, interstimulus interval 4.0 msec, pulse duration 500 μsec) and signal changes in DCS-MEPs (same parameters, 4 contact strip electrode). Motor function was assessed 1 day after surgery, at discharge, and at 3 months postoperatively. The lowest individual motor thresholds (MTs) were as follows (MT in mA, number of patients): > 20 mA, n = 12; 11-20 mA, n = 13; 6-10 mA, n = 20; 4-5 mA, n = 30; and 1-3 mA, n = 25. Direct cortical stimulation showed stable signals in 70 patients, unspecific changes in 18, irreversible alterations in 8, and irreversible loss in 4 patients. At 3 months, 5 patients had a postoperative new or worsened motor deficit (lowest mapping MT 20 mA, 13 mA, 6 mA, 3 mA, and 1 mA). In all 5 patients DCS-MEP monitoring alterations were documented (2 sudden irreversible threshold increases and 3 sudden irreversible MEP losses). Of these 5 patients, 2 had vascular ischemic lesions (MT 20 mA, 13 mA) and 3 had mechanical CST damage (MT 1 mA, 3 mA, and 6 mA; in the latter 2 cases the resection continued after mapping and severe DCS-MEP alterations occurred thereafter). In 80% of patients with a mapping MT of 1-3 mA and in 75% of patients with a mapping MT of 1 mA, DCS-MEPs were stable or showed unspecific reversible changes, and none had a permanent motor worsening at 3 months. In contrast, 25% of patients with irreversible DCS-MEP changes and 75% of patients with irreversible DCS-MEP loss had permanent motor deficits. Mapping should primarily guide tumor resection adjacent to the CST. DCS-MEP is a useful predictor of deficits, but its value as a warning sign is limited because signal alterations were reversible in only approximately 60% of the present cases and irreversibility is a post hoc definition. The true safe mapping MT is lower than previously thought. The authors postulate a mapping MT of 1 mA or less where irreversible DCS-MEP changes and motor deficits regularly occur. Therefore, they recommend stopping tumor resection at an MT of 2 mA at the latest. The limited spatial and temporal coverage of contemporary mapping may increase error and may contribute to false, higher MTs.

The polonium-210 poisoning of Mr Alexander Litvinenko

DOE PAGES

Harrison, John; Fell, Tim; Leggett, Rich; ...

2017-02-28

Mr Litvinenko died on 23rd November 2006 after having been poisoned with polonium-210 on 1st November. Measurements of the polonium-210 content of post-mortem tissue samples and samples of urine and blood showed the presence of large amounts of 210Po. Furthermore, autoradiography of hair samples showed two regions of 210Po activity, providing evidence of an earlier poisoning attempt during October 2006, resulting in absorption to blood of about one-hundredth of that estimated for 1st November. Intake by ingestion on 1st November was estimated to be around 4 GBq, assuming 10% absorption to blood, and the resulting organ doses reached estimatedmore » values that were generally in a range from about 20 Gy to over 100 Gy. In comparison with estimates of protracted alpha particle the doses required to cause irreversible organ damage support the conclusion that death was the inevitable consequence of multiple organ failure, with destruction of the haemopoietic bone marrow, as well as damage to kidneys and liver, being important contributors. If the earlier poisoning during October 2006 had not been followed by a second major intake on 1st November, it is possible that the earlier intake of around 40 MBq, with absorption of 4 MBq to blood, might have proved fatal over a prolonged period of months or years, primarily as a result of kidney damage following a dose of approaching 3 Gy.« less

The polonium-210 poisoning of Mr Alexander Litvinenko

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

Harrison, John; Fell, Tim; Leggett, Rich

Mr Litvinenko died on 23rd November 2006 after having been poisoned with polonium-210 on 1st November. Measurements of the polonium-210 content of post-mortem tissue samples and samples of urine and blood showed the presence of large amounts of 210Po. Furthermore, autoradiography of hair samples showed two regions of 210Po activity, providing evidence of an earlier poisoning attempt during October 2006, resulting in absorption to blood of about one-hundredth of that estimated for 1st November. Intake by ingestion on 1st November was estimated to be around 4 GBq, assuming 10% absorption to blood, and the resulting organ doses reached estimatedmore » values that were generally in a range from about 20 Gy to over 100 Gy. In comparison with estimates of protracted alpha particle the doses required to cause irreversible organ damage support the conclusion that death was the inevitable consequence of multiple organ failure, with destruction of the haemopoietic bone marrow, as well as damage to kidneys and liver, being important contributors. If the earlier poisoning during October 2006 had not been followed by a second major intake on 1st November, it is possible that the earlier intake of around 40 MBq, with absorption of 4 MBq to blood, might have proved fatal over a prolonged period of months or years, primarily as a result of kidney damage following a dose of approaching 3 Gy.« less

Degradation mechanism of SESAMs under intense ultrashort pulses in modelocked VECSELs

NASA Astrophysics Data System (ADS)

Addamane, Sadhvikas; Shima, Darryl; Laurain, Alexandre; Chan, Hsiu-Ting; Balakrishnan, Ganesh; Moloney, Jerome V.

2018-02-01

Mode-locked VECSELs using SESAMs are a relatively less complex and cost-effective alternative to state-of-the-art ultrafast lasers based on solid-state or fiber lasers. VECSELs have seen considerable progress in device performance in terms of pulse width and peak power in the recent years. However, it appears that the combination of high power and short pulses can cause some irreversible damage to the SESAM. The degradation mechanism, which can lead to a reduction of the VECSEL output power over time, is not fully understood and deserves to be investigated and alleviated in order to achieve stable mode-locking over long periods of time. It is particularly important for VECSEL systems meant to be commercialized, needing long term operation with a long product lifetime. Here, we investigate the performance and robustness of a SESAM-modelocked VECSEL system under intense pulse intensity excitation. The effect of the degradation on the VECSEL performance is investigated using the SESAM in a VECSEL cavity supporting ultrashort pulses, while the degradation mechanism was investigated by exciting the SESAMs with an external femtosecond laser source. The decay of the photoluminescence (PL) and reflectivity under high excitation was monitored and the damaged samples were further analyzed using a thorough Transmission Electron Microscopy (TEM) analysis. It is found that the major contribution to the degradation is the field intensity and that the compositional damage is confined to the DBR region of the SESAM.

Estimation of the chemical-induced eye injury using a Weight-of-Evidence (WoE) battery of 21 artificial neural network (ANN) c-QSAR models (QSAR-21): part II: corrosion potential.

PubMed

Verma, Rajeshwar P; Matthews, Edwin J

2015-03-01

This is part II of an in silico investigation of chemical-induced eye injury that was conducted at FDA's CFSAN. Serious eye damage caused by chemical (eye corrosion) is assessed using the rabbit Draize test, and this endpoint is an essential part of hazard identification and labeling of industrial and consumer products to ensure occupational and consumer safety. There is an urgent need to develop an alternative to the Draize test because EU's 7th amendment to the Cosmetic Directive (EC, 2003; 76/768/EEC) and recast Regulation now bans animal testing on all cosmetic product ingredients and EU's REACH Program limits animal testing for chemicals in commerce. Although in silico methods have been reported for eye irritation (reversible damage), QSARs specific for eye corrosion (irreversible damage) have not been published. This report describes the development of 21 ANN c-QSAR models (QSAR-21) for assessing eye corrosion potential of chemicals using a large and diverse CFSAN data set of 504 chemicals, ADMET Predictor's three sensitivity analyses and ANNE classification functionalities with 20% test set selection from seven different methods. QSAR-21 models were internally and externally validated and exhibited high predictive performance: average statistics for the training, verification, and external test sets of these models were 96/96/94% sensitivity and 91/91/90% specificity. Copyright © 2014 Elsevier Inc. All rights reserved.

Potential benefits of pH 8.8 alkaline drinking water as an adjunct in the treatment of reflux disease.

PubMed

Koufman, Jamie A; Johnston, Nikki

2012-07-01

At the cellular level, tissue-bound pepsin is fundamental to the pathophysiologic mechanism of reflux disease, and although the thresholds for laryngeal damage in laryngopharyngeal reflux and for esophageal damage in gastroesophageal reflux disease differ, both forms of damage are due to pepsin, which requires acid for its activation. In addition, human pepsin remains stable at pH 7.4 and may be reactivated by hydrogen ions from any source. Thus, most tap and bottled waters (typically pH 6.7 to 7.4) would not be expected to affect pepsin stability. The purposes of these in vitro studies were to investigate whether artesian well water containing natural bicarbonate (pH 8.8) might irreversibly denature (inactivate) human pepsin, and to establish its potential acid-buffering capacity. Laboratory studies were performed to determine whether human pepsin was inactivated by pH 8.8 alkaline water. In addition, the buffering capacity of the alkaline water was measured and compared to that of the two most popular commercially available bottled waters. The pH 8.8 alkaline water irreversibly inactivated human pepsin (in vitro), and its hydrochloric acid-buffering capacity far exceeded that of the conventional-pH waters. Unlike conventional drinking water, pH 8.8 alkaline water instantly denatures pepsin, rendering it permanently inactive. In addition, it has good acid-buffering capacity. Thus, the consumption of alkaline water may have therapeutic benefits for patients with reflux disease.

The Baroque monuments of Modica (Eastern Sicily): assessment of causes of chromatic alteration of stone building materials

NASA Astrophysics Data System (ADS)

Belfiore, Cristina M.; La Russa, Mauro F.; Pezzino, Antonino; Campani, Elisa; Casoli, Antonella

2010-09-01

The Baroque monuments of several cities in eastern Sicily, built of local calcarenitic stone, are often subjected to conservation treatments, since they undergo many forms of alteration and degradation which can cause significant damage. However, a recent study of these building materials (Barone et al. in Environ. Geol. 54:1501, 2008) has demonstrated that some protective products, once applied, cause irreversible chromatic alterations. The façades of the monuments of the historic city centre of Modica are typically creamy yellow in colour, sometimes varying slightly due to the use of various pigments, such as clayey and gypseous earths (La Russa et al. in Appl. Phys. A 92:185, 2008). However, in some cases, these nuances are lost due to the application of protective products. This work provides a petrographic and colorimetric characterisation of the calcarenitic stone used to create the façades of the churches of S. Pietro, S. Maria del Soccorso and S. Maria dell’Annunziata in Modica, also by comparisons with locally quarried samples. In addition, it aims to identify protective substances which may have been used during previous restoration work. Analytical techniques included polarising optical microscopy, spectrophotometric colorimetric tests, Fourier-transform infrared spectroscopy (FTIR) and gas chromatography coupled with mass spectrometry (GC-MS).

Unraveling the contribution of pancreatic beta-cell suicide in autoimmune type 1 diabetes✩

PubMed Central

Jaberi-Douraki, Majid; Schnell, Santiago; Pietropaolo, Massimo; Khadra, Anmar

2014-01-01

In type 1 diabetes, an autoimmune disease mediated by autoreactive T-cells that attack insulin-secreting pancreatic beta-cells, it has been suggested that disease progression may additionally require protective mechanisms in the target tissue to impede such auto-destructive mechanisms. We hypothesize that the autoimmune attack against beta-cells causes endoplasmic reticulum stress by forcing the remaining beta-cells to synthesize and secrete defective insulin. To rescue beta-cell from the endoplasmic reticulum stress, beta-cells activate the unfolded protein response to restore protein homeostasis and normal insulin synthesis. Here we investigate the compensatory role of unfolded protein response by developing a multi-state model of type 1 diabetes that takes into account beta-cell destruction caused by pathogenic autoreactive T-cells and apoptosis triggered by endoplasmic reticulum stress. We discuss the mechanism of unfolded protein response activation and how it counters beta-cell extinction caused by an autoimmune attack and/or irreversible damage by endoplasmic reticulum stress. Our results reveal important insights about the balance between beta-cell destruction by autoimmune attack (beta-cell homicide) and beta-cell apoptosis by endoplasmic reticulum stress (beta-cell suicide). It also provides an explanation as to why the unfolded protein response may not be a successful therapeutic target to treat type 1 diabetes. PMID:24831415

Physiotherapy in Rheumatoid Arthritis

PubMed Central

Kavuncu, Vural; Evcik, Deniz

2004-01-01

Rheumatoid arthritis (RA) is a chronic and painful clinical condition that leads to progressive joint damage, disability, deterioration in quality of life, and shortened life expectancy. Even mild inflammation may result in irreversible damage and permanent disability. The clinical course according to symptoms may be either intermittent or progressive in patients with RA. In most patients, the clinical course is progressive, and structural damage develops in the first 2 years. The aim of RA management is to achieve pain relief and prevent joint damage and functional loss. Physiotherapy and rehabilitation applications significantly augment medical therapy by improving the management of RA and reducing handicaps in daily living for patients with RA. In this review, the application of physiotherapy modalities is examined, including the use of cold/heat applications, electrical stimulation, and hydrotherapy. Rehabilitation treatment techniques for patients with RA such as joint protection strategies, massage, exercise, and patient education are also presented. PMID:15266230

Neonatal bone marrow transplantation prevents bone pathology in a mouse model of mucopolysaccharidosis type I.

PubMed

Pievani, Alice; Azario, Isabella; Antolini, Laura; Shimada, Tsutomu; Patel, Pravin; Remoli, Cristina; Rambaldi, Benedetta; Valsecchi, Maria Grazia; Riminucci, Mara; Biondi, Andrea; Tomatsu, Shunji; Serafini, Marta

2015-03-05

Neonatal bone marrow transplantation (BMT) could offer a novel therapeutic opportunity for genetic disorders by providing sustainable levels of the missing protein at birth, thus preventing tissue damage. We tested this concept in mucopolysaccharidosis type I (MPS IH; Hurler syndrome), a lysosomal storage disorder caused by deficiency of α-l-iduronidase. MPS IH is characterized by a broad spectrum of clinical manifestations, including severe progressive skeletal abnormalities. Although BMT increases the life span of patients with MPS IH, musculoskeletal manifestations are only minimally responsive if the timing of BMT delays, suggesting already irreversible bone damage. In this study, we tested the hypothesis that transplanting normal BM into newborn MPS I mice soon after birth can prevent skeletal dysplasia. We observed that neonatal BMT was effective at restoring α-l-iduronidase activity and clearing elevated glycosaminoglycans in blood and multiple organs. At 37 weeks of age, we observed an almost complete normalization of all bone tissue parameters, using radiographic, microcomputed tomography, biochemical, and histological analyses. Overall, the magnitude of improvements correlated with the extent of hematopoietic engraftment. We conclude that BMT at a very early stage in life markedly reduces signs and symptoms of MPS I before they appear. © 2015 by The American Society of Hematology.

Glaucoma –state of the art and perspectives on treatment

PubMed Central

Wójcik-Gryciuk, Anna; Skup, Małgorzata; Waleszczyk, Wioletta J.

2015-01-01

Glaucoma is a chronic optic neuropathy characterized by progressive damage to the optic nerve, death of retinal ganglion cells and ultimately visual field loss. It is one of the leading causes of irreversible loss of vision worldwide. The most important trigger of glaucomatous damage is elevated eye pressure, and the current standard approach in glaucoma therapy is reduction of intraocular pressure (IOP). However, despite the use of effective medications or surgical treatment leading to lowering of IOP, progression of glaucomatous changes and loss of vision among patients with glaucoma is common. Therefore, it is critical to prevent vision loss through additional treatment. To implement such treatment(s), it is imperative to identify pathophysiological changes in glaucoma and develop therapeutic methods taking into account neuroprotection. Currently, there is no method of neuroprotection with long-term proven effectiveness in the treatment of glaucoma. Among the most promising molecules shown to protect the retina and optic nerve are neurotrophic factors. Thus, the current focus is on the development of safe and non-invasive methods for the long-term elevation of the intraocular level of neurotrophins through advanced gene therapy and topical eye treatment and on the search for selective agonists of neurotrophin receptors affording more efficient neuroprotection. PMID:26684267

The role of immune cells, glia and neurons in white and gray matter pathology in multiple sclerosis

PubMed Central

Bernstock, Joshua D.; Pluchino, Stefano

2015-01-01

Multiple sclerosis is one of the most common causes of chronic neurological disability beginning in early to middle adult life. Multiple sclerosis is idiopathic in nature, yet increasing correlative evidence supports a strong association between one’s genetic predisposition, the environment and the immune system. Symptoms of multiple sclerosis have primarily been shown to result from a disruption in the integrity of myelinated tracts within the white matter of the central nervous system. However, recent research has also highlighted the hitherto underappreciated involvement of gray matter in multiple sclerosis disease pathophysiology, which may be especially relevant when considering the accumulation of irreversible damage and progressive disability. This review aims at providing a comprehensive overview of the interplay between inflammation, glial/neuronal damage and regeneration throughout the course of multiple sclerosis via the analysis of both white and gray matter lesional pathology. Further, we describe the common pathological mechanisms underlying both relapsing and progressive forms of multiple sclerosis, and analyze how current (as well as future) treatments may interact and/or interfere with its pathology. Understanding the putative mechanisms that drive disease pathogenesis will be key in helping to develop effective therapeutic strategies to prevent, mitigate, and treat the diverse morbidities associated with multiple sclerosis. PMID:25802011

Quantification of the degradation of Ni-YSZ anodes upon redox cycling

NASA Astrophysics Data System (ADS)

Song, Bowen; Ruiz-Trejo, Enrique; Bertei, Antonio; Brandon, Nigel P.

2018-01-01

Ni-YSZ anodes for Solid Oxide Fuel Cells are vulnerable to microstructural damage during redox cycling leading to a decrease in the electrochemical performance. This study quantifies the microstructural changes as a function of redox cycles at 800 °C and associates it to the deterioration of the mechanical properties and polarisation resistance. A physically-based model is used to estimate the triple-phase boundary (TPB) length from impedance spectra, and satisfactorily matches the TPB length quantified by FIB-SEM tomography: within 20 redox cycles, the TPB density decreases from 4.63 μm-2 to 1.06 μm-2. Although the polarisation resistance increases by an order of magnitude after 20 cycles, after each re-reduction the electrode polarisation improves consistently due to the transient generation of Ni nanoparticles around the TPBs. Nonetheless, the long-term degradation overshadows this transient improvement due to the nickel agglomeration. In addition, FIB-SEM tomography reveals fractures along YSZ grain boundaries, Ni-YSZ detachment and increased porosity in the composite that lead to irreversible mechanical damage: the elastic modulus diminishes from 36.4 GPa to 20.2 GPa and the hardness from 0.40 GPa to 0.15 GPa. These results suggest that microstructural, mechanical and electrochemical properties are strongly interdependent in determining the degradation caused by redox cycling.

Metallotherapeutics - Novel Strategies in Drug Design

PubMed Central

Hocharoen, Lalintip; Cowan, J. A.

2011-01-01

A new paradigm for drug activity is presented, which includes both recognition and subsequent irreversible inactivation of therapeutic targets. Application to both RNA and enzyme biomolecules has been demonstrated. In contrast to RNA targets that are subject to strand scission chemistry mediated by ribose H-atom abstraction, proteins appear to be inactivated through oxidative damage to amino acid side chains around the enzyme active site. PMID:19685535

Parkinson’s disease managing reversible neurodegeneration

PubMed Central

Hinz, Marty; Stein, Alvin; Cole, Ted; McDougall, Beth; Westaway, Mark

2016-01-01

Traditionally, the Parkinson’s disease (PD) symptom course has been classified as an irreversible progressive neurodegenerative disease. This paper documents 29 PD and treatment-induced systemic depletion etiologies which cause and/or exacerbate the seven novel primary relative nutritional deficiencies associated with PD. These reversible relative nutritional deficiencies (RNDs) may facilitate and accelerate irreversible progressive neurodegeneration, while other reversible RNDs may induce previously undocumented reversible pseudo-neurodegeneration that is hiding in plain sight since the symptoms are identical to the symptoms being experienced by the PD patient. Documented herein is a novel nutritional approach for reversible processes management which may slow or halt irreversible progressive neurodegenerative disease and correct reversible RNDs whose symptoms are identical to the patient’s PD symptoms. PMID:27103805

Dredging in the Spratly Islands: Gaining Land but Losing Reefs.

PubMed

Mora, Camilo; Caldwell, Iain R; Birkeland, Charles; McManus, John W

2016-03-01

Coral reefs on remote islands and atolls are less exposed to direct human stressors but are becoming increasingly vulnerable because of their development for geopolitical and military purposes. Here we document dredging and filling activities by countries in the South China Sea, where building new islands and channels on atolls is leading to considerable losses of, and perhaps irreversible damages to, unique coral reef ecosystems. Preventing similar damage across other reefs in the region necessitates the urgent development of cooperative management of disputed territories in the South China Sea. We suggest using the Antarctic Treaty as a positive precedent for such international cooperation.

Dredging in the Spratly Islands: Gaining Land but Losing Reefs

PubMed Central

Mora, Camilo; Caldwell, Iain R.; Birkeland, Charles; McManus, John W.

2016-01-01

Coral reefs on remote islands and atolls are less exposed to direct human stressors but are becoming increasingly vulnerable because of their development for geopolitical and military purposes. Here we document dredging and filling activities by countries in the South China Sea, where building new islands and channels on atolls is leading to considerable losses of, and perhaps irreversible damages to, unique coral reef ecosystems. Preventing similar damage across other reefs in the region necessitates the urgent development of cooperative management of disputed territories in the South China Sea. We suggest using the Antarctic Treaty as a positive precedent for such international cooperation. PMID:27031949

The immunogenicity of thin-film freeze-dried, aluminum salt-adjuvanted vaccine when exposed to different temperatures.

PubMed

Thakkar, Sachin G; Ruwona, Tinashe B; Williams, Robert O; Cui, Zhengrong

2017-04-03

Insoluble aluminum salts such as aluminum oxyhydroxide have been used for decades as adjuvants in human vaccines, and many vaccines contain aluminum salts as adjuvants. Aluminum salt-adjuvanted vaccines must be managed in cold-chain (2-8° C) during transport and storage, as vaccine antigens in general are too fragile to be stable in ambient temperatures, and unintentional slowing freezing causes irreversible aggregation and permanent damage to the vaccines. Previously, we reported that thin-film freeze-drying can be used to convert vaccines adjuvanted with an aluminum salt from liquid suspension into dry powder without causing particle aggregation or decreasing in immunogenicity following reconstitution. In the present study, using ovalbumin (OVA)-adsorbed Alhydrogel® (i.e. aluminum oxyhydroxide, 2% w/v) as a model vaccine, we showed that the immunogenicity of thin-film freeze-dried OVA-adsorbed Alhydrogel® vaccine powder was not significantly changed after it was exposed for an extended period of time in temperatures as high as 40° C or subjected to repeated slow freezing-and-thawing. It is expected that immunization programs can potentially benefit by integrating thin-film freeze-drying into vaccine preparations.

The immunogenicity of thin-film freeze-dried, aluminum salt-adjuvanted vaccine when exposed to different temperatures

PubMed Central

Thakkar, Sachin G.; Ruwona, Tinashe B.; Williams, Robert O.; Cui, Zhengrong

2017-01-01

ABSTRACT Insoluble aluminum salts such as aluminum oxyhydroxide have been used for decades as adjuvants in human vaccines, and many vaccines contain aluminum salts as adjuvants. Aluminum salt-adjuvanted vaccines must be managed in cold-chain (2–8° C) during transport and storage, as vaccine antigens in general are too fragile to be stable in ambient temperatures, and unintentional slowing freezing causes irreversible aggregation and permanent damage to the vaccines. Previously, we reported that thin-film freeze-drying can be used to convert vaccines adjuvanted with an aluminum salt from liquid suspension into dry powder without causing particle aggregation or decreasing in immunogenicity following reconstitution. In the present study, using ovalbumin (OVA)-adsorbed Alhydrogel® (i.e. aluminum oxyhydroxide, 2% w/v) as a model vaccine, we showed that the immunogenicity of thin-film freeze-dried OVA-adsorbed Alhydrogel® vaccine powder was not significantly changed after it was exposed for an extended period of time in temperatures as high as 40° C or subjected to repeated slow freezing-and-thawing. It is expected that immunization programs can potentially benefit by integrating thin-film freeze-drying into vaccine preparations. PMID:28051903

Vascular Repair by Circumferential Cell Therapy Using Magnetic Nanoparticles and Tailored Magnets.

PubMed

Vosen, Sarah; Rieck, Sarah; Heidsieck, Alexandra; Mykhaylyk, Olga; Zimmermann, Katrin; Bloch, Wilhelm; Eberbeck, Dietmar; Plank, Christian; Gleich, Bernhard; Pfeifer, Alexander; Fleischmann, Bernd K; Wenzel, Daniela

2016-01-26

Cardiovascular disease is often caused by endothelial cell (EC) dysfunction and atherosclerotic plaque formation at predilection sites. Also surgical procedures of plaque removal cause irreversible damage to the EC layer, inducing impairment of vascular function and restenosis. In the current study we have examined a potentially curative approach by radially symmetric re-endothelialization of vessels after their mechanical denudation. For this purpose a combination of nanotechnology with gene and cell therapy was applied to site-specifically re-endothelialize and restore vascular function. We have used complexes of lentiviral vectors and magnetic nanoparticles (MNPs) to overexpress the vasoprotective gene endothelial nitric oxide synthase (eNOS) in ECs. The MNP-loaded and eNOS-overexpressing cells were magnetic, and by magnetic fields they could be positioned at the vascular wall in a radially symmetric fashion even under flow conditions. We demonstrate that the treated vessels displayed enhanced eNOS expression and activity. Moreover, isometric force measurements revealed that EC replacement with eNOS-overexpressing cells restored endothelial function after vascular injury in eNOS(-/-) mice ex and in vivo. Thus, the combination of MNP-based gene and cell therapy with custom-made magnetic fields enables circumferential re-endothelialization of vessels and improvement of vascular function.

Toxic Myocarditis Caused by Acetaminophen in a Multidrug Overdose.

PubMed

Gosselin, Maxime; Dazé, Yann; Mireault, Pascal; Crahes, Marie

2017-12-01

We report the case of an 18-year-old woman with personality disorders who was hospitalized a few hours after suicidal ingestion of acetaminophen, quetiapine, acetylsalicylic acid, and ethanol. Twelve hours after admission, severe liver damage was evident, but the patient was stable and awaiting hepatic transplantation. Electrolytes were successfully controlled. The condition of the liver stabilized. Cardiac biomarkers then deteriorated unexpectedly. Localized ST-segment elevations were noted on electrocardiogram, but angiography ruled out myocardial infarction. A computed tomographic scan ruled out cerebral edema. The patient died of irreversible cardiac arrest 40 hours after admission. Heart failure remained unexplained, and the body underwent forensic autopsy.At autopsy, histologic findings were indicative of acute toxic myocarditis and were concluded to be caused by acetaminophen intoxication. Acetaminophen overdose is common and typically leads to liver failure requiring supportive treatment and emergency liver transplantation. Toxic myocarditis is an extremely rare complication of acetaminophen overdose. It has only been reported 4 times in the literature despite the widespread use and misuse of acetaminophen. Toxic myocarditis remains a possibility in many cases of overdose but can be overlooked in a clinical picture dominated by hepatorenal failure and encephalopathy. Clinicians and forensic pathologists should be aware of this rare potential complication.

Role of long-chain and very-long-chain polyunsaturated fatty acids in macular degenerations and dystrophies

PubMed Central

Liu, Aihua; Lin, Yanhua; Terry, Ryan; Nelson, Kelly; Bernstein, Paul S

2014-01-01

Macular degeneration is a progressive, bilateral eye disorder that damages the macula of the human eye. The most common form of macular degeneration is age-related macular degeneration (AMD), which is the leading cause of irreversible blindness in people older than 50 years in developed countries. Autosomal dominant Stargardt disease-3 (STGD3) is an inherited macular dystrophy that has clinical features similar to dry AMD, but occurs at a much earlier age. It is caused by a mutation in the elongation of very-long-chain fatty acids-like 4 (ELOVL4) gene, which is responsible for encoding the elongase enzyme that converts shorter chain fatty acids into C28–C38 very long-chain polyunsaturated fatty acids (VLCPUFAs, total number of carbons ≥24). Diets rich in long-chain polyunsaturated fatty acids (LCPUFAs) have inverse associations with the progression of AMD and STGD3, and a deficiency in retinal LCPUFAs and VLCPUFAs has been detected in AMD retinas and STGD3 animal models. This article systematically summarizes the roles of LCPUFAs and VLCPUFAs in AMD and STGD3, and discusses future research directions. PMID:25324899

Investigation of the instability and low water kefir grain growth during an industrial water kefir fermentation process.

PubMed

Laureys, David; Van Jean, Amandine; Dumont, Jean; De Vuyst, Luc

2017-04-01

A poorly performing industrial water kefir production process consisting of a first fermentation process, a rest period at low temperature, and a second fermentation process was characterized to elucidate the causes of its low water kefir grain growth and instability. The frozen-stored water kefir grain inoculum was thawed and reactivated during three consecutive prefermentations before the water kefir production process was started. Freezing and thawing damaged the water kefir grains irreversibly, as their structure did not restore during the prefermentations nor the production process. The viable counts of the lactic acid bacteria and yeasts on the water kefir grains and in the liquors were as expected, whereas those of the acetic acid bacteria were high, due to the aerobic fermentation conditions. Nevertheless, the fermentations progressed slowly, which was caused by excessive substrate concentrations resulting in a high osmotic stress. Lactobacillus nagelii, Lactobacillus paracasei, Lactobacillus hilgardii, Leuconostoc mesenteroides, Bifidobacterium aquikefiri, Gluconobacter roseus/oxydans, Gluconobacter cerinus, Saccharomyces cerevisiae, and Zygotorulaspora florentina were the most prevalent microorganisms. Lb. hilgardii, the microorganism thought to be responsible for water kefir grain growth, was not found culture-dependently, which could explain the low water kefir grain growth of this industrial process.

[Age-related macular degeneration as a local manifestation of atherosclerosis - a novel insight into pathogenesis].

PubMed

Machalińska, Anna

2013-01-01

Age-related macular degeneration is the leading cause of irreversible visual impairment and disability among the elderly in developed countries. There is compelling evidence that atherosclerosis and age-related macular degeneration share a similar pathogenic process. The association between atherosclerosis and age-related macular degeneration has been inferred from histological, biochemical and epidemiological studies. Many published data indicate that drusen are similar in molecular composition to plaques in atherosclerosis. Furthermore, a great body of evidence has emerged over the past decade that implicates the chronic inflammatory processes in the pathogenesis and progression of both disorders. We speculate that vascular atherosclerosis and age-related macular degeneration may represent different manifestations of the same disease induced by a pathologic tissue response to the damage caused by oxidative stress and local ischemia. In this review, we characterise in detail a strong association between age-related macular degeneration and atherosclerosis development, and we postulate the hypothesis that age-related macular degeneration is a local manifestation of a systemic disease. This provides a new approach for understanding the aspects of pathogenesis and might improve the prevention and treatment of both diseases which both result from ageing of the human body.

In vitro study of heat production during power reduction of equine mandibular teeth.

PubMed

Allen, Martin L; Baker, Gordon J; Freeman, David E; Holmes, Kenneth R; Marretta, Sandra Manfra; Scoggins, R Dean; Constable, Peter

2004-04-01

To measure the amount of heat generated during 3 methods of equine dental reduction with power instruments. In vitro study. 30 premolar and molar teeth removed from mandibles of 8 equine heads collected at an abbatoir. 38-gauge copper-constantan thermocouples were inserted into the lingual side of each tooth 15 mm (proximal) and 25 mm (distal) from the occlusal surface, at a depth of 5 mm, which placed the tip close to the pulp chamber. Group-NC1 (n = 10) teeth were ground for 1 minute without coolant, group-NC2 (10) teeth were ground for 2 minutes without coolant, and group-C2 (10) teeth were ground for 2 minutes with water for coolant. Mean temperature increase was 1.2 degrees C at the distal thermocouple and 6.6 degrees C at the proximal thermocouple for group-NC1 teeth, 4.1 degrees C at the distal thermocouple and 24.3 degrees C at the proximal thermocouple for group-NC2 teeth, and 0.8 degrees C at the distal thermocouple and -0.1 degrees C at the proximal thermocouple for group-C2 teeth. In general, an increase of 5 degrees C in human teeth is considered the maximum increase before there is permanent damage to tooth pulp. In group-NC2 teeth, temperature increased above this limit by several degrees, whereas in group-C2 teeth, there was little or no temperature increase. Our results suggest that major reduction of equine teeth by use of power instruments causes thermal changes that may cause irreversible pulp damage unless water cooling is used.

High Presence of Extracellular Hemoglobin in the Periventricular White Matter Following Preterm Intraventricular Hemorrhage

PubMed Central

Ley, David; Romantsik, Olga; Vallius, Suvi; Sveinsdóttir, Kristbjörg; Sveinsdóttir, Snjolaug; Agyemang, Alex A.; Baumgarten, Maria; Mörgelin, Matthias; Lutay, Nataliya; Bruschettini, Matteo; Holmqvist, Bo; Gram, Magnus

2016-01-01

Severe cerebral intraventricular hemorrhage (IVH) in preterm infants continues to be a major clinical problem, occurring in about 15–20% of very preterm infants. In contrast to other brain lesions the incidence of IVH has not been reduced over the last decade, but actually slightly increased. Currently over 50% of surviving infants develop post-hemorrhagic ventricular dilatation and about 35% develop severe neurological impairment, mainly cerebral palsy and intellectual disability. To date there is no therapy available to prevent infants from developing either hydrocephalus or serious neurological disability. It is known that blood rapidly accumulates within the ventricles following IVH and this leads to disruption of normal anatomy and increased local pressure. However, the molecular mechanisms causing brain injury following IVH are incompletely understood. We propose that extracellular hemoglobin is central in the pathophysiology of periventricular white matter damage following IVH. Using a preterm rabbit pup model of IVH the distribution of extracellular hemoglobin was characterized at 72 h following hemorrhage. Evaluation of histology, histochemistry, hemoglobin immunolabeling and scanning electron microscopy revealed presence of extensive amounts of extracellular hemoglobin, i.e., not retained within erythrocytes, in the periventricular white matter, widely distributed throughout the brain. Furthermore, double immunolabeling together with the migration and differentiation markers polysialic acid neural cell adhesion molecule (PSA-NCAM) demonstrates that a significant proportion of the extracellular hemoglobin is distributed in areas of the periventricular white matter with high extracellular plasticity. In conclusion, these findings support that extracellular hemoglobin may contribute to the pathophysiological processes that cause irreversible damage to the immature brain following IVH. PMID:27536248

Assessment of rat optic nerve damage due to microbeam radiation therapy in the treatment of glioblastomas.

PubMed

Mohamed, A; Worobec, S; Schultke, E

2008-01-01

Glioblastomas are the most common and aggressive subtype of human primary brain tumors. Due to their uncontrolled cellular proliferation, intense invasion, and lack of apoptosis, they are extremely difficult to treat. Currently, different approaches such as surgery, chemotherapy and radiation therapy have been employed as possible treatments however thus far; these treatments are not curative. Currently, microbeam radiation therapy (MRT) is being trialed in animal models of malignant brain tumors (rats) to aid in treatment. Some of the protocols tested have been shown to significantly increase survival rates. However, due to the high x-ray doses uses in MRT, the surrounding tissue of the targeted Glioblastomas may be irreversibly damaged. In previous studies, lens damage and clouding of the cornea have been observed in microbeam exposed eyes. However, to date no studies have assessed optic nerve damage. Therefore, this study examines the potential rat optic nerve damage following exposure to microbeam radiation therapy in the treatment of Glioblastomas. Although there appears to be no significant damage to the optic nerve, slight inflammation was observed within the extra ocular muscle.

X-tip intraosseous injection system as a primary anesthesia for irreversible pulpitis of posterior mandibular teeth: A randomized clinical trail

PubMed Central

Razavian, Hamid; Kazemi, Shantia; Khazaei, Saber; Jahromi, Maryam Zare

2013-01-01

Background: Successful anesthesia during root canal therapy may be difficult to obtain. Intraosseous injection significantly improves anesthesia's success as a supplemental pulpal anesthesia, particularly in cases of irreversible pulpitis. The aim of this study was to compare the efficacy of X-tip intraosseous injection and inferior alveolar nerve (IAN) block in primary anesthesia for mandibular posterior teeth with irreversible pulpitis. Materials and Methods: Forty emergency patients with an irreversible pulpitis of mandibular posterior teeth were randomly assigned to receive either intraosseous injection using the X-tip intraosseous injection system or IAN block as the primary injection method for pulpal anesthesia. Pulpal anesthesia was evaluated using an electric pulp tester and endo ice at 5-min intervals for 15 min. Anesthesia's success or failure rates were recorded and analyzed using SPSS version 12 statistical software. Success or failure rates were compared using a Fisher's exact test, and the time duration for the onset of anesthesia was compared using Mann–Whitney U test. P < 0.05 was considered significant. Results: Intraosseous injection system resulted in successful anesthesia in 17 out of 20 patients (85%). Successful anesthesia was achieved with the IAN block in 14 out of 20 patients (70%). However, the difference (15%) was not statistically significant (P = 0.2). Conclusion: Considering the relatively expensive armamentarium, probability of penetrator separation, temporary tachycardia, and possibility of damage to root during drilling, the authors do not suggest intraosseous injection as a suitable primary technique. PMID:23946738

X-tip intraosseous injection system as a primary anesthesia for irreversible pulpitis of posterior mandibular teeth: A randomized clinical trail.

PubMed

Razavian, Hamid; Kazemi, Shantia; Khazaei, Saber; Jahromi, Maryam Zare

2013-03-01

Successful anesthesia during root canal therapy may be difficult to obtain. Intraosseous injection significantly improves anesthesia's success as a supplemental pulpal anesthesia, particularly in cases of irreversible pulpitis. The aim of this study was to compare the efficacy of X-tip intraosseous injection and inferior alveolar nerve (IAN) block in primary anesthesia for mandibular posterior teeth with irreversible pulpitis. Forty emergency patients with an irreversible pulpitis of mandibular posterior teeth were randomly assigned to receive either intraosseous injection using the X-tip intraosseous injection system or IAN block as the primary injection method for pulpal anesthesia. Pulpal anesthesia was evaluated using an electric pulp tester and endo ice at 5-min intervals for 15 min. Anesthesia's success or failure rates were recorded and analyzed using SPSS version 12 statistical software. Success or failure rates were compared using a Fisher's exact test, and the time duration for the onset of anesthesia was compared using Mann-Whitney U test. P < 0.05 was considered significant. Intraosseous injection system resulted in successful anesthesia in 17 out of 20 patients (85%). Successful anesthesia was achieved with the IAN block in 14 out of 20 patients (70%). However, the difference (15%) was not statistically significant (P = 0.2). Considering the relatively expensive armamentarium, probability of penetrator separation, temporary tachycardia, and possibility of damage to root during drilling, the authors do not suggest intraosseous injection as a suitable primary technique.

Nitric oxide-related species-induced protein oxidation: reversible, irreversible, and protective effects on enzyme function of papain.

PubMed

Väänänen, Antti J; Kankuri, Esko; Rauhala, Pekka

2005-04-15

Protein oxidation, irreversible modification, and inactivation may play key roles in various neurodegenerative disorders. Therefore, we studied the effects of the potentially in vivo occurring nitric oxide-related species on two different markers of protein oxidation: protein carbonyl generation on bovine serum albumine (BSA) and loss of activity of a cysteine-dependent protease, papain, in vitro by using Angeli's salt, papanonoate, SIN-1, and S-nitrosoglutathione (GSNO) as donors of nitroxyl, nitric oxide, peroxynitrite, and nitrosonium ions, respectively. Angeli's salt, SIN-1, and papanonoate (0-1000 microM) all generated a concentration-dependent increase in carbonyl formation on BSA (107, 60, and 45%, respectively). GSNO did not affect carbonyl formation. Papain was inhibited by Angeli's salt, SIN-1, papanonoate, and GSNO with IC50 values of 0.62, 2.3, 54, and 80 microM, respectively. Angeli's salt (3.16 microM)-induced papain inactivation was only partially reversible, while the effects of GSNO (316 microM) and papanonoate (316 microM) were reversible upon addition of excess DTT. The Angeli's salt-mediated DTT-irreversible inhibition of papain was prevented by GSNO or papanonoate pretreatment, hypothetically through mixed disulfide formation or S-nitrosylation of the catalytically critical thiol group of papain. These results, for the first time, compare the generation of carbonyls in proteins by Angeli's salt, papanonoate, and SIN-1. Furthermore, these results suggest that S-nitrosothiols may have a novel function in protecting critical thiols from irreversible oxidative damage.

Interventions for Hip Pain in the Maturing Athlete

PubMed Central

Gomberawalla, M. Mustafa; Kelly, Bryan T.; Bedi, Asheesh

2014-01-01

Context: Femoroacetabular impingement (FAI) alters hip mechanics, results in hip pain, and may lead to secondary osteoarthritis (OA) in the maturing athlete. Hip impingement can be caused by osseous abnormalities in the proximal femur or acetabulum. These impingement lesions may cause altered loads within the hip joint, which result in repetitive collision damage or sheer forces to the chondral surfaces and acetabular labrum. These anatomic lesions and resultant abnormal mechanics may lead to early osteoarthritic changes. Evidence Acquisition: Relevant articles from the years 1995 to 2013 were identified using MEDLINE, EMBASE, and the bibliographies of reviewed publications. Level of Evidence: Level 4. Results: Improvements in hip arthroscopy have allowed FAI to be addressed utilizing the arthroscope. Adequately resecting the underlying osseous abnormalities is essential to improving hip symptomatology and preventing further chondral damage. Additionally, preserving the labrum by repairing the damaged tissue and restoring the suction seal may theoretically help normalize hip mechanics and prevent further arthritic changes. The outcomes of joint-preserving treatment options may be varied in the maturing athlete due to the degree of underlying OA. Irreversible damage to the hip joint may have already occurred in patients with moderate to advanced OA. In the presence of preexisting arthritis, these patients may only experience fair or even poor results after hip arthroscopy, with early conversion to hip replacement. For patients with advanced hip arthritis, total hip arthroplasty remains a treatment option to reliably improve symptoms with good to excellent outcomes and return to low-impact activities. Conclusion: Advances in the knowledge base and treatment techniques of intra-articular hip pain have allowed surgeons to address this complex clinical problem with promising outcomes. Traditionally, open surgical dislocations for hip preservation surgery have shown good long-term results. Improvements in hip arthroscopy have led to outcomes equivalent to open surgery while utilizing significantly less invasive techniques. However, outcomes may ultimately depend on the degree of underlying OA. When counseling the mature athlete with hip pain, an understanding of the underlying anatomy, degree of arthritis, and expectations will help guide the treating surgeon in offering appropriate treatment options. PMID:24427445

Experimental simulation of frost wedging-induced crack propagation in alpine rockwall

NASA Astrophysics Data System (ADS)

Jia, Hailiang; Leith, Kerry; Krautblatter, Michael

2016-04-01

Frost wedging is widely presumed to be the principal mechanism responsible for shattering jointed low-porosity rocks in high alpine rockwalls. The interaction of ice and rock physics regulates the efficacy of frost wedging. In order to better understand temporal aspects of this interaction, we present results of a series of laboratory experiments monitoring crack widening as a result of ice formation in an artificial crack (4mm wide, 80mm deep) cut 20 mm from the end of a rectangular granite block. Our results indicate that i) freezing direction plays a key role in determining the magnitude of crack widening; in short-term (1 day) experiments, maximum crack widening during top-down freezing (associated with 'autumn' conditions) was around 0.11mm, while inside-out freezing (resulting from 'spring' conditions) produced only 0.02 mm of deformation; ii) neither ice, nor water pressure (direct tension and hydraulic fracturing respectively) caused measurable irreversible crack widening during short-term tests, as the calculated maximum stress intensity at the crack tip was less than the fracture toughness of our granite sample; iii) development of ice pressure is closely related to the mechanical properties of the fracture in which it forms, and as such, the interaction of ice and rock is intrinsically dynamic; iv) irreversible crack widening (about 0.03mm) was only observed following a long-term (53 day) experiment representing a simplified transition from autumn to winter conditions. We suggest this is the result of stress corrosion aided by strong opening during freezing, and to a lesser degree by ice segregation up to one week after the initial freezing period, and downward migration of liquid water during the remainder of the test. Our results suggest the fundamental assumption of frost wedging, that rapid freezing from open ends of cracks can seal water inside the crack and thus cause damage through excessive stresses induced by volumetric expansion seems questionable.

Reversal of hepatic fibrosis: pathophysiological basis of antifibrotic therapies

PubMed Central

Ismail, Mona H; Pinzani, Massimo

2011-01-01

Chronic liver injuries of different etiologies eventually lead to fibrosis, a scarring process associated with increased and altered deposition of extracellular matrix in the liver. Progression of fibrosis has a major worldwide clinical impact due to the high number of patients affected by chronic liver disease which can lead to severe complications, expensive treatment, a possible need for liver transplantation, and death. Liver fibrogenesis is characterized by activation of hepatic stellate cells and other extracellular matrix producing cells. Liver fibrosis may regress following specific therapeutic interventions. Other than removing agents causing chronic liver damage, no antifibrotic drug is currently available in clinical practice. The extent of liver fibrosis is variable between individuals, even after controlling for exogenous factors. Thus, host genetic factors are considered to play an important role in the process of liver scarring. Until recently it was believed that this process was irreversible. However, emerging experimental and clinical evidence is starting to show that even cirrhosis in its early stages is potentially reversible. PMID:24367223

Evidence for a prolonged role of alpha 4 integrin throughout active experimental allergic encephalomyelitis.

PubMed

Keszthelyi, E; Karlik, S; Hyduk, S; Rice, G P; Gordon, G; Yednock, T; Horner, H

1996-10-01

The leukocyte integrin receptor, alpha 4 beta 1, and its endothelial cell ligand, vascular cell adhesion molecule 1, appear to be of critical importance in the leukocyte trafficking that accompanies CNS damage in experimental allergic encephalomyelitis (EAE). In this study, the persistence of the role for alpha 4 beta 1/VCAM-1 in EAE was established by observing antibody-mediated disease reversal up to 1 month following disease onset. Limited treatment with a monoclonal antibody against alpha 4 integrin, GG5/3, resulted in a significant decrease in both clinical and histopathologic signs. This was not observed in isotype control experiments. In the latter phase of progressive disease, widespread demyelination occurred in the animals that did not respond to 6 days of anti-alpha 4 treatment. These results demonstrate an essential role for alpha 4 beta 1 interactions throughout active EAE and illustrate the difference between reversible clinical deficits caused by edema and irreversible deficits associated with demyelination.

Strategic Protein Target Analysis for Developing Drugs to Stop Dental Caries

PubMed Central

Horst, J.A.; Pieper, U.; Sali, A.; Zhan, L.; Chopra, G.; Samudrala, R.; Featherstone, J.D.B.

2012-01-01

Dental caries is the most common disease to cause irreversible damage in humans. Several therapeutic agents are available to treat or prevent dental caries, but none besides fluoride has significantly influenced the disease burden globally. Etiologic mechanisms of the mutans group streptococci and specific Lactobacillus species have been characterized to various degrees of detail, from identification of physiologic processes to specific proteins. Here, we analyze the entire Streptococcus mutans proteome for potential drug targets by investigating their uniqueness with respect to non-cariogenic dental plaque bacteria, quality of protein structure models, and the likelihood of finding a drug for the active site. Our results suggest specific targets for rational drug discovery, including 15 known virulence factors, 16 proteins for which crystallographic structures are available, and 84 previously uncharacterized proteins, with various levels of similarity to homologs in dental plaque bacteria. This analysis provides a map to streamline the process of clinical development of effective multispecies pharmacologic interventions for dental caries. PMID:22899687

Metallothionein as a Scavenger of Free Radicals - New Cardioprotective Therapeutic Agent or Initiator of Tumor Chemoresistance?

PubMed

Heger, Zbynek; Rodrigo, Miguel Angel Merlos; Krizkova, Sona; Ruttkay-Nedecky, Branislav; Zalewska, Marta; Del Pozo, Elena Maria Planells; Pelfrene, Aurelie; Pourrut, Bertrand; Stiborova, Marie; Eckschlager, Tomas; Emri, Gabriella; Kizek, Rene; Adam, Vojtech

2016-01-01

Cardiotoxicity is a serious complication of anticancer therapy by anthracycline antibiotics. Except for intercalation into DNA/RNA structure, inhibition of DNA-topoisomerase and histone eviction from chromatin, the main mechanism of their action is iron-mediated formation of various forms of free radicals, which leads to irreversible damage to cancer cells. The most serious adverse effect of anthracyclines is, thus, cardiomyopathy leading to congestive heart failure, which is caused by the same mechanisms. Here, we briefly summarize the basic types of free radicals formed by anthracyclines and the main processes how to scavenge them. From these, the main attention is paid to metallothioneins. These low-molecular cysteine-rich proteins are introduced and their functions and properties are reviewed. Further, their role in detoxification of metals and drugs is discussed. Based on these beneficial roles, their use as a new therapeutic agent against oxidative stress and for cardioprotection is critically evaluated with respect to their ability to increase chemoresistance against some types of commonly used cytostatics.

Development of a screening tool for staging of diabetic retinopathy in fundus images

NASA Astrophysics Data System (ADS)

Dhara, Ashis Kumar; Mukhopadhyay, Sudipta; Bency, Mayur Joseph; Rangayyan, Rangaraj M.; Bansal, Reema; Gupta, Amod

2015-03-01

Diabetic retinopathy is a condition of the eye of diabetic patients where the retina is damaged because of long-term diabetes. The condition deteriorates towards irreversible blindness in extreme cases of diabetic retinopathy. Hence, early detection of diabetic retinopathy is important to prevent blindness. Regular screening of fundus images of diabetic patients could be helpful in preventing blindness caused by diabetic retinopathy. In this paper, we propose techniques for staging of diabetic retinopathy in fundus images using several shape and texture features computed from detected microaneurysms, exudates, and hemorrhages. The classification accuracy is reported in terms of the area (Az) under the receiver operating characteristic curve using 200 fundus images from the MESSIDOR database. The value of Az for classifying normal images versus mild, moderate, and severe nonproliferative diabetic retinopathy (NPDR) is 0:9106. The value of Az for classification of mild NPDR versus moderate and severe NPDR is 0:8372. The Az value for classification of moderate NPDR and severe NPDR is 0:9750.

Magnetic Resonance Spectroscopy: An In Vivo Molecular Imaging Biomarker for Parkinson's Disease?

PubMed Central

Ciurleo, Rosella; Di Lorenzo, Giuseppe; Marino, Silvia

2014-01-01

Parkinson's disease (PD) is a neurodegenerative disorder caused by selective loss of dopaminergic neurons in the substantia nigra pars compacta which leads to dysfunction of cerebral pathways critical for the control of movements. The diagnosis of PD is based on motor symptoms, such as bradykinesia, akinesia, muscular rigidity, postural instability, and resting tremor, which are evident only after the degeneration of a significant number of dopaminergic neurons. Currently, a marker for early diagnosis of PD is still not available. Consequently, also the development of disease-modifying therapies is a challenge. Magnetic resonance spectroscopy is a quantitative imaging technique that allows in vivo measurement of certain neurometabolites and may produce biomarkers that reflect metabolic dysfunctions and irreversible neuronal damage. This review summarizes the abnormalities of cerebral metabolites found in MRS studies performed in patients with PD and other forms of parkinsonism. In addition, we discuss the potential role of MRS as in vivo molecular imaging biomarker for early diagnosis of PD and for monitoring the efficacy of therapeutic interventions. PMID:25302300

Management of asymptomatic gene carriers of transthyretin familial amyloid polyneuropathy.

PubMed

Schmidt, Hartmut H-J; Barroso, Fabio; González-Duarte, Alejandra; Conceição, Isabel; Obici, Laura; Keohane, Denis; Amass, Leslie

2016-09-01

Transthyretin familial amyloid polyneuropathy (TTR-FAP) is a rare, severe, and irreversible, adult-onset, hereditary disorder caused by autosomal-dominant mutations in the TTR gene that increase the intrinsic propensity of transthyretin protein to misfold and deposit systemically as insoluble amyloid fibrils in nerve tissues, the heart, and other organs. TTR-FAP is characterized by relentless, progressively debilitating polyneuropathy, and leads to death, on average, within 10 years of symptom onset without treatment. With increased availability of disease-modifying treatment options for a wider spectrum of patients with TTR-FAP, timely detection of the disease may offer substantial clinical benefits. This review discusses mutation-specific predictive genetic testing in first-degree relatives of index patients diagnosed with TTR-FAP and the structured clinical follow-up of asymptomatic gene carriers for prompt diagnosis and early therapeutic intervention before accumulation of substantial damage. Muscle Nerve 54: 353-360, 2016. © 2016 The Authors Muscle & Nerve Published by Wiley Periodicals, Inc.

Nanotechnology-based intelligent drug design for cancer metastasis treatment.

PubMed

Gao, Yu; Xie, Jingjing; Chen, Haijun; Gu, Songen; Zhao, Rongli; Shao, Jingwei; Jia, Lee

2014-01-01

Traditional chemotherapy used today at clinics is mainly inherited from the thinking and designs made four decades ago when the Cancer War was declared. The potency of those chemotherapy drugs on in-vitro cancer cells is clearly demonstrated at even nanomolar levels. However, due to their non-specific effects in the body on normal tissues, these drugs cause toxicity, deteriorate patient's life quality, weaken the host immunosurveillance system, and result in an irreversible damage to human's own recovery power. Owing to their unique physical and biological properties, nanotechnology-based chemotherapies seem to have an ability to specifically and safely reach tumor foci with enhanced efficacy and low toxicity. Herein, we comprehensively examine the current nanotechnology-based pharmaceutical platforms and strategies for intelligent design of new nanomedicines based on targeted drug delivery system (TDDS) for cancer metastasis treatment, analyze the pros and cons of nanomedicines versus traditional chemotherapy, and evaluate the importance that nanomaterials can bring in to significantly improve cancer metastasis treatment. Copyright © 2013 Elsevier Inc. All rights reserved.

Flow characteristics in the airways of a COPD patient with a saber-sheath trachea

NASA Astrophysics Data System (ADS)

Jin, Dohyun; Choi, Haecheon; Lee, Changhyun; Choi, Jiwoong; Kim, Kwanggi

2016-11-01

The chronic obstructive pulmonary disease (COPD) is a lung disease characterized by the irreversible airflow limitation caused by the damaged small airways and air sacs. Although COPD is not a disease of the trachea, many patients with COPD have saber-sheath tracheas. The effects of this morphological change in the trachea geometry on airflow are investigated in the present study. An unstructured finite volume method is used for the simulations during tidal breathing in normal and COPD airways, respectively. During inspiration, local large pressure drop is observed in the saber-sheath region of the COPD patient. During expiration, vortical structures are observed at the right main bronchus of the COPD airway, while the flow in the normal airway remains nearly laminar. High wall shear stress exists at convex regions of both airways during inspiration and expiration. However, due to the morphological changes in the COPD airway, relatively higher wall shear stress is observed in the patient airways.

The use of chimeric vimentin citrullinated peptides for the diagnosis of rheumatoid arthritis.

PubMed

Malakoutikhah, Morteza; Gómara, María J; Gómez-Puerta, José A; Sanmartí, Raimon; Haro, Isabel

2011-11-10

Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes inflammation and, in many cases, destruction of the joints. To prevent progressive and irreversible structural damage, early diagnosis of RA is of paramount importance. The present study addresses the search of new RA citrullinated antigens that could supplement or complement diagnostic/prognostic existing tests. With this aim, the epitope anticitrullinated vimentin antibody response was mapped using synthetic peptides. To improve the sensitivity/specificity balance, a vimentin peptide that was selected, and its cyclic analogue, were combined with fibrin- and filaggrin-related peptides to render chimeric peptides. Our findings highlight the putative application of these chimeric peptides for the design of RA diagnosis systems and imply that more than one serological test is required to classify RA patients based on the presence or absence of ACPAs. Each of the target molecules reported here (fibrin, vimentin, filaggrin) has a specific utility in the identification of a particular subset of RA patients.

Cigarette-Smoke-Induced Dysregulation of MicroRNA Expression and Its Role in Lung Carcinogenesis

PubMed Central

Russ, Rebecca; Slack, Frank J.

2012-01-01

Dysregulation of microRNAs (miRNAs), particularly their downregulation, has been widely shown to be associated with the development of lung cancer. Downregulation of miRNAs leads to the overactivation of their oncogene targets, while upregulation of some miRNAs leads to inhibition of important tumor suppressors. Research has implicated cigarette smoke in miRNA dysregulation, leading to carcinogenesis. Cigarette smoke may lead to genetic or epigenetic damage to miRNAs, many of which map to fragile sites and some of which contain single nucleotide polymorphisms. Cigarette smoke may also cause dysregulation by affecting regulatory mechanisms controlling miRNA expression. Researchers have shown a correlation between smoke-exposure-induced dysregulation of miRNAs and age. Furthermore, dysregulation seems to be associated with intensity and duration of smoke exposure and duration of cessation. Longer exposure at a threshold level is needed for irreversibility of changes in expression. Better understanding of miRNA dysregulation may allow for improved biomonitoring and treatment regimens for lung cancer. PMID:22191027

Assessment of the impact of increased solar ultraviolet radiation upon marine ecosystems

NASA Technical Reports Server (NTRS)

Vandyke, H.; Worrest, R. C.

1976-01-01

Data was provided to assess the potential impact upon marine ecosystems if space shuttle operations contribute to a reduction of the stratospheric ozone layer. The potential for irreversible damage to the productivity, structure and/or functioning of a model estuarine ecosystem by increased UV-B radiation was established. The sensitivity of key community components (the primary producers) to increased UV-B radiation was delineated.

Thiyl radicals and induction of protein degradation

PubMed Central

Schöneich, Christian

2016-01-01

Thiyl radicals are important intermediates in the redox biology and chemistry of thiols. These radicals can react via hydrogen transfer with various C-H bonds in peptides and proteins, leading to the generation of carbon-centered radicals, and, potentially, to irreversible protein damage. This review summarizes quantitative information on reaction kinetics and product formation, and discusses the significance of these reactions for protein degradation induced by thiyl radical formation. PMID:26212409

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's disease. Cover Image for this issue: doi: 10.1111/jnc.13338. © 2016 International Society for Neurochemistry.

Fundamental studies of hydrogen attack in carbon-0.5molybdenum steel and weldments applied in petroelum and petrochemical industries

NASA Astrophysics Data System (ADS)

Liu, Peng

High temperature hydrogen attack (HTHA) is a form of surface decarburization, internal decarburization, and/or intergranular cracking in steels exposed to high temperature (>400°F) and high hydrogen pressure. Hydrogen attack is an irreversible process which can cause permanent damage resulting in degradation of mechanical properties and failures such as leakage, bursting, fire, and/or explosion. The continuous progression of hydrogen attack in C-0.5Mo steel and weldments below the C-0.5Mo Nelson Curve has caused a significant concern for the integrity and serviceability of C-0.5Mo steel utilized for pressure vessels and piping in the petroleum refinery and petrochemical industries. A state-of-the-art literature review was implemented to provide a comprehensive overview of the published research efforts on hydrogen attack studies. The evolution of "Nelson Curves" for carbon steel, C-0.5Mo, and Cr-Mo steels was historically reviewed in regard to design applications and limitations. Testing techniques for hydrogen attack assessment were summarized under the categories of hydrogen exposure testing, mechanical evaluation, and dilatometric swelling testing. In accord with the demands of these industries, fundamental studies of hydrogen attack in C-0.5Mo steel and weldments were accomplished in terms of quantitative methodologies for hydrogen damage evaluation; hydrogen damage assessment of service exposed weldments and autoclave exposed materials; effects of carbon and alloying elements, heat treatments, hot and cold working, welding processes and postweld heat treatment (PWHT) on hydrogen attack susceptibility; development of continuous cooling transformation (CCT) diagrams for C-0.5Mo base metals and the coarse grained heat-affected zone (CGHAZ); carbide evaluation for the C-0.5Mo steel after service exposure and heat treatment; methane evolution by the reaction of hydrogen and carbides; hydrogen diffusion and methane pressure through the wall thickness of one-sided hydrogen exposure assembly; hydrogen attack mechanism and hydrogen attack limit modeling.

The Making and Breaking of Yugoslavia and Its Impact on Health

PubMed Central

Kunitz, Stephen J.

2004-01-01

The creation of nation-states in Europe has generally been assumed to be intrinsic to modernization and to be irreversible. The disintegration of Czechoslovakia, the Soviet Union, and Yugoslavia demonstrates that the process is not irreversible. I argue that in the case of Yugoslavia, (1) disintegration was caused by the interaction between domestic policies with regard to nationalities and integration into the global economy and (2) the impact of the disintegration of the federation on health care and public health systems has been profound. Improving and converging measures of mortality before the collapse gave way to increasing disparities afterward. The lesson is that processes of individual and social modernization do not result in improvements in health and well-being that are necessarily irreversible or shared equally. PMID:15514224

Near-infrared diffuse reflectance imaging of infarct core and peri-infarct depolarization in a rat middle cerebral artery occlusion model

NASA Astrophysics Data System (ADS)

Kawauchi, Satoko; Nishidate, Izumi; Nawashiro, Hiroshi; Sato, Shunichi

2014-03-01

To understand the pathophysiology of ischemic stroke, in vivo imaging of the brain tissue viability and related spreading depolarization is crucial. In the infarct core, impairment of energy metabolism causes anoxic depolarization (AD), which considerably increases energy consumption, accelerating irreversible neuronal damage. In the peri-infarct penumbra region, where tissue is still reversible despite limited blood flow, peri-infarct depolarization (PID) occurs, exacerbating energy deficit and hence expanding the infarct area. We previously showed that light-scattering signal, which is sensitive to cellular/subcellular structural integrity, was correlated with AD and brain tissue viability in a rat hypoxia-reoxygenation model. In the present study, we performed transcranial NIR diffuse reflectance imaging of the rat brain during middle cerebral artery (MCA) occlusion and examined whether the infarct core and PIDs can be detected. Immediately after occluding the left MCA, light scattering started to increase focally in the occlusion site and a bright region was generated near the occlusion site and spread over the left entire cortex, which was followed by a dark region, showing the occurrence of PID. The PID was generated repetitively and the number of times of occurrence in a rat ranged from four to ten within 1 hour after occlusion (n=4). The scattering increase in the occlusion site was irreversible and the area with increased scattering expanded with increasing the number of PIDs, indicating an expansion of the infarct core. These results suggest the usefulness of NIR diffuse reflectance signal to visualize spatiotemporal changes in the infarct area and PIDs.

Microbial lipid extraction from Lipomyces starkeyi using irreversible electroporation.

PubMed

Karim, Ahasanul; Yousuf, Abu; Islam, M Amirul; Naif, Yasir H; Faizal, Che Ku Mohammad; Alam, Md Zahangir; Pirozzi, Domenico

2018-02-21

The aim of the study was to investigate the feasibility of using irreversible electroporation (EP) as a microbial cell disruption technique to extract intracellular lipid within short time and in an eco-friendly manner. An EP circuit was designed and fabricated to obtain 4 kV with frequency of 100 Hz of square waves. The yeast cells of Lipomyces starkeyi (L. starkeyi) were treated by EP for 2-10 min where the distance between electrodes was maintained at 2, 4, and 6 cm. Colony forming units (CFU) were counted to observe the cell viability under the high voltage electric field. The forces of the pulsing electric field caused significant damage to the cell wall of L. starkeyi and the disruption of microbial cells was visualized by field emission scanning electron microscopic (FESEM) image. After breaking the cell wall, lipid was extracted and measured to assess the efficiency of EP over other techniques. The extent of cell inactivation was up to 95% when the electrodes were placed at the distance of 2 cm, which provided high treatment intensity (36.7 kWh m -3 ). At this condition, maximum lipid (63 mg g -1 ) was extracted when the biomass was treated for 10 min. During the comparison, EP could extract 31.88% lipid while the amount was 11.89% for ultrasonic and 16.8% for Fenton's reagent. The results recommend that the EP is a promising technique for lowering the time and solvent usage for lipid extraction from microbial biomass. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 2018. © 2018 American Institute of Chemical Engineers.

3D papillary image capturing by the stereo fundus camera system for clinical diagnosis on retina and optic nerve

NASA Astrophysics Data System (ADS)

Motta, Danilo A.; Serillo, André; de Matos, Luciana; Yasuoka, Fatima M. M.; Bagnato, Vanderlei S.; Carvalho, Luis A. V.

2014-03-01

Glaucoma is the second main cause of the blindness in the world and there is a tendency to increase this number due to the lifetime expectation raise of the population. Glaucoma is related to the eye conditions, which leads the damage to the optic nerve. This nerve carries visual information from eye to brain, then, if it has damage, it compromises the visual quality of the patient. In the majority cases the damage of the optic nerve is irreversible and it happens due to increase of intraocular pressure. One of main challenge for the diagnosis is to find out this disease, because any symptoms are not present in the initial stage. When is detected, it is already in the advanced stage. Currently the evaluation of the optic disc is made by sophisticated fundus camera, which is inaccessible for the majority of Brazilian population. The purpose of this project is to develop a specific fundus camera without fluorescein angiography and red-free system to accomplish 3D image of optic disc region. The innovation is the new simplified design of a stereo-optical system, in order to make capable the 3D image capture and in the same time quantitative measurements of excavation and topography of optic nerve; something the traditional fundus cameras do not do. The dedicated hardware and software is developed for this ophthalmic instrument, in order to permit quick capture and print of high resolution 3D image and videos of optic disc region (20° field-of-view) in the mydriatic and nonmydriatic mode.

Dependence of Plastic TATB Shock-Wave Sensitivity on Temperature, Density and Technology Factors

NASA Astrophysics Data System (ADS)

Vlasov, Yu. A.; Kosolapov, V. B.; Fomicheva, L. V.; Khabarov, I. P.

1999-06-01

Mixed TATB-based HE is the most perspective because of the manufacture and exploitation safety of its items. At the same time the safety of these explosive, at high temperatures, which take place at emergencies, causes the certain anxiety. Plastic TATB shock-wave sensitivity (SWS) researches has shown that temperature as one of the important factors of external influence is not always the determining reason of SWS change. It is known that density influence on SWS significantly. At the same time density depends on temperature and technology of details manufacturing. In this connection in this work the temperature dependence of plastic TATB SWS was studied in view of convertible and irreversible changes of density (p) under heating at -50[C up to 90[C . It is shown that during these influences the dependence of threshold pressure of initiation (P) from temperature is explained, first of all, by change of HE density, caused by its thermal expansion (compression), and also by irreversible changes of p and HE structure, arising at heating. It is found also that the share of irreversible change of density depends on technology of HE details manufacturing and is explained by relaxation of residual pressure in them. The mentioned relaxation is finished after the first cycles of thermal influence. The value of density change, caused by this factor, depends on temperature and duration of heating.

Rapid-releasing of HI-6 via brain-targeted mesoporous silica nanoparticles for nerve agent detoxification

NASA Astrophysics Data System (ADS)

Yang, Jun; Fan, Lixue; Wang, Feijian; Luo, Yuan; Sui, Xin; Li, Wanhua; Zhang, Xiaohong; Wang, Yongan

2016-05-01

The toxic nerve agent (NA) soman is the most toxic artificially synthesized compound that can rapidly penetrate into the brain and irreversibly inhibit acetylcholinesterase (AChE) activity, leading to immediate death. However, there are currently few brain-targeted nanodrugs that can treat acute chemical brain poisoning owing to the limited drug-releasing speed. The present study investigated the effectiveness of a nanodrug against NA toxicity that has high blood-brain barrier penetration and is capable of rapid drug release. Transferrin-modified mesoporous silica nanoparticles (TF-MSNs) were conjugated with the known AChE reactivator HI-6. This nanodrug rapidly penetrated the blood-brain barrier in zebrafish and mice and restored cerebral AChE activity via the released HI-6, preventing the brain damage caused by soman poisoning and increasing the survival rate in mice. Furthermore, there was no toxicity associated with the MSNs in mice or rats. These results demonstrate that TF-MSNs loaded with HI-6 represent the most effective antidote against NA poisoning by soman reported to date, and suggest that MSNs are a safe alternative to conventional drugs and an optimal nanocarrier for treating brain poisoning, which requires acute pulse cerebral administration.The toxic nerve agent (NA) soman is the most toxic artificially synthesized compound that can rapidly penetrate into the brain and irreversibly inhibit acetylcholinesterase (AChE) activity, leading to immediate death. However, there are currently few brain-targeted nanodrugs that can treat acute chemical brain poisoning owing to the limited drug-releasing speed. The present study investigated the effectiveness of a nanodrug against NA toxicity that has high blood-brain barrier penetration and is capable of rapid drug release. Transferrin-modified mesoporous silica nanoparticles (TF-MSNs) were conjugated with the known AChE reactivator HI-6. This nanodrug rapidly penetrated the blood-brain barrier in zebrafish and mice and restored cerebral AChE activity via the released HI-6, preventing the brain damage caused by soman poisoning and increasing the survival rate in mice. Furthermore, there was no toxicity associated with the MSNs in mice or rats. These results demonstrate that TF-MSNs loaded with HI-6 represent the most effective antidote against NA poisoning by soman reported to date, and suggest that MSNs are a safe alternative to conventional drugs and an optimal nanocarrier for treating brain poisoning, which requires acute pulse cerebral administration. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr06658a

Thermal inactivation and chaperonin-mediated renaturation of mitochondrial aspartate aminotransferase.

PubMed Central

Lawton, J M; Doonan, S

1998-01-01

Mitochondrial aspartate aminotransferase is inactivated irreversibly on heating. The inactivated protein aggregates, but aggregation is prevented by the presence of the chaperonin 60 from Escherichia coli (GroEL). The chaperonin increases the rate of thermal inactivation in the temperature range 55-65 degrees C but not at lower temperatures. It has previously been shown [Twomey and Doonan (1997) Biochim. Biophys. Acta 1342, 37-44] that the enzyme switches to a modified, but catalytically active, conformation at approx. 55-60 degrees C and the present results show that this conformation is recognized by and binds to GroEL. The thermally inactivated protein can be released from GroEL in an active form by the addition of chaperonin 10 from E. coli (GroES)/ATP, showing that inactivation is not the result of irreversible chemical changes. These results suggest that the irreversibility of thermal inactivation is due to the formation of an altered conformation with a high kinetic barrier to refolding rather than to any covalent changes. In the absence of chaperonin the unfolded molecules aggregate but this is a consequence, rather than the cause, of irreversible inactivation. PMID:9693123

Senescence, apoptosis or autophagy? When a damaged cell must decide its path--a mini-review.

PubMed

Vicencio, José Miguel; Galluzzi, Lorenzo; Tajeddine, Nicolas; Ortiz, Carla; Criollo, Alfredo; Tasdemir, Ezgi; Morselli, Eugenia; Ben Younes, Amena; Maiuri, Maria Chiara; Lavandero, Sergio; Kroemer, Guido

2008-01-01

Many features of aging result from the incapacity of cells to adapt to stress conditions. When damage accumulates irreversibly, mitotic cells from renewable tissues rely on either of two mechanisms to avoid replication. They can permanently arrest the cell cycle (cellular senescence) or trigger cell death programs. Apoptosis (self-killing) is the best-described form of programmed cell death, but autophagy (self-eating), which is a lysosomal degradation pathway essential for homeostasis, reportedly contributes to cell death as well. Unlike mitotic cells, postmitotic cells like neurons or cardiomyocytes cannot become senescent since they are already terminally differentiated. The fate of these cells entirely depends on their ability to cope with stress. Autophagy then operates as a major homeostatic mechanism to eliminate damaged organelles, long-lived or aberrant proteins and superfluous portions of the cytoplasm. In this mini-review, we briefly summarize the molecular networks that allow damaged cells either to adapt to stress or to engage in programmed-cell-death pathways. (c) 2008 S. Karger AG, Basel.

Induction of a reversible cardiac lipidosis by a dietary long-chain fatty acid (erucic acid). Relationship to lipid accumulation in border zones of myocardial infarcts.

PubMed Central

Chien, K. R.; Bellary, A.; Nicar, M.; Mukherjee, A.; Buja, L. M.

1983-01-01

Previous studies have demonstrated that cardiac myocytes in the border zone of acute myocardial infarction become markedly overloaded with neutral lipid during the transition from reversible to irreversible injury. To examine directly the role of these changes in neutral lipid metabolism in the development of irreversible cellular injury and associated increases in tissue Ca2+ content, the authors fed rats large amounts of a fatty acid (erucic acid) that is poorly oxidized by the heart and that subsequently accumulates as neutral lipid. Rats fed a high erucic acid (C22:1) diet in the form of 20% rapeseed oil for 3-5 days had a fourfold increase in triglyceride (49.5 +/- 3.8 SEM mg/g wet wt versus 13.6 +/- 13, n = 4) and a 60% increase in long-chain acyl CoA content (166.0 +/- 21.9 versus 91.5 +/- 9.0 nM/g wet wt, n = 4), compared with controls. However, there was no change in long-chain acyl carnitine or total phospholipid content. Histochemical studies showed accumulation of numerous lipid droplets in the myocytes, and electron microscopy revealed localization of lipid vesicles in direct contact with mitochondria, thus mimicking the lipid-laden cells in the border zone regions of acute myocardial infarcts. The acute lipidosis was reversible with either continued feeding of erucic acid for several weeks or conversion to a normal diet. It was not associated with an increased tissue Ca2+ content, nor with cell necrosis. However, continued erucic acid intake for 3 months was associated with focal myocardial degeneration and loss of myocytes. These results suggest that acute increases in neutral lipids, as found in the border zone of acute myocardial infarction, may not be the cause of progression to irreversible damage during acute myocardial injury, but that the persistent presence of similar lipid material over months may result in focal myocardial degeneration. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:6859230

Biological Effects of Short, High-Level Exposure to Gases: Nitrogen Oxides.

DTIC Science & Technology

1980-07-01

damage. Proven effects are mainly on the respiratory tract. Intense exposures result in death, hospitalization with recovery, or severe responses not...and up, for single exposures of a few minutes up to 1 hour. At the other extreme the threshold of measurable respiratory impairment in volunteers is...reversible or irreversible respiratory impairment by NOx on oxygen sufficiency and,hence, physical and mental capacity has not been measured in man, but

Small RNA-mediated repair of UV-induced DNA lesions by the DNA DAMAGE-BINDING PROTEIN 2 and ARGONAUTE 1

PubMed Central

Schalk, Catherine; Cognat, Valérie; Graindorge, Stéfanie; Vincent, Timothée; Voinnet, Olivier; Molinier, Jean

2017-01-01

As photosynthetic organisms, plants need to prevent irreversible UV-induced DNA lesions. Through an unbiased, genome-wide approach, we have uncovered a previously unrecognized interplay between Global Genome Repair and small interfering RNAs (siRNAs) in the recognition of DNA photoproducts, prevalently in intergenic regions. Genetic and biochemical approaches indicate that, upon UV irradiation, the DNA DAMAGE-BINDING PROTEIN 2 (DDB2) and ARGONAUTE 1 (AGO1) of Arabidopsis thaliana form a chromatin-bound complex together with 21-nt siRNAs, which likely facilitates recognition of DNA damages in an RNA/DNA complementary strand-specific manner. The biogenesis of photoproduct-associated siRNAs involves the noncanonical, concerted action of RNA POLYMERASE IV, RNA-DEPENDENT RNA POLYMERASE-2, and DICER-LIKE-4. Furthermore, the chromatin association/dissociation of the DDB2-AGO1 complex is under the control of siRNA abundance and DNA damage signaling. These findings reveal unexpected nuclear functions for DCL4 and AGO1, and shed light on the interplay between small RNAs and DNA repair recognition factors at damaged sites. PMID:28325872

Protecting peroxidase activity of multilayer enzyme-polyion films using outer catalase layers.

PubMed

Lu, Haiyun; Rusling, James F; Hu, Naifei

2007-12-27

Films constructed layer-by-layer on electrodes with architecture {protein/hyaluronic acid (HA)}n containing myoglobin (Mb) or horseradish peroxidase (HRP) were protected against protein damage by H2O2 by using outer catalase layers. Peroxidase activity for substrate oxidation requires activation by H2O2, but {protein/HA}n films without outer catalase layers are damaged slowly and irreversibly by H2O2. The rate and extent of damage were decreased dramatically by adding outer catalase layers to decompose H2O2. Comparative studies suggest that protection results from catalase decomposing a fraction of the H2O2 as it enters the film, rather than by an in-film diffusion barrier. The outer catalase layers controlled the rate of H2O2 entry into inner regions of the film, and they biased the system to favor electrocatalytic peroxide reduction over enzyme damage. Catalase-protected {protein/HA}n films had an increased linear concentration range for H2O2 detection. This approach offers an effective way to protect biosensors from damage by H2O2.

A Numerical Investigation of the Electric and Thermal Cell Kill Distributions in Electroporation-Based Therapies in Tissue

PubMed Central

Garcia, Paulo A.; Davalos, Rafael V.; Miklavcic, Damijan

2014-01-01

Electroporation-based therapies are powerful biotechnological tools for enhancing the delivery of exogeneous agents or killing tissue with pulsed electric fields (PEFs). Electrochemotherapy (ECT) and gene therapy based on gene electrotransfer (EGT) both use reversible electroporation to deliver chemotherapeutics or plasmid DNA into cells, respectively. In both ECT and EGT, the goal is to permeabilize the cell membrane while maintaining high cell viability in order to facilitate drug or gene transport into the cell cytoplasm and induce a therapeutic response. Irreversible electroporation (IRE) results in cell kill due to exposure to PEFs without drugs and is under clinical evaluation for treating otherwise unresectable tumors. These PEF therapies rely mainly on the electric field distributions and do not require changes in tissue temperature for their effectiveness. However, in immediate vicinity of the electrodes the treatment may results in cell kill due to thermal damage because of the inhomogeneous electric field distribution and high current density during the electroporation-based therapies. Therefore, the main objective of this numerical study is to evaluate the influence of pulse number and electrical conductivity in the predicted cell kill zone due to irreversible electroporation and thermal damage. Specifically, we simulated a typical IRE protocol that employs ninety 100-µs PEFs. Our results confirm that it is possible to achieve predominant cell kill due to electroporation if the PEF parameters are chosen carefully. However, if either the pulse number and/or the tissue conductivity are too high, there is also potential to achieve cell kill due to thermal damage in the immediate vicinity of the electrodes. Therefore, it is critical for physicians to be mindful of placement of electrodes with respect to critical tissue structures and treatment parameters in order to maintain the non-thermal benefits of electroporation and prevent unnecessary damage to surrounding healthy tissue, critical vascular structures, and/or adjacent organs. PMID:25115970

Hypochlorous acid-promoted loss of metabolic energy in Escherichia coli.

PubMed Central

Barrette, W C; Albrich, J M; Hurst, J K

1987-01-01

Oxidation of Escherichia coli by hypochlorous acid (HOCl) or chloramine (NH2Cl) gives rise to massive hydrolysis of cytosolic nucleotide phosphoanhydride bonds, although no immediate change occurs in either the nucleotide pool size or the concentrations of extracellular end products of AMP catabolism. Titrimetric curves of the extent of hydrolysis coincide with curves for loss of cell viability, e.g., reduction in the adenylate energy charge from 0.8 to 0.1-0.2 accompanies loss of 99% of the bacterial CFU. The oxidative damage caused by HOCl is irreversible within 100 ms of exposure of the organism, although nucleotide phosphate bond hydrolysis requires several minutes to reach completion. Neither HOCl nor NH2Cl reacts directly with nucleotides to hydrolyze phosphoanhydride bonds. Loss of viability is also accompanied by inhibition of induction of beta-galactosidase. The proton motive force, determined from the distribution of 14C-radiolabeled lipophilic ions, declines with incremental addition of HOCl after loss of respiratory function; severalfold more oxidant is required for the dissipation of the proton motive force than for loss of viability. These observations establish a causal link between loss of metabolic energy and cellular death and indicate that the mechanisms of oxidant-induced nucleotide phosphate bond hydrolysis are indirect and that they probably involve damage to the energy-transducing and transport proteins located in the bacterial plasma membrane. PMID:2820883

Dietary and plant polyphenols exert neuroprotective effects and improve cognitive function in cerebral ischemia.

PubMed

Panickar, Kiran S; Jang, Saebyeol

2013-08-01

Cerebral ischemia is caused by an interruption of blood flow to the brain which generally leads to irreversible brain damage. Ischemic injury is associated with vascular leakage, inflammation, tissue injury, and cell death. Cellular changes associated with ischemia include impairment of metabolism, energy failure, free radical production, excitotoxicity, altered calcium homeostasis, and activation of proteases all of which affect brain functioning and also contribute to longterm disabilities including cognitive decline. Inflammation, mitochondrial dysfunction, increased oxidative/nitrosative stress, and intracellular calcium overload contribute to brain injury including cell death and brain edema. However, there is a paucity of agents that can effectively reduce cerebral damage and hence considerable attention has focused on developing newer agents with more efficacy and fewer side-effects. Polyphenols are natural compounds with variable phenolic structures and are rich in vegetables, fruits, grains, bark, roots, tea, and wine. Most polyphenols have antioxidant, anti-inflammatory, and anti-apoptotic properties and their protective effects on mitochondrial functioning, glutamate uptake, and regulating intracellular calcium levels in ischemic injury in vitro have been demonstrated. This review will assess the current status of the potential effects of polyphenols in reducing cerebral injury and improving cognitive function in ischemia in animal and human studies. In addition, the review will also examine available patents in nutrition and agriculture that relates to cerebral ischemic injury with an emphasis on plant polyphenols.

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).

Temperature evaluation of dental implant surface irradiated with high-power diode laser.

PubMed

Rios, F G; Viana, E R; Ribeiro, G M; González, J C; Abelenda, A; Peruzzo, D C

2016-09-01

The prevalence of peri-implantitis and the absence of a standard approach for decontamination of the dental implant surface have led to searches for effective therapies. Since the source of diode lasers is portable, has reduced cost, and does not cause damage to the titanium surface of the implant, high-power diode lasers have been used for this purpose. The effect of laser irradiation on the implants is the elevation of the temperature surface. If this elevation exceeds 47 °C, the bone tissue is irreversibly damaged, so for a safety therapy, the laser parameters should be controlled. In this study, a diode laser of GaAsAl was used to irradiate titanium dental implants, for powers 1.32 to 2.64 W (real) or 2.00 to 4.00 W (nominal), in continuous/pulsed mode DC/AC, with exposure time of 5/10 s, with/without air flow for cooling. The elevation of the temperature was monitored in real time in two positions: cervical and apical. The best results for decontamination using a 968-nm diode laser were obtained for a power of 1.65 and 1.98 W (real) for 10 s, in DC or AC mode, with an air flow of 2.5 l/min. In our perspective in this article, we determine a suggested approach for decontamination of the dental implant surface using a 968-nm diode laser.

Irradiation response of commercial, high-Tc superconducting tapes: Electromagnetic transport properties

DOE PAGES

Gapud, A. A.; Greenwood, N. T.; Alexander, J. A.; ...

2015-07-01

Effects of low dose irradiation on the electrical transport current properties of commercially available high-temperature superconducting, coated-conductor tapes were investigated, in view of potential applications in the irradiative environment of fusion reactors. Three different tapes, each with unique as-grown flux-pinning structures, were irradiated with Au and Ni ions at energies that provide a range of damage effects, with accumulated damage levels near that expected for conductors in a fusion reactor environment. Measurements using transport current determined the pre- and post-irradiation resistivity, critical current density, and pinning force density, yielding critical temperatures, irreversibility lines, and inferred vortex creep rates. Results showmore » that at the irradiation damage levels tested, any detriment to as-grown pre-irradiation properties is modest; indeed in one case already-superior pinning forces are enhanced, leading to higher critical currents.« less

Modeling of skin cooling, blood flow, and optical properties in wounds created by electrical shock

NASA Astrophysics Data System (ADS)

Nguyen, Thu T. A.; Shupp, Jeffrey W.; Moffatt, Lauren T.; Jordan, Marion H.; Jeng, James C.; Ramella-Roman, Jessica C.

2012-02-01

High voltage electrical injuries may lead to irreversible tissue damage or even death. Research on tissue injury following high voltage shock is needed and may yield stage-appropriate therapy to reduce amputation rate. One of the mechanisms by which electricity damages tissue is through Joule heating, with subsequent protein denaturation. Previous studies have shown that blood flow had a significant effect on the cooling rate of heated subcutaneous tissue. To assess the thermal damage in tissue, this study focused on monitoring changes of temperature and optical properties of skin next to high voltage wounds. The burns were created between left fore limb and right hind limb extremities of adult male Sprague-Dawley rats by a 1000VDC delivery shock system. A thermal camera was utilized to record temperature variation during the exposure. The experimental results were then validated using a thermal-electric finite element model (FEM).

Brain caspase-3 and intestinal FABP responses in preterm and term rats submitted to birth asphyxia.

PubMed

Figueira, R L; Gonçalves, F L; Simões, A L; Bernardino, C A; Lopes, L S; Castro E Silva, O; Sbragia, L

2016-06-23

Neonatal asphyxia can cause irreversible injury of multiple organs resulting in hypoxic-ischemic encephalopathy and necrotizing enterocolitis (NEC). This injury is dependent on time, severity, and gestational age, once the preterm babies need ventilator support. Our aim was to assess the different brain and intestinal effects of ischemia and reperfusion in neonate rats after birth anoxia and mechanical ventilation. Preterm and term neonates were divided into 8 subgroups (n=12/group): 1) preterm control (PTC), 2) preterm ventilated (PTV), 3) preterm asphyxiated (PTA), 4) preterm asphyxiated and ventilated (PTAV), 5) term control (TC), 6) term ventilated (TV), 7) term asphyxiated (TA), and 8) term asphyxiated and ventilated (TAV). We measured body, brain, and intestine weights and respective ratios [(BW), (BrW), (IW), (BrW/BW) and (IW/BW)]. Histology analysis and damage grading were performed in the brain (cortex/hippocampus) and intestine (jejunum/ileum) tissues, as well as immunohistochemistry analysis for caspase-3 and intestinal fatty acid-binding protein (I-FABP). IW was lower in the TA than in the other terms (P<0.05), and the IW/BW ratio was lower in the TA than in the TAV (P<0.005). PTA, PTAV and TA presented high levels of brain damage. In histological intestinal analysis, PTAV and TAV had higher scores than the other groups. Caspase-3 was higher in PTAV (cortex) and TA (cortex/hippocampus) (P<0.005). I-FABP was higher in PTAV (P<0.005) and TA (ileum) (P<0.05). I-FABP expression was increased in PTAV subgroup (P<0.0001). Brain and intestinal responses in neonatal rats caused by neonatal asphyxia, with or without mechanical ventilation, varied with gestational age, with increased expression of caspase-3 and I-FABP biomarkers.

Brain caspase-3 and intestinal FABP responses in preterm and term rats submitted to birth asphyxia

PubMed Central

Figueira, R.L.; Gonçalves, F.L.; Simões, A.L.; Bernardino, C.A.; Lopes, L.S.; Castro e Silva, O.; Sbragia, L.

2016-01-01

Neonatal asphyxia can cause irreversible injury of multiple organs resulting in hypoxic-ischemic encephalopathy and necrotizing enterocolitis (NEC). This injury is dependent on time, severity, and gestational age, once the preterm babies need ventilator support. Our aim was to assess the different brain and intestinal effects of ischemia and reperfusion in neonate rats after birth anoxia and mechanical ventilation. Preterm and term neonates were divided into 8 subgroups (n=12/group): 1) preterm control (PTC), 2) preterm ventilated (PTV), 3) preterm asphyxiated (PTA), 4) preterm asphyxiated and ventilated (PTAV), 5) term control (TC), 6) term ventilated (TV), 7) term asphyxiated (TA), and 8) term asphyxiated and ventilated (TAV). We measured body, brain, and intestine weights and respective ratios [(BW), (BrW), (IW), (BrW/BW) and (IW/BW)]. Histology analysis and damage grading were performed in the brain (cortex/hippocampus) and intestine (jejunum/ileum) tissues, as well as immunohistochemistry analysis for caspase-3 and intestinal fatty acid-binding protein (I-FABP). IW was lower in the TA than in the other terms (P<0.05), and the IW/BW ratio was lower in the TA than in the TAV (P<0.005). PTA, PTAV and TA presented high levels of brain damage. In histological intestinal analysis, PTAV and TAV had higher scores than the other groups. Caspase-3 was higher in PTAV (cortex) and TA (cortex/hippocampus) (P<0.005). I-FABP was higher in PTAV (P<0.005) and TA (ileum) (P<0.05). I-FABP expression was increased in PTAV subgroup (P<0.0001). Brain and intestinal responses in neonatal rats caused by neonatal asphyxia, with or without mechanical ventilation, varied with gestational age, with increased expression of caspase-3 and I-FABP biomarkers. PMID:27356106

Vision restoration after brain and retina damage: the "residual vision activation theory".

PubMed

Sabel, Bernhard A; Henrich-Noack, Petra; Fedorov, Anton; Gall, Carolin

2011-01-01

Vision loss after retinal or cerebral visual injury (CVI) was long considered to be irreversible. However, there is considerable potential for vision restoration and recovery even in adulthood. Here, we propose the "residual vision activation theory" of how visual functions can be reactivated and restored. CVI is usually not complete, but some structures are typically spared by the damage. They include (i) areas of partial damage at the visual field border, (ii) "islands" of surviving tissue inside the blind field, (iii) extrastriate pathways unaffected by the damage, and (iv) downstream, higher-level neuronal networks. However, residual structures have a triple handicap to be fully functional: (i) fewer neurons, (ii) lack of sufficient attentional resources because of the dominant intact hemisphere caused by excitation/inhibition dysbalance, and (iii) disturbance in their temporal processing. Because of this resulting activation loss, residual structures are unable to contribute much to everyday vision, and their "non-use" further impairs synaptic strength. However, residual structures can be reactivated by engaging them in repetitive stimulation by different means: (i) visual experience, (ii) visual training, or (iii) noninvasive electrical brain current stimulation. These methods lead to strengthening of synaptic transmission and synchronization of partially damaged structures (within-systems plasticity) and downstream neuronal networks (network plasticity). Just as in normal perceptual learning, synaptic plasticity can improve vision and lead to vision restoration. This can be induced at any time after the lesion, at all ages and in all types of visual field impairments after retinal or brain damage (stroke, neurotrauma, glaucoma, amblyopia, age-related macular degeneration). If and to what extent vision restoration can be achieved is a function of the amount of residual tissue and its activation state. However, sustained improvements require repetitive stimulation which, depending on the method, may take days (noninvasive brain stimulation) or months (behavioral training). By becoming again engaged in everyday vision, (re)activation of areas of residual vision outlasts the stimulation period, thus contributing to lasting vision restoration and improvements in quality of life. Copyright © 2011 Elsevier B.V. All rights reserved.

Magnetic irreversibility: An important amendment in the zero-field-cooling and field-cooling method

NASA Astrophysics Data System (ADS)

Teixeira Dias, Fábio; das Neves Vieira, Valdemar; Esperança Nunes, Sabrina; Pureur, Paulo; Schaf, Jacob; Fernanda Farinela da Silva, Graziele; de Paiva Gouvêa, Cristol; Wolff-Fabris, Frederik; Kampert, Erik; Obradors, Xavier; Puig, Teresa; Roa Rovira, Joan Josep

2016-02-01

The present work reports about experimental procedures to correct significant deviations of magnetization data, caused by magnetic relaxation, due to small field cycling by sample transport in the inhomogeneous applied magnetic field of commercial magnetometers. The extensively used method for measuring the magnetic irreversibility by first cooling the sample in zero field, switching on a constant applied magnetic field and measuring the magnetization M(T) while slowly warming the sample, and subsequently measuring M(T) while slowly cooling it back in the same field, is very sensitive even to small displacement of the magnetization curve. In our melt-processed YBaCuO superconducting sample we observed displacements of the irreversibility limit up to 7 K in high fields. Such displacements are detected only on confronting the magnetic irreversibility limit with other measurements, like for instance zero resistance, in which the sample remains fixed and so is not affected by such relaxation. We measured the magnetic irreversibility, Tirr(H), using a vibrating sample magnetometer (VSM) from Quantum Design. The zero resistance data, Tc0(H), were obtained using a PPMS from Quantum Design. On confronting our irreversibility lines with those of zero resistance, we observed that the Tc0(H) data fell several degrees K above the Tirr(H) data, which obviously contradicts the well known properties of superconductivity. In order to get consistent Tirr(H) data in the H-T plane, it was necessary to do a lot of additional measurements as a function of the amplitude of the sample transport and extrapolate the Tirr(H) data for each applied field to zero amplitude.

Evaluation of Nd:YAG laser on partial oxygen saturation of pulpal blood in anterior hypersensitive teeth.

PubMed

Birang, Reza; Kaviani, Naser; Mohammadpour, Mehdi; Abed, Ahmad Moghareh; Gutknecht, Norbert; Mir, Maziar

2008-07-01

Dentine hypersensitivity has of long been known to be a common clinical problem in dental practices. Lasers have recently come to play a prominent role in the treatment of this disorder. They might, however, cause dental pulp damage. This study was conducted to evaluate the effect of Nd:yttrium-aluminum-garnet (YAG) laser on partial oxygen saturation of pulpal blood in sensitive anterior teeth. In this clinical trial, 65 hypersensitive teeth were selected and randomly allocated to two groups. The study group involved Nd:YAG laser treatment, while no treatment was employed for the control group. Using a pulse oximetry system, evaluations were preformed of the partial oxygen saturation in the pulpal blood before, immediately after, 1 week after, and 1 month after the treatment. The results were analyzed using the SPSS software and repeated-measures analysis of variance and paired-samples t tests. The mean partial oxygen saturation of the blood was found to be 85.4% in the study group, which was not significantly different from that of the control group. No significant differences were observed in the control group between the means obtained from pretreatment and post-treatment intervals (P > 0.05). The Post-treatment partial oxygen saturation mean rose to 89.3% (P = 0.001) and remained constant throughout the following week after it. However, no significant differences were found between the pretreatment partial oxygen saturation mean and the same measurement 1 month after treatment (P = 0.702). Nd:YAG laser therapy for dentine desensitization of anterior teeth caused no persistent changes in the partial oxygen saturation of pulpal blood. It may, therefore, be concluded that the diffusion of heat induced by the Nd:YAG laser into the pulp within the limit of the desensitization parameters cause no irreversible damages in the dental pulp.

Effects of electrolysis by low-amperage electric current on the chlorophyll fluorescence characteristics of Microcystis aeruginosa.

PubMed

Lin, Li; Feng, Cong; Li, Qingyun; Wu, Min; Zhao, Liangyuan

2015-10-01

Effects of electrolysis by low-amperage electric current on the chlorophyll fluorescence characteristics of Microcystis aeruginosa were investigated in order to reveal the mechanisms of electrolytic inhibition of algae. Threshold of current density was found under a certain initial no. of algae cell. When current density was equal to or higher than the threshold (fixed electrolysis time), growth of algae was inhibited completely and the algae lost the ability to survive. Effect of algal solution volume on algal inhibition was insignificant. Thresholds of current density were 8, 10, 14, 20, and 22 mA cm(-2) at 2.5 × 10(7), 5 × 10(7), 1 × 10(8), 2.5 × 10(8), and 5 × 10(8) cells mL(-1) initial no. of algae cell, respectively. Correlativity between threshold of current and initial no. of algae cells was established for scale-up and determining operating conditions. Changes of chlorophyll fluorescence parameters demonstrated that photosystem (PS) II of algae was damaged by electrolysis but still maintained relatively high activity when algal solution was treated by current densities lower than the threshold. The activity of algae recovered completely after 6 days of cultivation. On the contrary, when current density was higher than the threshold, connection of phycobilisome (PBS) and PS II core complexes was destroyed, PS II system of algae was damaged irreversibly, and algae could not survive thoroughly. The inactivation of M. aeruginosa by electrolysis can be attributed to irreversible separation of PBS from PS II core complexes and the damage of PS II of M. aeruginosa.

Irreversible Electroporation in a Swine Lung Model

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

Dupuy, Damian E., E-mail: ddupuy@lifespan.org; Aswad, Bassam, E-mail: baswad@lifespan.org; Ng, Thomas, E-mail: tng@usasurg.org

2011-04-15

Purpose: This study was designed to evaluate the safety and tissue effects of IRE in a swine lung model. Methods: This study was approved by the institutional animal care committee. Nine anesthetized domestic swine underwent 15 percutaneous irreversible electroporation (IRE) lesion creations (6 with bipolar and 3 with 3-4 monopolar electrodes) under fluoroscopic guidance and with pancuronium neuromuscular blockade and EKG gating. IRE electrodes were placed into the central and middle third of the right mid and lower lobes in all animals. Postprocedure PA and lateral chest radiographs were obtained to evaluate for pneumothorax. Three animals were sacrificed at 2more » weeks and six at 4 weeks. Animals underwent high-resolution CT scanning and PA and lateral radiographs 1 h before sacrifice. The treated lungs were removed en bloc, perfused with formalin, and sectioned. Gross pathologic and microscopic changes after standard hematoxylin and eosin staining were analyzed within the areas of IRE lesion creation. Results: No significant adverse events were identified. CT showed focal areas of spiculated high density ranging in greatest diameter from 1.1-2.2 cm. On gross inspection of the sectioned lung, focal areas of tan discoloration and increased density were palpated in the areas of IRE. Histological analysis revealed focal areas of diffuse alveolar damage with fibrosis and inflammatory infiltration that respected the boundaries of the interlobular septae. No pathological difference could be discerned between the 2- and 4-week time points. The bronchioles and blood vessels within the areas of IRE were intact and did not show signs of tissue injury. Conclusion: IRE creates focal areas of diffuse alveolar damage without creating damage to the bronchioles or blood vessels. Short-term safety in a swine model appears to be satisfactory.« less

Endogenous E. coli endophthalmitis.

PubMed

Shammas, H F

1977-01-01

A case of Escherichia coli septicemia with associated metastatic en dophthalmitis and endocarditis is presented. The ocular signs and symptoms were the initial manifestations of sepsis. Irreversible damage to the eye occurred in less than 24 hours. The pattern of metastatic bacterial endophthalmitis has changed since the introduction of potent antimicrobial agents, with an increased incidence of Gram-negative bacillemia. E. coli endophthalmitis carries a poor prognosis. Early diagnosis and systemic treatment will prevent the life-threatening complications of sepsis.

Instabilities of Damage and Surface Degradation Mechanisms in Brittle Material Structural Systems

DTIC Science & Technology

1992-03-15

I INTRODUCTION AND SCOPE 1.1 General Brittle materials such as rock and concrete contain a multitude of defects in the form of micro-voids and/or...micro-cracks even before any external load is applied. The term "structure" is associated with such defects . During a loading- unloading process, these...voids/cracks may undergo irreversible growth and new ones may nucleate. The ultimate coalescence of such defects may result in macro- crack initiation

Optical fluorescence biosensor for plant water stress detection

NASA Astrophysics Data System (ADS)

Chong, Jenny P. C.; Liew, O. W.; Li, B. Q.; Asundi, A. K.

2007-05-01

Precision farming in arable agriculture and horticulture allows conservative use of resources that are applied according to plant needs. The growing concern for sustainability in crop production has accentuated the significance of our work to develop a rapid, sensitive and non-destructive spectroscopic method for real-time monitoring of plant water stress. Elucidation of crop water status before the onset of irreversible cellular damage is critical for effective water management to ensure maximum crop yield and profit margin. A two-component bio-sensing system comprising transgenic 'Indicator Plants' and a spectrometer-linked stereoscopic microscope was developed to detect early signs of water stress before the permanent wilting point is reached. The 'Indicator Plants' are transgenic Petunia hybrida genetically engineered with a drought-responsive promoter-linked enhanced green fluorescent protein marker gene (EGFP). No EGFP fluorescence was detected prior to induction of dehydration stress. Fluorescence emission intensity increased with dehydration period and was found mainly in the stems, leaf veins and leaf tips. While fluorescence emission above endogenous background was detectable after 2 hours of water stress treatment, the plants reached permanent wilting point after 6 hours, showing that our system was able to detect water stress prior to plant entry into the stage of irreversible damage. Future work will be geared towards overcoming biological and instrument-related difficulties encountered in our initial detection system.

Electron transfer processes occurring on platinum neural stimulating electrodes: pulsing experiments for cathodic-first/charge-balanced/biphasic pulses for 0.566 ≤ k ≤ 2.3 in oxygenated and deoxygenated sulfuric acid.

PubMed

Kumsa, Doe W; Montague, Fred W; Hudak, Eric M; Mortimer, J Thomas

2016-10-01

The application of a train of cathodic-first/charge-balanced/biphasic pulses applied to a platinum electrode resulted in a positive creep of the anodic phase potential that increases with increasing charge injection but reaches a steady-state value before 1000 pulses have been delivered. The increase follows from the fact that charge going into irreversible reactions occurring during the anodic phase must equal the charge going into irreversible reactions during the cathodic phase for charge-balanced pulses. In an oxygenated electrolyte the drift of the measured positive potential moved into the platinum oxidation region of the i(V e) profile when the charge injection level exceeds k = 1.75. Platinum dissolution may occur in this region and k = 1.75 defines a boundary between damaging and non-damaging levels on the Shannon Plot. In a very low oxygen environment, the positive potential remained below the platinum oxidation region for the highest charge injection values studied, k = 2.3. The results support the hypothesis that platinum dissolution is the defining factor for the Shannon limit, k = 1.75. Numerous instrumentation issues were encountered in the course of making measurements. The solutions to these issues are provided.

Stochastic integrated assessment of climate tipping points indicates the need for strict climate policy

NASA Astrophysics Data System (ADS)

Lontzek, Thomas S.; Cai, Yongyang; Judd, Kenneth L.; Lenton, Timothy M.

2015-05-01

Perhaps the most `dangerous’ aspect of future climate change is the possibility that human activities will push parts of the climate system past tipping points, leading to irreversible impacts. The likelihood of such large-scale singular events is expected to increase with global warming, but is fundamentally uncertain. A key question is how should the uncertainty surrounding tipping events affect climate policy? We address this using a stochastic integrated assessment model, based on the widely used deterministic DICE model. The temperature-dependent likelihood of tipping is calibrated using expert opinions, which we find to be internally consistent. The irreversible impacts of tipping events are assumed to accumulate steadily over time (rather than instantaneously), consistent with scientific understanding. Even with conservative assumptions about the rate and impacts of a stochastic tipping event, today’s optimal carbon tax is increased by ~50%. For a plausibly rapid, high-impact tipping event, today’s optimal carbon tax is increased by >200%. The additional carbon tax to delay climate tipping grows at only about half the rate of the baseline carbon tax. This implies that the effective discount rate for the costs of stochastic climate tipping is much lower than the discount rate for deterministic climate damages. Our results support recent suggestions that the costs of carbon emission used to inform policy are being underestimated, and that uncertain future climate damages should be discounted at a low rate.

A Topical Mitochondria-Targeted Redox Cycling Nitroxide Mitigates Oxidative Stress Induced Skin Damage

PubMed Central

Brand, Rhonda M.; Epperly, Michael W.; Stottlemyer, J. Mark; Skoda, Erin M.; Gao, Xiang; Li, Song; Huq, Saiful; Wipf, Peter; Kagan, Valerian E.; Greenberger, Joel S.; Falo, Louis D.

2017-01-01

Skin is the largest human organ and provides a first line of defense that includes physical, chemical, and immune mechanisms to combat environmental stress. Radiation is a prevalent environmental stressor. Radiation induced skin damage ranges from photoaging and cutaneous carcinogenesis from UV exposure, to treatment-limiting radiation dermatitis associated with radiotherapy, to cutaneous radiation syndrome, a frequently fatal consequence of exposures from nuclear accidents. The major mechanism of skin injury common to these exposures is radiation induced oxidative stress. Efforts to prevent or mitigate radiation damage have included development of antioxidants capable of reducing reactive oxygen species (ROS). Mitochondria are particularly susceptible to oxidative stress, and mitochondrial dependent apoptosis plays a major role in radiation induced tissue damage. We reasoned that targeting a redox cycling nitroxide to mitochondria could prevent ROS accumulation, limiting downstream oxidative damage and preserving mitochondrial function. Here we show that in both mouse and human skin, topical application of a mitochondrial targeted antioxidant prevents and mitigates radiation induced skin damage characterized by clinical dermatitis, loss of barrier function, inflammation, and fibrosis. Further, damage mitigation is associated with reduced apoptosis, preservation of the skin’s antioxidant capacity, and reduction of irreversible DNA and protein oxidation associated with oxidative stress. PMID:27794421

Learning from myocarditis: mimicry, chaos and black holes

PubMed Central

Rose, Noel R.

2014-01-01

Autoimmune myocarditis and its sequel, dilated cardiomyopathy, are major causes of heart failure, especially in children and young adults. We have developed animal models to investigate their pathogenesis by infecting genetically susceptible mice with coxsackievirus B3 or by immunizing them with cardiac myosin or its immunodominant peptide. A number of valuable lessons have emerged from our study of this paradigm of an infection-induced autoimmune disease. We understand more clearly how natural autoimmunity, as an important component of normal physiology, must be recalibrated regularly due to changes caused by infection or other internal and external stimuli. A new normal homeostatic platform will be established based on its evolutionary fitness. A loss of homeostasis with out-of-control normal autoimmunity leads to autoimmune disease. It is signified early on by a spread of an adaptive autoimmune response to novel epitopes and neighboring antigens. The progression from infection to normal, well-balanced autoimmunity to autoimmune disease and on to irreversible damage is a complex, step-wise process. Yet, chaos theory provides hope that the pattern is potentially predictable. Infection-induced autoimmune disease represents a sequence of events heading for a train wreck at the end of the line. Our aim in autoimmune disease research must be to stop the train before this happens. PMID:24904749

Learning from myocarditis: mimicry, chaos and black holes.

PubMed

Rose, Noel R

2014-01-01

Autoimmune myocarditis and its sequel, dilated cardiomyopathy, are major causes of heart failure, especially in children and young adults. We have developed animal models to investigate their pathogenesis by infecting genetically susceptible mice with coxsackievirus B3 or by immunizing them with cardiac myosin or its immunodominant peptide. A number of valuable lessons have emerged from our study of this paradigm of an infection-induced autoimmune disease. We understand more clearly how natural autoimmunity, as an important component of normal physiology, must be recalibrated regularly due to changes caused by infection or other internal and external stimuli. A new normal homeostatic platform will be established based on its evolutionary fitness. A loss of homeostasis with out-of-control normal autoimmunity leads to autoimmune disease. It is signified early on by a spread of an adaptive autoimmune response to novel epitopes and neighboring antigens. The progression from infection to normal, well-balanced autoimmunity to autoimmune disease and on to irreversible damage is a complex, step-wise process. Yet, chaos theory provides hope that the pattern is potentially predictable. Infection-induced autoimmune disease represents a sequence of events heading for a train wreck at the end of the line. Our aim in autoimmune disease research must be to stop the train before this happens.

Diabetic retinopathy: could the alpha-1 antitrypsin be a therapeutic option?

PubMed

Ortiz, Gustavo; Salica, Juan P; Chuluyan, Eduardo H; Gallo, Juan E

2014-11-18

Diabetic retinopathy is one of the most important causes of blindness. The underlying mechanisms of this disease include inflammatory changes and remodeling processes of the extracellular-matrix (ECM) leading to pericyte and vascular endothelial cell damage that affects the retinal circulation. In turn, this causes hypoxia leading to release of vascular endothelial growth factor (VEGF) to induce the angiogenesis process. Alpha-1 antitrypsin (AAT) is the most important circulating inhibitor of serine proteases (SERPIN). Its targets include elastase, plasmin, thrombin, trypsin, chymotrypsin, proteinase 3 (PR-3) and plasminogen activator (PAI). AAT modulates the effect of protease-activated receptors (PARs) during inflammatory responses. Plasma levels of AAT can increase 4-fold during acute inflammation then is so-called acute phase protein (APPs). Individuals with low serum levels of AAT could develop disease in lung, liver and pancreas. AAT is involved in extracellular matrix remodeling and inflammation, particularly migration and chemotaxis of neutrophils. It can also suppress nitric oxide (NO) by nitric oxide sintase (NOS) inhibition. AAT binds their targets in an irreversible way resulting in product degradation. The aim of this review is to focus on the points of contact between multiple factors involved in diabetic retinopathy and AAT resembling pleiotropic effects that might be beneficial.

The neuromuscular activity of Micrurus pyrrhocryptus venom and its neutralization by commercial and specific coral snake antivenoms.

PubMed

Camargo, Thiago Magalhães; de Roodt, Adolfo Rafael; da Cruz-Höfling, Maria Alice; Rodrigues-Simioni, Léa

2011-01-01

The neuromuscular activity ofMicrurus pyrrochryptus venom was studied in chick biventer cervicis (BC) and mouse phrenic nerve-diaphragm (PND) preparations. The venom (0.5-50μg/ml) caused irreversible, time- and concentration-dependent blockade, with BC being more sensitive than PND (50% blockade with 10μg/ml in 22±;3min and 62±4min, respectively; mean±SEM, n=6; p<0.05). In BC preparations, venom (0.5μg/ml) progressively abolished ACh-induced contractures, whereas contractures to exogenous KCl and muscle twitches in curarized preparations were unaffected. The venom neither altered creatine kinase release (venom: 25.8±1.75IU/l vs control: 24.3±2.2IU/l, n=6, after 120min), nor it caused significant muscle damage (50μg of venom/ml vs control: 3.5±0.8% vs 1.1±0.7% for PND; 4.3±1.5% vs 1.2±0.5% for BC, n=5). The venom had low PLA(2) activity. Neurotoxicity was effectively neutralized by commercial Micrurus antivenom and specific antivenom. These findings indicate that M. pyrrhocryptus venom acts postsynaptically on nicotinic receptors, with no significant myotoxicity.

Longitudinal analysis of hearing loss in a case of hemosiderosis of the central nervous system.

PubMed

Weekamp, H H; Huygen, P L M; Merx, J L; Kremer, H P H; Cremers, Cor W R J; Longridge, Neil S

2003-09-01

To describe cochleovestibular aspects of superficial hemosiderosis of the central nervous system. Superficial hemosiderosis of the central nervous system is a rare disease in which cochleovestibular impairment, cerebellar ataxia, and myelopathy are the most frequent signs. Chronic recurrent subarachnoidal hemorrhage with bleeding into the cerebrospinal fluid is the cause of deposition of hemosiderin in leptomeningeal and subpial tissue, cranial nerves, and spinal cord. Removing the cause of bleeding can prevent irreversible damage to these structures. Because this is the only effective treatment, an early diagnosis is crucial. Retrospective case review. Tertiary referral center. A 72-year-old woman with superficial hemosiderosis of the central nervous system that developed when she was age 39. Neurologic and imaging diagnostic examinations and longitudinal evaluation of cochleovestibular features were performed. Neurosurgery was not performed. Progressive bilateral sensorineural hearing loss and severe vestibular hyporeflexia developed within 15 years, which can be attributed to lesions in the cochleovestibular system. Additional pathology of the central nervous system developed later. The patient demonstrated cochlear and vestibular findings that are typical of this pathologic condition. It is the first documented case with extensive serial audiometry used to precisely outline the degree of hearing deterioration during the course of the disease.

Intrapulpal temperatures during pulsed Nd:YAG laser treatment of dentin, in vitro.

PubMed

White, J M; Fagan, M C; Goodis, H E

1994-03-01

Lasers are being used for soft tissue removal, caries removal, and treatment of root surface sensitivity. One concern for laser safety is that the heat produced at the irradiated root surface may diffuse to the pulp causing irreversible pulpal damage. To test this heat diffusion, copper-constantan thermocouples were inserted into the radicular pulp canals of extracted teeth. Simulating direct exposure which might occur during gingival excision, superficial caries removal, and modification of the dentin surface for treatment of root surface sensitivity, a 2 mm2 area of the external root surface was uniformly irradiated with a pulsed Nd:YAG laser using a 320 microns diameter fiber optic contact probe. Power was varied from 0.3 to 3.0 W with frequencies of 10 and 20 Hz. Temperature changes during cavity preparations using a high speed handpiece with air coolant were also recorded. Repeated measures ANOVA (P < or = 0.05) indicated that intrapulpal temperatures increased as a function of power, frequency, and time. Intrapulpal temperatures decreased as remaining dentin thickness (0.2 to 2.0 mm) increased for each laser parameter. Irradiation of dentin using a Nd:YAG pulsed laser, within the treatment times, powers, and frequencies with adequate remaining dentin thickness, as outlined in this paper, should not cause devitalizing intrapulpal temperature rises.

Exploratory urinary metabolomics of type 1 leprosy reactions.

PubMed

Mayboroda, Oleg A; van Hooij, Anouk; Derks, Rico; van den Eeden, Susan J F; Dijkman, Karin; Khadge, Saraswoti; Thapa, Pratibha; Kunwar, Chhatra B; Hagge, Deanna A; Geluk, Annemieke

2016-04-01

Leprosy is an infectious disease caused by Mycobacterium leprae that affects the skin and nerves. Although curable with multidrug therapy, leprosy is complicated by acute inflammatory episodes called reactions, which are the major causes of irreversible neuropathy in leprosy that occur before, during, and even after treatment. Early diagnosis and prompt treatment of reactions reduces the risk of permanent disability. This exploratory study investigated whether urinary metabolic profiles could be identified that correlate with early signs of reversal reactions (RR). A prospective cohort of leprosy patients with and without reactions and endemic controls was recruited in Nepal. Urine-derived metabolic profiles were measured longitudinally. Thus, a conventional area of biomarker identification for leprosy was extended to non-invasive urine testing. It was found that the urinary metabolome could be used to discriminate endemic controls from untreated patients with mycobacterial disease. Moreover, metabolic signatures in the urine of patients developing RR were clearly different before RR onset compared to those at RR diagnosis. This study indicates that urinary metabolic profiles are promising host biomarkers for the detection of intra-individual changes during acute inflammation in leprosy and could contribute to early treatment and prevention of tissue damage. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

The neuromuscular activity of Micrurus pyrrhocryptus venom and its neutralization by commercial and specific coral snake antivenoms

PubMed Central

Camargo, Thiago Magalhães; de Roodt, Adolfo Rafael; da Cruz-Höfling, Maria Alice; Rodrigues-Simioni, Léa

2011-01-01

The neuromuscular activity ofMicrurus pyrrochryptus venom was studied in chick biventer cervicis (BC) and mouse phrenic nerve-diaphragm (PND) preparations. The venom (0.5-50μg/ml) caused irreversible, time- and concentration-dependent blockade, with BC being more sensitive than PND (50% blockade with 10μg/ml in 22±;3min and 62±4min, respectively; mean±SEM, n=6; p<0.05). In BC preparations, venom (0.5μg/ml) progressively abolished ACh-induced contractures, whereas contractures to exogenous KCl and muscle twitches in curarized preparations were unaffected. The venom neither altered creatine kinase release (venom: 25.8±1.75IU/l vs control: 24.3±2.2IU/l, n=6, after 120min), nor it caused significant muscle damage (50μg of venom/ml vs control: 3.5±0.8% vs 1.1±0.7% for PND; 4.3±1.5% vs 1.2±0.5% for BC, n=5). The venom had low PLA2 activity. Neurotoxicity was effectively neutralized by commercial Micrurus antivenom and specific antivenom. These findings indicate that M. pyrrhocryptus venom acts postsynaptically on nicotinic receptors, with no significant myotoxicity. PMID:21858249

Near-Infrared Excited State Dynamics of Melanins: The Effects of Iron Content, Photo-Damage, Chemical Oxidation, and Aggregate Size

PubMed Central

2015-01-01

Ultrafast pump–probe measurements can discriminate the two forms of melanin found in biological tissue (eumelanin and pheomelanin), which may be useful for diagnosing and grading melanoma. However, recent work has shown that bound iron content changes eumelanin’s pump–probe response, making it more similar to that of pheomelanin. Here we record the pump–probe response of these melanins at a wider range of wavelengths than previous work and show that with shorter pump wavelengths the response crosses over from being dominated by ground-state bleaching to being dominated by excited-state absorption. The crossover wavelength is different for each type of melanin. In our analysis, we found that the mechanism by which iron modifies eumelanin’s pump–probe response cannot be attributed to Raman resonances or differences in melanin aggregation and is more likely caused by iron acting to broaden the unit spectra of individual chromophores in the heterogeneous melanin aggregate. We analyze the dependence on optical intensity, finding that iron-loaded eumelanin undergoes irreversible changes to the pump–probe response after intense laser exposure. Simultaneously acquired fluorescence data suggest that the previously reported “activation” of eumelanin fluorescence may be caused in part by the dissociation of metal ions or the selective degradation of iron-containing melanin. PMID:24446774

Application of exergetic sustainability index to a nano-scale irreversible Brayton cycle operating with ideal Bose and Fermi gasses

NASA Astrophysics Data System (ADS)

Açıkkalp, Emin; Caner, Necmettin

2015-09-01

In this study, a nano-scale irreversible Brayton cycle operating with quantum gasses including Bose and Fermi gasses is researched. Developments in the nano-technology cause searching the nano-scale machines including thermal systems to be unavoidable. Thermodynamic analysis of a nano-scale irreversible Brayton cycle operating with Bose and Fermi gasses was performed (especially using exergetic sustainability index). In addition, thermodynamic analysis involving classical evaluation parameters such as work output, exergy output, entropy generation, energy and exergy efficiencies were conducted. Results are submitted numerically and finally some useful recommendations were conducted. Some important results are: entropy generation and exergetic sustainability index are affected mostly for Bose gas and power output and exergy output are affected mostly for the Fermi gas by x. At the high temperature conditions, work output and entropy generation have high values comparing with other degeneracy conditions.

Biogenic methane, hydrogen escape, and the irreversible oxidation of early Earth.

PubMed

Catling, D C; Zahnle, K J; McKay, C

2001-08-03

The low O2 content of the Archean atmosphere implies that methane should have been present at levels approximately 10(2) to 10(3) parts per million volume (ppmv) (compared with 1.7 ppmv today) given a plausible biogenic source. CH4 is favored as the greenhouse gas that countered the lower luminosity of the early Sun. But abundant CH4 implies that hydrogen escapes to space (upward arrow space) orders of magnitude faster than today. Such reductant loss oxidizes the Earth. Photosynthesis splits water into O2 and H, and methanogenesis transfers the H into CH4. Hydrogen escape after CH4 photolysis, therefore, causes a net gain of oxygen [CO2 + 2H2O --> CH4 + 2O2 --> CO2 + O2 + 4H(upward arrow space)]. Expected irreversible oxidation (approximately 10(12) to 10(13) moles oxygen per year) may help explain how Earth's surface environment became irreversibly oxidized.

An experimental and numerical investigation of phase change electrodes for therapeutic irreversible electroporation.

PubMed

Arena, Christopher B; Mahajan, Roop L; Nichole Rylander, Marissa; Davalos, Rafael V

2013-11-01

Irreversible electroporation (IRE) is a new technology for ablating aberrant tissue that utilizes pulsed electric fields (PEFs) to kill cells by destabilizing their plasma membrane. When treatments are planned correctly, the pulse parameters and location of the electrodes for delivering the pulses are selected to permit destruction of the target tissue without causing thermal damage to the surrounding structures. This allows for the treatment of surgically inoperable masses that are located near major blood vessels and nerves. In select cases of high-dose IRE, where a large ablation volume is desired without increasing the number of electrode insertions, it can become challenging to design a pulse protocol that is inherently nonthermal. To solve this problem we have developed a new electrosurgical device that requires no external equipment or protocol modifications. The design incorporates a phase change material (PCM) into the electrode core that melts during treatment and absorbs heat out of the surrounding tissue. Here, this idea is reduced to practice by testing hollow electrodes filled with gallium on tissue phantoms and monitoring temperature in real time. Additionally, the experimental data generated are used to validate a numerical model of the heat transfer problem, which is then applied to investigate the cooling performance of other classes of PCMs. The results indicate that metallic PCMs, such as gallium, are better suited than organics or salt hydrates for thermal management, because their comparatively higher thermal conductivity aids in heat dissipation. However, the melting point of the metallic PCM must be properly adjusted to ensure that the phase transition is not completed before the end of treatment. When translated clinically, phase change electrodes have the potential to continue to allow IRE to be performed safely near critical structures, even in high-dose cases.

Reversibility and energy dissipation in adiabatic superconductor logic.

PubMed

Takeuchi, Naoki; Yamanashi, Yuki; Yoshikawa, Nobuyuki

2017-03-06

Reversible computing is considered to be a key technology to achieve an extremely high energy efficiency in future computers. In this study, we investigated the relationship between reversibility and energy dissipation in adiabatic superconductor logic. We analyzed the evolution of phase differences of Josephson junctions in the reversible quantum-flux-parametron (RQFP) gate and confirmed that the phase differences can change time reversibly, which indicates that the RQFP gate is physically, as well as logically, reversible. We calculated energy dissipation required for the RQFP gate to perform a logic operation and numerically demonstrated that the energy dissipation can fall below the thermal limit, or the Landauer bound, by lowering operation frequencies. We also investigated the 1-bit-erasure gate as a logically irreversible gate and the quasi-RQFP gate as a physically irreversible gate. We calculated the energy dissipation of these irreversible gates and showed that the energy dissipation of these gate is dominated by non-adiabatic state changes, which are induced by unwanted interactions between gates due to logical or physical irreversibility. Our results show that, in reversible computing using adiabatic superconductor logic, logical and physical reversibility are required to achieve energy dissipation smaller than the Landauer bound without non-adiabatic processes caused by gate interactions.

Detailed Modeling and Irreversible Transfer Process Analysis of a Multi-Element Thermoelectric Generator System

NASA Astrophysics Data System (ADS)

Xiao, Heng; Gou, Xiaolong; Yang, Suwen

2011-05-01

Thermoelectric (TE) power generation technology, due to its several advantages, is becoming a noteworthy research direction. Many researchers conduct their performance analysis and optimization of TE devices and related applications based on the generalized thermoelectric energy balance equations. These generalized TE equations involve the internal irreversibility of Joule heating inside the thermoelectric device and heat leakage through the thermoelectric couple leg. However, it is assumed that the thermoelectric generator (TEG) is thermally isolated from the surroundings except for the heat flows at the cold and hot junctions. Since the thermoelectric generator is a multi-element device in practice, being composed of many fundamental TE couple legs, the effect of heat transfer between the TE couple leg and the ambient environment is not negligible. In this paper, based on basic theories of thermoelectric power generation and thermal science, detailed modeling of a thermoelectric generator taking account of the phenomenon of energy loss from the TE couple leg is reported. The revised generalized thermoelectric energy balance equations considering the effect of heat transfer between the TE couple leg and the ambient environment have been derived. Furthermore, characteristics of a multi-element thermoelectric generator with irreversibility have been investigated on the basis of the new derived TE equations. In the present investigation, second-law-based thermodynamic analysis (exergy analysis) has been applied to the irreversible heat transfer process in particular. It is found that the existence of the irreversible heat convection process causes a large loss of heat exergy in the TEG system, and using thermoelectric generators for low-grade waste heat recovery has promising potential. The results of irreversibility analysis, especially irreversible effects on generator system performance, based on the system model established in detail have guiding significance for the development and application of thermoelectric generators, particularly for the design and optimization of TE modules.

Contribution of inflammatory pathways to Fabry disease pathogenesis.

PubMed

Rozenfeld, Paula; Feriozzi, Sandro

2017-11-01

Lysosomal storage diseases are usually considered to be pathologies in which the passive deposition of unwanted materials leads to functional changes in lysosomes. Lysosomal deposition of unmetabolized glycolipid substrates stimulates the activation of pathogenic cascades, including immunological processes, and particularly the activation of inflammation. In lysosomal storage diseases, the inflammatory response is continuously being activated because the stimulus cannot be eliminated. Consequently, inflammation becomes a chronic process. Lysosomes play a role in many steps of the immune response. Leukocyte perturbation and over-expression of immune molecules have been reported in Fabry disease. Innate immunity is activated by signals originating from dendritic cells via interactions between toll-like receptors and globotriaosylceramide (Gb3) and/or globotriaosylsphingosine (lyso-Gb3). Evidence indicates that these glycolipids can activate toll-like receptors, thus triggering inflammation and fibrosis cascades. In the kidney, Gb3 deposition is associated with the increased release of transforming growth factor beta and with epithelial-to-mesenchymal cell transition, leading to the over-expression of pro-fibrotic molecules and to renal fibrosis. Interstitial fibrosis is also a typical feature of heart involvement in Fabry disease. Endomyocardial biopsies show infiltration of lymphocytes and macrophages, suggesting a role for inflammation in causing tissue damage. Inflammation is present in all tissues and may be associated with other potentially pathologic processes such as apoptosis, impaired autophagy, and increases in pro-oxidative molecules, which could all contribute synergistically to tissue damage. In Fabry disease, the activation of chronic inflammation over time leads to organ damage. Therefore, enzyme replacement therapy must be started early, before this process becomes irreversible. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Quercetin-3-O-α-l-arabinopyranoside protects against retinal cell death via blue light-induced damage in human RPE cells and Balb-c mice.

PubMed

Kim, Jun; Jin, Hong Lan; Jang, Dae Sik; Jeong, Kwang Won; Choung, Se-Young

2018-04-25

Age-related macular degeneration (AMD) is among the increasing number of diseases causing irreversible blindness in the elderly. Dry AMD is characterized by the accumulation of lipofuscin in retinal pigment epithelium (RPE) cells. N-Retinylidene-N-retinylethanolamine (A2E), a component of lipofuscin, is oxidized to oxo-A2E under blue light illumination, leading to retinal cell death. The aim of this study was to investigate the protective effect and mechanism of quercetin-3-O-α-l-arabinopyranoside (QA) against blue light (BL)-induced damage in both RPE cells and mice models. Treatment by QA inhibited A2E uptake in RPE cells, as determined by a decrease in fluorescence intensity. QA also protected A2E-laden RPE cells against BL-induced apoptosis. QA inhibited C3 complement activation and poly (ADP-ribose) polymerase (PARP) cleavage, as determined by western blotting. QA showed an inhibitory effect on AP1 and NF-kB activity as estimated in a reporter gene assay. In addition, QA activated the gene expression of aryl hydrocarbon receptor target genes (CYP1A1, CYP1B1) in TCDD-treated RPE cells. In the mice model, oral administration of QA protected against retinal degeneration induced by BL exposure as determined by histological analyses (thickness of retinal layers and immunostaining for caspase-3). In addition, QA inhibited apoptosis and inflammation via inhibition of NF-kB p65 translocation, C3 activation, and PARP cleavage. Collectively, these results revealed the protective mechanism of QA against BL-induced retinal damage both in vitro and in vivo.

Pulmonary Administration of GW0742, a High-Affinity Peroxisome Proliferator-Activated Receptor Agonist, Repairs Collapsed Alveoli in an Elastase-Induced Mouse Model of Emphysema.

PubMed

Ozawa, Chihiro; Horiguchi, Michiko; Akita, Tomomi; Oiso, Yuki; Abe, Kaori; Motomura, Tomoki; Yamashita, Chikamasa

2016-01-01

Pulmonary emphysema is a disease in which lung alveoli are irreversibly damaged, thus compromising lung function. Our previous study revealed that all-trans-retinoic acid (ATRA) induces the differentiation of human lung alveolar epithelial type 2 progenitor cells and repairs the alveoli of emphysema model mice. ATRA also reportedly has the ability to activate peroxisome proliferator-activated receptor (PPAR) β/δ. A selective PPARβ/δ ligand has been reported to induce the differentiation of human keratinocytes during wound repair. Here, we demonstrate that treatment using a high-affinity PPARβ/δ agonist, GW0742, reverses the lung tissue damage induced by elastase in emphysema-model mice and improves respiratory function. Mice treated with elastase, which collapsed their alveoli, were then treated with either 10% dimethyl sulfoxide (DMSO) in saline (control group) or GW0742 (1.0 mg/kg twice a week) by pulmonary administration. Treatment with GW0742 for 2 weeks increased the in vivo expression of surfactant proteins A and D, which are known alveolar type II epithelial cell markers. GW0742 treatment also shortened the average distance between alveolar walls in the lungs of emphysema model mice, compared with a control group treated with 10% DMSO in saline. Treatment with GW0742 for 3 weeks also improved tissue elastance (cm H2O/mL), as well as the ratio of the forced expiratory volume in the first 0.05 s to the forced vital capacity (FEV 0.05/FVC). In each of these experiments, GW0742 treatment reversed the damage caused by elastase. In conclusion, PPARβ/δ agonists are potential therapeutic agents for pulmonary emphysema.

Extravasation of antineoplastic agents: prevention and treatments.

PubMed

Boschi, Rita; Rostagno, Elena

2012-07-31

The extravasation of antineoplastic agents is an unwanted and distressing situation that can easily occur. It may cause severe and irreversible local injuries. Left untreated, vesicant chemotherapy extravasation can potentially cause tissue necrosis, functional impairment and permanent disfigurement. This article provides a review of current literature regarding recommendations on the prevention and treatment of extravasation of antineoplastic agents.

Instrumentation to Support the Research Program of Pulsed Laser Deposition of Polymer Nanocomposite Films

DTIC Science & Technology

2015-05-19

ablated the targets in the same spots during the PLD process. The beams quickly created craters in these spots. That led to cracks and rapid (in...nanoparticles in the near-IR range taken with the newly acquired (with the support from the DoD Grant) UV -VIS-NIR Spectrophotometer Cary from Varian. As...reagent film has the capability of recovering from the exposure to very high ammonia concentrations without experiencing any irreversible damage . Based on

Diagnosis and management of dental erosion.

PubMed

Gandara, B K; Truelove, E L

1999-11-15

Early recognition of dental erosion is important to prevent serious irreversible damage to the dentition. This requires awareness of the clinical appearance of erosion compared to other forms of tooth wear. An understanding of the etiologies and risk factors for erosion is also important. These form the basis of a diagnostic protocol and management strategy that addresses the multifactorial nature of tooth wear. The primary dental care team has the expertise and the responsibility to provide this care for their patients with erosion.

Process Defects in Composites.

DTIC Science & Technology

1995-01-30

mean velocity, U, a high kinematic viscosity, v , and a small diameter of the fibers, D , lead to a very small Reynolds number Re = UD << 1 (1) where p is...partial credit to ARO). 9. D . Krajcinovic and S . Mastilovic, "Damage Evolution and Failure Modes", in: Proc. of the Int. Conf. on Computational...34Computer Simulation of a Model for Irreversible Gelation", Journal of Physics A, Vol. 16., pp. 1221-1239. Kuksenko, V . S . and Tamuzs, V . P., 1981

A Maxwell elasto-brittle rheology for sea ice modelling

NASA Astrophysics Data System (ADS)

Dansereau, Véronique; Weiss, Jérôme; Saramito, Pierre; Lattes, Philippe

2016-07-01

A new rheological model is developed that builds on an elasto-brittle (EB) framework used for sea ice and rock mechanics, with the intent of representing both the small elastic deformations associated with fracturing processes and the larger deformations occurring along the faults/leads once the material is highly damaged and fragmented. A viscous-like relaxation term is added to the linear-elastic constitutive law together with an effective viscosity that evolves according to the local level of damage of the material, like its elastic modulus. The coupling between the level of damage and both mechanical parameters is such that within an undamaged ice cover the viscosity is infinitely large and deformations are strictly elastic, while along highly damaged zones the elastic modulus vanishes and most of the stress is dissipated through permanent deformations. A healing mechanism is also introduced, counterbalancing the effects of damaging over large timescales. In this new model, named Maxwell-EB after the Maxwell rheology, the irreversible and reversible deformations are solved for simultaneously; hence drift velocities are defined naturally. First idealized simulations without advection show that the model reproduces the main characteristics of sea ice mechanics and deformation: strain localization, anisotropy, intermittency and associated scaling laws.

[Fluoridation of drinking water, why is it needed?].

PubMed

Zusman, S P; Natapov, L; Ramon, T

2004-01-01

Dental caries is a widespread disease. It causes irreversible damage, pain and considerable expense. Fluoride is the only known substance that raises the tooth's resistance to acid attack. Natural drinking waters contain fluoride at different concentration. The most effective method of fluoride administration to the community level is by adjustng the fluoride concentration in the drinking water to about 1 part per million. To describe the mode of action of fluoride, methods of administration and to describe water fluoridation, advantages and disadvantages. Fluoridation of drinking water started in 1945 in the world and in 1981 in Israel. Today more then 300 million people in some 60 countries enjoy the defending effect of fluoride in drinking water. This is the most effective method for decreasing incidence of caries, as well as being cost effective. Over the years there were many attempts to 'blame' fluoridation with negative side effects to human health. Till today, none of the allegations passed scientific scrutiny. There is overwhelming scientific support for the Regulations that oblige the Water supplier to adjust fluoride levels to 1 ppm in every town or municipality with more then 5,000 inhabitants.

Ablative therapies: Advantages and disadvantages of radiofrequency, cryotherapy, microwave and electroporation methods, or how to choose the right method for an individual patient?

PubMed

Seror, O

2015-06-01

Several ablation techniques are currently available. Except for electroporation, all of these methods cause fatal damage at a cellular level and irreversible architectural deconstruction at a tissue level by thermal effects. Ablation of a tumor using one of these techniques, whether thermal or otherwise, requires applicators to be positioned from which the energy is delivered in situ. Some techniques, however, require several applicators to be inserted (multibipolar radiofrequency, cryotherapy and electroporation) whereas a single applicator is often sufficient with other technologies (monopolar radiofrequency and microwave). These methods are conceptually very similar but are distinguished from each other in practice through the technologies they use. It is essential to understand these differences as they influence the advantages and limitations of each of the techniques. There is no such thing as the perfect multifunctional ablation device and choice is dictated on an individual patient basis depending on the aim of treatment, which itself depends on each patient's clinical situation. Copyright © 2015 Éditions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.

[Solar retinopathy].

PubMed

Kawa, P; Mańkowska, A; Mackiewicz, J; Zagórski, Z

1998-01-01

The purpose of this study is the present clinical evaluation of 21 patients (number of affected eyes--33), who watched eclipse of the sun on 12 October 1996. All patients had general ophthalmic examination with emphasis on visual acuity, visual field, Amsler test, fluorescein angiography and fundus appearance. Eleven out of 21 patients had at least one follow up examination (number of affected eyes--17). None of the patient received any treatment. All patients revealed tiny, central scotomata--positive Amsler test and decreased visual acuity on the first visit; reading Snellen chart could be improved in all patients by adequate head tilt or eye movement (improvement up to 3 Snellen chart lines). No signs of retinopathy were observed in two eyes with uncorrected refractive error and one amblyopic eye. After 7-8 weeks the visual acuity was decreased to 5/30 in two eyes and to 5/10 in ten eyes. In all those eyes persisted a tiny, central scotoma. Looking at the eclipse of the sun in spite of using primitive eye protection may cause irreversible retinal damage. Return of visual acuity to 5/5 does not always imply complete recovery because of persistent central scotoma.

Procedure to Measure Effect of Excess Body Mass on Musculoskeleture: II. Implementation

NASA Astrophysics Data System (ADS)

Shaibani, Saami J.

2008-03-01

There are a number of ways in which the musculoskeletal system can be affected by excess body mass. One representative quantity for these is the torque exerted on the spinal column about a horizontal lateral axis; hence, its use as an illustrative mechanical indicator in the research reported here. Values of the torque are determined for all subjects in an exceptionally broad adult population that was developed during a companion study. Increases in body mass index caused nearly uniform increases in torque for all height percentiles in both sexes. Overweight individuals had torques that were 35 and 30 percent greater (females and males, respectively) than those for healthy individuals of the same height. Corresponding increases for obese individuals occurred at the much higher levels of 75 and 66 percent. Any resulting musculosketal damage from this is in addition to other problems arising from obesity, such as heart disease, diabetes, and high blood pressure. However, whereas the latter can be treated or managed with medication, some facets of the former might be irreversible and/or irremediable.

Promise of periodontal ligament stem cells in regeneration of periodontium.

PubMed

Maeda, Hidefumi; Tomokiyo, Atsushi; Fujii, Shinsuke; Wada, Naohisa; Akamine, Akifumi

2011-07-28

A great number of patients around the world experience tooth loss that is attributed to irretrievable damage of the periodontium caused by deep caries, severe periodontal diseases or irreversible trauma. The periodontium is a complex tissue composed mainly of two soft tissues and two hard tissues; the former includes the periodontal ligament (PDL) tissue and gingival tissue, and the latter includes alveolar bone and cementum covering the tooth root. Tissue engineering techniques are therefore required for regeneration of these tissues. In particular, PDL is a dynamic connective tissue that is subjected to continual adaptation to maintain tissue size and width, as well as structural integrity, including ligament fibers and bone modeling. PDL tissue is central in the periodontium to retain the tooth in the bone socket, and is currently recognized to include somatic mesenchymal stem cells that could reconstruct the periodontium. However, successful treatment using these stem cells to regenerate the periodontium efficiently has not yet been developed. In the present article, we discuss the contemporary standpoints and approaches for these stem cells in the field of regenerative medicine in dentistry.

Discovery of 1-(4-((3-(4-methylpiperazin-1-yl)propyl)amino)benzyl)-5-(trifluoromethyl)pyridin-2(1H)-one, an orally active multi-target agent for the treatment of diabetic nephropathy.

PubMed

Chen, Jun; Peng, Zhangzhe; Lu, Miaomiao; Xiong, Xuan; Chen, Zhuo; Li, Qianbin; Cheng, Zeneng; Jiang, Dejian; Tao, Lijian; Hu, Gaoyun

2018-01-15

Oxidative stress, inflammation and fibrosis can cause irreversible damage on cell structure and function of kidney and are key pathological factors in Diabetic Nephropathy (DN). Therefore, multi-target agents are urgently need for the clinical treatment of DN. Using Pirfenidone as a lead compound and based on the previous research, two novel series (5-trifluoromethyl)-2(1H)-pyridone analogs were designed and synthesized. SAR of (5-trifluoromethyl)-2(1H)-pyridone derivatives containing nitrogen heterocyclic ring have been established for in vitro potency. In addition, compound 8, a novel agent that act on multiple targets of anti-DN with IC 50 of 90μM in NIH3T3 cell lines, t 1/2 of 4.89±1.33h in male rats and LD 50 >2000mg/kg in mice, has been advanced to preclinical studies as an oral treatment for DN. Copyright © 2017 Elsevier Ltd. All rights reserved.

Endodontic treatment of developmental anomalies in posterior teeth: treatment of geminated/fused teeth--report of two cases.

PubMed

Tsesis, I; Steinbock, N; Rosenberg, E; Kaufman, A Y

2003-05-01

Gemination or fusion is a rare occurrence in the mandibular posterior teeth. Endodontic treatment of these teeth needs special care and attention to the bizarre anatomy. The aim of this article is to describe the problems encountered and the strategy in treating such cases. Two cases of complex endodontic treatment of fused/geminated teeth are presented. The first is an 11-year-old girl with an anomalous 'double' first mandibular molar and premolar diagnosed as having necrotic pulp with chronic apical abscess of endodontic origin; the second is a 16-year-old boy with 'double' second and supernumerary mandibular molars, who was diagnosed with irreversible pulpitis. Both cases were treated successfully in multiple appointments. The common features and treatment modalities are discussed. Failure to diagnose fused/geminated teeth leads to misdiagnosis and a treatment plan that could cause permanent damage and tooth loss. Generally, there is communication between root canal systems of fused/geminated teeth which should be treated as one entity. Use of magnification is an important aid during treatment.

Assessment of Styrene Oxide Neurotoxicity Using In Vitro Auditory Cortex Networks

PubMed Central

Gopal, Kamakshi V.; Wu, Calvin; Moore, Ernest J.; Gross, Guenter W.

2011-01-01

Styrene oxide (SO) (C8H8O), the major metabolite of styrene (C6H5CH=CH2), is widely used in industrial applications. Styrene and SO are neurotoxic and cause damaging effects on the auditory system. However, little is known about their concentration-dependent electrophysiological and morphological effects. We used spontaneously active auditory cortex networks (ACNs) growing on microelectrode arrays (MEA) to characterize neurotoxic effects of SO. Acute application of 0.1 to 3.0 mM SO showed concentration-dependent inhibition of spike activity with no noticeable morphological changes. The spike rate IC50 (concentration inducing 50% inhibition) was 511 ± 60 μM (n = 10). Subchronic (5 hr) single applications of 0.5 mM SO also showed 50% activity reduction with no overt changes in morphology. The results imply that electrophysiological toxicity precedes cytotoxicity. Five-hour exposures to 2 mM SO revealed neuronal death, irreversible activity loss, and pronounced glial swelling. Paradoxical “protection” by 40 μM bicuculline suggests binding of SO to GABA receptors. PMID:23724250

The clinical spectrum of autoimmune congenital heart block

PubMed Central

Brito-Zerón, Pilar; Izmirly, Peter M.; Ramos-Casals, Manuel; Buyon, Jill P.; Khamashta, Munther A.

2017-01-01

Autoimmune congenital heart block (CHB) is an immune-mediated acquired disease that is associated with the placental transference of maternal antibodies specific for Ro and La autoantigens. The disease develops in a fetal heart without anatomical abnormalities that could otherwise explain the block, and which is usually diagnosed in utero, but also at birth or within the neonatal period. Autoantibody-mediated damage of fetal conduction tissues causes inflammation and fibrosis and leads to blockage of signal conduction at the atrioventricular (AV) node. Irreversible complete AV block is the principal cardiac manifestation of CHB, although some babies might develop other severe cardiac complications, such as endocardial fibroelastosis or valvular insufficiency, even in the absence of cardiac block. In this Review, we discuss the epidemiology, classification and management of women whose pregnancies are affected by autoimmune CHB, with a particular focus on the autoantibodies associated with autoimmune CHB and how we should test for these antibodies and diagnose this disease. Without confirmed effective preventive or therapeutic strategies and further research on the aetiopathogenic mechanisms, autoimmune CHB will remain a severe life-threatening disorder. PMID:25800217

Determining the maximum charging currents of lithium-ion cells for small charge quantities

NASA Astrophysics Data System (ADS)

Grimsmann, F.; Gerbert, T.; Brauchle, F.; Gruhle, A.; Parisi, J.; Knipper, M.

2017-10-01

In order to optimize the operating parameters of battery management systems for electric and hybrid vehicles, great interest has been shown in achieving the maximum permissible charging currents during recuperation, without causing a cell damage due to lithium plating, in relation to the temperature, charge quantity and state of charge. One method for determining these recuperation currents is measuring the cell thickness, where excessively high charging currents can be detected by an irreversible increase in thickness. It is not possible to measure particularly small charge quantities by employing mechanic dial indicators, which have a limited resolution of 1 μm. This is why we developed a measuring setup that has a resolution limit of less than 10 nm using a high-resolution contactless inductance sensor. Our results show that the permissible charging current I can be approximated in relation to the charge quantity x by a correlating function I =a /√{(x) } which is compliant with the Arrhenius law. Small charge quantities therefore have an optimization potential for energy recovery during recuperation.

Stainless steel surface biofunctionalization with PMMA-bioglass coatings: compositional, electrochemical corrosion studies and microbiological assay.

PubMed

Floroian, L; Samoila, C; Badea, M; Munteanu, D; Ristoscu, C; Sima, F; Negut, I; Chifiriuc, M C; Mihailescu, I N

2015-06-01

A solution is proposed to surpass the inconvenience caused by the corrosion of stainless steel implants in human body fluids by protection with thin films of bioactive glasses or with composite polymer-bioactive glass nanostructures. Our option was to apply thin film deposition by matrix-assisted pulsed laser evaporation (MAPLE) which, to the difference to other laser or plasma techniques insures the protection of a more delicate material (a polymer in our case) against degradation or irreversible damage. The coatings composition, modification and corrosion resistance were investigated by FTIR and electrochemical techniques, under conditions which simulate their biological interaction with the human body. Mechanical testing demonstrates the adhesion, durability and resistance to fracture of the coatings. The coatings biocompatibility was assessed by in vitro studies and by flow cytometry. Our results support the unrestricted usage of coated stainless steel as a cheap alternative for human implants manufacture. They will be more accessible for lower prices in comparison with the majority present day fabrication of implants using Ti or Ti alloys.

[Pulmonary involvement in connective tissue disease].

PubMed

Bartosiewicz, Małgorzata

2016-01-01

The connective tissue diseases are a variable group of autoimmune mediated disorders characterized by multiorgan damage. Pulmonary complications are common, usually occur after the onset of joint symptoms, but can also be initially presenting complaint. The respiratory system may be involved in all its component: airways, vessels, parenchyma, pleura and respiratory muscles. Lung involvement is an increasing cause of morbidity and mortality in the connective tissue diseases. Clinical course is highly variable - can range from mild to rapidly progressive, some processes are reversible, while others are irreversible. Thus, the identification of reversible disease , and separately progressive disease, are important clinical issues. The frequency, clinical presentation, prognosis and responce to therapy are different, depending on the pattern of involvement as well as on specyfic diagnostic method used to identify it. High- resolution computed tompography plays an important role in identifying patients with respiratory involvement. Pulmonary function tests are a sensitive tool detecting interstitial lung disease. In this article, pulmonary lung involvement accompanying most frequently apperaing connective tissue diseases - rheumatoid arthritis, systemic sclerosis, lupus erythematosus, polymyositis/dermatomyositis, Sjögrens syndrome and mixed connective tissue disaese are reviewed.

Research progress of cardioprotective agents for prevention of anthracycline cardiotoxicity.

PubMed

Zhang, Jing; Cui, Xiaohai; Yan, Yan; Li, Min; Yang, Ya; Wang, Jiansheng; Zhang, Jia

2016-01-01

Anthracyclines, including doxorubicin, epirubicin, daunorubicin and aclarubicin, are widely used as chemotherapeutic agents in the treatment of hematologic and solid tumor, including acute leukemia, lymphoma, breast cancer, gastric cancer, soft tissue sarcomas and ovarian cancer. In the cancer treatment, anthracyclines also can be combined with other chemotherapies and molecular-targeted drugs. The combination of anthracyclines with other therapies is usually the first-line treatment. Anthracyclines are effective and potent agents with a broad antitumor spectrum, but may cause adverse reactions, including hair loss, myelotoxicity, as well as cardiotoxicity. We used hematopoietic stimulating factors to control the myelotoxicity, such as G-CSF, EPO and TPO. However, the cardiotoxicity is the most serious side effect of anthracyclines. Clinical research and practical observations indicated that the cardiotoxicity of anthracyclines is commonly progressive and irreversible. Especially to those patients who have the first time use of anthracyclines, the damage is common. Therefore, early detection and prevention of anthracyclines induced cardiotoxicity are particularly important and has already aroused more attention in clinic. By literature review, we reviewed the research progress of cardioprotective agents for prevention of anthracycline cardiotoxicity.

Cost-effectiveness landscape analysis of treatments addressing xerostomia in patients receiving head and neck radiation therapy

PubMed Central

Sasportas, Laura S.; Hosford, Andrew T.; Sodini, Maria A.; Waters, Dale J.; Zambricki, Elizabeth A.; Barral, Joëlle K.; Graves, Edward E.; Brinton, Todd J.; Yock, Paul G.; Le, Quynh-Thu; Sirjani, Davud

2014-01-01

Head and neck (H&N) radiation therapy (RT) can induce irreversible damage to the salivary glands thereby causing long-term xerostomia or dry mouth in 68%–85% of the patients. Not only does xerostomia significantly impair patients’ quality-of-life (QOL) but it also has important medical sequelae, incurring high medical and dental costs. In this article, we review various measures to assess xerostomia and evaluate current and emerging solutions to address this condition in H&N cancer patients. These solutions typically seek to accomplish 1 of the 4 objectives: (1) to protect the salivary glands during RT, (2) to stimulate the remaining gland function, (3) to treat the symptoms of xerostomia, or (4) to regenerate the salivary glands. For each treatment, we assess its mechanisms of action, efficacy, safety, clinical utilization, and cost. We conclude that intensity-modulated radiation therapy is both the most widely used prevention approach and the most cost-effective existing solution and we highlight novel and promising techniques on the cost-effectiveness landscape. PMID:23643579

Early cystic fibrosis lung disease: Role of airway surface dehydration and lessons from preventive rehydration therapies in mice.

PubMed

Mall, Marcus A; Graeber, Simon Y; Stahl, Mirjam; Zhou-Suckow, Zhe

2014-07-01

Cystic fibrosis (CF) lung disease starts in the first months of life and remains one of the most common fatal hereditary diseases. Early therapeutic interventions may provide an opportunity to prevent irreversible lung damage and improve outcome. Airway surface dehydration is a key disease mechanism in CF, however, its role in the in vivo pathogenesis and as therapeutic target in early lung disease remains poorly understood. Mice with airway-specific overexpression of the epithelial Na(+) channel (βENaC-Tg) recapitulate airway surface dehydration and phenocopy CF lung disease. Recent studies in neonatal βENaC-Tg mice demonstrated that airway surface dehydration produces early mucus plugging in the absence of mucus hypersecretion, which triggers airway inflammation, promotes bacterial infection and causes early mortality. Preventive rehydration therapy with hypertonic saline or amiloride effectively reduced mucus plugging and mortality in neonatal βENaC-Tg mice. These results support clinical testing of preventive/early rehydration strategies in infants and young children with CF. Copyright © 2014 Elsevier Ltd. All rights reserved.

A randomized placebo-blind study of the effect of low power laser on pain caused by irreversible pulpitis.

PubMed

Ramalho, Karen Müller; de Souza, Lárissa Marcondes Paladini; Tortamano, Isabel Peixoto; Adde, Carlos Alberto; Rocha, Rodney Garcia; de Paula Eduardo, Carlos

2016-12-01

This randomized placebo-blind study aimed to evaluate the effect of laser phototherapy (LPT) on pain caused by symptomatic irreversible pulpitis (SIP). Sixty patients diagnosed with SIP were randomly assigned to treatment groups (n = 15): G1 (control), G2 (laser placebo-sham irradiation), G3 (laser irradiation at 780 nm, 40 mW, 4 J/cm 2 ), and G4 (laser irradiation at 780 nm, 40 mW, 40 J/cm 2 ). Spontaneous pain was recorded using a VAS score before (T0), immediately after (T1), and 15 min after treatment (T2). Local anesthetics failure during emergency endodontic treatment was also assessed. There was no pain difference in T1 and T2 between the experimental laser groups (G3 and G4) and the placebo group (G2). The 4-J/cm 2 (G3) irradiation resulted in significant increase in the local anesthetics failure in lower jar teeth. This effect could be suggested as consequence of the LPT improvement in local circulation and vasodilatation that would result in the increase of local anesthetic agent absorption. The application of 780-nm diode laser irradiation, at 4 and 40 J/cm 2 , showed no effect in reducing the pain in SIP in comparison to the placebo group. The fluence of 4 J/cm 2 showed a negative effect in local anesthetics, resulting in significant increase of complimentary local anesthesia during emergency endodontic treatment. This work provides evidence of the consequence of LPT application on teeth with symptomatic irreversible pulpitis. LPT should be avoided in teeth with pain due to irreversible pulpitis.

Kinetics of alkali-based photocathode degradation

DOE PAGES

Pavlenko, Vitaly; Liu, Fangze; Hoffbauer, Mark A.; ...

2016-11-02

Here, we report on a kinetic model that describes the degradation of the quantum efficiency (QE) of Cs 3Sb and negative electron affinity (NEA) GaAs photocathodes under UHV conditions. Additionally, the generally accepted irreversible chemical change of a photocathode’s surface due to reactions with residual gases, such as O 2, CO 2, and H 2O, the model incorporates an intermediate reversible physisorption step, similar to Langmuir adsorption. Moreover, this intermediate step is needed to satisfactorily describe the strongly non-exponential QE degradation curves for two distinctly different classes of photocathodes –surface-activated and “bulk,” indicating that in both systems the QE degradationmore » results from surface damage. The recovery of the QE upon improvement of vacuum conditions is also accurately predicted by this model with three parameters (rates of gas adsorption, desorption, and irreversible chemical reaction with the surface) comprising metrics to better characterize the lifetime of the cathodes, instead of time-pressure exposure expressed in Langmuir units.« less

A Monotonic Degradation Assessment Index of Rolling Bearings Using Fuzzy Support Vector Data Description and Running Time

PubMed Central

Shen, Zhongjie; He, Zhengjia; Chen, Xuefeng; Sun, Chuang; Liu, Zhiwen

2012-01-01

Performance degradation assessment based on condition monitoring plays an important role in ensuring reliable operation of equipment, reducing production downtime and saving maintenance costs, yet performance degradation has strong fuzziness, and the dynamic information is random and fuzzy, making it a challenge how to assess the fuzzy bearing performance degradation. This study proposes a monotonic degradation assessment index of rolling bearings using fuzzy support vector data description (FSVDD) and running time. FSVDD constructs the fuzzy-monitoring coefficient ε̄ which is sensitive to the initial defect and stably increases as faults develop. Moreover, the parameter ε̄ describes the accelerating relationships between the damage development and running time. However, the index ε̄ with an oscillating trend disagrees with the irreversible damage development. The running time is introduced to form a monotonic index, namely damage severity index (DSI). DSI inherits all advantages of ε̄ and overcomes its disadvantage. A run-to-failure test is carried out to validate the performance of the proposed method. The results show that DSI reflects the growth of the damages with running time perfectly. PMID:23112591

A monotonic degradation assessment index of rolling bearings using fuzzy support vector data description and running time.

PubMed

Shen, Zhongjie; He, Zhengjia; Chen, Xuefeng; Sun, Chuang; Liu, Zhiwen

2012-01-01

Performance degradation assessment based on condition monitoring plays an important role in ensuring reliable operation of equipment, reducing production downtime and saving maintenance costs, yet performance degradation has strong fuzziness, and the dynamic information is random and fuzzy, making it a challenge how to assess the fuzzy bearing performance degradation. This study proposes a monotonic degradation assessment index of rolling bearings using fuzzy support vector data description (FSVDD) and running time. FSVDD constructs the fuzzy-monitoring coefficient ε⁻ which is sensitive to the initial defect and stably increases as faults develop. Moreover, the parameter ε⁻ describes the accelerating relationships between the damage development and running time. However, the index ε⁻ with an oscillating trend disagrees with the irreversible damage development. The running time is introduced to form a monotonic index, namely damage severity index (DSI). DSI inherits all advantages of ε⁻ and overcomes its disadvantage. A run-to-failure test is carried out to validate the performance of the proposed method. The results show that DSI reflects the growth of the damages with running time perfectly.

Modified stoke ankylosing spondylitis spinal score as an outcome measure to assess the impact of treatment on structural progression in ankylosing spondylitis.

PubMed

van der Heijde, Désirée; Braun, Jürgen; Deodhar, Atul; Baraliakos, Xenofon; Landewé, Robert; Richards, Hanno B; Porter, Brian; Readie, Aimee

2018-05-30

In ankylosing spondylitis (AS), structural damage that occurs as a result of syndesmophyte formation and ankylosis of the vertebral column is irreversible. Structural damage is currently assessed by conventional radiography and scoring systems that reliably assess radiographic structural damage are needed to capture the differential effects of drugs on structural damage progression. The validity of the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) as a primary outcome measure in evaluating the effect of AS treatments on radiographic progression rates was assessed in this review. The mSASSS has not been used, to date, as a primary outcome measure in a prospective randomized controlled clinical trial of biologic therapy in AS. This review of the medical literature confirmed that the mSASSS is the most validated and widely used method for assessing radiographic progression in AS, correlating with worsening measures of disease signs and symptoms, spinal mobility and physical function, with a 2-year interval being required to ensure sufficient sensitivity to change.

Unveiling the irreversible performance degradation of organo-inorganic halide perovskite films and solar cells during heating and cooling processes.

PubMed

Mamun, Abdullah Al; Ava, Tanzila Tasnim; Byun, Hye Ryung; Jeong, Hyeon Jun; Jeong, Mun Seok; Nguyen, Loi; Gausin, Christine; Namkoong, Gon

2017-07-26

While organo-inorganic halide perovskite solar cells show great potential to meet future energy needs, their thermal instability raises serious questions about their commercialization viability. At present, the stability of perovskite solar cells has been studied under various environmental conditions including humidity and temperature. Nonetheless, understanding of the performance of CH 3 NH 3 PbI 3-x Cl x perovskite solar cells is limited. This study reports the irreversible performance degradation of CH 3 NH 3 PbI 3-x Cl x perovskite solar cells during the heating and cooling processes under AM 1.5 and unveils what triggers the irreversible performance degradation of solar cells. Particularly, the primary cause of the irreversible performance degradation of CH 3 NH 3 PbI 3-x Cl x is quantitatively analyzed by monitoring in real time the development of deteriorated crystallinity, charge trapping/detrapping, trap depth, and the PbI 2 phase, namely a critical signal of perovskite degradation while varying the temperature of the perovskite films and solar cells. Most surprisingly, it is revealed that the degradation of both perovskite films and solar cells was triggered at ∼70 °C. Remarkably, even after the device temperature cooled down to room temperature, the degraded performance of the solar cells persisted with increasing charge trapping and further development of the PbI 2 phase. Identification of the irreversible performance degradation of perovskite solar cells provides guidance for future development of more stable perovskite solar cells.

Prevalence of Obesity in Carpal Tunnel Syndrome Patients: A Cross-Sectional Survey.

PubMed

Mansoor, Salman; Siddiqui, Maimoona; Mateen, Farrukh; Saadat, Shoab; Khan, Zarak H; Zahid, Mehr; Khan, Hamza H; Malik, Shuja A; Assad, Salman

2017-07-26

Carpal tunnel syndrome (CTS) is the most common compressive entrapment neuropathy caused by the compression of the median nerve at the wrist space known as the carpal tunnel. The epidemiologic factors related to CTS include genetic, medical, social, vocational, and demographic factors. The common symptoms experienced include pain, paresthesia, and numbness in the median nerve distribution. If left untreated, it can lead to irreversible median nerve damage, causing a loss of hand function. Body mass index (BMI) has been attributed as a risk factor for the development of CTS. We planned to determine the frequency of obesity among CTS patients in the neurophysiology department of a tertiary care center in Islamabad, Pakistan. The survey was designed as a cross-sectional descriptive study from March 2016 to August 2016 using a consecutive nonprobability sampling technique. A total of 112 patients with a mean age of 54 ± 5 years were included in the study. In the study population, 39 patients (35 percent) were males and 73 were females (65 percent). Based on BMI, 74 patients (66 percent) had a normal weight and 38 (34 percent) were obese. The frequency of obesity in our study was 34 percent, excluding the other comorbid conditions, which is quite high. Targeted therapy in those with CTS should also include weight reduction measures because obesity poses a cause-and-effect relationship for both the severity and the pathogenesis of CTS.

Modelling of a Francis Turbine Runner Fatigue Failure Process Caused by Fluid-Structure Interaction

NASA Astrophysics Data System (ADS)

Lyutov, A.; Kryukov, A.; Cherny, S.; Chirkov, D.; Salienko, A.; Skorospelov, V.; Turuk, P.

2016-11-01

In the present paper considered is the problem of the numerical simulation of Francis turbine runner fatigue failure caused by fluid-structure interaction. The unsteady 3D flow is modeled simultaneously in the spiral chamber, each wicket gate and runner channels and in the draft tube using the Euler equations. Based on the unsteady runner loadings at each time step stresses in the whole runner are calculated using the elastic equilibrium equations solved with boundary element method. Set of static stress-strain states provides quasi-dynamics of runner cyclic loading. It is assumed that equivalent stresses in the runner are below the critical value after which irreversible plastic processes happen in the runner material. Therefore runner is subjected to the fatigue damage caused by high-cycle fatigue, in which the loads are generally low compared with the limit stress of the material. As a consequence, the stress state around the crack front can be fully characterized by linear elastic fracture mechanics. The place of runner cracking is determined as a point with maximal amplitude of stress oscillations. Stress pulsations amplitude is used to estimate the number of cycles until the moment of fatigue failure, number of loading cycles and oscillation frequency are used to calculate runner service time. Example of the real Francis runner which has encountered premature fatigue failure as a result of incorrect durability estimation is used to verify the developed numerical model.

Study of Ground Response Curve (GRC) Based on a Damage Model / Badanie Krzywej Odpowiedzi Gruntu (Grc) W Oparciu O Model Pękania Skał

NASA Astrophysics Data System (ADS)

Molladavoodi, H.

2013-09-01

Analysis of stresses and displacements around underground openings is necessary in a wide variety of civil, petroleum and mining engineering problems. In addition, an excavation damaged zone (EDZ) is generally formed around underground openings as a result of high stress magnitudes even in the absence of blasting effects. The rock materials surrounding the underground excavations typically demonstrate nonlinear and irreversible mechanical response in particular under high in situ stress states. The dominant cause of irreversible deformations in brittle rocks is damage process. One of the most widely used methods in tunnel design is the convergence-confinement method (CCM) for its practical application. The elastic-plastic models are usually used in the convergence-confinement method as a constitutive model for rock behavior. The plastic models used to simulate the rock behavior, do not consider the important issues such as stiffness degradation and softening. Therefore, the use of damage constitutive models in the convergence-confinement method is essential in the design process of rock structures. In this paper, the basic concepts of continuum damage mechanics are outlined. Then a numerical stepwise procedure for a circular tunnel under hydrostatic stress field, with consideration of a damage model for rock mass has been implemented. The ground response curve and radius of excavation damage zone were calculated based on an isotropic damage model. The convergence-confinement method based on damage model can consider the effects of post-peak rock behavior on the ground response curve and excavation damage zone. The analysis of results show the important effect of brittleness parameter on the tunnel wall convergence, ground response curve and excavation damage radius. Analiza naprężeń i przemieszczeń powstałych wokół otworu podziemnego wymagana jest przy szerokiej gamie projektów z zakresu budownictwa lądowego, inżynierii górniczej oraz naftowej. Ponadto, wokół otworu podziemnego powstaje strefa naruszona działalnością górniczą wskutek oddziaływania wysokich naprężeń, nawet w przypadku gdy nie są prowadzone prace strzałowe. Reakcja materiału skalnego znajdującego się w otoczeniu wyrobisk podziemnych jest zazwyczaj procesem nieliniowym i nieodwracalnym, zwłaszcza w stanach wysokich naprężeń in situ. Główną przyczyną nieodwracalnych odkształceń skał kruchych jest pękanie. Jedną z najczęściej stosowanych metod w projektowaniu tuneli (wyrobisk podziemnych) jest metoda konwergencji i zamknięcia, popularna ze względu na zakres zastosowań. Metoda ta zazwyczaj wykorzystuje modele sprężysto- plastyczne, jako konstytutywne modele zachowania skał. Modele plastyczne wykorzystywane dotychczas do symulacji zachowania skał nie uwzględniają pewnych kluczowych aspektów, takich jak obniżenie sztywności czy rozmiękczanie. Dlatego też zastosowanie konstytutywnych modeli w metodzie konwergencji i zamknięcia jest sprawą kluczową przy projektach obejmujących struktury skalne. W pracy tej omówiono podstawowe założenia modelu continuum uszkodzeń i spękań. Zaimplementowano wielostopniową procedurę do badania tunelu o przekroju kolistym znajdującego się pod polem naprężeń hydrostatycznych, przy wykorzystaniu modelu pękania górotworu. Krzywą odpowiedzi gruntu oraz promień strefy naruszonej wybieraniem obliczono przy wykorzystaniu izotropowego modelu uszkodzeń. Metoda konwergencji i zamykania oparta na tym modelu uwzględnia zachowanie skał po wystąpieniu szczytowych naprężeń i powstaniu strefy naruszonej wybieraniem. Analiza wyników wykazała znaczny wpływ parametrów związanych z kruchością na konwergencję ścian wyrobiska, kształt krzywej odpowiedzi gruntu oraz promień strefy naruszonej wybieraniem.

Imaging of the optic nerve and retinal nerve fiber layer: an essential part of glaucoma diagnosis and monitoring.

PubMed

Kotowski, Jacek; Wollstein, Gadi; Ishikawa, Hiroshi; Schuman, Joel S

2014-01-01

Because glaucomatous damage is irreversible early detection of structural changes in the optic nerve head and retinal nerve fiber layer is imperative for timely diagnosis of glaucoma and monitoring of its progression. Significant improvements in ocular imaging have been made in recent years. Imaging techniques such as optical coherence tomography, scanning laser polarimetry and confocal scanning laser ophthalmoscopy rely on different properties of light to provide objective structural assessment of the optic nerve head, retinal nerve fiber layer and macula. In this review, we discuss the capabilities of these imaging modalities pertinent for diagnosis of glaucoma and detection of progressive glaucomatous damage and provide a review of the current knowledge on the clinical performance of these technologies. Copyright © 2014 Elsevier Inc. All rights reserved.

Myocardial temperature distribution under cw Nd:YAG laser irradiation in in vitro and in vivo situations: theory and experiment

NASA Astrophysics Data System (ADS)

Splinter, Robert; Littmann, Laszlo; Tuntelder, Jan R.; Svenson, Robert H.; Chuang, Chi Hui; Tatsis, George P.; Semenov, Serguei Y.; Nanney, Glenn A.

1995-01-01

Tissue samples ranging from 2 to 16 mm in thickness were irradiated at 1064 nm with energies ranging from 40 to 2400 J. Coagulation lesions of in vitro and in vivo experiments were subjected to temperature profiling and submitted for histology. Irreversible damage was calculated with the damage integral formalism, following the bioheat equation solved with Monte Carlo computer light-distribution simula-tions. Numerical temperature rise and coagulation depth compared well with the in vitro results. The in vivo data required a change in the optical properties based on integrating sphere measurements for high irradiance to make the experimental and numerical data converge. The computer model has successfully solved several light-tissue interaction situations in which scattering dominates over absorption.

Behavioral effects of heavy ions and protons and potential countermeasure agents

NASA Astrophysics Data System (ADS)

Vazquez, M.; Gatley, J.; Bruneus, M.; Koslosky, S.; Billups, A.

Space travel beyond the Earth's protective magnetic field (for example, to Mars) will involve exposure of astronauts to irradiation by high-energy nuclei such as 56 Fe, which are a component of galactic cosmic rays. These particles have high linear energy transfer (LET) and are expected to irreversibly damage cells they traverse. Exposure to HZE radiation may therefore cause progressive deterioration of brain function, adding to other inescapable damage involved in normal aging. We propose a study of the hypothesis that long-term behavioral alterations are induced after exposure of the brain to 1 GeV/n iron and silicon particles with fluences of 1 to 8 particles/cell targets. Previous studies support this notion but are not definitive, especially with regard to long-term effects. Our principal goal is to examine the neurological effects of high-LET radiation on C57BL/6 mice using a series of behavioral tests to unveil the temporal expression of altered behaviors in the radiation response, as well as the means, which can modulate these responses. The studies planned in this project are designed to: 1) Characterize the behavioral consequences after exposure to low-fluences of heavy ions and protons on C57BL/6 mice. The main behavioral endpoints to be used in these studies are locomotor activity to evaluate the integrity of striatal dopaminergic pathways, and spatial reference memory to probe hippocampal cholinergic pathways. 2) Characterize the neurochemical and structural changes induced by heavy ions and protons. 3) To develop countermeasures to protect neural cell populations exposed to low fluences of heavy ions and protons. The project will test methods to protect injured neural cells based on their molecular and cellular mechanisms that may regulate neural cell survival in the central nervous system. Among the methods that will be studied is the direct administration of neuroprotective molecules as well as the modulation of apoptotic pathways by pharmacological manipulation. The effects of 3 different neuro/radioprotectors (GM1, melatonin and PTF-) on the levels of radiation induced neurochemical and structural damage will be compared with the level of behavioral alterations to determine a cause/effect relationship

The High Court's lost chance in medical negligence: Tabet v Gett (2010) 240 CLR 537.

PubMed

Faunce, Thomas; McEwan, Alexandra

2010-12-01

In 2010 the High Court of Australia in Tabet v Gett (2010) 240 CLR 537 determined an appeal in a medical negligence case concerning a six-year-old girl who had presented to a major paediatric hospital with symptoms over several weeks of headaches and vomiting after a recent history of chicken pox. The differential diagnosis was varicella, meningitis or encephalitis and two days later, after she deteriorated neurologically, she received a lumbar puncture. Three days later she suffered a seizure and irreversible brain damage. A CT scan performed at that point showed a brain tumour. As Australia does not have a no-fault system providing compensation to cover the long-term care required for such a condition, the girl (through her parents and lawyers) sued her treating physician. She alleged that, because a cerebral CT scan was not performed when clinically indicated after the diagnosis of meningitis or encephalitis and before the lumbar puncture, she had "lost the chance" to have her brain tumour treated before she sustained permanent brain damage. She succeeded at first instance, but lost on appeal. The High Court also rejected her claim, holding unanimously that there were no policy reasons to allow recovery of damages based on possible (less than 50%) "loss of a chance" of a better medical outcome. The court held that the law of torts in Australia required "all or nothing" proof that physical injury was caused or contributed to by a negligent party. The High Court, however, did not exclude loss of chance as forming the substance of a probable (greater than 50%) claim in medical negligence in some future case. In the meantime, patients injured in Australia as a result of possible medical negligence (particularly in the intractable difficult instances of late diagnosis) must face the injustice of the significant day-to-day care needs of victims being carried by family members and the taxpayer-funded public hospital system. The High Court in Tabet v Gett again provides evidence that, as currently constituted, it remains deaf to the injustice caused by State legislation excessively restricting the access to reasonable compensation by victims of medical negligence.

40 CFR 158.2203 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-07-01

..., that destroys or irreversibly inactivates bacteria, fungi and viruses, but not necessarily bacterial..., kills or inactivates all types of disease-causing microorganisms from the water, including bacteria... substance, or mixture of substances, that reduces the bacteria population in the inanimate environment by...

40 CFR 158.2203 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

..., that destroys or irreversibly inactivates bacteria, fungi and viruses, but not necessarily bacterial..., kills or inactivates all types of disease-causing microorganisms from the water, including bacteria... substance, or mixture of substances, that reduces the bacteria population in the inanimate environment by...

Agent Based Modeling of Atherosclerosis: A Concrete Help in Personalized Treatments

NASA Astrophysics Data System (ADS)

Pappalardo, Francesco; Cincotti, Alessandro; Motta, Alfredo; Pennisi, Marzio

Atherosclerosis, a pathology affecting arterial blood vessels, is one of most common diseases of the developed countries. We present studies on the increased atherosclerosis risk using an agent based model of atherogenesis that has been previously validated using clinical data. It is well known that the major risk in atherosclerosis is the persistent high level of low density lipoprotein (LDL) concentration. However, it is not known if short period of high LDL concentration can cause irreversible damage and if reduction of the LDL concentration (either by life style or drug) can drastically or partially reduce the already acquired risk. We simulated four different clinical situations in a large set of virtual patients (200 per clinical scenario). In the first one the patients lifestyle maintains the concentration of LDL in a no risk range. This is the control case simulation. The second case is represented by patients having high level of LDL with a delay to apply appropriate treatments; The third scenario is characterized by patients with high LDL levels treated with specific drugs like statins. Finally we simulated patients that are characterized by several oxidative events (smoke, sedentary life style, assumption of alcoholic drinks and so on so forth) that effective increase the risk of LDL oxidation. Those preliminary results obviously need to be clinically investigated. It is clear, however, that SimAthero has the power to concretely help medical doctors and clinicians in choosing personalized treatments for the prevention of the atherosclerosis damages.

Allicin protects auditory hair cells and spiral ganglion neurons from cisplatin - Induced apoptosis.

PubMed

Wu, Xianmin; Li, Xiaofei; Song, Yongdong; Li, He; Bai, Xiaohui; Liu, Wenwen; Han, Yuechen; Xu, Lei; Li, Jianfeng; Zhang, Daogong; Wang, Haibo; Fan, Zhaomin

2017-04-01

Cisplatin is a broad-spectrum anticancer drug that is commonly used in the clinic. Ototoxicity is one of the major side effects of this drug, which caused irreversible sensorineural hearing loss. Allicin, the main biologically active compound derived from garlic, has been shown to exert various anti-apoptotic and anti-oxidative activities in vitro and in vivo studies. We took advantage of C57 mice intraperitoneally injected with cisplatin alone or with cisplatin and allicin combined, to investigate whether allicin plays a protective role in vivo against cisplatin ototoxicity. The result showed that C57 mice in cisplatin group exhibited increased shift in auditory brainstem response, whereas the auditory fuction of mice in allicin + cisplatin group was protected in most frequencies, which was accordance with observed damages of outer hair cells (OHCs) and spiral ganglion neurons (SGNs) in the cochlea. Allicin markedly protected SGN mitochondria from damage and releasing cytochrome c, and significantly reduced pro-apoptosis factor expressions activated by cisplatin, including Bax, cleaved-caspase-9, cleaved-caspase-3and p53. Furthermore, allicin reduced the level of Malondialdehyde (MDA), but increased the level of superoxide dismutase (SOD). All data suggested that allicin could prevent hearing loss induced by cisplatin effectively, of which allicin protected SGNs from apoptosis via mitochondrial pathway while protected OHCs and supporting cells (SCs) from apoptosis through p53 pathway. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Case study with a gunshot fracture of lower extremities and damage of popliteal artery (case report)].

PubMed

Orakhelashvili, G A; Kapanadze, L P; Bregadze, G I; Kacharava, B D; Dzagnidze, E B

2011-12-01

Severe vascular gunshot injury (popliteal artery damage) and fractures of both low extremities are causes traumatic shock (stage III) and anemia in a 32 years female patient. Being the victim of crime, the patient for 5 hours was in a life-threatening condition that could develop the multiple organ system failure (MOSF) as a result of tissue ischemia and reperfusion and acute irreversible shock. There was an urgent necessity to perform three immediate operations at the same time. Successful recovery required rapid control of the inciting event (i.e., maintenance of effective hemodynamic stability and the body's ability to protect its vital organs, choice of the type of anesthesia with certain anesthetics) facilitated by resuscitative therapy directed toward minimizing the overall "dose" of shock. Oxybutirate sodium (a GABA analog, the only one narcotic drug and a natural metabolite of body) administered intravenously as a hypnotic agent and an important component of intensive care as well have had clearly anti-shock and antihypoxant effects. Rapid improving of circulation and using of medications with wide range of anti-stress action (such as oxybutirate sodium, dexamethazone and glucose) assisted successful resuscitation and possibility to perform three operations (duration: 6 hours and 45 minutes). An increasing emphasis was being placed on prevention of MOSF, including 1) maintenance of tissue oxygenation; 2) using above-mentioned anti-stress and antihypoxant medicines with mutually supportive effects and 3) infection control.

Sodium-23 magnetic resonance imaging has potential for improving penumbra detection but not for estimating stroke onset time

PubMed Central

Wetterling, Friedrich; Gallagher, Lindsay; Mullin, Jim; Holmes, William M; McCabe, Chris; Macrae, I Mhairi; Fagan, Andrew J

2015-01-01

Tissue sodium concentration increases in irreversibly damaged (core) tissue following ischemic stroke and can potentially help to differentiate the core from the adjacent hypoperfused but viable penumbra. To test this, multinuclear hydrogen-1/sodium-23 magnetic resonance imaging (MRI) was used to measure the changing sodium signal and hydrogen-apparent diffusion coefficient (ADC) in the ischemic core and penumbra after rat middle cerebral artery occlusion (MCAO). Penumbra and core were defined from perfusion imaging and histologically defined irreversibly damaged tissue. The sodium signal in the core increased linearly with time, whereas the ADC rapidly decreased by >30% within 20 minutes of stroke onset, with very little change thereafter (0.5–6 hours after MCAO). Previous reports suggest that the time point at which tissue sodium signal starts to rise above normal (onset of elevated tissue sodium, OETS) represents stroke onset time (SOT). However, extrapolating core data back in time resulted in a delay of 72±24 minutes in OETS compared with actual SOT. At the OETS in the core, penumbra sodium signal was significantly decreased (88±6%, P=0.0008), whereas penumbra ADC was not significantly different (92±18%, P=0.2) from contralateral tissue. In conclusion, reduced sodium-MRI signal may serve as a viability marker for penumbra detection and can complement hydrogen ADC and perfusion MRI in the time-independent assessment of tissue fate in acute stroke patients. PMID:25335803

Seasonal, Sex- and Plant Size-Related Effects on Photoinhibition and Photoprotection in the Dioecious Mediterranean Dwarf Palm, Chamaerops humilis.

PubMed

Morales, Melanie; Pintó-Marijuan, Marta; Munné-Bosch, Sergi

2016-01-01

In Mediterranean-type ecosystems plants are exposed to several adverse environmental conditions throughout the year, ranging from drought stress during the warm and dry summers to chilling stress due to the typical drop in temperatures during winters. Here we evaluated the ecophysiological response, in terms of photoinhibition and photoprotection, of the dioecious Mediterranean palm, Chamaerops humilis to seasonal variations in environmental conditions. Furthermore, we considered as well the influence of plant size, maturity, and sexual dimorphism. Results showed evidence of winter photoinhibition, with a marked decrease of the F v /F m ratio below 0.7 between January and March, which was coincident with the lowest temperatures. During this period, the de-epoxidation state of the xanthophyll cycle and zeaxanthin levels increased, which might serve as a photoprotection mechanism, owing the full recovery from winter photoinhibition during spring. Furthermore, mature plants showed lower chlorophyll levels and higher β-carotene levels per unit of chlorophyll than juvenile plants, and females displayed lower leaf water contents and higher photoinhibition than males during summer, probably due to increased reproductive effort of females. However, neither low temperatures during winter nor reproductive events in females during the summer led to irreversible damage to the photosynthetic apparatus. We conclude that (i) the Mediterranean dwarf palm, C. humilis, suffers from photoinhibition during winter, but this is transient and does not lead to irreversible damage, and (ii) females from this plant species are more sensitive than males to photoinhibition during reproductive events.

An investigation of heat transfer to the implant-bone interface when drilling through a zirconia crown attached to a titanium or zirconia abutment.

PubMed

Mason, Amy G; Sutton, Alan; Turkyilmaz, Ilser

2014-11-01

Thermal injury to the implant-bone interface may lead to bone necrosis and loss of osseointegration. This is a concern during manipulation of the implant throughout the restorative phase of treatment. The risk of heat transfer to the implant-bone interface during abutment preparation or prosthesis removal should be considered. The purpose of the study was to examine the amount of heat transferred to the implant-bone interface when a zirconia crown is drilled to access the screw channel or section a crown with a high-speed dental handpiece. Of the 64 ceramic-veneered zirconia crowns fabricated, 32 had a coping thickness of 0.5 mm and 32 had a coping thickness of 1.0 mm. The crowns were cemented on either titanium stock abutments or zirconia stock abutments. Each group was further subdivided to evaluate heat transfer when the screw channel was accessed or the crown was sectioned with a high-speed handpiece with or without irrigation. Temperature change was recorded for each specimen at the cervical and apical aspect of the implant with thermocouples and a logging thermometer. ANOVA was used to assess the statistical significance in temperature change between the test combinations, and nonparametric Mann-Whitney U tests were used to evaluate the findings. The use of irrigation during both crown removal processes yielded an average temperature increase of 3.59 ±0.35°C. Crown removal in the absence of irrigation yielded an average temperature increase of 18.76 ±3.09°C. When all parameter combinations in the presence of irrigation were evaluated, the maximum temperature change was below the threshold of thermal injury to bone. The maximum temperature change was above the threshold for thermal injury at the coronal aspect of the implant and below the threshold at the apical aspect in the absence of irrigation. Within the limitations of this investigation, the use of irrigation with a high-speed dental handpiece to remove a ceramic-veneered zirconia crown results in a temperature increase at the implant-bone interface insufficient to cause irreversible damage. Conversely, a lack of irrigation may yield a temperature increase capable of producing irreversible damage at the coronal aspect of the implant. Copyright © 2014 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Local Regeneration of Dentin-Pulp Complex Using Controlled Release of FGF-2 and Naturally Derived Sponge-Like Scaffolds

PubMed Central

Kitamura, Chiaki; Nishihara, Tatsuji; Terashita, Masamichi; Tabata, Yasuhiko; Washio, Ayako

2012-01-01

Restorative and endodontic procedures have been recently developed in an attempt to preserve the vitality of dental pulp after exposure to external stimuli, such as caries infection or traumatic injury. When damage to dental pulp is reversible, pulp wound healing can proceed, whereas irreversible damage induces pathological changes in dental pulp, eventually requiring its removal. Nonvital teeth lose their defensive abilities and become severely damaged, resulting in extraction. Development of regeneration therapy for the dentin-pulp complex is important to overcome limitations with presently available therapies. Three strategies to regenerate the dentin-pulp complex have been proposed; regeneration of the entire tooth, local regeneration of the dentin-pulp complex from amputated dental pulp, and regeneration of dental pulp from apical dental pulp or periapical tissues. In this paper, we focus on the local regeneration of the dentin-pulp complex by application of exogenous growth factors and scaffolds to amputated dental pulp. PMID:22174717

Variation of mechanical properties due to hygrothermal ageing and permanent changes upon redrying in clay/epoxy nanocomposites

NASA Astrophysics Data System (ADS)

Hamim, Salah Uddin Ahmed

2011-12-01

Epoxy polymers are an important class of material for use in various applications. Due to their hydrophilic nature, epoxy resins tend to absorb moisture. Absorption of moisture degrades the functional, structural and mechanical properties. For polymers, moisture absorption can lead to both reversible and irreversible changes. In this study, the combined effect of moisture and elevated temperature on the mechanical properties of Epon 862 and its nanocomposites were investigated. The extent of permanent damage on fracture toughness and flexural properties of epoxy, due to the aggressive degradation provided by hygrothermal ageing, was determined by drying the epoxy and their clay/epoxy nanocomposites after moisture absorption. From the investigation it was found out that, clay can help in reducing the negative effect of hygrothermal ageing. Significant permanent damage was observed for fracture toughness and modulus, while the extent of permanent damage was less significant for flexural strength. Failure mechanism of this nanocomposites were studied by using Scanning Electron Microscopy (SEM).

Early axonal damage and progressive myelin pathology define the kinetics of CNS histopathology in a mouse model of multiple sclerosis.

PubMed

Recks, Mascha S; Stormanns, Eva R; Bader, Jonas; Arnhold, Stefan; Addicks, Klaus; Kuerten, Stefanie

2013-10-01

Studies of MS histopathology are largely dependent on suitable animal models. While light microscopic analysis gives an overview of tissue pathology, it falls short in evaluating detailed changes in nerve fiber morphology. The ultrastructural data presented here and obtained from studies of myelin oligodendrocyte glycoprotein (MOG):35-55-induced experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice delineate that axonal damage and myelin pathology follow different kinetics in the disease course. While myelin pathology accumulated with disease progression, axonal damage coincided with the initial clinical disease symptoms and remained stable over time. This pattern applied both to irreversible axolysis and early axonal pathology. Notably, these histopathological patterns were reflected by the normal-appearing white matter (NAWM), suggesting that the NAWM is also in an active neurodegenerative state. The data underline the need for neuroprotection in MS and suggest the MOG model as a highly valuable tool for the assessment of different therapeutic strategies. Copyright © 2013 Elsevier Inc. All rights reserved.

Three-Dimensional Blood Vessel Model with Temperature-Indicating Function for Evaluation of Thermal Damage during Surgery

PubMed Central

Watanabe, Takafumi; Arai, Fumihito

2018-01-01

Surgical simulators have recently attracted attention because they enable the evaluation of the surgical skills of medical doctors and the performance of medical devices. However, thermal damage to the human body during surgery is difficult to evaluate using conventional surgical simulators. In this study, we propose a functional surgical model with a temperature-indicating function for the evaluation of thermal damage during surgery. The simulator is made of a composite material of polydimethylsiloxane and a thermochromic dye, which produces an irreversible color change as the temperature increases. Using this material, we fabricated a three-dimensional blood vessel model using the lost-wax process. We succeeded in fabricating a renal vessel model for simulation of catheter ablation. Increases in the temperature of the materials can be measured by image analysis of their color change. The maximum measurement error of the temperature was approximately −1.6 °C/+2.4 °C within the range of 60 °C to 100 °C. PMID:29370139

A review of second law techniques applicable to basic thermal science research

NASA Astrophysics Data System (ADS)

Drost, M. Kevin; Zamorski, Joseph R.

1988-11-01

This paper reports the results of a review of second law analysis techniques which can contribute to basic research in the thermal sciences. The review demonstrated that second law analysis has a role in basic thermal science research. Unlike traditional techniques, second law analysis accurately identifies the sources and location of thermodynamic losses. This allows the development of innovative solutions to thermal science problems by directing research to the key technical issues. Two classes of second law techniques were identified as being particularly useful. First, system and component investigations can provide information of the source and nature of irreversibilities on a macroscopic scale. This information will help to identify new research topics and will support the evaluation of current research efforts. Second, the differential approach can provide information on the causes and spatial and temporal distribution of local irreversibilities. This information enhances the understanding of fluid mechanics, thermodynamics, and heat and mass transfer, and may suggest innovative methods for reducing irreversibilities.

Clinical features and long-term outcomes of systemic lupus erythematosus: comparative data of childhood, adult and late-onset disease in a national register.

PubMed

Sousa, S; Gonçalves, M J; Inês, L S; Eugénio, G; Jesus, D; Fernandes, S; Terroso, G; Romão, V C; Cerqueira, M; Raposo, A; Couto, M; Nero, P; Sequeira, G; Nóvoa, T; Melo Gomes, J A; da Silva, J Canas; Costa, L; Macieira, C; Silva, C; Silva, J A P; Canhão, H; Santos, M J

2016-07-01

Systemic lupus erythematosus (SLE) affects predominantly women at reproductive age but may present at any age. Age at disease onset has a modulating effect on presentation and course of disease, but controversies persist regarding its impact on long-term outcome. Our aims were to characterize clinical features, co-morbidities and cumulative damage in childhood-onset, adult-onset and late-onset SLE. Patients with childhood-onset SLE fulfilling ACR 1997 criteria were identified in a nationwide register-Reuma.pt/SLE (N = 89) and compared with adult-onset and late-onset counterparts matched 1:1:1 for disease duration. 267 SLE patients with mean disease duration of 11.9 ± 9.3 years were analyzed. Skin (62 %), kidney (58 %), neurological (11 %) and hematologic involvement (76 %) were significantly more common in childhood-onset SLE and disease activity was higher in this subset than in adult- and late-onset disease (SLEDAI-2K 3.4 ± 3.8 vs. 2.2 ± 2.7 vs. 1.6 ± 2.8, respectively; p = 0.004). Also, more childhood-onset patients received cyclophosphamide (10 %) and mycophenolate mofetil (34 %). A greater proportion of women (96 %), prevalence of arthritis (89 %) and anti-SSA antibodies (34 %) were noted in the adult-onset group. There was a significant delay in the diagnosis of SLE in older ages. Co-morbidities such as hypertension, diabetes and thyroid disease were significantly more frequent in late-onset SLE, as well as the presence of irreversible damage evaluated by the SLICC/ACR damage index (20 vs. 26 vs. 40 %; p < 0.001). Greater organ involvement as well as the frequent need for immunosuppressants supports the concept of childhood-onset being a more severe disease. In contrast, disease onset is more indolent but co-morbidity burden and irreversible damage are greater in late-onset SLE, which may have implications for patients' management.

Pacific Ciguatoxin Induces Excitotoxicity and Neurodegeneration in the Motor Cortex Via Caspase 3 Activation: Implication for Irreversible Motor Deficit.

PubMed

Asthana, Pallavi; Zhang, Ni; Kumar, Gajendra; Chine, Virendra Bhagawan; Singh, Kunal Kumar; Mak, Yim Ling; Chan, Leo Lai; Lam, Paul Kwan Sing; Ma, Chi Him Eddie

2018-01-18

Consumption of fish containing ciguatera toxins or ciguatoxins (CTXs) causes ciguatera fish poisoning (CFP). In some patients, CFP recurrence occurs even years after exposure related to CTXs accumulation. Pacific CTX-1 (P-CTX-1) is one of the most potent natural substances known that causes predominantly neurological symptoms in patients; however, the underlying pathogenies of CFP remain unknown. Using clinically relevant neurobehavioral tests and electromyography (EMG) to assess effects of P-CTX-1 during the 4 months after exposure, recurrent motor strength deficit occurred in mice exposed to P-CTX-1. We detected irreversible motor strength deficits accompanied by reduced EMG activity, demyelination, and slowing of motor nerve conduction, whereas control unexposed mice fully recovered in 1 month after peripheral nerve injury. Finally, to uncover the mechanism underlying CFP, we detected reduction of spontaneous firing rate of motor cortical neurons even 6 months after exposure and increased number of glial fibrillary acidic protein (GFAP)-immunoreactive astrocytes. Increased numbers of motor cortical neuron apoptosis were detected by dUTP-digoxigenin nick end labeling assay along with activation of caspase 3. Taken together, our study demonstrates that persistence of P-CTX-1 in the nervous system induces irreversible motor deficit that correlates well with excitotoxicity and neurodegeneration detected in the motor cortical neurons.

[Penoscrotal elephantiasis: diagnostics and treatment options].

PubMed

Zugor, V; Horch, R E; Labanaris, A P; Schreiber, M; Schott, G E

2008-04-01

Penoscrotal elephantiasis is a symptom that can be caused by local but also by systemic disorders. When the changes are reversible, conservative measures such as physical and antiphlogistic approaches lead to success. In cases of irreversible penoscrotal elephantiasis, excision and amputation of the affected penoscrotal areas are recommended to eliminate the functional disturbances. In all manifestations it is important to prevent and treat those diseases known to cause elephantiasis.

Review of avian mortality studies at concentrating solar power plants

NASA Astrophysics Data System (ADS)

Ho, Clifford K.

2016-05-01

This paper reviews past and current avian mortality studies at concentrating solar power (CSP) plants and facilities including Solar One in California, the Solar Energy Development Center in Israel, Ivanpah Solar Electric Generating System in California, Crescent Dunes in Nevada, and Gemasolar in Spain. Findings indicate that the leading causes of bird deaths at CSP plants are from collisions (primarily with reflective surfaces; i.e., heliostats) and singeing caused by concentrated solar flux. Safe irradiance levels for birds have been reported to range between 4 and 50 kW/m2. Above these levels, singeing and irreversible damage to the feathers can occur. Despite observations of large numbers of "streamers" in concentrated flux regions and reports that suggest these streamers indicate complete vaporization of birds, analyses in this paper show that complete vaporization of birds is highly improbable, and the observed streamers are likely due to insects flying into the concentrated flux. The levelized avian mortality rate during the first year of operation at Ivanpah was estimated to be 0.7 - 3.5 fatalities per GWh, which is less than the levelized avian mortality reported for fossil fuel plants but greater than that for nuclear and wind power plants. Mitigation measures include acoustic, visual, tactile, and chemosensory deterrents to keep birds away from the plant, and heliostat aiming strategies that reduce the solar flux during standby.

MiR-21 is required for efficient kidney regeneration in fish.

PubMed

Hoppe, Beate; Pietsch, Stefan; Franke, Martin; Engel, Sven; Groth, Marco; Platzer, Matthias; Englert, Christoph

2015-11-17

Acute kidney injury in mammals, which is caused by cardiovascular diseases or the administration of antibiotics with nephrotoxic side-effects is a life-threatening disease, since loss of nephrons is irreversible in mammals. In contrast, fish are able to generate new nephrons even in adulthood and thus provide a good model to study renal tubular regeneration. Here, we investigated the early response after gentamicin-induced renal injury, using the short-lived killifish Nothobranchius furzeri. A set of microRNAs was differentially expressed after renal damage, among them miR-21, which was up-regulated. A locked nucleic acid-modified antimiR-21 efficiently knocked down miR-21 activity and caused a lag in the proliferative response, enhanced apoptosis and an overall delay in regeneration. Transcriptome profiling identified apoptosis as a process that was significantly affected upon antimiR-21 administration. Together with functional data this suggests that miR-21 acts as a pro-proliferative and anti-apoptotic factor in the context of kidney regeneration in fish. Possible downstream candidate genes that mediate its effect on proliferation and apoptosis include igfbp3 and fosl1, among other genes. In summary, our findings extend the role of miR-21 in the kidney. For the first time we show its functional involvement in regeneration indicating that fast proliferation and reduced apoptosis are important for efficient renal tubular regeneration.

[PATHOPHYSIOLOGY OF THE CARDIORENAL SYNDROME].

PubMed

Balint, I; Vučak, J; Bašić-Marković, N; Klarić, D; Šakić, V Amerl

2016-12-01

Cardiorenal syndrome, a complex pathophysiological disorder of both the heart and kidneys, is a condition in which acute or chronic damage to one organ can lead to acute or chronic dysfunction of the other organ. Depending on primary organ dysfunction and disease duration, there are five different types of cardiorenal syndrome. Type 1 cardiorenal syndrome (acute cardiorenal syndrome) is defined as acute kidney injury caused by sudden decrease in heart function. Type 2 cardiorenal syndrome (chronic cardiorenal syndrome) refers to chronic kidney disease linked to chronic heart failure. Type 3 cardiorenal syndrome (acute renocardial syndrome) is caused by acute kidney injury that leads to heart failure. Type 4 cardiorenal syndrome (chronic renocardial syndrome) includes chronic heart failure due to chronic kidney disease. Type 5 cardiorenal syndrome (secondary cardiorenal syndrome) is reversible or irreversible condition marked by simultaneous heart and kidney insufficiency, as a result of multiorgan disease such as sepsis, diabetes mellitus, sarcoidosis, amyloidosis, etc. The pathophysiological patterns of cardiorenal syndrome are extremely complicated. Despite numerous publications, perplexed physiological, biochemical and hormonal disturbances as parts of the main pathogenic mechanisms of cardiorenal syndrome remain obscure. Even though there are guidelines for the treatment of patients with heart failure and chronic kidney disease, similar guidelines for the treatment of cardiorenal syndrome are lacking. In everyday practice, it is crucial to diagnose cardiorenal syndrome and use all diagnostic and therapeutic procedures available to prevent or alleviate kidney and heart failure.

Disease course and long-term outcome of juvenile localized scleroderma: Experience from a single pediatric rheumatology Centre and literature review.

PubMed

Martini, Giorgia; Fadanelli, Gloria; Agazzi, Anna; Vittadello, Fabio; Meneghel, Alessandra; Zulian, Francesco

2018-05-03

Juvenile Localized Scleroderma (JLS) is a rare disorder that may cause severe aesthetic sequelae and functional disability. To date, data on natural history and long-term outcome are discordant and difficult to compare due to the heterogeneity of clinical subtypes, treatments and methods to evaluate activity and outcome in previous studies. A retrospective and cross-sectional study including 133 patients followed between January 1991 and December 2016 was conducted at our Pediatric Rheumatology Centre. Disease course was drawn by retrospective analysis of patients' clinical features, treatment, disease course and outcome at the last evaluation. Disease activity and severity of tissue damage were assessed by using parameters derived from the Localized Scleroderma Cutaneous Assessment Tool (LoSCAT) and thermography. Most patients achieved complete remission, as only 12.5%, all with the linear subtype, had still active disease after over 10 years of follow-up. At least one disease relapse occurred in 22.2% of patients and first flare was observed 20 months after first treatment discontinuation. Mild tissue damage was observed in more than half of patients, in 25.4% was moderate and in 23.0% severe; 19.8% presented a functional limitation. The entity of skin and subcutaneous fat loss established at the early stages of the disease as 27.8% of patients with shorter disease duration had severe damage and the rates remained constant in patients with longer follow-up. The delay in start of systemic treatment was associated with longer disease activity and higher relapse rate. Patients with linear scleroderma (LS), pansclerotic morphea (PM) and mixed subtype (MS) presented more severe aesthetic and functional damage but did not differ from other subtypes as for rate of complete remission. JLS in some patients can be a very aggressive disease with persistent activity after >10 years and/or several disease relapses. As tissue damage establishes early in disease course a prompt diagnosis and start of appropriate treatment is crucial to control inflammation, to limit and stabilize damage, before it become irreversible. Clinicians must be aware that children with JLS may present disease reactivation so it is important to closely follow-up patients, particularly in the first 2 years after discontinuation of treatment when disease relapses may occur more frequently. Copyright © 2018 Elsevier B.V. All rights reserved.

Optical spectroscopy for the detection of ischemic tissue injury

DOEpatents

Demos, Stavros [Livermore, CA; Fitzgerald, Jason [Sacramento, CA; Troppmann, Christoph [Sacramento, CA; Michalopoulou, Andromachi [Athens, GR

2009-09-08

An optical method and apparatus is utilized to quantify ischemic tissue and/or organ injury. Such a method and apparatus is non-invasive, non-traumatic, portable, and can make measurements in a matter of seconds. Moreover, such a method and apparatus can be realized through optical fiber probes, making it possible to take measurements of target organs deep within a patient's body. Such a technology provides a means of detecting and quantifying tissue injury in its early stages, before it is clinically apparent and before irreversible damage has occurred.

Elevated anticardiolipin antibodies in a patient with vibration-white-finger, valvular heart disease and psoriatic arthritis.

PubMed

McHugh, N J; Elvins, D M; Ring, E F

1993-03-01

We describe a case of irreversible severe vibration-white-finger (VWF) occurring in a male who used a compression-hammer daily at work for a 20-year period. Infra-red thermography following either a cold provocation or a vibratory stress was a sensitive objective method of documenting the condition. Persistent elevation of IgG anticardiolipin antibodies (aCL) was found in his serum and may be a marker of endothelial damage associated with either VWF or the patient's coincidental valvular heart disease.

Doxorubicin, mesenchymal stem cell toxicity and antitumour activity: implications for clinical use.

PubMed

Baxter-Holland, Mia; Dass, Crispin R

2018-03-01

The use of doxorubicin, an antineoplastic medication used for the treatment of cancers via mechanisms that prevent replication of cells or lead to their death, can result in damage to healthy cells as well as malignant. Among the affected cells are mesenchymal stem cells (MSCs), which are involved in the maintenance and repair of tissues in the body. This review explores the mechanisms of biological effects and damage attributed to doxorubicin on MSCs. The PubMed database was used as a source of literature for this review. Doxorubicin has the potential to lead to significant and irreversible damage to the human bone marrow environment, including MSCs. The primary known mechanism of these changes is through free radical damage and activation of apoptotic pathways. The presence of MSCs in culture or in vivo appears to either suppress or promote tumour growth. Interactions between doxorubicin and MSCs have the potential to increase chemotherapy resistance. Doxorubicin-induced damage to MSCs is of concern clinically. However, MSCs also have been associated with resistance of tumour cells to drugs including doxorubicin. Further studies, particularly in vivo, are needed to provide consistent results of how the doxorubicin-induced changes to MSCs affect treatment and patient health. © 2018 Royal Pharmaceutical Society.

Irreversible electron attachment--a key to DNA damage by solvated electrons in aqueous solution.

PubMed

Westphal, K; Wiczk, J; Miloch, J; Kciuk, G; Bobrowski, K; Rak, J

2015-11-07

The TYT and TXT trimeric oligonucleotides, where X stands for a native nucleobase, T (thymine), C (cytosine), A (adenine), or G (guanine), and Y indicates a brominated analogue of the former, were irradiated with ionizing radiation generated by a (60)Co source in aqueous solutions containing Tris as a hydroxyl radical scavenger. In the past, these oligomers were bombarded with low energy electrons under an ultra-high vacuum and significant damage to TXT trimers was observed. However, in aqueous solution, hydrated electrons do not produce serious damage to TXT trimers although the employed radiation dose exceeded many times the doses used in radiotherapy. Thus, our studies demonstrate unequivocally that hydrated electrons, which are the major form of electrons generated during radiotherapy, are a negligible factor in damage to native DNA. It was also demonstrated that all the studied brominated nucleobases have a potential to sensitize DNA under hypoxic conditions. Strand breaks, abasic sites and the products of hydroxyl radical attachment to nucleobases have been identified by HPLC and LC-MS methods. Although all the bromonucleobases lead to DNA damage under the experimental conditions of the present work, bromopyrimidines seem to be the radiosensitizers of choice since they lead to more strand breaks than bromopurines.

Cumulative mtDNA damage and mutations contribute to the progressive loss of RGCs in a rat model of glaucoma

PubMed Central

Nickerson, John M.; Gao, Feng-juan; Sun, Zhongmou; Chen, Xin-ya; Zhang, Shu-jie; Gao, Feng; Chen, Jun-yi; Luo, Yi; Wang, Yan; Sun, Xing-huai

2015-01-01

Glaucoma is a chronic neurodegenerative disease characterized by the progressive loss of retinal ganglion cells (RGCs). Mitochondrial DNA (mtDNA) alterations have been documented as a key component of many neurodegenerative disorders. However, whether mtDNA alterations contribute to the progressive loss of RGCs and the mechanism whereby this phenomenon could occur are poorly understood. We investigated mtDNA alterations in RGCs using a rat model of chronic intraocular hypertension and explored the mechanisms underlying progressive RGC loss. We demonstrate that the mtDNA damage and mutations triggered by intraocular pressure (IOP) elevation are initiating, crucial events in a cascade leading to progressive RGC loss. Damage to and mutation of mtDNA, mitochondrial dysfunction, reduced levels of mtDNA repair/replication enzymes, and elevated reactive oxygen species form a positive feedback loop that produces irreversible mtDNA damage and mutation and contributes to progressive RGC loss, which occurs even after a return to normal IOP. Furthermore, we demonstrate that mtDNA damage and mutations increase the vulnerability of RGCs to elevated IOP and glutamate levels, which are among the most common glaucoma insults. This study suggests that therapeutic approaches that target mtDNA maintenance and repair and that promote energy production may prevent the progressive death of RGCs. PMID:25478814

Analytical and numerical analysis of frictional damage in quasi brittle materials

NASA Astrophysics Data System (ADS)

Zhu, Q. Z.; Zhao, L. Y.; Shao, J. F.

2016-07-01

Frictional sliding and crack growth are two main dissipation processes in quasi brittle materials. The frictional sliding along closed cracks is the origin of macroscopic plastic deformation while the crack growth induces a material damage. The main difficulty of modeling is to consider the inherent coupling between these two processes. Various models and associated numerical algorithms have been proposed. But there are so far no analytical solutions even for simple loading paths for the validation of such algorithms. In this paper, we first present a micro-mechanical model taking into account the damage-friction coupling for a large class of quasi brittle materials. The model is formulated by combining a linear homogenization procedure with the Mori-Tanaka scheme and the irreversible thermodynamics framework. As an original contribution, a series of analytical solutions of stress-strain relations are developed for various loading paths. Based on the micro-mechanical model, two numerical integration algorithms are exploited. The first one involves a coupled friction/damage correction scheme, which is consistent with the coupling nature of the constitutive model. The second one contains a friction/damage decoupling scheme with two consecutive steps: the friction correction followed by the damage correction. With the analytical solutions as reference results, the two algorithms are assessed through a series of numerical tests. It is found that the decoupling correction scheme is efficient to guarantee a systematic numerical convergence.

A Novel ATM/TP53/p21-Mediated Checkpoint Only Activated by Chronic γ-Irradiation

PubMed Central

Sasatani, Megumi; Iizuka, Daisuke; Masuda, Yuji; Inaba, Toshiya; Suzuki, Keiji; Ootsuyama, Akira; Umata, Toshiyuki; Kamiya, Kenji; Suzuki, Fumio

2014-01-01

Different levels or types of DNA damage activate distinct signaling pathways that elicit various cellular responses, including cell-cycle arrest, DNA repair, senescence, and apoptosis. Whereas a range of DNA-damage responses have been characterized, mechanisms underlying subsequent cell-fate decision remain elusive. Here we exposed cultured cells and mice to different doses and dose rates of γ-irradiation, which revealed cell-type-specific sensitivities to chronic, but not acute, γ-irradiation. Among tested cell types, human fibroblasts were associated with the highest levels of growth inhibition in response to chronic γ-irradiation. In this context, fibroblasts exhibited a reversible G1 cell-cycle arrest or an irreversible senescence-like growth arrest, depending on the irradiation dose rate or the rate of DNA damage. Remarkably, when the same dose of γ-irradiation was delivered chronically or acutely, chronic delivery induced considerably more cellular senescence. A similar effect was observed with primary cells isolated from irradiated mice. We demonstrate a critical role for the ataxia telangiectasia mutated (ATM)/tumor protein p53 (TP53)/p21 pathway in regulating DNA-damage-associated cell fate. Indeed, blocking the ATM/TP53/p21 pathway deregulated DNA damage responses, leading to micronucleus formation in chronically irradiated cells. Together these results provide insights into the mechanisms governing cell-fate determination in response to different rates of DNA damage. PMID:25093836

[Complex application 2-ethyl-6-methyl-3-hydroxypyridine-succinate and vinpocetine in cerebrovascular disorder.

PubMed

Solovyeva, E Yu; Karneev, A N; Chekanov, A V; Baranova, O A; Choi, I V

Developing brain ischemia due to cerebral vascularization leads to disruption of brain metabolism. Chronic cerebral hypoperfusion leads to irreversible brain damage and plays an important role in the development of some types of dementia. Early use of antioxidants such as ethyl ether apovincamine acid (vinpocetine) and 2-ethyl-6-methyl-3-hydroxypyridine-succinate in the treatment of this pathology is seen as a real pathogenetically based method of correction of cerebral metabolism with cerebral vascular disorders, demonstrating the increase in cerebral blood flow and also neuroprotective effects. Clinical studies and studies on biological models show that the main mechanisms of action of vinpocetine and 2-ethyl-6-methyl-3-hydroxypyridine-succinate, although have a similar focus, but implementing neuroprotective and nootropic effects via various links in the pathogenesis of ischemic brain damage.

Structural Engineering Managers - Innovation Challenges for their Skills

NASA Astrophysics Data System (ADS)

Linkeschová, D.; Tichá, A.

2015-11-01

The profession of a structural engineer is highly responsible, because the consequences of a structural engineer's errors result not only in economic damage to the property and often irreversible damage to the environment, they can also lead to direct loss of lives. In the current turbulent, dynamically developing society the managerial methods of structural engineers should not stagnate at the level of the last century applications. This paper deals with the challenges which the ongoing century poses to structural engineers and managers. It compares the results of research regarding the current state of managerial skills of structural engineers in Czech building companies to the defined skills of the 21st century's managers according to the global research programme ITL Research and according to the Vision for the Future of Structural Engineering, drawn up by Structural Engineering Institute - SEI ASCE.

[Eyeball structure changes in high myopic patients and their significance for forensic assessment].

PubMed

Liu, Yi-Chang; Xia, Wen-Tao; Zhou, Xing-Tao; Liu, Rui-Jue; Bian, Shi-Zhong; Ying, Chong-Liang; Zhu, Guang-You

2008-10-01

There are irreversible eyeball structural changes in high myopic patients. These changes include axial length, corneal radius, anterior chamber depth, fundus degeneration, macula thickness, etc. There is a close relationship between the damage degree of visual function and these changes. The incidence of complications, such as vitreous opacity, posterior vitreous detachment, cataract, glaucoma, posterior staphyloma and retina detachment, is also highly related to the myopia diopter. More and more researches have indicated that the myopia diopter and the level of visual function are affected by multiple factors. It is promising to detect all of these changes by different kinds of methods, and to assess visual function through these changes. By clarifying these changes, it is also useful to distinguish traumatic damage from disease to provide evidence for forensic assessment of eye injuries.

Mixed-Mode Decohesion Finite Elements for the Simulation of Delamination in Composite Materials

NASA Technical Reports Server (NTRS)

Camanho, Pedro P.; Davila, Carlos G.

2002-01-01

A new decohesion element with mixed-mode capability is proposed and demonstrated. The element is used at the interface between solid finite elements to model the initiation and non-self-similar growth of delaminations. A single relative displacement-based damage parameter is applied in a softening law to track the damage state of the interface and to prevent the restoration of the cohesive state during unloading. The softening law for mixed-mode delamination propagation can be applied to any mode interaction criterion such as the two-parameter power law or the three-parameter Benzeggagh-Kenane criterion. To demonstrate the accuracy of the predictions and the irreversibility capability of the constitutive law, steady-state delamination growth is simulated for quasistatic loading-unloading cycles of various single mode and mixed-mode delamination test specimens.

Positive Feedback of NDT80 Expression Ensures Irreversible Meiotic Commitment in Budding Yeast

PubMed Central

Tsuchiya, Dai; Yang, Yang; Lacefield, Soni

2014-01-01

In budding yeast, meiotic commitment is the irreversible continuation of the developmental path of meiosis. After reaching meiotic commitment, cells finish meiosis and gametogenesis, even in the absence of the meiosis-inducing signal. In contrast, if the meiosis-inducing signal is removed and the mitosis-inducing signal is provided prior to reaching meiotic commitment, cells exit meiosis and return to mitosis. Previous work has shown that cells commit to meiosis after prophase I but before entering the meiotic divisions. Since the Ndt80 transcription factor induces expression of middle meiosis genes necessary for the meiotic divisions, we examined the role of the NDT80 transcriptional network in meiotic commitment. Using a microfluidic approach to analyze single cells, we found that cells commit to meiosis in prometaphase I, after the induction of the Ndt80-dependent genes. Our results showed that high-level expression of NDT80 is important for the timing and irreversibility of meiotic commitment. A modest reduction in NDT80 levels delayed meiotic commitment based on meiotic stages, although the timing of each meiotic stage was similar to that of wildtype cells. A further reduction of NDT80 resulted in the surprising finding of inappropriately uncommitted cells: withdrawal of the meiosis-inducing signal and addition of the mitosis-inducing signal to cells at stages beyond metaphase I caused return to mitosis, leading to multi-nucleate cells. Since Ndt80 enhances its own transcription through positive feedback, we tested whether positive feedback ensured the irreversibility of meiotic commitment. Ablating positive feedback in NDT80 expression resulted in a complete loss of meiotic commitment. These findings suggest that irreversibility of meiotic commitment is a consequence of the NDT80 transcriptional positive feedback loop, which provides the high-level of Ndt80 required for the developmental switch of meiotic commitment. These results also illustrate the importance of irreversible meiotic commitment for maintaining genome integrity by preventing formation of multi-nucleate cells. PMID:24901499

Magnetic resonance imaging characteristics of nonthermal irreversible electroporation in vegetable tissue.

PubMed

Hjouj, Mohammad; Rubinsky, Boris

2010-07-01

We introduce and characterize the use of MRI for studying nonthermal irreversible electroporation (NTIRE) in a vegetative tissue model. NTIRE is a new minimally invasive surgical technique for tissue ablation in which microsecond, high electric-field pulses form nanoscale defects in the cell membrane that lead to cell death. Clinical NTIRE sequences were applied to a potato tuber tissue model. The potato is used for NTIRE studies because cell damage is readily visible with optical means through a natural oxidation process of released intracellular enzymes (polyphenol oxidase) and the formation of brown-black melanins. MRI sequences of the treated area were taken at various times before and after NTIRE and compared with photographic images. A comparison was made between T1W, T2W, FLAIR and STIR MRIs of NTIRE and photographic images. Some MRI sequences show changes in areas treated by irreversible electroporation. T1W and FLAIR produce brighter images of the treated areas. In contrast, the signal was lost from the treated area when a suppression technique, STIR, was used. There was similarity between optical photographic images of the treated tissue and MRIs of the same areas. This is the first study to characterize MRI of NTIRE in vegetative tissue. We find that NTIRE produces changes in vegetative tissue that can be imaged by certain MRI sequences. This could make MRI an effective tool to study the fundamentals of NTIRE in nonanimal tissue.

[Four cases of bacterial meningitis after epidural anesthesia].

PubMed

Garlicki, A; Caban, J; Krukowiecki, J; Kluba-Wojewoda, U

1994-01-01

Four patients with bacterial meningitis, previously anaesthetized epidurally, have been described. In one case the course of the disease was very serious and resulted in irreversible neurological lesion. Although epidural anaesthesia is considered to be a harmless procedure it can cause some purulent complications.

Effect of Detergent on Electrical Properties of Squid Axon Membrane

PubMed Central

Kishimoto, Uichiro; Adelman, William J.

1964-01-01

The effects of detergents on squid giant axon action and resting potentials as well as membrane conductances in the voltage clamp have been studied. Anionic detergents (sodium lauryl sulfate, 0.1 to 1.0 mM; dimethyl benzene sulfonate, 1 to 20 mM, pH 7.6) cause a temporary increase and a later decrease of action potential height and the value of the resting potential. Cationic detergent (cetyl trimethyl ammonium chloride, 6 x 10-5 M or more, pH 7.6) generally brings about immediate and irreversible decreases in the action and resting potentials. Non-ionic detergent (tween 80, 0.1 M, pH 7.6) causes a slight reversible reduction of action potential height without affecting the value of the resting potential. Both anionic and cationic detergents generally decrease the sodium and potassium conductances irreversibly. The effect of non-ionic detergent is to decrease the sodium conductance reversibly, leaving the potassium conductance almost unchanged. PMID:14158665

Nutrient-Dependent Endocycling in Steroidogenic Tissue Dictates Timing of Metamorphosis in Drosophila melanogaster

PubMed Central

Ohhara, Yuya; Kobayashi, Satoru

2017-01-01

Many animals have an intrinsic growth checkpoint during juvenile development, after which an irreversible decision is made to upregulate steroidogenesis, triggering the metamorphic juvenile-to-adult transition. However, a molecular process underlying such a critical developmental decision remains obscure. Here we show that nutrient-dependent endocycling in steroidogenic cells provides the machinery necessary for irreversible activation of metamorphosis in Drosophila melanogaster. Endocycle progression in cells of the prothoracic gland (PG) is tightly coupled with the growth checkpoint, and block of endocycle in PG cells causes larval developmental arrest due to reduction in biosynthesis of the steroid hormone ecdysone. Moreover, inhibition of the nutrient sensor target of rapamycin (TOR) in the PG during the checkpoint period causes endocycle inhibition and developmental arrest, which can be rescued by inducing additional rounds of endocycles by Cyclin E. We propose that a TOR-mediated cell cycle checkpoint in steroidogenic tissue provides a systemic growth checkpoint for reproductive maturation. PMID:28121986

Response to short term ultraviolet stress in the reef-building coral Pocillopora capitata (Anthozoa: Scleractinia).

PubMed

Liñán-Cabello, Marco A; Flores-Ramírez, Laura A; Cobo-Díaz, José Francisco; Zenteno-Savin, Tania; Olguín-Monroy, Norma O; Olivos-Ortiz, Aramís; Tintos-Gómez, Adrián

2010-03-01

Coral reefs are impacted by a range of environmental variables that affect their growth and survival, the main factors being the high irradiance and temperature fluctuations. Specimens of Pocillopora capitata Verrill 1864 were exposed to photosynthetically active radiation (PAR) and ultraviolet radiation (UVR) for 32 h under laboratory conditions. We examined lipid peroxidation (MDA), antioxidant enzyme activities (SOD, CAT, GPx and GST), chlorophyll a (Chl a), carotenoid pigments (CPs), mycosporine-like amino acids (MAAs), and expulsion of zooxanthellae. Our results revealed that corals exposed to UVR had relatively low levels of carotenoids and antioxidant enzyme activities compared to those exposed to PAR, as well as lower CPs/Chl a ratios. Although MAAs and CPs are rapidly produced as non-enzymatic antioxidants in response to UVR in corals, these were not sufficient, even in the dark phase of the experiment, to mitigate the damage caused by formation of reactive oxygen species (ROS), which caused breakdown of the symbiotic relationship between the zooxanthellae and the host animal to an extent 33 times greater than in the PAR treatment. In this study, it could be possible to distinguish that, parallel to the short-term adjustments, such as the amount of pigment in the algae or the sensitivity of the photosynthetic response reported in other species of coral, P. capitata exhibits at the enzymatic level a series of responses oriented to resist the effects derived from the propagation of ROS and, thus, to adapt to and maintain its reproductive capacity in shallow oceanic environments that commonly exhibit high UVR levels. Nevertheless, as a result of the inappropriate location of the artificial intercommunication structure of the Juluapan Lagoon with respect to the arrecifal area of study and therefore of the tides influence, other variables, such as the changes in short-term in turbidity, sediment inputs, nutrients, temperature and osmolarity, can act in combination and cause irreversible damage. The implementation of a management plan for the coralline reefs of the Mexican Pacific coast is required.

Disruption of the outer mitochondrial membrane as a result of large amplitude swelling: the impact of irreversible permeability transition.

PubMed

Petit, P X; Goubern, M; Diolez, P; Susin, S A; Zamzami, N; Kroemer, G

1998-04-10

Upon induction of permeability transition with different agents (Ca2+, tert-butyl hydroperoxide, atractyloside), mouse hepatocyte mitochondria manifest a disruption of outer membrane integrity leading to the release of cytochrome c and apoptosis-inducing factor (AIF), two proteins which are involved in programmed cell death (apoptosis). Chelation of Ca2+ shortly (within 2 min) after its addition to isolated mitochondria reestablished the mitochondrial transmembrane potential (deltapsi(m)), prevented induction of large amplitude swelling and release of both cytochrome c and AIF. In contrast, late Ca2+ chelation (10 min after addition of Ca2+) failed to affect these parameters. Cytochrome c appears to be released through a mechanically damaged outer mitochondrial membrane rather than via a specific release mechanism. These findings clarify the mechanisms through which irreversible permeability transition occurs with subsequent large amplitude swelling culminating in the release of intermembrane proteins from mitochondria. Moreover, they confirm the hypothesis formulated by Skulachev [FEBS Lett. 397 (1996) 7-10 and Q. Rev. Biophys. 29 (1996) 169-2021 linking permeability transition to activation of the apoptogenic catabolic enzymes.

Dual echelon femtosecond single-shot spectroscopy

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

Shin, Taeho; Wolfson, Johanna W.; Teitelbaum, Samuel W.

We have developed a femtosecond single-shot spectroscopic technique to measure irreversible changes in condensed phase materials in real time. Crossed echelons generate a two-dimensional array of time-delayed pulses with one femtosecond probe pulse. This yields 9 ps of time-resolved data from a single laser shot, filling a gap in currently employed measurement methods. We can now monitor ultrafast irreversible dynamics in solid-state materials or other samples that cannot be flowed or replenished between laser shots, circumventing limitations of conventional pump-probe methods due to sample damage or product buildup. Despite the absence of signal-averaging in the single-shot measurement, an acceptable signal-to-noisemore » level has been achieved via background and reference calibration procedures. Pump-induced changes in relative reflectivity as small as 0.2%−0.5% are demonstrated in semimetals, with both electronic and coherent phonon dynamics revealed by the data. The optical arrangement and the space-to-time conversion and calibration procedures necessary to achieve this level of operation are described. Sources of noise and approaches for dealing with them are discussed.« less

In vivo confocal Raman spectroscopic analysis of the effects of IR radiation in the stratum corneum of human skin (Conference Presentation)

NASA Astrophysics Data System (ADS)

Rajasekaran, Ramu; Bergamo Lopes, Monica; Magrini, Taciana D.; Figueira Lopes Cançado, Ana Clara; Abrahao Martin, Airton

2017-02-01

Stratum Corneum is the outer covering of the body, which serves as a barrier to infection. The composition of the skin changes withexternal environmental factors, such as temperature, sun irradiation, air pollutants, chemical hazards, as well as other factors.Solar radiation,especially IR radiation is being used as medicine for wound healing processes, in cosmetology, in physiotherapy and warming of muscles. Also, it was reported that the IR radiation produces free radicals and the excess production of free radicals causes irreversible damages. It has been reported that heat may be transmitted by IR radiation, which results in raised skin temperature and the chronic heat exposure of human skin may cause alterations. Erythema igne is one such disease known to be caused by chronic heat exposure. Many techniques have been adopted for monitoring the changes in the skin, which includes the tape stripping and biopsy as the primary methodology. However, these in vitro techniques are invasive, time consuming, and may not provide the actual information as in in vivo conditions. Confocal Raman spectroscopy,which is non-invasive and real time was considered as a potential tool for the in vivo analysis of the distribution and characteristics of different metabolic conditions and their variations of the skin. In this regard, we aimed at in vivo characterization of the IR induced changes in the stratum corneum of human volunteers. The results of Raman spectral signatures with respect to the control and IR exposed skin will be discussed.

Dural closure for the treatment of superficial siderosis.

PubMed

Egawa, Satoru; Yoshii, Toshitaka; Sakaki, Kyohei; Inose, Hiroyuki; Kato, Tsuyoshi; Kawabata, Shigenori; Tomizawa, Shoji; Okawa, Atsushi

2013-04-01

Superficial siderosis (SS) of the CNS is a rare disease caused by repeated hemorrhages in the subarachnoid space. The subsequent deposition of hemosiderin in the brain and spinal cord leads to the progression of neurological deficits. The causes of bleeding include prior intradural surgery, carcinoma, arteriovenous malformation, nerve root avulsion, and dural abnormality. Recently, surgical treatment of SS associated with dural defect has been reported. The authors of the present report describe 2 surgically treated SS cases and review the literature on surgically treated SS. The patients had dural defects with fluid-filled collections in the spinal canal. In both cases, the dural defects were successfully closed, and the fluid collection was resolved postoperatively. In one case, the neurological symptoms did not progress postoperatively. In the other case, the patient had long history of SS, and the clinical manifestations partially deteriorated after surgery, despite the successful dural closure. In previously reported surgically treated cases, the dural defects were closed by sutures, patches, fibrin glue, or muscle/fat grafting. Regardless of the closing method, dural defect closure has been shown to stop CSF leakage and subarachnoid hemorrhaging. Successfully repairing the defect can halt the disease progression in most cases and may improve the symptoms that are associated with CSF hypovolemia. However, the effect of the dural closure may be limited in patients with long histories of SS because of the irreversibility of the neural tissue damage caused by hemosiderin deposition. In patients with SS, it is important to diagnose and repair the dural defect early to minimize the neurological impairments that are associated with dural defects.

Magnetic resonance spectroscopy of normal appearing white matter in early relapsing-remitting multiple sclerosis: correlations between disability and spectroscopy

PubMed Central

Ruiz-Peña, Juan Luis; Piñero, Pilar; Sellers, Guillermo; Argente, Joaquín; Casado, Alfredo; Foronda, Jesus; Uclés, Antonio; Izquierdo, Guillermo

2004-01-01

Background What currently appears to be irreversible axonal loss in normal appearing white matter, measured by proton magnetic resonance spectroscopy is of great interest in the study of Multiple Sclerosis. Our aim is to determine the axonal damage in normal appearing white matter measured by magnetic resonance spectroscopy and to correlate this with the functional disability measured by Multiple Sclerosis Functional Composite scale, Neurological Rating Scale, Ambulation Index scale, and Expanded Disability Scale Score. Methods Thirty one patients (9 male and 22 female) with relapsing remitting Multiple Sclerosis and a Kurtzke Expanded Disability Scale Score of 0–5.5 were recruited from four hospitals in Andalusia, Spain and included in the study. Magnetic resonance spectroscopy scans and neurological disability assessments were performed the same day. Results A statistically significant correlation was found (r = -0.38 p < 0.05) between disability (measured by Expanded Disability Scale Score) and N-Acetyl Aspartate (NAA/Cr ratio) levels in normal appearing white matter in these patients. No correlation was found between the NAA/Cr ratio and disability measured by any of the other disability assessment scales. Conclusions There is correlation between disability (measured by Expanded Disability Scale Score) and the NAA/Cr ratio in normal appearing white matter. The lack of correlation between the NAA/Cr ratio and the Multiple Sclerosis Functional Composite score indicates that the Multiple Sclerosis Functional Composite is not able to measure irreversible disability and would be more useful as a marker in stages where axonal damage is not a predominant factor. PMID:15191618

Radiation damage to amorphous carbon thin films irradiated by multiple 46.9 nm laser shots below the single-shot damage threshold

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

Juha, L.; Hajkova, V.; Vorlicek, V.

2009-05-01

High-surface-quality amorphous carbon (a-C) optical coatings with a thickness of 45 nm, deposited by magnetron sputtering on a silicon substrate, were irradiated by the focused beam of capillary-discharge Ne-like Ar extreme ultraviolet laser (CDL=capillary-discharge laser; XUV=extreme ultraviolet, i.e., wavelengths below 100 nm). The laser wavelength and pulse duration were 46.9 nm and 1.7 ns, respectively. The laser beam was focused onto the sample surface by a spherical Sc/Si multilayer mirror with a total reflectivity of about 30%. The laser pulse energy was varied from 0.4 to 40 muJ on the sample surface. The irradiation was carried out at five fluencemore » levels between 0.1 and 10 J/cm{sup 2}, accumulating five different series of shots, i.e., 1, 5, 10, 20, and 40. The damage to the a-C thin layer was investigated by atomic force microscopy (AFM) and Nomarski differential interference contrast (DIC) optical microscopy. The dependence of the single-shot-damaged area on pulse energy makes it possible to determine a beam spot diameter in the focus. Its value was found to be equal to 23.3+-3.0 mum using AFM data, assuming the beam to have a Gaussian profile. Such a plot can also be used for a determination of single-shot damage threshold in a-C. A single-shot threshold value of 1.1 J/cm{sup 2} was found. Investigating the consequences of the multiple-shot exposure, it has been found that an accumulation of 10, 20, and 40 shots at a fluence of 0.5 J/cm{sup 2}, i.e., below the single-shot damage threshold, causes irreversible changes of thin a-C layers, which can be registered by both the AFM and the DIC microscopy. In the center of the damaged area, AFM shows a-C removal to a maximum depth of 0.3, 1.2, and 1.5 nm for 10-, 20- and 40-shot exposure, respectively. Raman microprobe analysis does not indicate any change in the structure of the remaining a-C material. The erosive behavior reported here contrasts with the material expansion observed earlier [L. Juha et al., Proc. SPIE 5917, 91 (2005)] on an a-C sample irradiated by a large number of femtosecond pulses of XUV high-order harmonics.« less

BYK191023 (2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-3h-imidazo[4,5-b]pyridine) is an NADPH- and time-dependent irreversible inhibitor of inducible nitric-oxide synthase.

PubMed

Tiso, Mauro; Strub, Andreas; Hesslinger, Christian; Kenney, Claire T; Boer, Rainer; Stuehr, Dennis J

2008-04-01

Imidazopyridine derivates were recently shown to be a novel class of selective and arginine-competitive inhibitors of inducible nitric-oxide synthase (iNOS), and 2-[2-(4-methoxypyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridine (BYK191023) was found to have very high selectivity in enzymatic and cellular models ( Mol Pharmacol 69: 328-337, 2006 ). Here, we show that BYK191023 irreversibly inactivates murine iNOS in an NADPH- and time-dependent manner, whereas it acts only as a reversible l-arginine-competitive inhibitor in the absence of NADPH or during anaerobic preincubation. Time-dependent irreversible inhibition by BYK191023 could also be demonstrated in intact cells using the RAW macrophage or iNOS-overexpressing human embryonic kidney 293 cell lines. The mechanism of BYK191023 inhibition in the presence of NADPH was studied using spectral, kinetic, chromatographic, and radioligand binding methods. BYK191023-bound iNOS was spectrally indistinguishable from l-arginine-bound iNOS, pointing to an interaction of BYK191023 with the catalytic center of the enzyme. [(3)H]BYK191023 was recovered quantitatively from irreversibly inactivated iNOS, and no inhibitor metabolite was detected by high-performance liquid chromatography (HPLC). Size exclusion chromatography revealed only about 20% iNOS dissociation into monomers. Furthermore, HPLC and spectrophotometric analysis showed that the irreversible inhibition was associated with loss of heme from iNOS and a reduced ability to form the distinctive ferrous heme-CO complex (cytochrome P450). Thus, enzyme inactivation is mainly caused by heme loss, and it occurs in the inhibitor-bound enzyme in the presence of electron flux from NADPH.

Abandon the dead donor rule or change the definition of death?

PubMed

Veatch, Robert M

2004-09-01

Research by Siminoff and colleagues reveals that many lay people in Ohio classify legally living persons in irreversible coma or persistent vegetative state (PVS) as dead that additional respondents, although classifying such patients as living, would be willing to procure organs from them. This paper analyzes possible implications of these findings for public policy. A majority would procure organs from those in irreversible coma or in PVS. Two strategies for legitimizing such procurement are suggested. One strategy would be to make exceptions to the dead donor rule permitting procurement from those in PVS or at least those who are in irreversible coma while continuing to classify them as living. Another strategy would be to further amend the definition of death to classify one or both groups as deceased, thus permitting procurement without violation of the dead donor rule. Permitting exceptions to the dead donor rule would require substantial changes in law--such as authorizing procuring surgeons to end the lives of patients by means of organ procurement--and would weaken societal prohibitions on killing. The paper suggests that it would be easier and less controversial to further amend the definition of death to classify those in irreversible coma and PVS as dead. Incorporation of a conscience clause to permit those whose religious or philosophical convictions support whole-brain or cardiac-based death pronouncement would avoid violating their beliefs while causing no more than minimal social problems. The paper questions whether those who would support an exception to the dead donor rule in these cases and those who would support a further amendment to the definition of death could reach agreement to adopt a public policy permitting organ procurement of those in irreversible coma or PVS when proper consent is obtained.

Mildly Acidic pH Triggers an Irreversible Conformational Change in the Fusion Domain of Herpes Simplex Virus 1 Glycoprotein B and Inactivation of Viral Entry.

PubMed

Weed, Darin J; Pritchard, Suzanne M; Gonzalez, Floricel; Aguilar, Hector C; Nicola, Anthony V

2017-03-01

Herpes simplex virus (HSV) entry into a subset of cells requires endocytosis and endosomal low pH. Preexposure of isolated virions to mildly acidic pH of 5 to 6 partially inactivates HSV infectivity in an irreversible manner. Acid inactivation is a hallmark of viruses that enter via low-pH pathways; this occurs by pretriggering conformational changes essential for fusion. The target and mechanism(s) of low-pH inactivation of HSV are unclear. Here, low-pH-treated HSV-1 was defective in fusion activity and yet retained normal levels of attachment to cell surface heparan sulfate and binding to nectin-1 receptor. Low-pH-triggered conformational changes in gB reported to date are reversible, despite irreversible low-pH inactivation. gB conformational changes and their reversibility were measured by antigenic analysis with a panel of monoclonal antibodies and by detecting changes in oligomeric conformation. Three-hour treatment of HSV-1 virions with pH 5 or multiple sequential treatments at pH 5 followed by neutral pH caused an irreversible >2.5 log infectivity reduction. While changes in several gB antigenic sites were reversible, alteration of the H126 epitope was irreversible. gB oligomeric conformational change remained reversible under all conditions tested. Altogether, our results reveal that oligomeric alterations and fusion domain changes represent distinct conformational changes in gB, and the latter correlates with irreversible low-pH inactivation of HSV. We propose that conformational change in the gB fusion domain is important for activation of membrane fusion during viral entry and that in the absence of a host target membrane, this change results in irreversible inactivation of virions. IMPORTANCE HSV-1 is an important pathogen with a high seroprevalence throughout the human population. HSV infects cells via multiple pathways, including a low-pH route into epithelial cells, the primary portal into the host. HSV is inactivated by low-pH preexposure, and gB, a class III fusion protein, undergoes reversible conformational changes in response to low-pH exposure. Here, we show that low-pH inactivation of HSV is irreversible and due to a defect in virion fusion activity. We identified an irreversible change in the fusion domain of gB following multiple sequential low-pH exposures or following prolonged low-pH treatment. This change appears to be separable from the alteration in gB quaternary structure. Together, the results are consistent with a model by which low pH can have an activating or inactivating effect on HSV depending on the presence of a target membrane. Copyright © 2017 American Society for Microbiology.

Exotic invasive plants

Treesearch

Carolyn Hull Sieg; Barbara G. Phillips; Laura P. Moser

2003-01-01

Ecosystems worldwide are threatened by nonnative plant invasions that can cause undesirable, irreversible changes. They can displace native plants and animals, out-cross with native flora, alter nutrient cycling and other ecosystem functions, and even change an ecosystem's flammability (Walker and Smith 1997). After habitat loss, the spread of exotic species is...

Block selective redaction for minimizing loss during de-identification of burned in text in irreversibly compressed JPEG medical images.

PubMed

Clunie, David A; Gebow, Dan

2015-01-01

Deidentification of medical images requires attention to both header information as well as the pixel data itself, in which burned-in text may be present. If the pixel data to be deidentified is stored in a compressed form, traditionally it is decompressed, identifying text is redacted, and if necessary, pixel data are recompressed. Decompression without recompression may result in images of excessive or intractable size. Recompression with an irreversible scheme is undesirable because it may cause additional loss in the diagnostically relevant regions of the images. The irreversible (lossy) JPEG compression scheme works on small blocks of the image independently, hence, redaction can selectively be confined only to those blocks containing identifying text, leaving all other blocks unchanged. An open source implementation of selective redaction and a demonstration of its applicability to multiframe color ultrasound images is described. The process can be applied either to standalone JPEG images or JPEG bit streams encapsulated in other formats, which in the case of medical images, is usually DICOM.

Carnot's cycle for small systems: Irreversibility and cost of operations

NASA Astrophysics Data System (ADS)

Sekimoto, Ken; Takagi, Fumiko; Hondou, Tsuyoshi

2000-12-01

In the thermodynamic limit, the existence of a maximal efficiency of energy conversion attainable by a Carnot cycle consisting of quasistatic isothermal and adiabatic processes precludes the existence of a perpetual machine of the second kind, whose cycles yield positive work in an isothermal environment. We employ the recently developed framework of the energetics of stochastic processes (called ``stochastic energetics'') to reanalyze the Carnot cycle in detail, taking account of fluctuations, without taking the thermodynamic limit. We find that in this nonmacroscopic situation both processes of connection to and disconnection from heat baths and adiabatic processes that cause distortion of the energy distribution are sources of inevitable irreversibility within the cycle. Also, the so-called null-recurrence property of the cumulative efficiency of energy conversion over many cycles and the irreversible property of isolated, purely mechanical processes under external ``macroscopic'' operations are discussed in relation to the impossibility of a perpetual machine, or Maxwell's demon. This analysis may serve as the basis for the design and analysis of mesoscopic energy converters in the near future.

Irreversible covalent modification of type I dehydroquinase with a stable Schiff base.

PubMed

Tizón, Lorena; Maneiro, María; Peón, Antonio; Otero, José M; Lence, Emilio; Poza, Sergio; van Raaij, Mark J; Thompson, Paul; Hawkins, Alastair R; González-Bello, Concepción

2015-01-21

The irreversible inhibition of type I dehydroquinase (DHQ1), the third enzyme of the shikimic acid pathway, is investigated by structural, biochemical and computational studies. Two epoxides, which are mimetics of the natural substrate, were designed as irreversible inhibitors of the DHQ1 enzyme and to study the binding requirements of the linkage to the enzyme. The epoxide with the S configuration caused the covalent modification of the protein whereas no reaction was obtained with its epimer. The first crystal structure of DHQ1 from Salmonella typhi covalently modified by the S epoxide, which is reported at 1.4 Å, revealed that the modified ligand is surprisingly covalently attached to the essential Lys170 by the formation of a stable Schiff base. The experimental and molecular dynamics simulation studies reported here highlight the huge importance of the conformation of the C3 carbon of the ligand for covalent linkage to this type of aldolase I enzyme, revealed the key role played by the essential His143 as a Lewis acid in this process and show the need for a neatly closed active site for catalysis.

Congenital brainstem disconnection associated with a syrinx of the brainstem.

PubMed

Barth, P G; de Vries, L S; Nikkels, P G J; Troost, D

2008-02-01

We report a case of congenital brainstem disconnection including the second detailed autopsy. A full-term newborn presented with irreversible apnoea and died on the fifth day. MRI revealed disconnection of the brainstem. The autopsy included a series of transverse sections of the mesencephalon, medulla oblongata and bridging tissue fragments. A fragile tube walled by mature brainstem tissue could be reconstructed. It enveloped a cylinder of fluid within the ventral pons extending to the mesencephalon and the lower brainstem. The aqueduct was patent and outside the lesion. The basilar artery was represented by a tiny median vessel. The ventral and lateral parts of the posterior brainstem were surrounded by heterotopic glial tissue. The olivary nucleus was absent and the cerebellar dentate nucleus was dysplastic. Considering the maturity of the remaining parts of the pons, the onset of structural decline is likely to be close to the time of birth. Probable causes are progressively insufficient perfusion through an hypoplastic basilar artery, and obstructed venous drainage through an abnormal glial barrier surrounding the posterior brainstem. The morphological findings can be characterized as a syrinx, known from disorders in which brainstem or spinal cord are damaged by a combination of mechanical and circulatory factors.

The Feasibility of Using Thermal Strain Imaging to Regulate Energy Delivery During Intracardiac Radio-Frequency Ablation

PubMed Central

Seo, Chi Hyung; Stephens, Douglas N.; Cannata, Jonathan; Dentinger, Aaron; Lin, Feng; Park, Suhyun; Wildes, Douglas; Thomenius, Kai E.; Chen, Peter; Nguyen, Tho; de La Rama, Alan; Jeong, Jong Seob; Mahajan, Aman; Shivkumar, Kalyanam; Nikoozadeh, Amin; Oralkan, Omer; Truong, Uyen; Sahn, David J.; Khuri-Yakub, Pierre T.; O’Donnell, Matthew

2011-01-01

A method is introduced to monitor cardiac ablative therapy by examining slope changes in the thermal strain curve caused by speed of sound variations with temperature. The sound speed of water-bearing tissue such as cardiac muscle increases with temperature. However, at temperatures above about 50°C, there is no further increase in the sound speed and the temperature coefficient may become slightly negative. For ablation therapy, an irreversible injury to tissue and a complete heart block occurs in the range of 48 to 50°C for a short period in accordance with the well-known Arrhenius equation. Using these two properties, we propose a potential tool to detect the moment when tissue damage occurs by using the reduced slope in the thermal strain curve as a function of heating time. We have illustrated the feasibility of this method initially using porcine myocardium in vitro. The method was further demonstrated in vivo, using a specially equipped ablation tip and an 11-MHz microlinear intracardiac echocardiography (ICE) array mounted on the tip of a catheter. The thermal strain curves showed a plateau, strongly suggesting that the temperature reached at least 50°C. PMID:21768025

Protective effect of conditioning agents on Afro-ethnic hair chemically treated with thioglycolate-based straightening emulsion.

PubMed

Dias, Tania Cristina de Sá; Baby, André Rolim; Kaneko, Telma Mary; Velasco, Maria Valéria Robles

2008-06-01

Straightening is a chemical process by which excessively curly hair is straightened in an irreversible way. Generally, products are formulated as emulsions with high pH value (9.0-12.0), which, after applied on hair, cause considerable damage, making it dry and fragile. This research work evaluated the protective effect of lauryl PEG/PPG-18/18 methicone, cyclopentasiloxane (and) PEG-12 dimethicone cross-polymer, jojoba oil, and aqua (and) cystine bis-PG propyl silanetriol, as conditioning agents, on Afro-ethnic hair locks treated with thioglycolate-based straightening emulsions by protein loss, combability, and traction to rupture. Standard Afro-ethnic hair locks were prepared following a protocol for straightening emulsion application. Considering the assays performed, the addition of conditioning agents to the straightening emulsion with ammonium thioglycolate benefited the hair fiber, thus diminishing protein loss, protecting the hair thread, and improving resistance to breakage. Jojoba oil and lauryl PEG/PPG-18/18 methicone were the conditioning agents that presented the best results. Straightening emulsions with ammonium thioglycolate containing aqua (and) cystine bis-PG propyl silanetriol and cyclopentasiloxane (and) PEG-12 dimethicone cross-polymer were the ones that provided higher breakage resistance of the thread.

Hypericin in cancer treatment: more light on the way.

PubMed

Agostinis, Patrizia; Vantieghem, Annelies; Merlevede, Wilfried; de Witte, Peter A M

2002-03-01

Photodynamic therapy (PDT) has been described as a promising new modality for the treatment of cancer. PDT involves the combination of a photosensitizing agent (photosensitizer), which is preferentially taken up and retained by tumor cells, and visible light of a wavelength matching the absorption spectrum of the drug. Each of these factors is harmless by itself, but when combined they ultimately produce, in the presence of oxygen, cytotoxic products that cause irreversible cellular damage and tumor destruction. Hypericin, a powerful naturally occurring photosensitizer, is found in Hypericum perforatum plants, commonly known as St. John's wort. In recent years increased interest in hypericin as a potential clinical anticancer agent has arisen since several studies established its powerful in vivo and in vitro antineoplastic activity upon irradiation. Investigations of the molecular mechanisms underlying hypericin photocytotoxicity in cancer cells have revealed that this photosensitizer can induce both apoptosis and necrosis in a concentration and light dose-dependent fashion. Moreover, PDT with hypericin results in the activation of multiple pathways that can either promote or counteract the cell death program. This review focuses on the more recent advances in the use of hypericin as a photodynamic agent and discusses the current knowledge on the signaling pathways underlying its photocytotoxic action.

Impact of nanosecond pulsed electric fields on primary hippocampal neurons

NASA Astrophysics Data System (ADS)

Roth, Caleb C.; Payne, Jason A.; Kuipers, Marjorie A.; Thompson, Gary L.; Wilmink, Gerald J.; Ibey, Bennett L.

2012-02-01

Cellular exposure to nanosecond pulsed electric fields (nsPEF) are believed to cause immediate creation of nanopores in the plasma membrane. These nanopores enable passage of small ions, but remain impermeable to larger molecules like propidium iodide. Previous work has shown that nanopores are stable for minutes after exposure, suggesting that formation of nanopores in excitable cells could lead to prolonged action potential inhibition. Previously, we measured the formation of nanopores in neuroblastoma cells by measuring the influx of extracellular calcium by preloading cells with Calcium Green-AM. In this work, we explored the impact of changing the width of a single nsPEF, at constant amplitude, on uptake of extracellular calcium ions by primary hippocampal neurons (PHN). Calcium Green was again used to measure the influx of extracellular calcium and FM1-43 was used to monitor changes in membrane conformation. The observed thresholds for nanopore formation in PHN by nsPEF were comparable to those measured in neuroblastoma. This work is the first study of nsPEF effects on PHN and strongly suggests that neurological inhibition by nanosecond electrical pulses is highly likely at doses well below irreversible damage.

Model assessing thermal changes during high temperature root canal irrigation

PubMed Central

Bartolo, Analise; Koyess, Edmond; Micallef, Christopher

2016-01-01

The main aim of root canal irrigation is to eliminate micro-organisms. Sodium hypochlorite (NaOCl) is considered to be the ideal material and raising its temperature potentiates the antimicrobial activity. NaOCl may lead to localised tissue necrosis when extruded past the root apex. This study analyses the use of high temperature root canal irrigation as an alternative process for the elimination of microorganisms from the root canal system. An experimental set-up was designed where a constant supply of heat was passed from a heat source through a copper wire inside the root canal. The data acquired together with known constants pertaining to enamel and dentine was used to numerically model the thermal changes in a tooth using a finite element method. Results obtained from the finite element thermal model of the tooth were repeatable and were validated with the experimental results. The thermo-physical properties of the tooth were varied and convergence criteria met. The temperatures reached were below what has been reported to cause irreversible damage to the bone. This was further confirmed from a series of simulations that were undertaken. The temperatures achieved were suitable for the elimination of microorganisms during root canal therapy. PMID:27733934

Theranostic Nanoseeds for Efficacious Internal Radiation Therapy of Unresectable Solid Tumors

NASA Astrophysics Data System (ADS)

Moeendarbari, Sina; Tekade, Rakesh; Mulgaonkar, Aditi; Christensen, Preston; Ramezani, Saleh; Hassan, Gedaa; Jiang, Ruiqian; Öz, Orhan K.; Hao, Yaowu; Sun, Xiankai

2016-02-01

Malignant tumors are considered “unresectable” if they are adhere to vital structures or the surgery would cause irreversible damages to the patients. Though a variety of cytotoxic drugs and radiation therapies are currently available in clinical practice to treat such tumor masses, these therapeutic modalities are always associated with substantial side effects. Here, we report an injectable nanoparticle-based internal radiation source that potentially offers more efficacious treatment of unresectable solid tumors without significant adverse side effects. Using a highly efficient incorporation procedure, palladium-103, a brachytherapy radioisotope in clinical practice, was coated to monodispersed hollow gold nanoparticles with a diameter about 120 nm, to form 103Pd@Au nanoseeds. The therapeutic efficacy of 103Pd@Au nanoseeds were assessed when intratumorally injected into a prostate cancer xenograft model. Five weeks after a single-dose treatment, a significant tumor burden reduction (>80%) was observed without noticeable side effects on the liver, spleen and other organs. Impressively, >95% nanoseeds were retained inside the tumors as monitored by Single Photon Emission Computed Tomography (SPECT) with the gamma emissions of 103Pd. These findings show that this nanoseed-based brachytherapy has the potential to provide a theranostic solution to unresectable solid tumors.

Gluteal Compartment Syndrome following an Iliac Bone Marrow Aspiration

PubMed Central

Vega-Najera, Carlos; Leal-Contreras, Carlos; Leal-Berumen, Irene

2013-01-01

The compartment syndrome is a condition characterized by a raised hydraulic pressure within a closed and non expandable anatomical space. It leads to a vascular insufficiency that becomes critical once the vascular flow cannot return the fluids back to the venous system. This causes a potential irreversible damage of the contents of the compartment, especially within the muscle tissues. Gluteal compartment syndrome (GCS) secondary to hematomas is seldom reported. Here we present a case of a 51-year-old patient with history of a non-Hodgkin lymphoma who underwent a bone marrow aspiration from the posterior iliac crest that had excessive bleeding at the puncture zone. The patient complained of increasing pain, tenderness, and buttock swelling. Intraoperative pressure validation of the gluteal compartment was performed, and a GCS was diagnosed. The patient was treated with a gluteal region fasciotomy. The patient recovered from pain and swelling and was discharged shortly after from the hospital. We believe clotting and hematologic disorders are a primary risk factor in patients who require bone marrow aspirations or biopsies. It is important to improve awareness of GCS in order to achieve early diagnosis, avoid complications, and have a better prognosis. PMID:24392235

Effects of Acutely Elevated Hydrostatic Pressure in a Rat Ex Vivo Retinal Preparation

PubMed Central

Yoshitomi, Takeshi; Zorumski, Charles F.; Izumi, Yukitoshi

2010-01-01

Purpose. A new experimental glaucoma model was developed by using an ex vivo rat retinal preparation to examine the effects of elevated hydrostatic pressure on retinal morphology and glutamine synthetase (GS) activity. Methods. Ex vivo rat retinas were exposed to elevated hydrostatic pressure for 24 hours in the presence of glutamate or glutamate receptor antagonists and examined histologically. GS activity was assessed by colorimetric assay. Results. Pressure elevation induced axonal swelling in the nerve fiber layer. Axonal swelling was prevented by a combination of non-N-methyl-d-aspartate (non-NMDA) receptor antagonist and an NMDA receptor antagonist, indicating that the damage results from activation of both types of glutamate receptor. When glial function was preserved, the typical changes induced by glutamate consisted of reversible Müller cell swelling resulting from excessive glial glutamate uptake. The irreversible Müller cell swelling in hyperbaric conditions may indicate that pressure disrupts glutamate metabolism. Indeed, elevated pressure inhibited GS activity. In addition, glutamate exposure after termination of pressure exposure exhibited apparent Müller cell swelling. Conclusions. These results suggest that the neural degeneration observed during pressure elevation is caused by impaired glial glutamate metabolism after uptake. PMID:20688725

Hemorheological changes in ischemia-reperfusion: an overview on our experimental surgical data.

PubMed

Nemeth, Norbert; Furka, Istvan; Miko, Iren

2014-01-01

Blood vessel occlusions of various origin, depending on the duration and extension, result in tissue damage, causing ischemic or ischemia-reperfusion injuries. Necessary surgical clamping of vessels in vascular-, gastrointestinal or parenchymal organ surgery, flap preparation-transplantation in reconstructive surgery, as well as traumatological vascular occlusions, all present special aspects. Ischemia and reperfusion have effects on hemorheological state by numerous ways: besides the local metabolic and micro-environmental changes, by hemodynamic alterations, free-radical and inflammatory pathways, acute phase reactions and coagulation changes. These processes may be harmful for red blood cells, impairing their deformability and influencing their aggregation behavior. However, there are still many unsolved or non-completely answered questions on relation of hemorheology and ischemia-reperfusion. How do various organ (liver, kidney, small intestine) or limb ischemic-reperfusionic processes of different duration and temperature affect the hemorheological factors? What is the expected magnitude and dynamics of these alterations? Where is the border of irreversibility? How can hemorheological investigations be applied to experimental models using laboratory animals in respect of inter-species differences? This paper gives a summary on some of our research data on organ/tissue ischemia-reperfusion, hemorheology and microcirculation, related to surgical research and experimental microsurgery.

Renal microvascular disease determines the responses to revascularization in experimental renovascular disease.

PubMed

Chade, Alejandro R; Kelsen, Silvia

2010-08-01

Percutaneous transluminal renal angioplasty (PTRA) is the most frequent therapeutic approach to resolving renal artery stenosis (RAS). However, renal function recovers in only 30% of the cases. The causes of these poor outcomes are still unknown. We hypothesized that preserving the renal microcirculation distal to RAS will improve the responses to PTRA. RAS was induced in 28 pigs. In 14, vascular endothelial growth factor (VEGF)-165 0.05 microg/kg was infused intrarenally (RAS+VEGF). Single-kidney function was assessed in all pigs in vivo using ultrafast CT after 6 weeks. Observation of half of the RAS and RAS+VEGF pigs was completed. The other half underwent PTRA and repeated VEGF, and CT studies were repeated 4 weeks later. Pigs were then euthanized, the stenotic kidney removed, renal microvascular (MV) architecture reconstructed ex vivo using 3D micro-CT, and renal fibrosis quantified. The degree of RAS and hypertension were similar in RAS and RAS+VEGF. Renal function and MV density were decreased in RAS but improved in RAS+VEGF. PTRA largely resolved RAS, but the improvements of hypertension and renal function were greater in RAS+VEGF+PTRA than in RAS+PTRA, accompanied by a 34% increase in MV density and decreased fibrosis. Preservation of the MV architecture and function in the stenotic kidney improved the responses to PTRA, indicating that renal MV integrity plays a role in determining the responses to PTRA. This study indicates that damage and early loss of renal MV is an important determinant of the progression of renal injury in RAS and instigates often irreversible damage.

RENAL MICROVASCULAR DISEASE DETERMINES THE RESPONSES TO REVASCULARIZATION IN EXPERIMENTAL RENOVASCULAR DISEASE

PubMed Central

Chade, Alejandro R.; Kelsen, Silvia

2011-01-01

Background Percutaneous trasluminal renal angioplasty (PTRA) is the most frequent therapeutic approach to resolve renal artery stenosis (RAS). However, renal function recovers in only 30% of the cases. The causes of these poor outcomes are still unknown. We hypothesize that preserving the renal microcirculation distal to RAS will improve the responses to PTRA. Methods and Results RAS was induced in 28 pigs. In 14, vascular endothelial growth factor (VEGF)-165 was infused intra-renally (RAS+VEGF, 0.05 µg/kg). Single-kidney function was assessed in all pigs in vivo using ultra-fast CT after 6 weeks. Half of the RAS/RAS+VEGF completed their observation, and the other half underwent PTRA, VEGF was repeated, and CT studies repeated 4 weeks later. Pigs were then euthanized, the stenotic kidney removed, renal microvascular (MV) architecture reconstructed ex-vivo using 3D micro-CT, and renal fibrosis quantified. Degree of RAS and hypertension were similar in RAS and RAS+VEGF. Renal function and MV density were decreased in RAS but improved in RAS+VEGF. PTRA largely resolved RAS, but the improvements of hypertension and renal function were greater in RAS+VEGF+PTRA than in RAS+PTRA, accompanied by a 34% increase in MV density and decreased fibrosis. Conclusion Preservation of the MV architecture and function in the stenotic kidney improved the responses to PTRA, indicating that renal MV integrity plays a role in determining the responses to PTRA. This study indicates that damage and early loss of renal MV is an important determinant of the progression of renal injury in RAS and instigates often irreversible damage. PMID:20587789

Cinnamic acid induces apoptotic cell death and cytoskeleton disruption in human melanoma cells

PubMed Central

2013-01-01

Anticancer activities of cinnamic acid derivatives include induction of apoptosis by irreversible DNA damage leading to cell death. The present work aimed to compare the cytotoxic and genotoxic potential of cinnamic acid in human melanoma cell line (HT-144) and human melanocyte cell line derived from blue nevus (NGM). Viability assay showed that the IC50 for HT-144 cells was 2.4 mM, while NGM cells were more resistant to the treatment. The growth inhibition was probably associated with DNA damage leading to DNA synthesis inhibition, as shown by BrdU incorporation assay, induction of nuclear aberrations and then apoptosis. The frequency of cell death caused by cinnamic acid was higher in HT-144 cells. Activated-caspase 3 staining showed apoptosis after 24 hours of treatment with cinnamic acid 3.2 mM in HT-144 cells, but not in NGM. We observed microtubules disorganization after cinnamic acid exposure, but this event and cell death seem to be independent according to M30 and tubulin labeling. The frequency of micronucleated HT-144 cells was higher after treatment with cinnamic acid (0.4 and 3.2 mM) when compared to the controls. Cinnamic acid 3.2 mM also increased the frequency of micronucleated NGM cells indicating genotoxic activity of the compound, but the effects were milder. Binucleation and multinucleation counting showed similar results. We conclude that cinnamic acid has effective antiproliferative activity against melanoma cells. However, the increased frequency of micronucleation in NGM cells warrants the possibility of genotoxicity and needs further investigation. PMID:23701745

Cinnamic acid induces apoptotic cell death and cytoskeleton disruption in human melanoma cells.

PubMed

Niero, Evandro Luís de Oliveira; Machado-Santelli, Gláucia Maria

2013-05-23

Anticancer activities of cinnamic acid derivatives include induction of apoptosis by irreversible DNA damage leading to cell death. The present work aimed to compare the cytotoxic and genotoxic potential of cinnamic acid in human melanoma cell line (HT-144) and human melanocyte cell line derived from blue nevus (NGM). Viability assay showed that the IC50 for HT-144 cells was 2.4 mM, while NGM cells were more resistant to the treatment. The growth inhibition was probably associated with DNA damage leading to DNA synthesis inhibition, as shown by BrdU incorporation assay, induction of nuclear aberrations and then apoptosis. The frequency of cell death caused by cinnamic acid was higher in HT-144 cells. Activated-caspase 3 staining showed apoptosis after 24 hours of treatment with cinnamic acid 3.2 mM in HT-144 cells, but not in NGM. We observed microtubules disorganization after cinnamic acid exposure, but this event and cell death seem to be independent according to M30 and tubulin labeling. The frequency of micronucleated HT-144 cells was higher after treatment with cinnamic acid (0.4 and 3.2 mM) when compared to the controls. Cinnamic acid 3.2 mM also increased the frequency of micronucleated NGM cells indicating genotoxic activity of the compound, but the effects were milder. Binucleation and multinucleation counting showed similar results. We conclude that cinnamic acid has effective antiproliferative activity against melanoma cells. However, the increased frequency of micronucleation in NGM cells warrants the possibility of genotoxicity and needs further investigation.

Identification and characterization of cannabinoids that induce cell death through mitochondrial permeability transition in Cannabis leaf cells.

PubMed

Morimoto, Satoshi; Tanaka, Yumi; Sasaki, Kaori; Tanaka, Hiroyuki; Fukamizu, Tomohide; Shoyama, Yoshinari; Shoyama, Yukihiro; Taura, Futoshi

2007-07-13

Cannabinoids are secondary metabolites stored in capitate-sessile glands on leaves of Cannabis sativa. We discovered that cell death is induced in the leaf tissues exposed to cannabinoid resin secreted from the glands, and identified cannabichromenic acid (CBCA) and Delta(1)-tetrahydrocannabinolic acid (THCA) as unique cell death mediators from the resin. These cannabinoids effectively induced cell death in the leaf cells or suspension-cultured cells of C. sativa, whereas pretreatment with the mitochondrial permeability transition (MPT) inhibitor cyclosporin A suppressed this cell death response. Examinations using isolated mitochondria demonstrated that CBCA and THCA mediate opening of MPT pores without requiring Ca(2+) and other cytosolic factors, resulting in high amplitude mitochondrial swelling, release of mitochondrial proteins (cytochrome c and nuclease), and irreversible loss of mitochondrial membrane potential. Therefore, CBCA and THCA are considered to cause serious damage to mitochondria through MPT. The mitochondrial damage was also confirmed by a marked decrease of ATP level in cannabinoid-treated suspension cells. These features are in good accord with those of necrotic cell death, whereas DNA degradation was also observed in cannabinoid-mediated cell death. However, the DNA degradation was catalyzed by nuclease(s) released from mitochondria during MPT, indicating that this reaction was not induced via a caspase-dependent apoptotic pathway. Furthermore, the inhibition of the DNA degradation only slightly blocked the cell death induced by cannabinoids. Based on these results, we conclude that CBCA and THCA have the ability to induce necrotic cell death via mitochondrial dysfunction in the leaf cells of C. sativa.

Light Chain Amyloidosis

PubMed Central

Milani, Paolo; Merlini, Giampaolo

2018-01-01

Light chain (AL) amyloidosis is caused by a usually small plasma-cell clone that is able to produce the amyloidogenic light chains. They are able to misfold and aggregate, deposit in tissues in the form of amyloid fibrils and lead to irreversible organ dysfunction and eventually death if treatment is late or ineffective. Cardiac damage is the most important prognostic determinant. The risk of dialysis is predicted by the severity of renal involvement, defined by the baseline proteinuria and glomerular filtration rate, and by the response to therapy. The specific treatment is chemotherapy targeting the underlying plasma-cell clone. It needs to be risk-adapted, according to the severity of cardiac and/or multi-organ involvement. Autologous stem cell transplant (preceded by induction and/or followed by consolidation with bortezomib-based regimens) can be considered for low-risk patients (~20%). Bortezomib combined with alkylators is used in the majority of intermediate-risk patients, and with possible dose escalation in high-risk subjects. Novel, powerful anti-plasma cell agents were investigated in the relapsed/refractory setting, and are being moved to upfront therapy in clinical trials. In addition, the use of novel approaches based on antibodies targeting the amyloid deposits or small molecules interfering with the amyloidogenic process gave promising results in preliminary studies. Some of them are under evaluation in controlled trials. These molecules will probably add powerful complements to standard chemotherapy. The understanding of the specific molecular mechanisms of cardiac damage and the characteristics of the amyloidogenic clone are unveiling novel potential treatment approaches, moving towards a cure for this dreadful disease. PMID:29531659

Zeaxanthin Accumulation in the Absence of a Functional Xanthophyll Cycle Protects Chlamydomonas reinhardtii from Photooxidative Stress

PubMed Central

Baroli, Irene; Do, An D.; Yamane, Tomoko; Niyogi, Krishna K.

2003-01-01

Xanthophylls participate in light harvesting and are essential in protecting the chloroplast from photooxidative damage. To investigate the roles of xanthophylls in photoprotection, we isolated and characterized extragenic suppressors of the npq1 lor1 double mutant of Chlamydomonas reinhardtii, which lacks zeaxanthin and lutein and undergoes irreversible photooxidative bleaching and cell death at moderate to high light intensities. Here, we describe three suppressor strains that carry point mutations in the coding sequence of the zeaxanthin epoxidase gene, resulting in the constitutive accumulation of zeaxanthin in a range of concentrations. The presence of zeaxanthin in these strains was sufficient to prevent photooxidative damage in the npq1 lor1 background. The size of the light-harvesting antenna in the suppressors decreased in high light in a manner that was proportional to the relative content of zeaxanthin, with the strain having the most zeaxanthin showing a severe reduction in levels of the major light-harvesting complex II proteins in high light. We show that the effect of constitutive zeaxanthin on light harvesting is not the main cause of increased photoprotection, because in the absence of zeaxanthin, a strain with a smaller light-harvesting antenna showed only minor protection against photobleaching in high light. Furthermore, the zeaxanthin-accumulating suppressors were able to tolerate higher levels of exogenous reactive oxygen than their parental strain under conditions that did not affect light harvesting. Our results are consistent with an antioxidant role of zeaxanthin in the quenching of singlet oxygen and/or free radicals in the thylakoid membrane in vivo. PMID:12671093

Morphology of ejected particles and impact sites on intercepting substrates following exit-surface laser damage with nanosecond pulses in silica

DOE PAGES

Demos, Stavros G.; Negres, Raluca A.

2016-09-08

A volume of superheated material reaching localized temperatures of the order of 1 eV and pressures of the order of 10 GPa is generated following laser-induced damage (breakdown) on the surface of transparent dielectric materials using nanosecond pulses. This leads to material ejection and the formation of a crater. To elucidate the material behaviors involved, we examined the morphologies of the ejected particles and found distinctive features that support their classification into different types. The different morphologies arise from the difference in the structure and physical properties (such as the dynamic viscosity and presence of instabilities) of the superheated andmore » surrounding affected material at the time of ejection of each individual particle. In addition, the temperature and kinetic energy of a subset of the ejected particles were found to be sufficient to initiate irreversible modification on the intercepting silica substrates. Finally, the modifications observed are associated with mechanical damage and fusion of melted particles on the collector substrate.« less

Small Molecular, Macromolecular and Cellular Chloramines React with Thiocyanate to Give the Human Defense Factor Hypothiocyanite†

PubMed Central

Xulu, Bheki A.; Ashby, Michael T.

2010-01-01

Thiocyanate reacts non-catalytically with myeloperoxidase-derived HOCl to produce hypothiocyanite (OSCN−), thereby potentially limiting the propensity of HOCl to inflict host tissue damage that can lead to inflammatory diseases. However, the efficiency with which SCN− captures HOCl in vivo depends on the concentration of SCN− relative to other chemical targets. In blood plasma, where the concentration of SCN− is relatively low, proteins may be the principal initial targets of HOCl, and chloramines are a significant product. Chloramines eventually decompose to irreversibly damage proteins. In the present study, we demonstrate that SCN− reacts efficiently with chloramines in small molecules, in proteins, and in Escherichia coli cells to give OSCN− and the parent amine. Remarkably, OSCN− reacts faster than SCN− with chloramines. These reactions of SCN− and OSCN− with chloramines may repair some of the damage that is inflicted on protein amines by HOCl. Our observations are further evidence for the importance of secondary reactions during the redox cascades that are associated with oxidative stress by hypohalous acids. PMID:20085320

Myotoxic effects of clenbuterol in the rat heart and soleus muscle.

PubMed

Burniston, Jatin G; Ng, Yeelan; Clark, William A; Colyer, John; Tan, Lip-Bun; Goldspink, David F

2002-11-01

Myocyte-specific necrosis in the heart and soleus muscle of adult male Wistar rats was investigated in response to a single subcutaneous injection of the anabolic beta(2)-adrenergic receptor agonist clenbuterol. Necrosis was immunohistochemically detected by administration of a myosin antibody 1 h before the clenbuterol challenge and quantified by using image analysis. Clenbuterol-induced myocyte necrosis occurred against a background of zero damage in control muscles. In the heart, the clenbuterol-induced necrosis was not uniform, being more abundant in the left subendocardium and peaking 2.4 mm from the apex. After position (2.4 mm from the apex), dose (5 mg clenbuterol/kg), and sampling time (12 h) were optimized, maximum cardiomyocyte necrosis was found to be 1.0 +/- 0.2%. In response to the same parameters (i.e., 5 mg of clenbuterol and sampled at 12 h), skeletal myocyte necrosis was 4.4 +/- 0.8% in the soleus. These data show significant myocyte-specific necrosis in the heart and skeletal muscle of the rat. Such irreversible damage in the heart suggests that clenbuterol may be damaging to long-term health.

Cortical damage following traumatic brain injury evaluated by iomazenil SPECT and in vivo microdialysis.

PubMed

Koizumi, Hiroyasu; Fujisawa, Hirosuke; Suehiro, Eiichi; Iwanaga, Hideyuki; Nakagawara, Jyoji; Suzuki, Michiyasu

2013-01-01

[(123)I] iomazenil (IMZ) single photon emission computed tomography (SPECT) has been reported to be a useful marker of neuronal integrity. We evaluated cortical damage following traumatic brain injury (TBI) with IMZ SPECT at the acute stage. After conventional therapy for a cranial trauma, an IMZ SPECT re-evaluation was performed at the chronic stage. A reduction in IMZ uptake in the location of cerebral contusions was observed during the TBI acute phase; however, images of IMZ SPECT obtained during the chronic phase showed that areas with decreased IMZ distribution were remarkably reduced compared with those obtained during the acute phase. As a result of in vivo microdialysis study, the extracellular levels of glutamate in the cortex, where decreased IMZ distribution was shown during the acute phase, were increased during the 168-h monitoring period. During the chronic phase, IMZ uptake in the region with the microdialysis probes was recovered. The results suggest that this reduction in IMZ uptake might not be a sign of irreversible tissue damage in TBI.

Dissimilar effect of perming and bleaching treatments on cuticles: advanced hair damage model based on elution and oxidation of S100A3 protein.

PubMed

Kizawa, Kenji; Inoue, Takafumi; Yamaguchi, Masahito; Kleinert, Peter; Troxler, Heinz; Heizmann, Claus W; Iwamoto, Yoshimichi

2005-01-01

Hair treatment chemicals induce sudden and severe hair damage. In this study, we examined cuticles from untreated, permed, and bleached hair that were mechanically discriminated by shaking in water. Both perming and bleaching treatments are prone to easily delaminate cuticles. Confocal microscopy revealed that the cuticles of permed hair were delaminated with larger pieces than untreated ones. On the other hand, the cuticles of bleached hair tend to fragment into small peptides. At the minimum concentration of thioglycolate required to elute S100A3 protein from the endocuticle into the reductive permanent waving lotion, enlarged delaminated cuticle fragments were observed. Although S100A3 is retained in bleached hair, S100A3 is irreversibly oxidized upon bleaching treatment. It is likely that the oxidative cleavage of disulfide bonds between cuticle-constituting proteins, including S100A3, results in the fragile property of cuticles. Here we present a more comprehensive model of hair damage based on a diverse mechanism of cuticle delamination.

Terminal Deoxynucleotidyl Transferase-Mediated Deoxyuridine Triphosphate Nick End Labeling (TUNEL) Assay to Characterize Histopathologic Changes Following Thermal Injury

PubMed Central

Lee, Ji Min; Park, Ji Hyun; Kim, Bo Young

2018-01-01

Background Despite the wide application of lasers and radiofrequency (RF) surgery in dermatology, it is difficult to find studies showing the extent of damage dependent on cell death. Objective We evaluated histopathologic changes following in vivo thermal damage generated by CO2 laser, 1,444 nm long-pulsed neodymium:yttrium-aluminum-garnet (LP Nd:YAG) laser and RF emitting electrosurgical unit. Methods Thermal damage was induced by the above instruments on ventral skin of rat. Specimens were stained with hematoxylin and eosin, along with a terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) assay, to highlight the degree of irreversible cellular injury. Results The volume of vaporization was largest with the CO2 laser. Area of cell death area identified by TUNEL assay, when arranged from widest to narrowest, was 1,444 nm LP Nd:YAG laser, CO2 laser, and RF emitting electrosurgical unit. Conclusion This histopathologic evaluation of the acute characterization of injury across devices may be advantageous for attaining better treatment outcomes. PMID:29386831

Research on the effect of formononetin on photodynamic therapy in K562 cells.

PubMed

Sun, Dan; Lu, Yao; Zhang, Su-Juan; Wang, Kai-Ge; Sun, Zhe

2017-10-01

At the present time, many cancer patients combine some forms of complementary and alternative medicine therapies with their conventional therapies. The most common choice of these therapies is the use of antioxidants. Formononetin is presented in different foods. It has a variety of biological activities including antioxidant and anti-cancer properties. On account of its antioxidant activity, formononetin might protect cancer cells from free radical damage in photodynamic therapy (PDT) during which reactive oxygen species (ROS) production was stimulated leading to irreversible tumor cell injury. In this study, the influence of formononetin on K562 cells in PDT was demonstrated. The results showed that formononetin supplementation alone did not affect the lipid peroxidation, DNA damage and apoptosis in K562 cells. It increases the lipid peroxidation, DNA damage and apoptosis in K562 cells induced by PDT. The singlet oxygen quencher sodium azide suppresses the apoptosis induced by PDT with formononetin. In conclusion, formononetin consumption during PDT increases the effectiveness of cancer therapy on malignant cells. The effect of antioxidants on PDT maybe was determined by its sensitization ability to singlet oxygen.

Reversibility of red blood cell deformation

NASA Astrophysics Data System (ADS)

Zeitz, Maria; Sens, P.

2012-05-01

The ability of cells to undergo reversible shape changes is often crucial to their survival. For red blood cells (RBCs), irreversible alteration of the cell shape and flexibility often causes anemia. Here we show theoretically that RBCs may react irreversibly to mechanical perturbations because of tensile stress in their cytoskeleton. The transient polymerization of protein fibers inside the cell seen in sickle cell anemia or a transient external force can trigger the formation of a cytoskeleton-free membrane protrusion of μm dimensions. The complex relaxation kinetics of the cell shape is shown to be responsible for selecting the final state once the perturbation is removed, thereby controlling the reversibility of the deformation. In some case, tubular protrusion are expected to relax via a peculiar “pearling instability.”

Reversibility of red blood cell deformation.

PubMed

Zeitz, Maria; Sens, P

2012-05-01

The ability of cells to undergo reversible shape changes is often crucial to their survival. For red blood cells (RBCs), irreversible alteration of the cell shape and flexibility often causes anemia. Here we show theoretically that RBCs may react irreversibly to mechanical perturbations because of tensile stress in their cytoskeleton. The transient polymerization of protein fibers inside the cell seen in sickle cell anemia or a transient external force can trigger the formation of a cytoskeleton-free membrane protrusion of μm dimensions. The complex relaxation kinetics of the cell shape is shown to be responsible for selecting the final state once the perturbation is removed, thereby controlling the reversibility of the deformation. In some case, tubular protrusion are expected to relax via a peculiar "pearling instability."

Investigating radiation induced damage processes with femtosecond x-ray pulses (Conference Presentation)

NASA Astrophysics Data System (ADS)

Song, Changyong

2017-05-01

Interest in high-resolution structure investigation has been zealous, especially with the advent of X-ray free electron lasers (XFELs). The intense and ultra-short X-ray laser pulses ( 10 GW) pave new routes to explore structures and dynamics of single macromolecules, functional nanomaterials and complex electronic materials. In the last several years, we have developed XFEL single-shot diffraction imaging by probing ultrafast phase changes directly. Pump-probe single-shot imaging was realized by synchronizing femtosecond (<10 fs in FWHM) X-ray laser (probe) with femtosecond (50 fs) IR laser (pump) at better than 1 ps resolution. Nanoparticles under intense fs-laser pulses were investigated with fs XFEL pulses to provide insight into the irreversible particle damage processes with nanoscale resolution. Research effort, introduced, aims to extend the current spatio-temporal resolution beyond the present limit. We expect this single-shot dynamic imaging to open new science opportunity with XFELs.

Discrete Spring Model for Predicting Delamination Growth in Z-Fiber Reinforced DCB Specimens

NASA Technical Reports Server (NTRS)

Ratcliffe, James G.; OBrien, T. Kevin

2004-01-01

Beam theory analysis was applied to predict delamination growth in Double Cantilever Beam (DCB) specimens reinforced in the thickness direction with pultruded pins, known as Z-fibers. The specimen arms were modeled as cantilever beams supported by discrete springs, which were included to represent the pins. A bi-linear, irreversible damage law was used to represent Z-fiber damage, the parameters of which were obtained from previous experiments. Closed-form solutions were developed for specimen compliance and displacements corresponding to Z-fiber row locations. A solution strategy was formulated to predict delamination growth, in which the parent laminate mode I critical strain energy release rate was used as the criterion for delamination growth. The solution procedure was coded into FORTRAN 90, giving a dedicated software tool for performing the delamination prediction. Comparison of analysis results with previous analysis and experiment showed good agreement, yielding an initial verification for the analytical procedure.

Discrete Spring Model for Predicting Delamination Growth in Z-Fiber Reinforced DCB Specimens

NASA Technical Reports Server (NTRS)

Ratcliffe, James G.; O'Brien, T. Kevin

2004-01-01

Beam theory analysis was applied to predict delamination growth in DCB specimens reinforced in the thickness direction with pultruded pins, known as Z-fibers. The specimen arms were modeled as cantilever beams supported by discrete springs, which were included to represent the pins. A bi-linear, irreversible damage law was used to represent Z-fiber damage, the parameters of which were obtained from previous experiments. Closed-form solutions were developed for specimen compliance and displacements corresponding to Z-fiber row locations. A solution strategy was formulated to predict delamination growth, in which the parent laminate mode I fracture toughness was used as the criterion for delamination growth. The solution procedure was coded into FORTRAN 90, giving a dedicated software tool for performing the delamination prediction. Comparison of analysis results with previous analysis and experiment showed good agreement, yielding an initial verification for the analytical procedure.

A Method of Effective Quarry Water Purifying Using Artificial Filtering Arrays

NASA Astrophysics Data System (ADS)

Tyulenev, M.; Garina, E.; Khoreshok, A.; Litvin, O.; Litvin, Y.; Maliukhina, E.

2017-01-01

The development of open pit mining in the large coal basins of Russia and other countries increases their negative impact on the environment. Along with the damage of land and air pollution by dust and combustion gases of blasting, coal pits have a significant negative impact on water resources. Polluted quarry water worsens the ecological situation on a much larger area than covered by air pollution and land damage. This significantly worsens the conditions of people living in cities and towns located near the coal pits, and complicates the subsequent restoration of the environment, irreversibly destroying the nature. Therefore, the research of quarry wastewater purifying is becoming an important mater for scholars of technical colleges and universities in the regions with developing open-pit mining. This paper describes the method of determining the basic parameters of the artificial filtering arrays formed on coal pits of Kuzbass (Western Siberia, Russia), and gives recommendations on its application.

Biomaterial-based delivery for skeletal muscle repair

PubMed Central

Cezar, Christine A.; Mooney, David J.

2015-01-01

Skeletal muscle possesses a remarkable capacity for regeneration in response to minor damage, but severe injury resulting in a volumetric muscle loss can lead to extensive and irreversible fibrosis, scarring, and loss of muscle function. In early clinical trials, the intramuscular injection of cultured myoblasts was proven to be a safe but ineffective cell therapy, likely due to rapid death, poor migration, and immune rejection of the injected cells. In recent years, appropriate therapeutic cell types and culturing techniques have improved progenitor cell engraftment upon transplantation. Importantly, the identification of several key biophysical and biochemical cues that synergistically regulate satellite cell fate has paved the way for the development of cell-instructive biomaterials that serve as delivery vehicles for cells to promote in vivo regeneration. Material carriers designed to spatially and temporally mimic the satellite cell niche may be of particular importance for the complete regeneration of severely damaged skeletal muscle. PMID:25271446

A model of the thermal-spike mechanism in graphite/epoxy laminates

NASA Technical Reports Server (NTRS)

Adamson, M. J.

1982-01-01

The influence of a thermal spike on a moisture-saturated graphite/epoxy composite was studied in detail. A single thermal spike from 25 C to 132 C was found to produce damage as evidenced by a significant increase in the level of moisture saturation in the composite. Approximately half of this increase remained after a vacuum anneal at 150 C for 7 days, suggesting the presence of an irreversible damage component. Subsequent thermal spikes created less and less additional moisture absorption, with the cumulative effect being a maximum or limiting moisture capacity of the composite. These observations are explained in terms of a model previously developed to explain the reverse thermal effect of moisture absorption in epoxy and epoxy matrix composites. This model, based on the inverse temperature dependence of free volume, contributes an improved understanding of thermal-spike effects in graphite/epoxy composites.

Transplantation of Endothelial Cells to Mitigate Acute and Chronic Radiation Injury to Vital Organs.

PubMed

Rafii, Shahin; Ginsberg, Michael; Scandura, Joseph; Butler, Jason M; Ding, Bi-Sen

2016-08-01

Current therapeutic approaches for treatment of exposure to radiation involve the use of antioxidants, chelating agents, recombinant growth factors and transplantation of stem cells (e.g., hematopoietic stem cell transplantation). However, exposure to high-dose radiation is associated with severe damage to the vasculature of vital organs, often leading to impaired healing, tissue necrosis, thrombosis and defective regeneration caused by aberrant fibrosis. It is very unlikely that infusion of protective chemicals will reverse severe damage to the vascular endothelial cells (ECs). The role of irradiated vasculature in mediating acute and chronic radiation syndromes has not been fully appreciated or well studied. New approaches are necessary to replace and reconstitute ECs in organs that are irreversibly damaged by radiation. We have set forth the novel concept that ECs provide paracrine signals, also known as angiocrine signals, which not only promote healing of irradiated tissue but also direct organ regeneration without provoking fibrosis. We have developed innovative technologies that enable manufacturing and banking of human GMP-grade ECs. These ECs can be transplanted intravenously to home to and engraft to injured tissues where they augment organ repair, while preventing maladaptive fibrosis. In the past, therapeutic transplantation of ECs was not possible due to a shortage of availability of suitable donor cell sources and preclinical models, a lack of understanding of the immune privilege of ECs, and inadequate methodologies for expansion and banking of engraftable ECs. Recent advances made by our group as well as other laboratories have breached the most significant of these obstacles with the development of technologies to manufacture clinical-scale quantities of GMP-grade and human ECs in culture, including genetically diverse reprogrammed human amniotic cells into vascular ECs (rAC-VECs) or human pluripotent stem cells into vascular ECs (iVECs). This approach provides a path to therapeutic EC transplantation that can be infused concomitantly or sequentially with hematopoietic stem cell transplantation more than 24 h after irradiation to support multi-organ regeneration, thereby improving immediate and long-term survival, while limiting long-term morbidity resulting from nonregenerative damage repair pathways.

Irreversible commitment to flowering in two mango cultivars

USDA-ARS?s Scientific Manuscript database

In recent years, the state of Nayarit, Mexico has experienced variations in rainfall distribution and warmer temperatures during the autumn-winter season which have caused erratic flowering of mango. The early-flowering cultivars, such as ‘Ataulfo’, have been less affected than tardy ones such as ‘T...

Environmental Problems and the Social Sciences: What Should We Teach?

ERIC Educational Resources Information Center

Cylke, F. Kurt, Jr.

1995-01-01

Environmental issues that can be explored in social science courses include problems with potential to cause serious or irreversible change to an ecosystem or biosphere. Areas for discussion include: environmental attitudes, values, and behaviors; the environmental movement; risk perceptions; and the political economy of the environment and…

Management dilemma in penetrating head injuries in comatose patients: Scenario in underdeveloped countries

PubMed Central

Wani, Abrar Ahad; Ramzan, Altaf Umar; Dar, Tanveer Iqbal; Malik, Nayil K.; Khan, Abdul Quyoom; Wani, Mohd Afzal; Alam, Shafeeq; Nizami, Furqan A.

2012-01-01

Background: The optimal management of patients with minimal injury to brain has been a matter of controversy and this is especially intensified when the patient has a poor neurological status. This is important in the regions where neurosurgical services are limited and patient turnover is disproportionate to the available resources. We aimed to determine the effectiveness of aggressive management in coma patients after penetrating missile injuries of the brain. Methods: All the patients of gunshots or blast injuries were included if they had a Glasgow Coma Scale score of less than 8 after initial resuscitation and had no other injury that could explain their poor neurological status. The indication for emergency surgery was evidence of a mass lesion causing a significant mass effect; otherwise, debridement was done in a delayed fashion. The patients who were not operated were those with irreversible shock or having small intracranial pellets with no significant scalp wounds. The patients who had a Glasgow outcome score of 1, 2, or 3 were classified as having an unfavorable outcome (UO) and those with scores 4 and 5 were classified as having a favorable outcome (FO). Results: We operated 13 patients and the rest 13 were managed conservatively. The characteristics of the patients having a favorable outcome were young age (OR = 28, P = 0 .031), normal hemodynamic status (OR = 18, P = 0.08), presence of pupillary reaction (OR = 9.7, P = 0.1), and injury restricted to one hemisphere only (OR = 15, P = 0.07). All of the patients who were in shock after resuscitation died while 25% of the patients with a normal hemodynamic status had a favorable outcome. Conclusions: In developing countries with limited resources, the patients who are in a comatose condition after sustaining penetrating missile injuries should not be managed aggressively if associated with bihemispheric damage, irreversible shock, or bilateral dilated nonreacting pupils. This is especially important in the event of receiving numerous patients with the same kind of injuries. PMID:23050203

Analysis of the Magneto-Hydrodynamic (MHD) Energy Bypass Engine for High-Speed Air-Breathing Propulsion

NASA Technical Reports Server (NTRS)

Riggins, David W.

2002-01-01

The performance of the MHD energy bypass air-breathing engine for high-speed propulsion is analyzed in this investigation. This engine is a specific type of the general class of inverse cycle engines. In this paper, the general relationship between engine performance (specific impulse and specific thrust) and the overall total pressure ratio through an engine (from inlet plane to exit plane) is first developed and illustrated. Engines with large total pressure decreases, regardless of cause or source, are seen to have exponentially decreasing performance. The ideal inverse cycle engine (of which the MHD engine is a sub-set) is then demonstrated to have a significant total pressure decrease across the engine; this total pressure decrease is cycle-driven, degrades rapidly with energy bypass ratio, and is independent of any irreversibility. The ideal MHD engine (inverse cycle engine with no irreversibility other than that inherent in the MHD work interaction processes) is next examined and is seen to have an additional large total pressure decrease due to MHD-generated irreversibility in the decelerator and the accelerator. This irreversibility mainly occurs in the deceleration process. Both inherent total pressure losses (inverse cycle and MHD irreversibility) result in a significant narrowing of the performance capability of the MHD bypass engine. The fundamental characteristics of MHD flow acceleration and flow deceleration from the standpoint of irreversibility and second-law constraints are next examined in order to clarify issues regarding flow losses and parameter selection in the MM modules. Severe constraints are seen to exist in the decelerator in terms of allowable deceleration Mach numbers and volumetric (length) required for meaningful energy bypass (work interaction). Considerable difficulties are also encountered and discussed due to thermal/work choking phenomena associated with the deceleration process. Lastly, full engine simulations utilizing inlet shock systems, finite-rate chemistry, wall cooling with thermally balanced engine (fuel heat sink), fuel injection and mixing, friction, etc. are shown and discussed for both the MHD engine and the conventional scramjet. The MHD bypass engine has significantly lower performance in all categories across the Mach number range (8 to 12.2). The lower performance is attributed to the combined effects of 1) additional irreversibility and cooling requirements associated with the MHD components and 2) the total pressure decrease associated with the inverse cycle itself.

Structural integrity and developmental potential of spermatozoa following microwave-assisted drying in the domestic cat model.

PubMed

Patrick, Jennifer L; Elliott, Gloria D; Comizzoli, Pierre

2017-11-01

Characterizing the resilience of mammalian cells to non-physiological conditions is necessary to develop preservation and long-term storage strategies at low or ambient temperatures. Using the domestic cat model, the objective of the study was to characterize structural integrity (morphology and DNA damage) as well as functional properties (sperm aster formation and embryo formation after sperm injection) of spermatozoa after microwave-assisted drying to a moisture content compatible with storage in a glassy state at supra-zero temperatures. In Experiment 1, cat epididymal spermatozoa were porated with hemolysin and dried (using a commercial microwave oven set to 20% power) in the presence of trehalose for up to 50 min in a low humidity environment (11%) before measuring moisture content and sample temperature. In Experiment 2, morphology and DNA integrity were evaluated in sperm dried for up to 30 min (using the same method as above) versus fresh spermatozoa. In Experiment 3, the functionality of sperm dried for 30 min versus fresh sperm cells was evaluated after injection into oocytes based on sperm aster formation (5 h post-injection) and embryo development in vitro over 7 days. Moisture contents compatible with dry state storage were reached after 30 min of microwave-assisted drying. After rehydration, sperm morphology was not affected and the percentages of cells with damaged DNA (∼6.5%) was similar to the fresh controls. Sperm aster diameters appeared to be generally smaller for dried-rehydrated cells compared to the fresh controls. This observation was consistent with a lower proportion of blastocyst formation after injection with dried spermatozoa (6.5%) compared to fresh spermatozoa (15%). However, the blastocyst quality based on the total blastomere number was not affected by the sperm treatment. This is the first and encouraging report in any species so far demonstrating that spermatozoa can be dried using microwaves without causing irreversible damage to the cellular structure and function. Published by Elsevier Inc.

GLOBAL DISASTERS: Geodynamics and Society

NASA Astrophysics Data System (ADS)

Vikulina, Marina; Vikulin, Alexander; Semenets, Nikolai

2013-04-01

The problem of reducing the damage caused by geodynamic and social disasters is a high priority and urgent task facing the humanity. The vivid examples of the earthquake in Japan in March 2011 that generated a new kind of threat - the radiation pollution, and the events in the Arabic world that began in the same year, are dramatic evidences. By the middle of this century, the damage from such disastrous events is supposed to exceed the combined GDP of all countries of the world. The database of 287 large-scale natural and social disasters and global social phenomena that have occurred in the period of II B.C.E. - XXI A.D. was compiled by the authors for the first time. We have proposed the following phenomenological model: the scale of disasters over the time does not decrease, there is a minimum of accidents in the XV century; the numbers of accidents have cycles lasting until the first thousand years, natural and social disasters in the aggregate are uniformly distributed in time, but separately natural and social disasters are nonuniform. Thus, due to the evaluation, a 500-year cycle of catastrophes and 200-300 and 700-800-year periodicities are identified. It is shown that catastrophes are grouped into natural and social types by forming clusters. The hypothesis of the united geo-bio-social planetary process is founded. A fundamentally new feature of this research is the assumptions about the statistical significance of the biosphere and the impact of society on the geodynamic processes. The results allow to formulate a new understanding of global disaster as an event the damage from which the humanity will be unable to liquidate even by means of the total resource potential and the consequence of which may turn into the irreversible destruction of civilization. The correlation between the natural and social phenomena and the possible action mechanism is suggested.

Aspergillus spondylodiscitis after multivisceral transplantation.

PubMed

Gerlach, Undine A; Kohler, Sven; Sauer, Igor M; Joerres, Dinah; Kandziora, Frank; Neuhaus, Peter; Pratschke, Johann; Pascher, Andreas

2009-01-01

Although spondylodiscitis is rare, it is increasingly described in patients with compromised immunity due to malignancy, chemotherapy or immunosuppression. Typical pathogens are staphylococcus aureus and enterobacteria; fungal spondylodiscitis is uncommon. We present a case of aspergillus spondylodiscitis following pulmonary aspergillosis in a patient with multivisceral and kidney transplantation. Due to irreversible disc destruction, surgical restoration by autologous iliac crest graft was required in addition to intravenous antifungal therapy, which consisted of voriconazole, caspofungin and liposomal amphotericin B. Aspergillus spondylodiscitis is a diagnostic and therapeutic challenge, a combination of surgical debridement and antifungal therapy is inevitable to prevent rapid progression of invasive aspergillosis and neurological damage.

Cauda equina syndrome associated with multiple lumbar arachnoid cysts in ankylosing spondylitis: improvement following surgical therapy.

PubMed Central

Shaw, P J; Allcutt, D A; Bates, D; Crawford, P J

1990-01-01

A case of cauda equina syndrome with multiple lumbar arachnoid cysts complicating ankylosing spondylitis (AS) is described. The value of computerised tomography (CT) and magnetic resonance imaging (MRI) as a non-invasive means of establishing the diagnosis is emphasised. In contrast to previously reported cases the patient showed neurological improvement following surgical therapy. Surgery may be indicated in some patients, particularly when there is nerve root compression by the arachnoid cysts and when the patient is seen early before irreversible damage to the cauda equina has occurred. Images PMID:2292702

[Truth at bedside in relation to poor prognosis. Legal aspects].

PubMed

Schreiber, H L

1988-01-01

Adjudicary decisions dating from the past have demanded unqualified enlightenment of the patient about his illness. Physicians could disregard this requirement only if there was a danger that this policy might result in severe, irreversible and permanent damage. This interpretation seems too narrow. The physician must carefully weigh what he can and must demand of the patient, depending on the personal situation. Neither rigorous truth at any cost nor the principle of concealment of the hopelessness for the patient's condition is correct. Telling the patient the truth "costs" the physician personal involvement, explanation and human assistance.

[Digital archiving of imaged heart catheter studies on CD-R. Detection of irreversible CD damage].

PubMed

Erbel, R; Ge, J; Haude, M

1998-12-01

The digital archiving has great advantages compared to the standard 35-mm X-ray cinefilm documentation. The data are immediately available and quantitative coronary angiography possible. In addition the technical progress is enhancing the availability of data. The loss of films is nearly eliminated, as only copies of the digital archive data are delivered. In addition a big advantage concerning pollution is present, when CD Rs are used. We report about the damage of CD Rs after 89, 162, 181 and 252 days when they were stored in polypropylene material containing envelopes. The damaged CD Rs all belonged to the provider Verbatim, whereas CD Rs of the provider Rank Xerox or Kodak were never damaged. In contrary to the Verbatim company, Rank Xerox gave written confirmation for 10-year storage and a written confirmation, that the storage in the polypropylene envelopes is possible. Mechanical, thermal damage and damage by humidity have to be discussed as well as chemical interactions of the CD Rs surface with the polypropylene material. As the digital storage for X-ray images has to be provided for 10 years in Germany, it is concluded, that the storage in polypropylene envelopes has to be avoided, when a written confirmation by the company is not given. These observations should stimulate to better control and analyze the real storage availabilities of digital data and provide in the future other media than CD R for long-term archiving.

Comparison of neural damage induced by electrical stimulation with faradaic and capacitor electrodes.

PubMed

McCreery, D B; Agnew, W F; Yuen, T G; Bullara, L A

1988-01-01

Arrays of platinum (faradaic) and anodized, sintered tantalum pentoxide (capacitor) electrodes were implanted bilaterally in the subdural space of the parietal cortex of the cat. Two weeks after implantation both types of electrodes were pulsed for seven hours with identical waveforms consisting of controlled-current, charge-balanced, symmetric, anodic-first pulse pairs, 400 microseconds/phase and a charge density of 80-100 microC/cm2 (microcoulombs per square cm) at 50 pps (pulses per second). One group of animals was sacrificed immediately following stimulation and a second smaller group one week after stimulation. Tissues beneath both types of pulsed electrodes were damaged, but the difference in damage for the two electrode types was not statistically significant. Tissue beneath unpulsed electrodes was normal. At the ultrastructural level, in animals killed immediately after stimulation, shrunken and hyperchromic neurons were intermixed with neurons showing early intracellular edema. Glial cells appeared essentially normal. In animals killed one week after stimulation most of the damaged neurons had recovered, but the presence of shrunken, vacuolated and degenerating neurons showed that some of the cells were damaged irreversibly. It is concluded that most of the neural damage from stimulations of the brain surface at the level used in this study derives from processes associated with passage of the stimulus current through tissue, such as neuronal hyperactivity rather than electrochemical reactions associated with current injection across the electrode-tissue interface, since such reactions occur only with the faradaic electrodes.

Mechanisms of ultraviolet disinfection and chlorination of Escherichia coli: Culturability, membrane permeability, metabolism, and genetic damage.

PubMed

Xu, Limei; Zhang, Chongmiao; Xu, Pengcheng; Wang, Xiaochang C

2018-03-01

Traditional culture methods may underestimate the tolerance of microorganisms to disinfectants because of the existence of viable but nonculturable or sublethally injured cells after disinfection. The selection of a strict method is crucial for the evaluation of disinfection performance. The actions of 2 typical disinfectants - ultraviolet (UV) and chlorine - on the fecal indicator Escherichia coli were investigated by the detection of culturability, membrane permeability, metabolic activity, deoxyribonucleic acid (DNA), and messenger ribonucleic acid (mRNA). During UV disinfection, the irreversible damages in the cell membrane and cellular adenosine triphosphate (ATP) were negligible at low UV doses (<80mJ/cm 2 ). However, membrane permeability was damaged at low doses of chlorine (<5mg/L), leading to leakage of cellular ATP. Our study showed that a slight lesion in DNA was detected even at high doses of UV (400mJ/cm 2 ) and chlorine (>5mg/L) treatments. The decay of mRNA was more rapid than that of DNA. The degradation level of mRNA depended on the choice of target genes. After exposure to 50mJ/cm 2 UV dose or 5mg/L chlorine for 30min, the DNA damage repair function (RecA mRNA) was inhibited. The mRNA involved in the DNA damage repair function can be a potential indicator of bacterial viability. Copyright © 2017. Published by Elsevier B.V.

Cumulative mtDNA damage and mutations contribute to the progressive loss of RGCs in a rat model of glaucoma.

PubMed

Wu, Ji-Hong; Zhang, Sheng-Hai; Nickerson, John M; Gao, Feng-Juan; Sun, Zhongmou; Chen, Xin-Ya; Zhang, Shu-Jie; Gao, Feng; Chen, Jun-Yi; Luo, Yi; Wang, Yan; Sun, Xing-Huai

2015-02-01

Glaucoma is a chronic neurodegenerative disease characterized by the progressive loss of retinal ganglion cells (RGCs). Mitochondrial DNA (mtDNA) alterations have been documented as a key component of many neurodegenerative disorders. However, whether mtDNA alterations contribute to the progressive loss of RGCs and the mechanism whereby this phenomenon could occur are poorly understood. We investigated mtDNA alterations in RGCs using a rat model of chronic intraocular hypertension and explored the mechanisms underlying progressive RGC loss. We demonstrate that the mtDNA damage and mutations triggered by intraocular pressure (IOP) elevation are initiating, crucial events in a cascade leading to progressive RGC loss. Damage to and mutation of mtDNA, mitochondrial dysfunction, reduced levels of mtDNA repair/replication enzymes, and elevated reactive oxygen species form a positive feedback loop that produces irreversible mtDNA damage and mutation and contributes to progressive RGC loss, which occurs even after a return to normal IOP. Furthermore, we demonstrate that mtDNA damage and mutations increase the vulnerability of RGCs to elevated IOP and glutamate levels, which are among the most common glaucoma insults. This study suggests that therapeutic approaches that target mtDNA maintenance and repair and that promote energy production may prevent the progressive death of RGCs. Copyright © 2014 Elsevier Inc. All rights reserved.

The Sokoto Blind Beggars: Causes of Blindness and Barriers to Rehabilitation Services

PubMed Central

Balarabe, Aliyu Hamza; Mahmoud, Abdulraheem O.; Ayanniyi, Abdulkabir Ayansiji

2014-01-01

Purpose: To determine the causes of blindness and the barriers to accessing rehabilitation services (RS) among blind street beggars (bsb) in Sokoto, Nigeria. Materials and Methods: A cross-sectional survey of 202 bsb (VA < 3/60) using interviewer administered questionnaire. The causes of blindness were diagnosed by clinical ophthalmic examination. Results: There were 107 (53%) males and 95 (47%) females with a mean age of 49 years (SD 12.2). Most bsb 191 (94.6%) had non-formal education. Of 190 (94.1%) irreversibly bsb, 180/190 (94.7%) had no light perception (NPL) bilaterally. The major causes of blindness were non-trachomatous corneal opacity (60.8%) and trachoma corneal opacity (12.8%). There were 166 (82%) blind from avoidable causes and 190 (94.1%) were irreversibly blind with 76.1% due to avoidable causes. The available sub-standard RS were educational, vocational and financial support. The barriers to RS in the past included non-availability 151 (87.8%), inability to afford 2 (1.2%), unfelt need 4 (2.3%), family refusal 1 (0.6), ignorance 6 (3.5%) and being not linked 8 (4.7%). The barriers to RS during the study period included inability of 72 subjects (35.6%) to access RS and 59 (81.9%) were due to lack of linkage to the existing services. Conclusion: Corneal opacification was the major cause of blindness among bsb. The main challenges to RS include the inadequate services available, societal and users factors. Renewed efforts are warranted toward the prevention of avoidable causes of blindness especially corneal opacities. The quality of life of the blind street beggar should be improved through available, accessible and affordable well-maintained and sustained rehabilitation services. PMID:24791106

The Sokoto blind beggars: causes of blindness and barriers to rehabilitation services.

PubMed

Balarabe, Aliyu Hamza; Mahmoud, Abdulraheem O; Ayanniyi, Abdulkabir Ayansiji

2014-01-01

To determine the causes of blindness and the barriers to accessing rehabilitation services (RS) among blind street beggars (bsb) in Sokoto, Nigeria. A cross-sectional survey of 202 bsb (VA < 3/60) using interviewer administered questionnaire. The causes of blindness were diagnosed by clinical ophthalmic examination. There were 107 (53%) males and 95 (47%) females with a mean age of 49 years (SD 12.2). Most bsb 191 (94.6%) had non-formal education. Of 190 (94.1%) irreversibly bsb, 180/190 (94.7%) had no light perception (NPL) bilaterally. The major causes of blindness were non-trachomatous corneal opacity (60.8%) and trachoma corneal opacity (12.8%). There were 166 (82%) blind from avoidable causes and 190 (94.1%) were irreversibly blind with 76.1% due to avoidable causes. The available sub-standard RS were educational, vocational and financial support. The barriers to RS in the past included non-availability 151 (87.8%), inability to afford 2 (1.2%), unfelt need 4 (2.3%), family refusal 1 (0.6), ignorance 6 (3.5%) and being not linked 8 (4.7%). The barriers to RS during the study period included inability of 72 subjects (35.6%) to access RS and 59 (81.9%) were due to lack of linkage to the existing services. Corneal opacification was the major cause of blindness among bsb. The main challenges to RS include the inadequate services available, societal and users factors. Renewed efforts are warranted toward the prevention of avoidable causes of blindness especially corneal opacities. The quality of life of the blind street beggar should be improved through available, accessible and affordable well-maintained and sustained rehabilitation services.

Effects of orally administered chemotherapeutics (quinine, salinomycin) against Henneguya sp. Thelohán, 1892 (Myxozoa: Myxobolidae), a gill parasite in the tapir fish Gnathonemus petersii Günther, 1862 (Teleostei).

PubMed

Dohle, Angelika; Schmahl, Günter; Raether, Wolfgang; Schmidt, Hartmut; Ritter, Günter

2002-09-01

When given orally, quinine or salinomycin cause irreversible damage to the plasmodial developmental stages of Henneguya sp., a gill parasite in the tapir fish Gnathonemus petersii. Naturally infected tapir fish measured 75-169 mm in total length and their total weight ranged over 4.3-11.7 g. The fish bore 7-77 plasmodia in their gill arches. Medicinal food containing either quinine (5 g/1000 g food) or salinomycin (0.075 g/1000 g food) was given once a day to naturally infected fish in a food chain via water fleas ( Daphnia spp) for a period of 3, 6, or 9 days. From the monitored feeding of the tapir fish and weight determinations of the water fleas, it was calculated that gross uptake was 18.5 micro g/kg body weight fish daily for pure salinomycin and was 1.25 mg/kg body weight daily for quinine. After the end of the experiments, the fish were sacrificed and the plasmodia were carefully prepared from the gill arches and processed for transmission electron microscopy. As seen by ultrastructure investigations, for both substances the grade of damage in the parasites correlated positively with the period of application. When quinine was given for a 3-day period, the trophozoite ecto- and endoplasm exerted numerous vacuoles, caused by the drug, and the presporogonous and the pansporoblastic stages were malformed. Following a 6-day period, numerous abortive polar capsules were found in the trophozoite cytoplasm. To a large extent, the limiting membranes of the polaroblasts and valvogenic cells were destroyed. In addition, deep clefts between the polaroblasts, the valvogenic cells and between the two sporoblasts were observed. Following a 9-day treatment, all damage increased and, in addition, generative cells and two-cell stages were no longer detectable. As a first sign for the effects of salinomycin, following a 3-day treatment, a shrinking of the whole plasmodia occurred and the sutures in the pansporoblasts were enlarged. The polar capsules were malformed and the zonar structures of the polar filament were no longer detectable. The sporoplasmosomes were more electron-pale than those of the control samples. After a 9-day treatment, the pansporoblasts were completely destroyed. Under the experimental conditions chosen, both compounds were very well tolerated by the fishes.

Secondary arterial hypertension: when, who, and how to screen?

PubMed

Rimoldi, Stefano F; Scherrer, Urs; Messerli, Franz H

2014-05-14

Secondary hypertension refers to arterial hypertension due to an identifiable cause and affects ∼5-10% of the general hypertensive population. Because secondary forms are rare and work up is time-consuming and expensive, only patients with clinical suspicion should be screened. In recent years, some new aspects gained importance regarding this screening. In particular, increasing evidence suggests that 24 h ambulatory blood pressure (BP) monitoring plays a central role in the work up of patients with suspected secondary hypertension. Moreover, obstructive sleep apnoea has been identified as one of the most frequent causes. Finally, the introduction of catheter-based renal denervation for the treatment of patients with resistant hypertension has dramatically increased the interest and the number of patients evaluated for renal artery stenosis. We review the clinical clues of the most common causes of secondary hypertension. Specific recommendations are given as to evaluation and treatment of various forms of secondary hypertension. Despite appropriate therapy or even removal of the secondary cause, BP rarely ever returns to normal with long-term follow-up. Such residue hypertension indicates either that some patients with secondary hypertension also have concomitant essential hypertension or that irreversible vascular remodelling has taken place. Thus, in patients with potentially reversible causes of hypertension, early detection and treatment are important to minimize/prevent irreversible changes in the vasculature and target organs. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2013. For permissions please email: journals.permissions@oup.com.

Using insurance data to learn more about damages to buildings caused by surface runoff

NASA Astrophysics Data System (ADS)

Bernet, Daniel; Roethlisberger, Veronika; Prasuhn, Volker; Weingartner, Rolf

2015-04-01

In Switzerland, almost forty percent of total insurance loss due to natural hazards in the last two decades was caused by flooding. Those flood damages occurred not only within known inundation zones of water courses. Practitioners expect that roughly half of all flood damages lie outside of known inundation zones. In urban areas such damages may simply be caused by drainage system overload for instance. However, as several case studies show, natural and agricultural land play a major role in surface runoff formation leading to damages in rural and peri-urban areas. Although many damages are caused by surface runoff, the whole process chain including surface runoff formation, propagation through the landscape and damages to buildings is not well understood. Therefore, within the framework of a project, we focus our research on this relevant process. As such flash flood events have a very short response time and occur rather diffusely in the landscape, this process is very difficult to observe directly. Therefore indirect data sources with the potential to indicate spatial and temporal distributions of the process have to be used. For that matter, post-flood damage data may be a profitable source. Namely, insurance companies' damage claim records could provide a good picture about the spatial and temporal distributions of damages caused by surface runoff and, thus, about the process itself. In our research we analyze insurance data records of flood damage claims systematically to infer main drivers and influencing factors of surface runoff causing damages to buildings. To demonstrate the potential and drawbacks of using data from insurance companies in relation to damages caused by surface runoff, a case study is presented. A well-documented event with data from a public as well as a private insurance company is selected. The case study focuses on the differences of the datasets as well as the associated problems and advantages respectively. Furthermore, the analysis of the data, especially the crucial identification of damages caused by surface runoff opposed to damages caused by other processes such as riverine flooding, drainage system surcharges etc. are discussed.

CCL22 and CCR4 Gene Polymorphisms in Myocardial Infarction: Risk Assessment of rs4359426 and rs2228428 in Iranian Population.

PubMed

Noori, Farideh; Naeimi, Sirous; Zibaeenezhad, Mohammad J; Gharemirshamlu, Fatemeh R

2018-06-01

Myocardial infarction (MI) is an irreversible damage of myocardial tissue caused by prolonged ischemia and hypoxia. A local hypoxia-induced inflammation causes recruitment of leukocytes to the inflammatory site to aid cardiac remodeling and tissue healing. Among various chemokines involved in the process, CCL22 plays an essential role in cardiac cell migrations. In this study, we evaluated the incidence of rs4359426 and rs2228428 SNPs in CCL22/CCR4 genes of MI patients and studied their association with the physiology of the disease. Two hundred patients aged 30 - 70 years diagnosed with myocardial infarction along with 200 agematched healthy controls were registered in the study and their pathophysiological findings were recorded. Genotypic analysis of rs4359426 and rs2228428 in CCL22 and CCR4 genes, respectively, were carried out in patients using PCR-RFLP method and compared with the control group. Successively genotyped SNPs were reviewed for their possible association with the disease or physiological findings using Fisher's exact test. The frequency of CC genotypes atboth SNPs rs4359426 and rs2228428 in CCL22 and CCR4 genes was significantly higher in MI patients compared to other genotypes. Although we could not establish any direct association with the disease due to restricted population size, it is possible that CC genotypesin CCL22 and CCR4 could be considered as risk factors in myocardial infarction.

Buccal infiltration versus inferior alveolar nerve block in mandibular 2nd premolars with irreversible pulpitis.

PubMed

Yilmaz, K; Tunga, U; Ozyurek, T

2018-04-01

The purpose of this study is to compare the success rates of inferior alveolar nerve block (IANB) and buccal infiltration anesthesia of mandibular second premolar with irreversible pulpitis and to evaluate the level of patient discomfort with these methods. Forty patients, who had irreversible pulpitis in the mandibular 2 nd premolar teeth, were included in the study. Patients were randomly distributed in two groups. In one group IANB, in the other group buccal infiltration anesthesia were performed. The efficacy of these two different anesthesia techniques on the related teeth was investigated with the Heft-Parker visual analog scale. In addition, with a pulse oximetry device, the changes in the patients' heart rates were compared between the groups. The obtained data were evaluated statistically. Both anesthesia techniques reduced the pain significantly in patients before the administration (P < 0.05), but there was no significant difference among the groups regarding the pain control and success rates of anesthesia (P > 0.05). Both of the anesthesia techniques increased the heart rate (P < 0.05). The increase in the heart rate of the patients was significantly higher in the buccal infiltration anesthesia group than the other anesthesia group (P < 0.05). Within the limitation of this in vivo study, there was no difference between the efficacies of the buccal infiltration anesthesia and IANB anesthesia in the mandibular 2 nd premolar teeth with irreversible pulpitis. Buccal infiltration anesthesia caused more discomfort in the patients compared with the IANB during the administration.

Selection and constraint underlie irreversibility of tooth loss in cypriniform fishes

PubMed Central

Aigler, Sharon R.; Jandzik, David; Hatta, Kohei; Uesugi, Kentaro; Stock, David W.

2014-01-01

The apparent irreversibility of the loss of complex traits in evolution (Dollo’s Law) has been explained either by constraints on generating the lost traits or the complexity of selection required for their return. Distinguishing between these explanations is challenging, however, and little is known about the specific nature of potential constraints. We investigated the mechanisms underlying the irreversibility of trait loss using reduction of dentition in cypriniform fishes, a lineage that includes the zebrafish (Danio rerio) as a model. Teeth were lost from the mouth and upper pharynx in this group at least 50 million y ago and retained only in the lower pharynx. We identified regional loss of expression of the Ectodysplasin (Eda) signaling ligand as a likely cause of dentition reduction. In addition, we found that overexpression of this gene in the zebrafish is sufficient to restore teeth to the upper pharynx but not to the mouth. Because both regions are competent to respond to Eda signaling with transcriptional output, the likely constraint on the reappearance of oral teeth is the alteration of multiple genetic pathways required for tooth development. The upper pharyngeal teeth are fully formed, but do not exhibit the ancestral relationship to other pharyngeal structures, suggesting that they would not be favored by selection. Our results illustrate an underlying commonality between constraint and selection as explanations for the irreversibility of trait loss; multiple genetic changes would be required to restore teeth themselves to the oral region and optimally functioning ones to the upper pharynx. PMID:24821783

Efficacy of orally administered prednisolone versus partial endodontic treatment on pain reduction in emergency care of acute irreversible pulpitis of mandibular molars: study protocol for a randomized controlled trial.

PubMed

Kérourédan, Olivia; Jallon, Léonard; Perez, Paul; Germain, Christine; Péli, Jean-François; Oriez, Dominique; Fricain, Jean-Christophe; Arrivé, Elise; Devillard, Raphaël

2017-03-28

Irreversible pulpitis is a highly painful inflammatory condition of the dental pulp which represents a common dental emergency. Recommended care is partial endodontic treatment. The dental literature reports major difficulties in achieving adequate analgesia to perform this emergency treatment, especially in the case of mandibular molars. In current practice, short-course, orally administered corticotherapy is used for the management of oral pain of inflammatory origin. The efficacy of intraosseous local steroid injections for irreversible pulpitis in mandibular molars has already been demonstrated but resulted in local comorbidities. Oral administration of short-course prednisolone is simple and safe but its efficacy to manage pain caused by irreversible pulpitis has not yet been demonstrated. This trial aims to evaluate the noninferiority of short-course, orally administered corticotherapy versus partial endodontic treatment for the emergency care of irreversible pulpitis in mandibular molars. This study is a noninferiority, open-label, randomized controlled clinical trial conducted at the Bordeaux University Hospital. One hundred and twenty subjects will be randomized in two 1:1 parallel arms: the intervention arm will receive one oral dose of prednisolone (1 mg/kg) during the emergency visit, followed by one morning dose each day for 3 days and the reference arm will receive partial endodontic treatment. Both groups will receive planned complete endodontic treatment 72 h after enrollment. The primary outcome is the proportion of patients with pain intensity below 5 on a Numeric Scale 24 h after the emergency visit. Secondary outcomes include comfort during care, the number of injected anesthetic cartridges when performing complete endodontic treatment, the number of antalgic drugs and the number of patients coming back for consultation after 72 h. This randomized trial will assess the ability of short-term corticotherapy to reduce pain in irreversible pulpitis as a simple and rapid alternative to partial endodontic treatment and to enable planning of endodontic treatment in optimal analgesic conditions. ClinicalTrials.gov, identifier: NCT02629042 . Registered on 7 December 2015. (Version n°1.1 28 July 2015).

Indocyanine green video angiography predicts outcome of extravasation injuries.

PubMed

Haslik, Werner; Pluschnig, Ursula; Steger, Günther G; Zielinski, Christoph C; Schrögendorfer, K F; Nedomansky, Jakob; Bartsch, Rupert; Mader, Robert M

2014-01-01

Extravasation of cytotoxic drugs is a serious complication of systemic cancer treatment. Still, a reliable method for early assessment of tissue damage and outcome prediction is missing. Here, we demonstrate that the evaluation of blood flow by indocyanine green (ICG) angiography in the extravasation area predicts for the need of surgical intervention. Twenty-nine patients were evaluated by ICG angiography after extravasation of vesicant or highly irritant cytotoxic drugs administered by peripheral i.v. infusion. Tissue perfusion as assessed by this standardized method was correlated with clinical outcome. The perfusion index at the site of extravasation differed significantly between patients with reversible tissue damage and thus healing under conservative management (N = 22) versus those who needed surgical intervention due to the development of necrosis (N = 7; P = 0.0001). Furthermore, in patients benefiting from conservative management, the perfusion index was significantly higher in the central extravasation area denoting hyperemia, when compared with the peripheral area (P = 0.0001). In this patient cohort, ICG angiography as indicator of local perfusion within the extravasation area was of prognostic value for tissue damage. ICG angiography could thus be used for the early identification of patients at risk for irreversible tissue damage after extravasation of cytotoxic drugs.

Spontaneous rupture of a hepatic epithelioid angiomyolipoma: damage control surgery. A case report.

PubMed

Occhionorelli, S; Dellachiesa, L; Stano, R; Cappellari, L; Tartarini, D; Severi, S; Palini, G M; Pansini, G C; Vasquez, G

2013-01-01

Angiomyolipoma (AML) is a rare mesenchymal tumor composed by blood vessels, adipose tissue and smooth muscle cells in variable proportions. Although it is most often diagnosed in the kidney, this tumor may originate from any part of the liver. It is often misdiagnosed as hepatocellular carcinoma (HCC) or other benign liver tumor. We describe a case of spontaneous rupture of hepatic angiomyolipoma in a young woman, with evidence of internal hemorrhage and hemoperitoneum. Liver tumor rupture is a rare but real surgical emergency. In our case it has been managed according to the trauma principles of the damage control surgery. At the time of the observation, the patient presented an instable condition, so the decision-making was oriented toward a less invasive first step of liver packing instead of a more aggressive intervention such as one shot hepatic resection. Damage control surgery with deep parenchymal sutures of the liver and pro-coagulant tissue adhesives packing abbreviates surgical time before the development of critical and irreversible physiological endpoints and permits a more confident second time surgery. This surgical management concept helps to reduce the mortality rate and the incidence of complications not only in traumatic liver damages, it works very well in spontaneous liver ruptures as well.

Damage Caused by the Rogue Trustee

ERIC Educational Resources Information Center

O'Banion, Terry

2009-01-01

Fifty-nine community college presidents and chancellors in 16 states report on the damage caused by rogue trustees. While the damage to presidents, other trustees, and faculty and staff is alarming, the damage these trustees cause the college suggests that the rogue trustee may be the single most destructive force ever to plague an educational…

Neurotoxicity of developmental hypothyroxinemia and hypothyroidism in rats: Impairments of long-term potentiation are mediated by phosphatidylinositol 3-kinase signaling pathway

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

Wang, Yi; Wei, Wei; Wang, Yuan

Neurotoxicity of iodine deficiency-induced hypothyroidism during developmental period results in serious impairments of brain function, such as learning and memory. These impairments are largely irreversible, and the underlying mechanisms remain unclear. In addition to hypothyroidism, iodine deficiency may cause hypothyroxinemia, a relatively subtle form of thyroid hormone deficiency. Neurotoxicity of developmental hypothyroxinemia also potentially impairs learning and memory. However, more direct evidence of the associations between developmental hypothyroxinemia and impairments of learning and memory should be provided, and the underlying mechanisms remain to be elucidated. Thus, in the present study, we investigated the effects of developmental hypothyroxinemia and hypothyroidism onmore » long-term potentiation (LTP), a widely accepted cellular model of learning and memory, in the hippocampal CA1 region. The activation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway – a pathway closely associated with synaptic plasticity and learning and memory – was also investigated. Wistar rats were treated with iodine deficient diet or methimazole (MMZ) to induce developmental hypothyroxinemia or hypothyroidism. The results showed that developmental hypothyroxinemia caused by mild iodine deficiency and developmental hypothyroidism caused by severe iodine deficiency or MMZ significantly reduced the field-excitatory postsynaptic potential (f-EPSP) slope and the population spike (PS) amplitude. Decreased activation of the PI3K signaling pathway was also observed in rats subjected to developmental hypothyroxinemia or hypothyroidism. Our results may support the hypothesis that neurotoxicity of both developmental hypothyroxinemia and hypothyroidism causes damages to learning and memory. Our results also suggest that decreased activation of the PI3K signaling pathway may contribute to impairments of LTP caused by neurotoxicity of both developmental hypothyroxinemia and hypothyroidism. - Highlights: • Neurotoxicity of developmental hypothyroxinemia impaired LTP. • Decreased activation of PI3K signaling contributed to LTP impairments. • The recovery of TH after the developmental period did not prevent LTP impairments. • ID diet successfully induced neurotoxicity of developmental hypothyroxinemia.« less

A viscoelastic damage rheology and rate- and state-dependent friction

NASA Astrophysics Data System (ADS)

Lyakhovsky, Vladimir; Ben-Zion, Yehuda; Agnon, Amotz

2005-04-01

We analyse the relations between a viscoelastic damage rheology model and rate- and state-dependent (RS) friction. Both frameworks describe brittle deformation, although the former models localization zones in a deforming volume while the latter is associated with sliding on existing surfaces. The viscoelastic damage model accounts for evolving elastic properties and inelastic strain. The evolving elastic properties are related quantitatively to a damage state variable representing the local density of microcracks. Positive and negative changes of the damage variable lead, respectively, to degradation and recovery of the material in response to loading. A model configuration having an existing narrow zone with localized damage produces for appropriate loading and temperature-pressure conditions an overall cyclic stick-slip motion compatible with a frictional response. Each deformation cycle (limit cycle) can be divided into healing and weakening periods associated with decreasing and increasing damage, respectively. The direct effect of the RS friction and the magnitude of the frictional parameter a are related to material strengthening with increasing rate of loading. The strength and residence time of asperities (model elements) in the weakening stage depend on the rates of damage evolution and accumulation of irreversible strain. The evolutionary effect of the RS friction and overall change in the friction parameters (a-b) are controlled by the duration of the healing period and asperity (element) strengthening during this stage. For a model with spatially variable properties, the damage rheology reproduces the logarithmic dependency of the steady-state friction coefficient on the sliding velocity and the normal stress. The transition from a velocity strengthening regime to a velocity weakening one can be obtained by varying the rate of inelastic strain accumulation and keeping the other damage rheology parameters fixed. The developments unify previous damage rheology results on deformation localization leading to formation of new fault zones with detailed experimental results on frictional sliding. The results provide a route for extending the formulation of RS friction into a non-linear continuum mechanics framework.

Interplay of different NOM fouling mechanisms during ultrafiltration for drinking water production.

PubMed

Jermann, D; Pronk, W; Meylan, S; Boller, M

2007-04-01

Ultrafiltration is an emerging technology for drinking water production, but a main challenge remains the lack of understanding about fouling. This paper investigates the impact of molecular interactions between different natural organic matter (NOM) compounds on ultrafiltration fouling mechanisms. We performed dead-end filtration experiments with individual and mixed humic acid and alginate (polysaccharide). Alginate showed detrimental, but mostly reversible, flux decline and high solute retention. Our results indicate that this was caused by pore blocking transformed into cake building and weak molecular foulant-membrane and foulant-foulant interactions. In the presence of calcium, aggravated fouling was observed, related to complexation of alginate and its subsequently induced gel formation. With humic acid, more severe irreversible fouling occurred due to humic acid adsorption. Minor adsorption of alginate onto the membrane was also observed, which probably caused the substantial irreversible flux decline. The fouling characteristics in the mixtures reflected a combination of the individual humic acid and alginate experiments and we conclude, that the individual fouling mechanisms mutually influence each other. A model elucidates this interplay of the individual fouling mechanisms via hydrophobic and electrostatic interactions. In our study such an interplay resulted in an alginate cake, or gel in the presence of calcium, which is relatively irreversibly adsorbed onto the membrane by humic acid associations. This study shows the importance of mutual influences between various foulants for improved understanding of fouling phenomena. Furthermore it shows that substances with a minor individual influence might have a large impact in mixed systems such as natural water.

Learning Sustainability by Developing a Solar Dryer for Microalgae Retrieval

ERIC Educational Resources Information Center

Malheiro, Benedita; Ribeiro, Cristina; Silva, Manuel F.; Caetano, Nídia; Paulo Ferreira,; Guedes, Pedro

2015-01-01

The development of nations depends on energy consumption, which is generally based on fossil fuels. This dependency produces irreversible and dramatic effects on the environment, e.g. large greenhouse gas emissions, which in turn cause global warming and climate changes, responsible for the rise of the sea level, floods, and other extreme weather…

Economic impacts of invasive species in forest past, present, and future

Treesearch

Thomas P. Holmes; Juliann E. Aukema; Betsy Von Holle; Andrew Liebhold; Erin Sills

2009-01-01

Biological invasions by nonnative species are a by-product of economic activities, with the vast majority of nonnative species introduced by trade and transport of products and people. Although most introduced species are relatively innocuous, a few species ultimately cause irreversible economic and ecological impacts, such as the chestnut blight that functionally...

REPEATED TREATMENTS WITH DOXORUBICIN CAUSES ELECTROCARDIOGRAM (ECG) CHANGES AND INCREASED VENTRICULAR PREMATURE BEATS IN WISTAR-KYOTO (WKY) RATS

EPA Science Inventory

Doxorubicin (DOX) is a widely used anthracycline anti-neoplastic drug used to treat tumors. However it has been implicated in irreversible cardiac toxicity via the generation of a proxidant semiquinone free radical, which often results in cardiomyopathy and changes in the ECG. Ac...

Stress-induced premature senescence (SIPS)--influence of SIPS on radiotherapy.

PubMed

Suzuki, Masatoshi; Boothman, David A

2008-03-01

Replicative senescence is a fundamental feature in normal human diploid cells and results from dysfunctional telomeres at the Hayflick cell division limit. Ionizing radiation (IR) prematurely induces the same phenotypes as replicative senescence prior to the Hayflick limit. This process is known as stress-induced premature senescence (SIPS). Since the cell cycle is irreversibly arrested in SIPS-induced cells, even if they are stimulated by various growth factors, it is thought that SIPS is a form of cell death, irreversibly eliminating replicating cells. IR-induced-focus formation of DNA repair proteins, a marker of DNA damage, is detected in SIPS as well as replicative senescent cells. Furthermore, both processes persistently induce cell cycle checkpoint mechanisms, indicating DNA damage created by ionizing radiation induces SIPS in normal cells, possibly by the same mechanisms as those occurring in replicative senescence. Interestingly, IR induces SIPS not only in normal cells, but also in tumor cells. Due to the expression of telomerase in tumor cells, telomere-dependent replicative senescence does not occur. However, SIPS is induced under certain conditions after IR exposure. Thus, cell death triggered by IR can be attributed to apoptosis or SIPS in tumor cells. However, metabolic function remains intact in SIPS-induced cancer cells, and recent studies show that senescence eliminate cells undergoing SIPS secrete various kinds of factors outside the cell, changing the microenvironment. Evidence using co-culture systems containing normal senescent stromal cells and epithelial tumor cells show that factors secreted from senescent stroma cells promote the growth of tumor epithelial cells both in vitro and in vivo. Thus, regulation of factors secreted from SIPS-induced stromal cells, as well as tumor cells, may affect radiotherapy.

Elimination of the negative component of the unipolar atrial electrogram as an in vivo marker of transmural lesion creation: acute study in canines.

PubMed

Bortone, Agustín; Brault-Noble, Guillaume; Appetiti, Anthony; Marijon, Eloi

2015-08-01

It has been experimentally shown that elimination of the negative component of the unipolar atrial electrogram (R morphology completion) during radiofrequency applications reflects transmural lesions creation. Subsequently, it has been clinically suggested that such a transmurality can be either irreversible or reversible. The present study is aimed to determine, at the histological level, whether transmural lesions, assessed by R morphology completion, might indeed be reversible in some circumstances or not. In 6 Mongrel hound dogs, superior and inferior vena cavae were isolated and individual lesions were created in the right atrium using radiofrequency energy (30 W/48°C/17 mL/min as presettings and 10g of force in average) under CARTO guidance. Five types of lesions were created; R+0: termination of ablation at the time of R morphology completion; R+5, R+10, or R+20: extension of ablation for 5, 10, or 20 seconds, respectively, after R morphology achievement; and conventional: radiofrequency applications lasting 30 seconds irrespective of the atrial electrogram modification. All conventional, R+5, R+10, and R+20 lesions were necrotic and transmural, whereas some R+0 lesions were not (comprising a part of necrosis and a part of reversible cell damage). Interestingly, surrounding organ injuries were observed after conventional, R+10, and R+20 radiofrequency applications but were not observed after R+0 and R+5 applications. Elimination of the negative component of the unipolar atrial electrogram reflects, in general, irreversible transmural necrosis creation. In some cases, however, it translates transmural lesion only (with potential reversibility) likely related to transient cell damage creation. © 2015 American Heart Association, Inc.

Later Onset Fabry Disease, Cardiac Damage Progress in Silence: Experience With a Highly Prevalent Mutation.

PubMed

Hsu, Ting-Rong; Hung, Sheng-Che; Chang, Fu-Pang; Yu, Wen-Chung; Sung, Shih-Hsien; Hsu, Chia-Lin; Dzhagalov, Ivan; Yang, Chia-Feng; Chu, Tzu-Hung; Lee, Han-Jui; Lu, Yung-Hsiu; Chang, Sheng-Kai; Liao, Hsuan-Chieh; Lin, Hsiang-Yu; Liao, Tsan-Chieh; Lee, Pi-Chang; Li, Hsing-Yuan; Yang, An-Hang; Ho, Hui-Chen; Chiang, Chuan-Chi; Lin, Ching-Yuang; Desnick, Robert J; Niu, Dau-Ming

2016-12-13

Recently, several studies revealed a much higher prevalence of later onset Fabry disease (FD) than previously expected. It suggested that later onset FD might present as an important hidden health issue in certain ethnic or demographic populations in the world. However, the natural history of its phenotype has not been systemically investigated, especially the cardiac involvement. The study analyzed a large-scale newborn screening program for FD to understand the natural course of later onset FD. To date, 916,383 newborns have been screened for FD in Taiwan, including more than 1,200 individuals with the common, later onset IVS4+919G>A (IVS4) mutation. Echocardiography was performed in 620 adults with the IVS4 mutation to analyze the prevalence of left ventricular hypertrophy (LVH), and gadolinium-enhanced cardiac magnetic resonance imaging was performed in 129 patients with FD, including 100 IVS4 adults. LVH was observed in 67% of men and 32% of women older than 40 years. Imaging evidenced significant late gadolinium enhancement in 38.1% of IVS4 men and 16.7% of IVS4 women with the IVS4 mutation but without LVH. Seventeen patients underwent endomyocardial biopsies, which revealed significant globotriaosylceramide substrate accumulation in their cardiomyocytes. Significant cardiomyocyte substrate accumulation in IVS4 patients led to severe and irreversible cardiac fibrosis before development of LVH or other significant cardiac manifestations. Thus, it might be too late to start enzyme replacement therapy after the occurrence of LVH or other significant cardiac manifestations in patients with later onset FD. This study also indicated the importance of newborn screening for early detection of the insidious, ongoing, irreversible cardiac damage in patients with later onset FD. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Anisotropy in the Ratchet Growth of PBX 9502

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

Schwarz, Ricardo Blum; Liu, Cheng; Thompson, Darla Graff

2015-03-12

TATB-based compactions and composites are known to undergo “ratchet growth”, an irreversible volume increase that occurs upon heating or cooling of a specimen. Ratchet growth likely arises because the coefficient of thermal expansion of the TATB crystals is strongly anisotropic, but the exact mechanism is not well-understood. TATB crystals in solid, plastic-bonded, explosive PBX 9502 parts can have a preferred crystallographic orientation (texture) caused by the compaction process. As a result, the irreversible strain associated with PBX 9502 ratchet growth is anisotropic. The present paper relates the magnitude of ratchet growth to the crystalline anisotropy of the TATB crystals. Themore » crystalline anisotropy is measured by x-ray diffraction and the ratchet growth is measured by a digital image-correlation technique.« less

[Facial nerve injuries cause changes in central nervous system microglial cells].

PubMed

Cerón, Jeimmy; Troncoso, Julieta

2016-12-01

Our research group has described both morphological and electrophysiological changes in motor cortex pyramidal neurons associated with contralateral facial nerve injury in rats. However, little is known about those neural changes, which occur together with changes in surrounding glial cells. To characterize the effect of the unilateral facial nerve injury on microglial proliferation and activation in the primary motor cortex. We performed immunohistochemical experiments in order to detect microglial cells in brain tissue of rats with unilateral facial nerve lesion sacrificed at different times after the injury. We caused two types of lesions: reversible (by crushing, which allows functional recovery), and irreversible (by section, which produces permanent paralysis). We compared the brain tissues of control animals (without surgical intervention) and sham-operated animals with animals with lesions sacrificed at 1, 3, 7, 21 or 35 days after the injury. In primary motor cortex, the microglial cells of irreversibly injured animals showed proliferation and activation between three and seven days post-lesion. The proliferation of microglial cells in reversibly injured animals was significant only three days after the lesion. Facial nerve injury causes changes in microglial cells in the primary motor cortex. These modifications could be involved in the generation of morphological and electrophysiological changes previously described in the pyramidal neurons of primary motor cortex that command facial movements.

[Orbital compartment syndrome. The most frequent cause of blindness following facial trauma].

PubMed

Klenk, Gusztáv; Katona, József; Kenderfi, Gábor; Lestyán, János; Gombos, Katalin; Hirschberg, Andor

2017-09-01

Although orbital compartment syndrome is a rare condition, it is still the most common cause of blindness following simple or complicated facial fractures. Its pathomechanism is similar to the compartment syndrome in the limb. Little extra fluid (blood, oedema, brain, foreign body) in a non-space yielding space results with increasingly higher pressures within a short period of time. Unless urgent surgical intervention is performed the blocked circulation of the central retinal artery will result irreversible ophthalmic nerve damage and blindness. Aim, material and method: A retrospective analysis of ten years, 2007-2017, in our hospital among those patients referred to us with facial-head trauma combined with blindness. 571 patients had fractures involving the orbit. 23 patients become blind from different reasons. The most common cause was orbital compartment syndrome in 17 patients; all had retrobulbar haematomas as well. 6 patients with retrobulbar haematoma did not develop compartment syndrome. Compartment syndrome was found among patient with extensive and minimal fractures such as with large and minimal haematomas. Early lateral canthotomy and decompression saved 7 patients from blindness. We can not predict and do not know why some patients develop orbital compartment syndrome. Compartment syndrome seems independent from fracture mechanism, comminution, dislocation, amount of orbital bleeding. All patients are in potential risk with midface fractures. We have a high suspicion that orbital compartment syndrome has been somehow missed out in the recommended textbooks of our medical universities and in the postgraduate trainings. Thus compartment syndrome is not recognized. Teaching, training and early surgical decompression is the only solution to save the blind eye. Orv Hetil. 2017; 158(36): 1410-1420.

Using the brain criterion in organ donation after the circulatory determination of death.

PubMed

Dalle Ave, Anne L; Bernat, James L

2016-06-01

The UK, France, and Switzerland determine death using the brain criterion even in organ donation after the circulatory determination of death (DCDD), in which the United States and Canada use the circulatory-respiratory criterion. In our analysis of the scientific validity of the brain criterion in DCDD, we concluded that although it may be attractive in theory because it conceptualizes death as a unitary phenomenon, its use in practice is invalid. The preconditions (ie, the absence of reversible causes, such as toxic or metabolic disorders) for determining brain death cannot be met in DCDD. Thus, although brain death tests prove the cessation of tested brain functions, they do not prove that their cessation is irreversible. A stand-off period of 5 to 10 minutes is insufficient to achieve the irreversibility requirement of brain death. Because circulatory cessation inevitably leads to cessation of brain functions, first permanently and then irreversibly, the use of brain criterion is unnecessary to determine death in DCDD. Expanding brain death to permit it to be satisfied by permanent cessation of brain functions is controversial but has been considered as a possible means to declare death in uncontrolled DCDD. Copyright © 2016 Elsevier Inc. All rights reserved.

Age-related Changes in the Alkaline Phosphatase Activity of Healthy and Inflamed Human Dental Pulp.

PubMed

Aslantas, Eda E; Buzoglu, Hatice Dogan; Karapinar, Senem Pinar; Cehreli, Zafer C; Muftuoglu, Sevda; Atilla, Pergin; Aksoy, Yasemin

2016-01-01

Alkaline phosphatase (ALP) plays an important role in inducing mineralization events in the dental pulp. This study investigated and compared the ALP levels in healthy and inflamed pulp in young and old human pulp. Tissue samples were collected from young (<30 years) and old (>60 years) donors. In both age groups, healthy human pulp (n = 18) were collected from extracted wisdom teeth. For reversible and irreversible pulpitis, pulp samples (n = 18 each) were obtained during endodontic treatment. ALP activity was assessed by spectrophotometry and immunhistochemistry. Regardless of age, reversible pulpitis group samples showed a slight elevation in ALP activity compared with normal healthy pulp. In elderly patients, ALP expression with irreversible pulpitis was significantly higher than those with a healthy pulp (P < .05). In the hyperemic state, both the young and old pulp shows a slight increase in ALP activity, whereas in irreversible pulpitis, only the old pulp shows significantly elevated ALP levels. Such an increase may trigger calcification events, which may eventually cause difficulties in endodontic treatment procedures in elderly individuals. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Comparison of fibroblast cell regeneration in three different concentrations of Wharton’s Jelly mesenchymal stem cells conditioned medium (WJMSCs-CM)

NASA Astrophysics Data System (ADS)

Untoro, E. G.; Asrianti, D.; Usman, M.; Meidyawati, R.; Margono, A.

2017-08-01

Wharton’s Jelly-derived mesenchymal stem cells (WJMSCs) have gained interest as an alternative source of stem cells for regenerative medicine. Although many studies have characterized Wharton’s Jelly biologically, the effects of different concentrations in a cultured medium have not yet been compared. Damaged fibroblasts, the primary components of irreversible dental pulpitis, irreversibly impair the ability to regenerate and lead to the disruption of extracellular matrix. This study was performed to evaluate the potency of three WJMSCs-CM concentrations in improving serum-starved fibroblasts. Fibroblasts were cultivated in five passages, and divided into four groups. The first group (the control group) consisted of fibroblast cells that had been treated using starvation methods. The other groups (the treatment groups) were treated with various concentration of WJMSCs-CM (50%, 25% and 12.5%). Proliferative ability was evaluated using a cell count method and analyzed with a one-way ANOVA. Cultivation of serum-starved fibroblasts produced significantly higher cell counts in 12.5% WJMSCs-CM compared to the 50% group. It can be concluded that 12.5% WJMSCs-CM is the most efficient concentration for fibroblast proliferation.

Osteochondral lesions in developing rats intoxicated with thallium twenty four hours after birth.

PubMed

Barroso-Moguel, R; Villeda-Hernández, J; Méndez-Armenta, M; Ríos, C; Galván-Arzate, S

1992-01-01

An i.p. injection of a solution of thallium acetate in deionized water at a dose of 32 mg/kg, in 24-h-old rats, produces morphological and biochemical alterations in both cartilaginous and osseous tissues. From the beginning, there are alterations in the cartilaginous cell as well as in chrondrine, osteoblasts, osseous tissue and bone marrow. Rats were sacrificed at 24, 48, and 72 h and also at 7 days. Two animals survived for 50 days. One showed total irreversible alopecia while the other one had partial alopecia with discrete recovery. Both showed a low weight and a size of 8 cm. Microscopically, degenerative changes were produced consisting of alteration and death of many cartilaginous cells, uneven metachromasia and the chondrine and decrease of the growth cartilage, scanty bone trabeculae with few osteoblasts. The bone marrow showed few myeloblasts and megakaryocytes. Progressive cellular damage throughout the 50 days of survival represents a response of the thallium ionic accumulation and recycling in cellular mitochondria of all the body's cells. This appeared in our study as irreversible and progressive osteochondral alterations with atrophy of the skin and its adnexa, hyalinization of elastic and collagenous fibers with intense interstitial edema.

Multiscale multifractal time irreversibility analysis of stock markets

NASA Astrophysics Data System (ADS)

Jiang, Chenguang; Shang, Pengjian; Shi, Wenbin

2016-11-01

Time irreversibility is one of the most important properties of nonstationary time series. Complex time series often demonstrate even multiscale time irreversibility, such that not only the original but also coarse-grained time series are asymmetric over a wide range of scales. We study the multiscale time irreversibility of time series. In this paper, we develop a method called multiscale multifractal time irreversibility analysis (MMRA), which allows us to extend the description of time irreversibility to include the dependence on the segment size and statistical moments. We test the effectiveness of MMRA in detecting multifractality and time irreversibility of time series generated from delayed Henon map and binomial multifractal model. Then we employ our method to the time irreversibility analysis of stock markets in different regions. We find that the emerging market has higher multifractality degree and time irreversibility compared with developed markets. In this sense, the MMRA method may provide new angles in assessing the evolution stage of stock markets.

Protective activity of (1S,2E,4R,6R,7E,11E)-2,7,11-cembratriene-4,6-diol analogues against diisopropylfluorophosphate neurotoxicity: preliminary structure-activity relationship and pharmacophore modeling.

PubMed

Eterović, Vesna A; Del Valle-Rodriguez, Angelie; Pérez, Dinely; Carrasco, Marimée; Khanfar, Mohammad A; El Sayed, Khalid A; Ferchmin, Pedro A

2013-08-01

Diisopropylfluorophosphate (DFP) is an organophosphorous insecticide used as a surrogate for the more toxic chemical warfare nerve agent sarin. DFP produces neurotoxicity in vivo and irreversibly decreases the area of population spikes recorded from the CA1 region of acute hippocampal slices. (1S,2E,4R,6R,7E,11E)-2,7,11-Cembratriene-4,6-diol (1) is a neuroprotective natural cembranoid that reverses DFP-induced damage both in vivo and in the hippocampal slice. Cembranoid 1 acts by noncompetitive inhibition of the α7 nicotinic acetylcholine receptor. This study aims at establishing a preliminary structure-activity relationship to define the neuroprotective cembranoid pharmacophores using the hippocampal slice assay and pharmacophore modeling. Fourteen natural, semisynthetic, or biocatalytic cembranoid analogues 2-15 related to 1 were tested for their capacity to protect the population spikes from DFP-induced damage and intrinsic toxicity. Twelve cembranoids caused significant reversal of DFP toxicity; only 3 active analogues displayed minor intrinsic toxicity at 10 μM. The C-4 epimer of 1 (2) and the 4-O-methyl ether analogue of 1 (3), were totally devoid of neuroprotective activity. The results suggested a model for cembranoid binding where the hydrophobic ring surface binds to a hydrophobic (Hbic) patch on the receptor molecule and an electronegative atom (oxygen or sulfur) in proper spatial relationship to the ring surface interacts with an electropositive group in the receptor binding site. A pharmacophore model consisting of 1 hydrogen bond acceptor (HBA), 2 Hbic, and 10 exclusion spheres was established using HipHop-REFINE and supported the above mentioned pharmacophoric hypothesis. Copyright © 2013 Elsevier Ltd. All rights reserved.

Relative Sensitivity of Photosynthesis and Respiration to Freeze-Thaw Stress in Herbaceous Species 1

PubMed Central

Steffen, Kenneth L.; Arora, Rajeev; Palta, Jiwan P.

1989-01-01

The relative effect of a freeze-thaw cycle on photosynthesis, respiration, and ion leakage of potato leaf tissue was examined in two potato species, Solanum acaule Bitt. and Solanum commersonii Dun. Photosynthesis was found to be much more sensitive to freezing stress than was respiration, and demonstrated more than a 60% inhibition before any impairment of respiratory function was observed. Photosynthesis showed a slight to moderate inhibition when only 5 to 10% of the total electrolytes had leaked from the tissue (reversible injury). This was in contrast to respiration which showed no impairment until temperatures at which about 50% ion leakage (irreversible injury) had occurred. The influence of freeze-thaw protocol was further examined in S. acaule and S. commersonii, in order to explore discrepancies in the literature as to the relative sensitivities of photosynthesis and respiration. As bath cooling rates increased from 1°C/hour to about 3 or 6°C/hour, there was a dramatic increase in the level of damage to all measured cellular functions. The initiation of ice formation in deeply supercooled tissue caused even greater damage. As the cooling rates used in stress treatments increased, the differential sensitivity between photosynthesis and respiration nearly disappeared. Examination of agriculturally relevant, climatological data from an 11 year period confirmed that air cooling rates in the freezing range do not exceed 2°C/hour. It was demonstrated, in the studies presented here, that simply increasing the actual cooling rate from 1.0 to 2.9°C/hour, in frozen tissue from paired leaflet halves, meant the difference between cell survival and cell death. Images Figure 4 Figure 5 PMID:16666712

Use and isolation of urinary exosomes as biomarkers for diabetic nephropathy.

PubMed

Musante, Luca; Tataruch, Dorota Ewa; Holthofer, Harry

2014-01-01

Diabetes represents a major threat to public health and the number of patients is increasing alarmingly in the global scale. Particularly, the diabetic kidney disease (nephropathy, DN) together with its cardiovascular complications cause immense human suffering, highly increased risk of premature deaths, and lead to huge societal costs. DN is first detected when protein appears in urine (microalbuminuria). As in other persisting proteinuric diseases (like vasculitis) it heralds irreversible damage of kidney functions up to non-functional (end-stage) kidney and ultimately calls for kidney replacement therapy (dialysis or kidney transplantation). While remarkable progress has been made in understanding the genetic and molecular factors associating with chronic kidney diseases, breakthroughs are still missing to provide comprehensive understanding of events and mechanisms associated. Non-invasive diagnostic tools for early diagnostics of kidney damage are badly needed. Exosomes - small vesicular structures present in urine are released by all cell types along kidney structures to present with distinct surface assembly. Furthermore, exosomes carry a load of special proteins and nucleic acids. This "cargo" faithfully reflects the physiological state of their respective cells of origin and appears to serve as a new pathway for downstream signaling to target cells. Accordingly, exosome vesicles are emerging as a valuable source for disease stage-specific information and as fingerprints of disease progression. Unfortunately, technical issues of exosome isolation are challenging and, thus, their full potential remains untapped. Here, we review the molecular basis of exosome secretion as well as their use to reveal events along the nephron. In addition to novel molecular information, the new methods provide the needed accurate, personalized, non-invasive, and inexpensive future diagnostics.